Devices for biological analysis

Abstract

One aspect provided herein is an analyte processing device, comprising one or more flow channels, wherein at least one flow channel of the one or more flow channels comprise an analyte processing area; one or more excitation sources in optical communication with the analyte processing area, and comprising an optical path from the one or more excitation sources to the analyte processing area; and one or more photodetectors in optical communication with the analyte processing area, wherein the optical path comprises a light scattering control system.

Description

WSGR Reference No.64149-703.601 DEVICES FOR BIOLOGICAL ANALYSIS CROSS REFERENCE

[0001] This application claims benefit of U.S. Provisional Patent Application No.63 / 621,950, filed on January 17, 2024, which is incorporated herein by reference in its entirety. BACKGROUND

[0002] Flow cytometry (FC) devices and systems can be used to characterize and analyze particles in fluid, e.g., physical and biochemical properties of cells and biochemical molecules or molecule clusters based on their optical responses as they are interrogated by external light sources in a serial manner. Optical signals from such particles can be collected by an optical detector, such as a photomultiplier tube (PMT), and are analyzed or processed to extract information carried by the optical properties of the particles. The optical signals from the particles can be caused by one or more interactions between the input light and the particles such as forward scattering (FSC), side scattering (SSC), and fluorescence. There is currently a gap between demand to characterize biological systems and the devices which are capable to perform such characterization. SUMMARY

[0003] Efficient and favorable conditions for characterizing biological systems optically are valuable to human endeavors.

[0004] In one aspect disclosed herein is a device for processing an analyte in a biological sample, the device comprising: an inlet configured to receive a container comprising the biological sample; a first chamber in fluidic communication the inlet, wherein the first chamber comprises a filter configured to remove contaminants from the biological sample; a second chamber comprising one or more reagents for configuring the analyte for optical detection, wherein the second chamber is in fluidic communication with the first chamber; and a microfluidic chip in fluidic communication with the second chamber, wherein the microfluidic chip comprises: one or more channels, a channel of the one or more channels comprises a plurality of detection zones, wherein the device is configured to be received by a housing in electrical communication with a detector. In some embodiments, the received container is in an upside-down position relative to the device. In some embodiments, the received container is configured to provide the biological sample using a mild vacuum. In some embodiments, the device further comprises one or more valves disposed between: the inlet and the first chamber; the first chamber and the second chamber; the second chamber and the microfluidic chip; or any combination thereof; the one or more valves is configured to open when the device is receivedWSGR Reference No.64149-703.601 by the housing. In some embodiments, the device further comprises a third chamber in fluidic communication with the second chamber, the microfluidic device, or both, and the third chamber is configured to collect the analyte. In some embodiments, the device further comprises one or more reagent reservoirs. In some embodiments, the second chamber comprises one or more reagents are dried and coupled to an inner surface of the second chamber. In some embodiments, the one or more reagents are dried and coupled to the inner surface of the second chamber comprise an antibody configured to bind to the analyte. In some embodiments, the device further comprises a first reagent reservoir in fluidic communication with the second chamber, the first reagent reservoir comprises one or more reagents configured to facilitate binding of the analyte and the antibody configured to bind to the analyte. In some embodiments, the device further comprises a second reagent reservoir in fluidic communication with the microfluidic chip, the second reagent reservoir comprises one or more reagents configured to facilitate transport of the analyte through the one or more channels. In some embodiments, the device further comprises a lysis reagent reservoir in fluidic communication with the first chamber. In some embodiments, the device further comprises a cooling unit in communication with the second chamber. In some embodiments, the device is configured to align the one or more detection zones with one or more optical paths of the detector such that the one or more detection zones are in optical communication with the detector upon the housing receiving the detector. In some embodiments, the inlet comprises one or more protrusions or prongs, the one or more protrusions or prongs comprise one or more channels in fluidic communication with the first chamber. In some embodiments, the one or more protrusions or prongs are configured to couple to the container comprising the biological sample and to form a sealed coupling to the container. In some embodiments, the one or more protrusions or prongs are configured to collect the analyte and facilitate transport of the analyte to the first chamber. In some embodiments, the first chamber, the third chamber, the microfluidic chip, or any combination thereof, is in fluidic communication with one or more waste reservoirs. In some embodiments, the one or more reagents dried and coupled to the inner surface of the second chamber are lyophilized. In some embodiments, the first reagent reservoir comprises one or more reagents for fluorescent- activation cell sorting (FACS) analysis of the analyte. In some embodiments, the second reagent reservoir comprises one or more surfactants. In some embodiments, the microfluidic chip comprises one or more single photon avalanche diode (SPAD) arrays.

[0005] In another aspect disclosed herein is a method of screening a particle, the method comprising: subjecting the particle to flow in a channel, wherein the orientation of the particle is manipulated at least once in a single pass of the particle along the channel; providing a first light beam diffracted into at least a second light beam and a third light beam, wherein the second lightWSGR Reference No.64149-703.601 beam exposes a first location on the channel and the third light beam exposes a second location on the channel, and wherein the particle has a first orientation in the first location and a second orientation at the second location, thereby generating a first photon from the first location and a second photon from the second location; and detecting the first photon and the second photon using a single photon avalanche diode (SPAD) array in proximity of the channel. In some embodiments, the first photon is emitted from a first region on a surface of the particle and the second photon is emitted from a second region on the surface. In some embodiments, the channel is part of a microfluidic device. In some embodiments, the microfluidic device is part of an integrated system, and the system further comprises the SPAD array. In some embodiments, the system further comprises a photonics circuit configured to diffract the first light beam into the second and the third light beams. In some embodiments, the channel comprises a physical bump configured to manipulate the orientation of the particle. In some embodiments, the channel comprises a surface acoustic wave (SAW) source configured to generate one or more acoustic waves, the one or more acoustic waves manipulate the orientation of the particle. In some embodiments, the channel comprises a plurality of SAW sources. In some embodiments, the first location and the second location are spatially separate detection regions separated by at least one re-orientation region configured to manipulate the orientation of the cell. In some embodiments, the re-orientation region comprises at least one of: a bump, a surface acoustic wave source (SAW), a channel segment with a different channel width compared to the channel, or any combination thereof. In some embodiments, the re-orientation region comprises a relaxation segment of the channel having a width wider that the width of the channel, and the particle relaxes and re-orients as it passes through the relaxation segment. In some embodiments, the re-orientation region comprises a constriction segment having a width narrower that the width of the channel, and the particle stretches and re-orients as it passes through the constriction segment. In some embodiments, the channel comprises a serpentine channel, a spiral channel, or both. In some embodiments, the integrated system further comprises an inlet. In some embodiments, the integrated system further comprises a filtration module. In some embodiments, the integrated system further comprises a sample preparation module configured to prepare the particle for screening. In some embodiments, the sample preparation module is configured to enrich the particle, stain the particle with a dye, add a reagent onto the particle, perform an assay on the particle, inject a reagent inside the particle, or any combination thereof. In some embodiments, the reagent comprises a fluorescent entity. In some embodiments, the reagent comprises a fluorescent dye, a fluorophore, an antibody, a nucleic acid molecule, or any combination thereof, the reagent is excitable by a light to emit the first photon, the second photon, or both. In some embodiments, further comprising characterizing a surface of theWSGR Reference No.64149-703.601 particle and generating a topographic map of the surface. In some embodiments, the topographic map comprises a location map of one or more markers, an intensity map of one or more markers, a density map of one or more markers, or any combination thereof. In some embodiments, the analyte comprises or is an aerosol. In some embodiments, the analyte comprises or is a cell. In some embodiments, the analyte comprises or is a cell, and the topographic map is a topographic map of a cell surface marker. In some embodiments, further comprising diagnosing the subject with a condition or disease. In some embodiments, further comprising classifying the cell into one or more classifications, providing one or more insights about the condition of the subject, or both. In some embodiments, further comprising an analyte sorting module. In some embodiments, the analyte sorting module is configured to sort the analyte based on a classification of the one or more classifications. In some embodiments, the analyte sorting module comprises a valve. In some embodiments, the channel comprises a plurality of spatially separate detection regions, a detection region comprises a vortex, the particle is trapped in the vortex for a duration of time and screened. In some embodiments, the channel comprises an inlet connect to a sample reservoir containing the particle. In some embodiments, the particle is stirred, mixed, vortexed, rotated, or any combination thereof in the sample reservoir to prevent the sedimentation of the particle in the sample reservoir.

[0006] In another aspect disclosed herein is a system comprising a screening module comprising a plurality of layers, wherein the plurality of layers comprise: a first layer comprising a microfluidic device, wherein the microfluidic device comprises a flow channel configured to flow a particle therein, wherein the flow channel comprises a plurality of detection regions therein, a second layer adjacent to the first layer comprising a photonic circuit configured to diffract a single beam into two or more diffracted beams, wherein the two or more diffracted beams expose the plurality of detection regions, thereby generating a plurality of photons from the particle; and, a third layer comprising a single photon avalanche diode (SPAD) array configured to detect the plurality of photons. In some embodiments, the plurality of detection regions is spatially separated. In some embodiments, the plurality of detection regions each comprise a vortex, the particle is trapped in the vortex. In some embodiments, the flow channel comprises a bump or a surface acoustic wave (SAW) source between a first detection region and a second detection region of the plurality of detection regions, the bump or the SAW source is configured to re-orient the particle. In some embodiments, the flow channel comprises a serpentine channel, a spiral channel, or both. In some embodiments, the flow channel further comprises a re-orientation region comprising at least one of: a bump, a surface acoustic wave source (SAW), a relaxation region wider than the flow channel, a constriction region narrower than the flow channel, a slow-down structure, or any combination thereof. In someWSGR Reference No.64149-703.601 embodiments, the microfluidic device further comprises an inlet. In some embodiments, the system further comprises a filtration module configured to filter the particle prior to entering the microfluidic device. In some embodiments, the system further comprises a sample preparation module configured to prepare the particle for screening. In some embodiments, the sample preparation module is configured to enrich the particle, stain the particle with a dye, add a reagent onto the particle, perform an assay on the particle, inject a reagent inside the particle, or any combination thereof. In some embodiments, the reagent comprises a fluorescent entity. In some embodiments, the reagent comprises a fluorescent dye, a fluorophore, an antibody, a nucleic acid molecule, or any combination thereof, the reagent is excitable by a light to emit the first photon, the second photon, or both. In some embodiments, further comprising a sample barcode reader configured to detect and record a barcode associated with a sample comprising the particle. In some embodiments, further comprising a processor configured to analyze data generated by the system. In some embodiments, the processor is further configured to link a sample barcode to data generated by the system. In some embodiments, the particle comprises a biological material. In some embodiments, the biological material comprises one or more cells or one or more cell organelles. In some embodiments, the particle is contained in an exosome. In some embodiments, the particle is extravesicular. In some embodiments, the particle comprises a microorganism or microbe.

[0007] In another aspect disclosed herein is a method of morphological reconstruction of an analyte in-motion, the method comprising: subjecting the analyte to flow through a channel; subjecting the analyte to a light from one or more excitation sources, wherein the light is interacted with by the analyte, thereby emitting a plurality of photons from the analyte; detecting the plurality of photons using an image sensor placed in proximity of the channel, thereby generating an image; repeating the subjecting the analyte to the light operation and the detecting operation to generate a plurality of images; and processing the plurality of images using a machine learning model to generate a morphological reconstruction of the analyte, wherein the machine learning model is configured to perform operations including: segmenting the plurality of images to identify the pixels corresponding to the analyte, using an encoder-decoder architecture to generate the morphological reconstruction of the analyte. In some embodiments, the machine learning model is further configured perform operations including cropping the plurality of images to center the analyte in each of the plurality of images. In some embodiments, the morphological reconstruction generated by the encoder-decoder architecture is a higher resolution than the plurality of images generated from the detection of the plurality of photons by the image sensor. In some embodiments, the morphological reconstruction generated by the encoder-decoder architecture is at least one two-dimensional image, the at least one two-WSGR Reference No.64149-703.601 dimensional image is a higher resolution than the plurality of images generated from the detection of the plurality of photons by the image sensor. In some embodiments, the morphological reconstruction generated by the encoder-decoder architecture is at least one three- dimensional image, the at least one three-dimensional image is a higher resolution than the plurality of images generated from the detection of the plurality of photons by the image sensor. In some embodiments, the morphological reconstruction generated by the encoder-decoder architecture is optimized in comparison to the plurality of images generated from the detection of the plurality of photons by the image sensor. In some embodiments, the optimized morphological reconstruction undergoes differentiable optimization comprising one optimization per interference and does not require training data. In some embodiments, the optimized morphological reconstruction occurs only at the forward pass and requires training data. In some embodiments, the deep neutral network simulates training data using a physical process for which the parameters are defined. In some embodiments, further comprising applying a machine learning classifier to obtain one or more characteristics of the analyte from the morphological reconstruction of the analyte. In some embodiments, the one or more characteristics of the analyte comprise an analyte size, an analyte length, an analyte thickness, an analyte roughness, an analyte type, an analyte morphology, or an analyte shape. In some embodiments, the analyte shape comprises a round shape, a cubic shape, an oval shape, or a tangled shape. In some embodiments, the machine learning classifier comprises a neural network. In some embodiments, the machine learning classifier is initially trained on a library of data comprising one or both of a plurality of synthetic analytes or a plurality of simulated analytes. In some embodiments, the machine learning model is initially trained on a library of data comprising one or both of a plurality of synthetic analytes or a plurality of simulated analytes. In some embodiments, the plurality of synthetic analytes has a diameter of about 800 nm to about 5000 nm. In some embodiments, the machine learning model comprises at least one of a convolutional neural network (CNN), a long-short-term-memory (LSTM) network, a recurrent neural network (RNN), a transformer, or an encoder-decoder network. In some embodiments, the encoder-decoder network comprises a pre-trained VGG19 encoder network. In some embodiments, further comprising performing the method on a population of analytes to obtain an analyte size distribution. In some embodiments, further comprising performing the method on multiple analytes. In some embodiments, further comprising performing the method on a population of analytes to obtain for a plurality of the population of analytes one or more metrics comprising an analyte size, an analyte length, an analyte roughness, an analyte type, an analyte morphology, or an analyte shape. In some embodiments, the operations of (e) further include applying a confidence threshold to the detection of the analyte. In some embodiments,WSGR Reference No.64149-703.601 the machine learning model is further configured to perform operations including up-sampling the morphological reconstruction of the analyte. In some embodiments, the light from one or more excitation sources comprises an intensity-modulated laser light. In some embodiments, the intensity-modulated laser light is split into a plurality of laser light beams. In some embodiments, the light from one or more excitation sources comprises a discrete laser light. In some embodiments, the plurality of images is generated at a rate of at least 1 KHz. In some embodiments, the plurality of images is generated at a rate of at least 5 KHz. In some embodiments, the plurality of images is generated at a rate of at least 10 KHz. In some embodiments, the image sensor comprises a complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) array. In some embodiments, the image sensor comprises a confocal microscope or a high-speed camera. In some embodiments, the analyte comprises an aerosol. In some embodiments, the channel is one of a plurality of channels. In some embodiments, the channel is a microfluidic device channel. In some embodiments, the morphological reconstruction comprises a topographic map of the analyte. In some embodiments, the light is diffracted into one or more beams exposing a plurality of separate locations along the channel, thereby exciting the analyte repeatedly in one pass of the analyte along the channel, the excitation of the analyte emits one or more photons of the plurality of photons. In some embodiments, the morphological reconstruction comprises a surface of the analyte. In some embodiments, the flow is from about 1 cell per second to about 10,000 cells per second.

[0008] In another aspect disclosed herein is a labelling complex comprising: an antibody configured to bind to an analyte; a circularized nucleic acid molecule, the circularized nucleic acid molecule is engineered to: conjugate to the antibody; comprise a binding site for one or more labeled oligonucleotides comprising a label, wherein the circularized nucleic acid molecule comprises a first binding site for a first labeled oligonucleotide of the one or more labeled oligonucleotides, and wherein the circularized nucleic acid molecule comprises a second binding site for a second oligonucleotide of the one or more labeled oligonucleotides; and wherein the one or more labeled oligonucleotides, the one or more labeled oligonucleotides are bound to the circularized nucleic acid molecule.

[0009] In another aspect disclosed herein is a labelling complex comprising: an antibody configured to bind to an analyte; a circularized nucleic acid molecule, wherein the circularized nucleic acid molecule is engineered to: conjugate to the antibody; comprise one or more binding sites for one or more labeled oligonucleotides comprising a label, wherein a binding site on the circularized nucleic acid molecule is specific to a labeled oligonucleotide of the one or moreWSGR Reference No.64149-703.601 labeled oligonucleotides; and the one or more labeled oligonucleotides, wherein the one or more labeled oligonucleotides are bound to the circularized nucleic acid molecule. In some embodiments, the label comprises a secondary antibody conjugated to a signal-emitting moiety. The signal-emitting moiety of any one of the preceding claims, the signal-emitting moiety comprises a fluorescence mechanism. The signal-emitting moiety of any one of the preceding claims, the signal-emitting moiety comprises a fluorophore, a fluorescent dye, or a quantum dot. In some embodiments, the one or more labeled oligonucleotides comprises at least 2, 3, 4, 5, 6, or 7 labeled oligonucleotides. In some embodiments, the one or more labeled oligonucleotides comprise a length of at least about 2 bases. In some embodiments, the first binding site is located at least about 4 bases from the second binding site on the circularized nucleic acid molecule. In some embodiments, the first labeled oligonucleotide comprises at least about 2 signal-emitting moieties. In some embodiments, the circularized nucleic acid molecule comprises a length of at least about 100 bases. In some embodiments, the circularized nucleic acid molecule comprises a length of at least about 40 bases. In some embodiments, the circularized nucleic acid molecule comprises a length of at least about 10 bases.

[0010] In another aspect disclosed herein is a method of detecting an analyte, the method comprising: providing an antibody configured to bind to the analyte, wherein the antibody is conjugated to a circularized nucleic acid molecule, wherein the circularized nucleic acid molecule is engineered to: conjugate to the antibody; comprise one or more binding sites for one or more labeled oligonucleotides comprising a label, wherein a binding site on the circularized nucleic acid molecule is specific to a labeled oligonucleotide of the one or more labeled oligonucleotides; contacting the analyte with the antibody; and detecting a signal from the one or more labeled oligonucleotides.

[0011] In another aspect disclosed herein is a method of detecting an analyte, the method comprising: providing an antibody configured to bind to the analyte, wherein the antibody is conjugated to a circularized nucleic acid molecule, wherein the circularized nucleic acid molecule is engineered to: conjugate to the antibody; comprise one or more labeled oligonucleotides, wherein the one or more labeled oligonucleotides comprises: a first labeled oligonucleotide comprising a first binding site on the circularized nucleic acid molecule; and a second labeled oligonucleotide comprising a second binding site on the circularized nucleic acid molecule; and detecting a signal from the one or more labeled oligonucleotides. In some embodiments, the one or more labeled oligonucleotides comprises at least about 2 labeled oligonucleotides. In some embodiments, the one or mor labeled oligonucleotides comprise a length of at least about 2 bases. In some embodiments, the first binding site is located at leastWSGR Reference No.64149-703.601 about 2 bases from the second binding site on the circularized nucleic acid molecule. In some embodiments, the first labeled oligonucleotide comprises at least about 2 signal-emitting moieties. In some embodiments, the circularized nucleic acid molecule comprises a length of at least about 100 bases. In some embodiments, the circularized nucleic acid molecule comprises a length of at least about 40 bases. In some embodiments, the circularized nucleic acid molecule comprises a length of at least about 4 bases. In some embodiments, the method further comprises disposing one or more metal particles within proximity of the one or more labeled oligonucleotides. In some embodiments, the one or more labeled oligonucleotides are disposed no more than 15 nanometers from a labeled oligonucleotide of the one or more labeled oligonucleotides.

[0012] A labelling complex comprising: one or more antibodies engineered to bind to an analyte; and a hollow mesoporous silica nanoparticle engineered to: conjugate to the one or more antibodies, and contain at least one luminescent dye. In some embodiments, wherein the at least one luminescent dye comprises a fluorescent molecule. In some embodiments, the hollow mesoporous silica nanoparticle is a mesoporous fused silica nanoparticle. In some embodiments, the hollow mesoporous silica has a tunable pore size, where the tunable pore size is from about 2 nanometers to 50 nanometers in diameter. In some embodiments, the hollow mesoporous silica has a tunable shell thickness that ranges from about 1 nanometer to about 1 micrometer. In some embodiments, the hollow mesoporous silica has a tunable shell thickness of less than 1 nanometer. In some embodiments, one or more parameters of the labeling complex can be altered by a change in a synthesis condition, the one or more parameters comprises stability, absorption, or label loading, and the synthesis condition comprises one or more of temperature, pH, or silica-to-antigen ratio.

[0013] In another aspect disclosed herein is a chip with a layered architecture, comprising: a first layer comprising one or more flow channels, wherein at least one flow channel of the one or more flow channels comprises an analyte processing area; a second layer comprising one or more excitation sources in optical communication with the first and an optical path from the one or more excitation sources to the analyte processing area; and a third layer comprising an array of one or more photodetectors in optical communication with the analyte processing area and an application specific integrated circuit (ASIC), wherein the optical path comprises a light scattering control system. In some embodiments, the third layer comprises at least one single- photon avalanche diodes (SPAD). In some embodiments, the array comprises a plurality of SPAD pixels, the array is in optical communication with the first layer. In some embodiments, the array is engineered to allow space in between each of the plurality of SPAD pixels, the spaceWSGR Reference No.64149-703.601 permits circuitry to surround at least a portion of each of the plurality of SPAD pixels. In some embodiments, a total area of the array and the circuitry comprises an area of the third layer. In some embodiments, the space between each of the plurality of pixels reduces the cross-talk between pixels. In some embodiments, the first layer is engineered to detect one or more morphological characteristic. In some embodiments, the one or more morphological characteristic comprises a dataset used for assessment of a chemical or a biological test. In some embodiments, the one or more morphological characteristic comprises a dataset used for improvement of a chemical or a biological test. In some embodiments, the array and the ASIC creates free space on the third layer. In some embodiments, the free space comprises one or more additional lasers bonded to the third layer. In some embodiments, the one or more excitation sources comprises at least one laser. In some embodiments, the array comprises a complementary metal-oxide semiconductor (CMOS) SPAD array. In some embodiments, at least two of the three layers are combined into a single layer. In some embodiments, all three layers are combined into a single layer.

[0014] In some embodiments, provided herein is an analyte processing device, comprising: one or more flow channels, wherein at least one flow channel of the one or more flow channels comprise an analyte processing area; one or more excitation sources in optical communication with the analyte processing area and comprising an optical path from the one or more excitation sources to the analyte processing area; and one or more photodetectors in optical communication with the analyte processing area, wherein the optical path comprises a light scattering control system.

[0015] In some embodiments, provided herein is an analyte processing device, comprising: one or more flow channels, wherein at least one flow channel of the one or more flow channels comprise an analyte processing area; one or more excitation sources in optical communication with the analyte processing area and comprising an optical path from the one or more excitation sources to the analyte processing area; and one or more photodetectors in optical communication with the analyte processing area, wherein the optical path comprises a light scattering control system, wherein (i), (ii), (iii), or any combination thereof are integrated monolithically, system- in-package, heterogeneously, three-dimensionally integrated, or a combination thereof. In some embodiments, the optical path is configured to yield an evanescent light beam from the one or more excitation sources. In some embodiments, the one or more flow channels comprise more than one analyte processing area. In some embodiments, the one or more excitation sources are integrated with the analyte processing device. In some embodiments, the one or more photodetectors are layered below the one or more flow channels. In some embodiments, the light scattering control system comprises an optical membrane comprising a polarizer, waveplate,WSGR Reference No.64149-703.601 absorber, filter, blocker, concentrator, reflector, or mirror. In some embodiments, the one or more photodetectors comprise a shutter configured to reduce overexposure of light. In some embodiments, the one or more photodetectors comprise a single photodetector pixel. In some embodiments, the one or more photodetector pixels are 10 microns by 10 microns in size. In some embodiments, the one or more photodetector pixels are 20 microns by 20 microns in size. In some embodiments, the one or more photodetector pixels are 20 microns by 10 microns in size. In some embodiments, the analyte processing device comprises two or more photodetectors, wherein the two or more photodetectors are positioned 20 microns apart from one another. In some embodiments, at least one of the one or more excitation sources is a reference excitation source. In some embodiments, the one or more excitation sources is integrated with the analyte processing device. In some embodiments, the one or more photodetectors is integrated with the analyte processing device. In some embodiments, the light scattering control system comprises a dichroic optical component configured to redirect scattered light distal from the one or more photodetectors. In some embodiments, the light scattering control system is configured to improve signal to noise ratio by at least a factor of five. In some embodiments, the filter is comprised of at least one layer of dielectric material configured to absorb unwanted light wavelengths and improve signal to noise ratio by a factor of at least five. In some embodiments, the filter is comprised of at least one layer of semiconductor material configured to absorb unwanted light wavelengths and improve signal to noise ratio by a factor of at least five. In some embodiments, the filter is comprised of at least one layer of metallic material configured to absorb unwanted light wavelengths and improve signal to noise ratio by a factor of at least five. In some embodiments, the filter is comprised of at least two layers of dielectric, semiconductor, or metallic material configured to absorb unwanted light wavelengths and improve signal to noise ratio by a factor of at least 5. In some embodiments, the blocker comprises a layer of absorptive material configured to transmit specific wavelengths. In some embodiments, the blocker is tuned to absorb specific photonic wavelength ranges. In some embodiments, the filter is comprised of at least two layers of dielectric, semiconductor, or metallic material configured to absorb unwanted light wavelengths and improve signal to noise ratio. In some embodiments, the filter is comprised of a polarizing light filter. In some embodiments, the blocker comprises a layer of absorptive material configured to transmit specific wavelengths of light. In some embodiments, the blocker is tuned to absorb specific photonic wavelength ranges. In some embodiments, the one or more photodetectors comprise a complementary metal oxide sensor (CMOS) imager. In some embodiments, the CMOS imager is configured to flush electrons generated with scattered light upon excitation. In some embodiments, the CMOS imager is spectral. In some embodiments, the CMOS imager isWSGR Reference No.64149-703.601 configured for photon intensity. In some embodiments, the CMOS imager is configured for photon wavelength. In some embodiments, the CMOS imager is a pinned photodiode. In some embodiments, the CMOS imager is a single photon avalanche diode array. In some embodiments, the CMOS imager comprises one or more arrays of single photon avalanche diodes. In some embodiments, the CMOS imager further comprises one or more event cameras. In some embodiments, the CMOS imager further comprises one or more time-delay integration (TDI) camera. In some embodiments, the one or more excitation sources further comprise a waveguide. In some embodiments, the one or more flow channels comprise multiple single inlets and a single outlet. In some embodiments, the one or more flow channels comprise multiple single inlets and a doublet outlet. In some embodiments, the one or more flow channels comprise a single inlet and multiple outlets. In some embodiments, the one or more excitation sources further comprise an interposer. In some embodiments, the one or more excitation sources further comprise a transducer. In some embodiments, the transducer is integrated into the chip. In some embodiments, the transducer is external to the chip. In some embodiments, the one or more excitation sources comprise one laser. In some embodiments, the one or more excitation sources comprises one or more light emitting diodes (LED). In some embodiments, the LED is a micro-LED. In some embodiments, the one or more excitation sources comprise multiple lasers. In some embodiments, the one or more excitation sources comprise external lasers. In some embodiments, the one or more excitation sources comprise bonded lasers. In some embodiments, the one or more excitation sources comprise at least one continuous laser. In some embodiments, the one or more excitation sources comprise at least one pulsed laser. In some embodiments, the one or more excitation sources comprise at least one tunable laser. In some embodiments, the one or more excitation sources comprise at least one laser tuned to near IR to visible range wavelengths of light. In some embodiments, the concentrator is a microlens concentrator. In some embodiments, the concentrator comprises a flat lens concentrator. In some embodiments, the concentrator comprises a diffractive lens. In some embodiments, the concentrator comprises an absorptive lens. In some embodiments, the concentrator comprises a non-absorptive lens. In some embodiments, the concentrator comprises a polarization sensitive lens. In some embodiments, the concentrator comprises a dielectric. In some embodiments, the concentrator comprises a dielectric block. In some embodiments, the concentrator comprises a dielectric block at least 100 nanometers thick. In some embodiments, the concentrator comprises a dielectric block at least one micrometer thick. In some embodiments, the one or more excitation sources comprise an optical circuit comprising one or more light entry sections, one or more optical dividers, and a light delivery section. In some embodiments, the light delivery section further comprises one or more dichroic optical components configured to redirectWSGR Reference No.64149-703.601 scattered light away from the light delivery section. In some embodiments, the light entry section comprises vertical couplers. In some embodiments, the light entry section comprises optical grating. In some embodiments, the light entry section further comprises a lateral coupler. In some embodiments, the light entry section is a pinhole. In some embodiments, the reflector is configured to improve the coupling efficiency of the vertical couplers. In some embodiments, the mirror is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the analyte processing area is located at a bottom surface of one or more flow channels. In some embodiments, the one or more flow channels is configured to generate a displacement effect on an analyte located in the at least one flow channel, thereby selectively displacing the analyte in the one or more analyte processing areas. In some embodiments, the displacement is acoustical. In some embodiments, the displacement is electrical. In some embodiments, the displacement is magnetic. In some embodiments, the displacement is caused by a fluid wave. In some embodiments, the displacement is caused by a structure of a flow channel. In some embodiments, the displacement is caused by a density wave. In some embodiments, the displacement is via droplet displacement. In some embodiments, the one or more flow channels further comprises a gate. In some embodiments, the one or more flow channels further comprises a sealable chamber. In some embodiments, the one or more flow channels further comprises one or more pneumatically driven valves. In some embodiments, the one or more flow channels further comprises one or more fluid reservoirs. In some embodiments, the one or more flow channels further comprises one or more peristaltic pumps.

[0016] In some embodiments, provided herein is an analyte imaging device comprising: a light modifying substrate; one or more photodetectors, wherein the one or more photodetectors is adjacent to the light modifying substrate; and one or more flow channels, wherein the one or more flow channels is adjacent to a surface of the light modifying substrate, and wherein a cross sectional dimension of the one or more flow channels is configured to allow the passage of a single cell.

[0017] In some embodiments, the light modifying substrate is displaced between the one or more photodetectors and the one or more flow channels. In some embodiments, the light modifying substrate comprises a diffractive optic layer. In some embodiments, the light modifying substrate is displaced between the one or more photodetectors and the one or more flow channels. In some embodiments, a diffractive optic layer is displaced between the one or more photodetectors and the one or more flow channels. In some embodiments, the one or more flow channels are displaced on or above the diffractive optic layer. In some embodiments, the light modifying substrate is configured to send and receive one or more photons to and from theWSGR Reference No.64149-703.601 one or more flow channels. In some embodiments, the diffractive optic layer is configured to send and receive one or more photons to and from the one or more flow channels. In some embodiments, the one or more photodetectors is configured to receive one or more photons from the light modifying substrate.

[0018] In some embodiments, the one or more photodetectors is configured to receive one or more photons from the diffractive optic layer.

[0019] In some embodiments, provided herein is a chip comprising one or more flow channels, wherein the one or more flow channels comprise one or more light scatter control elements adjacent to one or more analyte processing areas. In some embodiments, the one or more flow channels are configured to rotate a cell on an axis. In some embodiments, the one or light scatter control elements comprise one or more diffractive optic layers. In some embodiments, the one or light scatter control elements comprise one or more light scattering control elements. In some embodiments, the one or light scatter control elements are integrated with the chip. In some embodiments, the flow channel comprises one or more features configured to displace the cell. In some embodiments, the flow channel comprises one or more chemical functionalizations. In some embodiments, the one or more chemical functionalizations are configured to interact with one or more analytes. In some embodiments, the one or more flow channels is configured to receive an acoustic wave, wherein the acoustic wave is configured to rotate the cell on an axis. In some embodiments, the flow channel comprises one or more features configured to rotate the cell on an axis. In some embodiments, the one or more flow channels are configured to contact a light scattering control system. In some embodiments, the one or more flow channels have a width configured to pass one cell at a time. In some embodiments, the width of the one or more flow channels is 100 nanometers. In some embodiments, the one or more light scatter control elements reduces the signal to noise ratio of one or more optical signals emitted from the chip by at least a factor of 10. In some embodiments, the chip comprises at least 20 flow channels. In some embodiments, the chip comprises at least 100 flow channels. In some embodiments, the chip is integrated with a circuit. In some embodiments, the chip is integrated with a microfluidic circuit. In some embodiments, the chip is integrated with an electrical circuit. In some embodiments, the chip is integrated with a photonic circuit. In some embodiments, the chip is configured to connect to an analyte processing device disclosed herein.

[0020] In some embodiments, provided herein is an analyte processing device, comprising: one or more flow channels, at least one flow channel of the one or more flow channels comprising an analyte processing area; one or more excitation sources in optical communication with the analyte processing area; and one or more photodetectors in optical communication with theWSGR Reference No.64149-703.601 analyte processing area, the one or more photodetectors being configured to perform detection of a surface of one or more analytes in fluid motion, wherein the one or more photodetectors are configured to collect one or more two-dimensional images of one or more analytes, wherein the one or more two-dimensional images undergo processing to produce a three-dimensional structure of the one or more analytes.

[0021] In some embodiments, the one or more photodetectors are configured to simultaneously collect the one or more two-dimensional images. In some embodiments, the one or more photodetectors are configured to simultaneously collect the one or more two-dimensional images. In some embodiments, the one or more photodetectors are configured to collect the one or more two-dimensional images without the use of markers or labels. In some embodiments, the one or more photodetector(s) comprises at least one of: a spectral detector, an emissions detector, or a scattering detector. In some embodiments, the analyte processing device comprises at least one emissions detector and at least one scattering detector. In some embodiments, the one or more two-dimensional images determines the absolute or relative size of the analyte. In some embodiments, the three-dimensional structure of the analyte maps the surface of the analyte. In some embodiments, the three-dimensional structure of the analyte comprises deformed representations of the analyte. In some embodiments, the deformed representations of the same analyte represent different deformations. In some embodiments, the deformed representations of the analyte represent an unchanged deformation. In some embodiments, the one or more flow channels are a space-constrained tube relative to the analyte. In some embodiments, the three-dimensional structure of the analyte comprises stretched representations of the analyte while the analyte passes through the space-constrained tube. In some embodiments, the stretched representations of the analyte are differently stretched. In some embodiments, the stretched representations of the analyte are identically stretched. In some embodiments, the stretched representations of the analyte determine elasticity. In some embodiments, the stretched representations of the analyte determine granularity. In some embodiments, the one or more excitation sources in optical communication with the analyte processing area comprises an optical path from the one or more excitation sources to the analyte processing area, the optical path comprising a light scattering control system. In some embodiments, the analyte comprises multiple analytes comprising at least one of: small molecules, polymers, cellular structures, or surface markers. In some embodiments, the multiple analytes comprise materials from biological systems. In some embodiments, the materials from biological systems comprise cells or internal cell organelles. In some embodiments, the multiple analytes comprise free floating or secreted proteins. In some embodiments, the multiple analytes comprise a nucleotide. In some embodiments, the multiple analytes comprise or are containedWSGR Reference No.64149-703.601 within exosomes. In some embodiments, the multiple analytes comprise or are contained within neutrophils. In some embodiments, the multiple analytes comprise nucleotides. In some embodiments, the multiple analytes are extravesicular. In some embodiments, the multiple analytes comprise at least one of microorganisms or microbes. In some embodiments, the three- dimensional structures of each of the multiple analytes is analyzed individually. In some embodiments, the three-dimensional structure of each of the multiple analytes may produce a new three-dimensional structure of an additional, larger analyte. In some embodiments, structural integrity of the multiple analytes is preserved after displacement in the one or more flow channels. In some embodiments, the surface markers comprise cell surface markers. In some embodiments, the processing is performed using Artificial Intelligence (AI). In some embodiments, the analyte processing area comprises a photomultiplier tube. In some embodiments, the one or more photodetectors comprises one or more single-photon avalanche diode (SPAD) arrays. In some embodiments, the one or more photodetectors comprise a single- photon avalanche diodes (SPAD) array. In some embodiments, the one or more photodetectors comprise one or more silicon photomultipliers (SiPM). In some embodiments, the one or more two-dimensional images comprises 1 pixel. In some embodiments, the one or more two- dimensional images has a 1:1 aspect ratio of the analyte. In some embodiments, the one or more two-dimensional images each depict an area on a surface of the analyte having a length of from 0.5 microns to 100 microns and a width from 0.5 microns to 100 microns, and a width being equal to or smaller than the length. In some embodiments, the one or more two-dimensional images having the 1:1 aspect ratio are combined with separate two-dimensional images of the same analyte with the same aspect ratio to produce the three-dimensional structure of an analyte. In some embodiments, the aspect ratios from the one or more two-dimensional images with the 1:1 aspect ratio are combined with separate two-dimensional images with different aspect ratios when producing the three-dimensional structure of one or more analytes. In some embodiments, the three-dimensional structure depicts a holistic distribution of surface markers of the one or more analytes. In some embodiments, the holistic distribution of surface markers can be defined as localized or partial. In some embodiments, the holistic distribution of surface markers can be defined as random. In some embodiments, the holistic distribution of surface markers can determine a parameter of a chemical or biological test. In some embodiments, a defined stretch or a deformation can determine a false positive for a chemical or biological test. In some embodiments, the parameter of a chemical or biological test can separate a false positive from a true positive. In some embodiments, the light scattering control system is configured to improve signal to noise ratio by at least a factor of five relative to photodetecting only unscattered or specular light.WSGR Reference No.64149-703.601

[0022] In some embodiments, provided herein is a method for analyzing an analyte, comprising: providing a device comprising (i) a flow channel and (ii) one or more photodetectors in optical communication with the flow channel, wherein the one or more photodetectors comprises a light scattering control element; using the one or more photodetectors to acquire an optical signal from the analyte flowing through the flow channel; and processing the optical signal to identify a presence of the cell in the fluid flowing through the flow channel.

[0023] In some embodiments, provided herein is a method for analyzing an analyte, comprising: providing a device comprising (i) a flow channel comprising the analyte, and (ii) one or more photodetectors in optical communication with the flow channel; using the one or more photodetectors to acquire a first optical signal from the flow channel at a first position within the flow channel at a first time point; using the one or more photodetectors to acquire a second optical signal from the flow channel at a second position within the flow channel at a second time point subsequent to the first time point, wherein the second position is downstream of the first position; and processing the first optical signal and the second optical signal to identify the analyte flowing through the flow channel.

[0024] In some embodiments, the method further comprises using the one or more photodetectors to acquire a third optical signal at a third position within the flow channel. In some embodiments, the third position is downstream from the second position. In some embodiments, the first position, the second position, and the third position are equidistant from one other. In some embodiments, the difference between the second time point and the first time point is substantially equal to a difference between the third time point and the second time point. In some embodiments, the device comprises one or more excitation sources. In some embodiments, the one or more excitation sources provide excitation energy to the flow channel to yield the first optical signal, the second optical signal, or the third optical signal. In some embodiments, the one or more excitation sources comprises at least one continuous wave laser. In some embodiments, the one or more excitation sources comprises at least one pulsed laser. In some embodiments, the one or more excitation sources comprises at least one tunable laser. In some embodiments, the one or more excitation sources comprises a laser tuned to near IR to visible wavelengths. In some embodiments, the one or more excitation sources comprises a single laser. In some embodiments, the one or more excitation sources comprises multiple lasers. In some embodiments, the one or more excitation sources comprises bonded lasers. In some embodiments, the one or more excitation sources comprises external lasers. In some embodiments, the one or more photodetectors comprise a single pixel photodetector. In some embodiments, the flow channel is on a substrate. In some embodiments, the photodetectors areWSGR Reference No.64149-703.601 on the substrate. In some embodiments, the flow channel and the one or more photodetectors are on layers on the substrate. In some embodiments, the processing comprises Time-correlated Single Photon Counting (TCSPC). In some embodiments, the processing comprises Uncorrelated Time-lapse Microscopy (UTLM). In some embodiments, the method further comprises an analyte sorting operation. In some embodiments, the analyte motion is laminar. In some embodiments, the analyte motion is turbulent. In some embodiments, the analyte is not in motion. In some embodiments, the analyte is an aerosol. In some embodiments, the analyte is in the gas phase. In some embodiments, the analyte is in the liquid phase. In some embodiments, the analyte is an aqueous solution. In some embodiments, the analyte is at least one of a gas or a vapor, wherein said gas or vapor analyte is dissolved in an aqueous solution. In some embodiments the analyte is a gas in at least one of an aqueous solution or a fluidic solution. In some embodiments the concentration of the gas analyte dissolved in an aqueous or fluidic solution ranges from 1 cell per microliter to 1 billion cells per microliter. In some embodiments, the analyte comprises one or more cells. In some embodiments, the analyte comprises blood. In some embodiments, the analyte comprises lymph. In some embodiments, the analyte comprises a cell line. In some embodiments, the analyte comprises a cell culture. In some embodiments, the analyte comprises a human cell. In some embodiments, the analyte comprises a bacterial cell. In some embodiments, the analyte comprises urine. In some embodiments, the analyte comprises bodily fluids. In some embodiments, the analyte comprises feces. In some embodiments, the analyte comprises peritoneal cavity fluid. In some embodiments, the analyte comprises bone marrow fluid. In some embodiments, the analyte comprises cerebrospinal fluid. In some embodiments, the analyte comprises cells purified from a subject’s blood sample. In some embodiments, the analyte comprises blood serum or plasma. In some embodiments, the flow channel is configured to result in displacement of the analyte. In some embodiments, the displacement is electrical. In some embodiments, the displacement is magnetic. In some embodiments, the analyte displacement is thermal. In some embodiments, the one or more photodetectors is configured for spectral range. In some embodiments, the one or more photodetectors is configured for photon intensity. In some embodiments, the one or more photodetectors is configured for photon wavelength. In some embodiments, the one or more photodetectors comprises a pinned photodiode. In some embodiments, the one or more photodetectors comprises a single photon avalanche diode. In some embodiments, the processing comprises time of flight processing.

[0025] In some embodiments, provided herein is a method of imaging an analyte in motion, comprising: providing a flow channel adjacent to one or more photodetectors, wherein the flow channel comprises an analyte processing area configured for one or more photodetection events;WSGR Reference No.64149-703.601 providing conditions sufficient for the analyte to travel along a path in the flow channel; using the one or more photodetectors to probe the analyte in motion N times within the analyte processing area, wherein N is a number greater than one; repeating the first through third operation (i-iii) M times to generate an N x M time of flight (TOF) data for the analyte in motion, wherein M is a number greater than one; and using the N x M TOF data to classify the analyte in motion at an accuracy greater than 80 %.

[0026] In some embodiments, using the N x M TOF data classifies the analyte in motion at an accuracy greater than 90 %. In some embodiments, using the N x M TOF data classifies the analyte in motion at an accuracy greater than 95 %. In some embodiments, using the N x M TOF data classifies the analyte in motion at an accuracy greater than 98 %. In some embodiments, using the N x M TOF data classifies the analyte in motion at an accuracy greater than 99 %. In some embodiments, the analyte in motion is probed at spatially separate locations along the analyte processing area. In some embodiments, the flow channel further comprises one or more pneumatically driven valves. In some embodiments, the flow channel further comprises one or more fluid reservoirs. In some embodiments, the flow channel further comprises one or more peristaltic pump valves. In some embodiments, the flow channel further comprises one or more peristaltic pump valves. In some embodiments, the classification confirms a biotherapeutic analytical characterization. In some embodiments, the classification comprises classifying a cellular phenotype. In some embodiments, the classification comprises using a machine learning algorithm. In some embodiments, the machine learning algorithm is a convolutional neural network. In some embodiments, the machine learning algorithm is a generational neural network. In some embodiments, the convolutional neural network is a 1D neural network trained using a training data set comprising at least 100 data sets. In some embodiments, the machine learning algorithm classifies cells as cancerous or non-cancerous. In some embodiments, the machine learning algorithm classifies at least 100,000 cells per second. In some embodiments, the machine learning algorithm classifies with a false negative rate of less than one in one billion. In some embodiments, the machine learning algorithm classifies with a false positive rate of less than one in one billion. In some embodiments, the machine learning algorithm classifies with a true positive rate of at least 99.9 percent.

[0027] In some embodiments, provided herein is a method of determining a dimension of an analyte or a cell, the method comprising subjecting the analyte or the cell to flow along a flow channel; and repeatedly detecting one or more beams of light, wherein the one or more beams of light are scattered by the analyte or the cell, and wherein the one or more beams of light comprise an angular light scattering pattern, wherein the angular light scattering patternWSGR Reference No.64149-703.601 identifies the dimension of the analyte or the cell. In some embodiments, provided herein is a method of determining a dimension of an analyte or a cell, the method comprising subjecting the analyte or the cell to flow along a flow channel; and repeatedly detecting one or more beams of light, wherein the one or more beams of light are scattered by the particle or the cell, and wherein the one or more beams of light comprise a light scattering spectral pattern, wherein the light scattering spectral pattern identifies the dimension of the analyte or the cell. In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting a signal from the cell to identify the cellular size at an accuracy of at least 10-9 m in a time period of at most 10 minutes. In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting a signal from the cell to identify the cellular organelle size at an accuracy of at least 10-9 m in a time period of at most 10 minutes. In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting a signal from the cell to identify a number of cellular mitochondria at an accuracy of at least 95 percent in a time period of at most 10 minutes. In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting a signal from the cell to identify a population of at least 1,000 cells in a time period of at most 10 minutes. In some embodiments, provided herein is a method of imaging a surface of a cell, the method comprising: providing a fluidic microchannel configured to receive the cell, wherein the fluidic microchannel comprises at least two detection zones along a length of the fluidic microchannel, wherein each of the at least two detection zones comprise an imager, and wherein the microfluidic channel comprises a feature adjacent to the at least two detection zones, wherein the feature is configured to induce a rotation along an axis of the cell upon contact with the cell; disposing the cell in the fluidic microchannel; providing a force adjacent to the fluidic microchannel, thereby traversing the cell across the length of the fluidic microchannel, wherein the feature does not terminate the traversing of the cell across the length of the fluidic microchannel; and capturing at least two, two dimensional images of the cell. In some embodiments, the at least two, two dimensional images of the cell are at least super-resolution. In some embodiments, the method further comprises generating a three-dimensional structure of the cell derived from the at least two, two dimensional images of the cell. In some embodiments, provided herein is a method of imaging a surface of a cell in three dimensions, the method comprising: a. providing a flow channel configured to receive the cell, wherein the flow channel comprises at least a first detection zone and a second detection zone along a length of the flow channel, wherein the first detection zone, the second detectionWSGR Reference No.64149-703.601 zone, or both, comprises an imager, and wherein the microfluidic channel comprises a feature adjacent to the first detection zone or the second detection zone, wherein the feature is configured to induce a rotation along an axis of the cell upon contact with the cell; (b) disposing the cell in the flow channel; (c) subjecting the cell to flow through the flow channel; (d) capturing one or more images of the cell as the cell passes the first detection zone and the second detection zone; and (e) generating a three-dimensional structure of the cell derived from the one or more images of the cell. In some embodiments, the feature does not terminate the flow of the cell through the fluidic microchannel. In some embodiments, the three-dimensional structure comprises an atlas of the cell. In some embodiments, the three-dimensional structure of the cell is at least super-resolution. In some embodiments, the three-dimensional structure comprises a classification of one or more membrane bound structures of the cell. In some embodiments, the three-dimensional structure comprises a morphometric classification of the cell. In some embodiments, the three-dimensional structure comprises a topography map of one or more membrane bound structures of the cell. In some embodiments, the three-dimensional structure comprises a map comprising a location of the one or more membrane bound structures on the surface of the cell. In some embodiments, the three-dimensional structure further comprises a motion dynamic characterization of the cell. In some embodiments, the detection comprises a spatial density map of one or more analytes. In some embodiments, the three-dimensional structure comprises one or more dynamic topographical data of the cell. In some embodiments, the cell is a single cell of a population of cells, and wherein the method further comprises repeating (b)-(e) for a second cell of the population of cells. In some embodiments, the steps (b)- (e) for the second cell of the population of cells occurs simultaneously to the first cell. In some embodiments, the repeating (b)-(e) for the second cell of the population of cells occurs subsequent to the first cell. In some embodiments, the first cell is a single cell of a population of cells, and wherein the method further comprises repeating (b)-(e) for a hundredth cell of the population of cells. In some embodiments, the repeating (b)-(e) for the hundredth cell of the population of cells occurs simultaneously to the first cell. In some embodiments, the repeating (b)-(e) for the hundredth cell of the population of cells occurs subsequent to the first cell. In some embodiments, provided herein is a method of analyzing a subject’s blood comprising connecting a subject’s blood flow to a device or analyte processing device disclosed herein. In some embodiments, the analysis comprises cancer cell detection. In some embodiments, the analysis comprises preparation of a subject’s blood prior to analysis. In some embodiments, the analysis further comprises removal of cancer cells. In some embodiments, the analysis comprises intermittent sampling of the subject’s blood. In some embodiments, provided herein is a method of spatially identifying one or more markers on an analyte surface, comprising:WSGR Reference No.64149-703.601 subjecting the analyte to flow through a flow channel; subjecting the analyte to one or more excitation sources, wherein the one or more excitation sources generates a light scattering pattern of the analyte surface; processing the light scattering pattern algorithmically to generate a topographic map of the analyte surface. In some embodiments, the topographic map comprises a location map of one or more markers. In some embodiments, the topographic map comprises an intensity map of one or more markers. In some embodiments, the topographic map comprises a density map of one or more markers.

[0028] In some embodiments, the analyte comprises a plurality of particles. In some embodiments, the plurality of particles can be a plurality of cells or a plurality of molecules. In some embodiments, the first detection zone and / or the second detection zone can accommodate the plurality of particles at the same time. In some embodiments, the width of the first detection zone and / or the second detection zone can accommodate the plurality of particles at the same time. In some embodiments, the height of the first detection zone and / or the second detection zone can accommodate the plurality of particles at the same time. In some embodiments, the first detection zone and / or the second detection zone can accommodate at least 1, at least 2, at least 3, at least 4, at least 4, at least 5, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 120, at least 140, at least 160, at least 180, at least 200, at least 300, at least 400, or at least 500 particles of the plurality of particles at the same time. In some embodiments, the width of the first detection zone and / or the second detection zone can accommodate at least 1, at least 2, at least 3, at least 4, at least 4, at least 5, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 120, at least 140, at least 160, at least 180, at least 200, at least 300, at least 400, or at least 500 particles of the plurality of particles at the same time. In some embodiments, the height of the first detection zone and / or the second detection zone can accommodate at least 1, at least 2, at least 3, at least 4, at least 4, at least 5, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 120, at least 140, at least 160, at least 180, at least 200, at least 300, at least 400, or at least 500 particles of the plurality of particles at the same time. In some embodiments, the width and / or the height of the first detection zone and / or the second detection zone can accommodate at least 1, at least 2, at least 3, at least 4, at least 4, at least 5, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 120, at least 140, at least 160, at least 180, at least 200, at least 300, at least 400, or at least 500 particles of the plurality of particles at the same time. In some embodiments, the plurality of particles has freedom of motion as passes the channel between the first detection zone and the secondWSGR Reference No.64149-703.601 detection zone. In some embodiments, the freedom of motion is perpendicular to the direction of the flow of the channel. In some embodiments, the first detection zone and / or the second detection zone comprises a width of between about 10 μm to about 100 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a width of between about 10 μm to about 30 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a width of between about 1 μm to about 10 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a width of between about 0.1 μm to about 1.0 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a width of between about 0.01 μm to about 0.1 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a width of between about 0.001 μm to about 0.01 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a width of between about 0.001 μm to about 1.0 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a height of between about 10 μm to about 100 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a height of between about 10 μm to about 30 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a height of between about 1 μm to about 10 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a height of between about 0.1 μm to about 1.0 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a height of between about 0.01 μm to about 0.1 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a height of between about 0.001 μm to about 0.01 μm. In some embodiments, the first detection zone and / or the second detection zone comprises a height of between about 0.001 μm to about 1.0 μm. In some embodiments, at the same time refers to parallel or substantially parallel travel of two or more analytes in the same plane. For example, when viewing flowing analytes from above, two analytes may pass through a detection zone side-by-side. Generally, the previous example may be extended to three dimensions, such that a flow channel containing the plurality of analytes may not constrain the plurality of analytes in any dimension, optionally wherein the flow channel has a height, a width, radius, etc. at least about two times the diameter of an analyte of the plurality of analytes.

[0029] In some embodiments, provided herein is a method for analyzing an analyte, comprising: providing a device comprising (i) a flow channel comprising the analyte, and (ii) one or more photodetectors in optical communication with the one or more flow channels; using the one or more photodetectors to acquire a first optical signal from the one or more flow channels at a first time point; using the one or more photodetectors to acquire a second optical signal from the one or more flow channels at a second time point subsequent to the first time point; and processingWSGR Reference No.64149-703.601 the first optical signal and the second optical signal to identify the analyte flowing through the one or more flow channels, collecting one or more two-dimensional images of the analyte, wherein the one or more two-dimensional images are combined and optimized algorithmically to produce a three-dimensional structure of the analyte, wherein the analyte in fluid motion is imaged as if it were static.

[0030] In some embodiments, the method further comprises using the one or more photodetectors to acquire a third optical signal at a third time point within the one or more flow channels. In some embodiments, the device further comprises one or more excitation sources in optical communication with the analyte processing area. In some embodiments, the method further comprises processing the three-dimensional structures to improve analyte analysis. In some embodiments, the method further comprises using the three-dimensional structure to determine analyte characteristics for a chemical or biological test. In some embodiments, the analyte characteristics reduce the number of false positives. In some embodiments, the analyte characteristics of multiple analytes is used to determine analyte characteristic distribution of a population of analytes. In some embodiments, the reduced number of false positives results in a change in a treatment protocol. In some embodiments, the method further comprises using the three-dimensional structure to separate false positive cancer tests from true cancer positives, wherein the results are used to create an individualized cancer treatment plan. In some embodiments, the analyte characteristic distribution of a population of analytes indicates the severity of multiple myeloma for a subject. In some embodiments, the characterization of the population of analytes can be used to extrapolate a causal factor of multiple myeloma present in the subject.

[0031] In some embodiments, provided herein is a method of spatially identifying one or more characteristics on an analyte surface, comprising: subjecting the analyte to flow through a flow channel; photodetecting by a single-photon avalanche diode (SPAD) array light emission from the analyte during the flow through the flow channel, wherein the analyte is in motion; and processing the light emission to generate a topographic map of the analyte surface.

[0032] In some embodiments, provided herein is a method of spatially identifying one or more characteristics on an analyte surface, comprising: subjecting the analyte to flow through a flow channel; subjecting the analyte to light from one or more excitation sources, wherein the light is polarized by a light scattering control system; photodetecting by a single-photon avalanche diode (SPAD) array light emission from the analyte; and processing the light emission to generate a topographic map of the analyte surface.WSGR Reference No.64149-703.601

[0033] In some embodiments, provided herein is a method of spatially identifying one or more characteristics on an analyte surface, comprising: subjecting the analyte to flow through a flow channel; photodetecting by a single-photon avalanche diode (SPAD) array light emission from the analyte due to light from one or more excitation sources, wherein the light is polarized by a light scattering control system; and algorithmically processing the light emission to generate a topographic map of the analyte surface.

[0034] In some embodiments, provided herein is a method of spatially identifying one or more characteristics on an analyte surface, comprising: subjecting the analyte to flow through a flow channel, wherein the analyte; photodetecting by a single-photon avalanche diode (SPAD) array light emission from the analyte the analyte to one or more excitation sources, wherein the one or more excitation sources generates a polarized light scattering pattern of the analyte surface; processing the polarized light scattering pattern algorithmically to generate a topographic map of the analyte surface. In some embodiments, the light scattering control system is adjacent to one or more photodetectors. In some embodiments, the light scattering control system is adjacent to the flow channel. In some embodiments, the light scattering control system is adjacent to the light scattering control system. In some embodiments, the topographic map comprises an atlas of cellular expression.

[0035] In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting one or more two-dimensional images from the cell to generate a two-dimensional structure of the cell, wherein the two-dimensional structure comprises a topographic map.

[0036] In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting one or more two-dimensional images from the cell to generate a three-dimensional structure of the cell, wherein the three-dimensional structure comprises a topographic map.

[0037] In some embodiments, provided herein is a method for processing or analyzing a population of cells, comprising (a) subjecting the population of cells to flow along a flow channel and (b) detecting one or more two-dimensional images from the population of cells to generate one or more three-dimensional structures of the population of cells, wherein the population of cells is at least 1,000 cells, wherein the three-dimensional structures comprise a topographic map.

[0038] In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting one or moreWSGR Reference No.64149-703.601 two-dimensional images from the cell to generate a three-dimensional structure of the cell in a time period of at most 10 minutes, wherein the three-dimensional structure comprises a topographic map. In some embodiments, the cell is amongst a population of at least 1,000 cells.

[0039] In some embodiments, provided herein is a system for spatially identifying one or more markers on an analyte surface, the system comprising: subjecting the analyte to flow through a flow channel; subjecting the analyte to one or more excitation sources, wherein the one or more excitation sources generates a light scattering pattern of the analyte surface; and processing the light scattering pattern algorithmically to generate a topographic map of the analyte surface.

[0040] In some embodiments, provided herein is a method of spatially identifying one or more markers on an analyte surface, comprising: subjecting the analyte to flow through a flow channel; subjecting the analyte to one or more excitation sources, wherein the one or more excitation sources generates a light scattering pattern of the analyte surface; using the light scattering pattern of the analyte surface to generate a topographic map of the analyte surface.

[0041] In some embodiments, provided herein is a system for spatially identifying one or more markers on an analyte surface, comprising: subjecting the analyte to flow through a flow channel; subjecting the analyte to one or more excitation sources, wherein the one or more excitation sources generates a light scattering pattern of the analyte surface; and using the light scattering pattern of a surface of an analyte to generate a topographic map of the analyte surface.

[0042] In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting one or more two-dimensional images from the cell to generate a three-dimensional structure of the cell, wherein the three-dimensional structure comprises a topographic map.

[0043] In some embodiments, provided herein is a method for processing or analyzing a population of cells, comprising (a) subjecting the population of cells to flow along a flow channel and (b) detecting one or more two-dimensional images from the population of cells to generate one or more three-dimensional structures of the population of cells, wherein the population of cells is at least 1,000 cells, wherein the three-dimensional structure comprises a topographic map.

[0044] In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting one or more two-dimensional images from the cell to generate a three-dimensional structure of the cell in a time period of at most 10 minutes, wherein the three-dimensional structure comprises a topographic map. In some embodiments, the cell is amongst a population of at least 1,000 cells.WSGR Reference No.64149-703.601

[0045] In some embodiments, provided herein is a system for spatially identifying one or more markers on an analyte surface, the system comprising: subjecting the analyte to flow through a flow channel; subjecting the analyte to one or more excitation sources, wherein the one or more excitation sources generates a light scattering pattern of the analyte surface; and processing the light scattering pattern algorithmically to generate a topographic map of the analyte surface.

[0046] In some embodiments, provided herein is a method of spatially identifying one or more markers on an analyte surface, comprising: subjecting the analyte to flow through a flow channel; subjecting the analyte to one or more excitation sources, wherein the one or more excitation sources generates a light scattering pattern of the analyte surface; using the light scattering pattern of a surface of an analyte to generate a topographic map of the analyte surface.

[0047] In some embodiments, provided herein is a system for spatially identifying one or more markers on an analyte surface, comprising: subjecting the analyte to flow through a flow channel; subjecting the analyte to one or more excitation sources, wherein the one or more excitation sources generates a light scattering pattern of the analyte surface; and using the light scattering pattern of a surface of an analyte to generate a topographic map of the analyte surface. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0049] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also "figure" and "FIG." herein), of which:

[0050] FIG.1A illustrates aspects of the sensitivity and specificity improvements with the analyte processing device disclosed herein. analyte processing device disclosed herein, including run multiplexing, cell imaging modality, cell multi-imaging, and cell sorting.

[0051] FIG.1B shows digital cell analysis possible with the analyte processing device disclosed herein.

[0052] FIG.1C shows a cell imaging modality.

[0053] FIG.1D shows a cell multi-imaging modality.

[0054] FIG.1E shows run multiplexing with enclosed microfluidic chambers disclosed herein.WSGR Reference No.64149-703.601

[0055] FIG.1F shows a cell sorting modality.

[0056] FIG.2 illustrates a time-of-flight cell imaging modality of the device described herein via a single photon avalanche diode (SPAD) array.

[0057] FIG.3 depicts cells entering in a single column into the detector.

[0058] FIG.4 depicts acoustophoresis effect on cells.

[0059] FIG.5 depicts a cell moving through a microfluidic channel.

[0060] FIG.6 depicts microfluidic channel system.

[0061] FIG.7 shows an example of an integrated circuit disclosed herein.

[0062] FIG.8 shows an example of layers comprising a microfluidic device disclosed herein.

[0063] FIG.9A shows the impact of the correlation between an optical signal collected by two adjacent pixels and sensitivity across 20, 50, and 100 stations, illustrating the effect of independent imaging counts on sensitivity.

[0064] FIG.9B shows error rate as a function of photon count, for various separation between average lifetimes.

[0065] FIG.10A shows a comparison of measurement sensitivity of optical signals from dyed microspheres between time correlated single photon counting imaging and uncorrelated time lapse imaging.

[0066] FIG.10B shows the error rate as a function of photon count, for various separation between average lifetimes.

[0067] FIG.11 shows an example of a distribution of the time-of-flight intervals computed for each cell. Each pulse excitement (green bar on top chart) produces an avalanche that leads to a current that follows it (the yellow bar on top chart). A time-of-flight is the time interval between these two events. The distribution of these TOF events are accumulated (the bottom chart).

[0068] FIG.12 shows an example of a distribution of the time-of-flight intervals are computed for each cell. Each pulse excitement (green bar on top chart) produces an avalanche that leads to a current that follows it (the yellow bar on top chart). A time-of-flight is the time interval between these two events. The distribution of these TOF events are accumulated (the bottom chart).

[0069] FIG.13. shows the fate of light sources within time correlated single photon counting (TCSPC).WSGR Reference No.64149-703.601

[0070] FIG.14 illustrates operations 1-9 in fabrication of a microfluidic channel for imaging via uncorrelated time lapse microscopy.

[0071] FIG.15 illustrates operations 10-15 in fabrication of a microfluidic channel of the device described herein.

[0072] FIG.16 illustrates a computer system utilizing the methods and systems described herein.

[0073] FIG.17 shows a schematic of cell-analysis solution with diffractive optics to probe dynamic cells at multiple locations in a microfluidic channel.

[0074] FIG.18A shows examples of distributions of TOF photons.

[0075] FIG.18B shows examples of distributions of TOF photons, one for a cell in a given waveguide.

[0076] FIG.19 shows examples of a M by N array of TOF data.

[0077] FIG.20 Schematics of an example of a closed loop microfluidic circuit.

[0078] FIG.21 shows an example of deep-learning network architecture.

[0079] FIG.22 shows three optical arrangements of devices described herein.

[0080] FIG.23 shows an example of operating capability of devices described herein.

[0081] FIG.24 shows detection mapping of biomarkers via imaging.

[0082] FIG.25A shows a snapshot of cellular movement within a flow channel of a device described herein.

[0083] FIG.25B shows a snapshot of cellular movement within a flow channel of a device described herein.

[0084] FIG.26 shows 3-D construction of a cell imaged via a device herein using AI and machine learning.

[0085] FIG.27 shows a diagram illustrating cell expression index correlation with AI and machine learning classification.

[0086] FIG.28 shows an all-in-one cartridge for processing and analyzing a sample.

[0087] FIG.29 shows a sample tube and a diagram of sample tube connection to a cartridge.

[0088] FIG.30 shows a sample tube labeled with a barcode.

[0089] FIG.31 shows a channel modified with a bump for analyte re-orientation.WSGR Reference No.64149-703.601

[0090] FIG.32 shows a channel modified with SAW sources for analyte re-orientation.

[0091] FIG.33 shows a channel modified with a relaxation region and optionally with a post for analyte re-orientation.

[0092] FIG.34 shows a channel modified with a narrowed region for analyte stretching.

[0093] FIG.35 shows a channel with a serpentine or spiral configuration.

[0094] FIG.36 shows a diagram for using a vortex to separate components of samples.

[0095] FIG.37 shows a diagram for using channel width to separate components of samples.

[0096] FIG.38 shows a diagram of a modular system for processing a sample using a series of sample processing modules.

[0097] FIG.39 shows a number of options to prevent sedimentation and minimize dead volume for interfacing samples with a microfluidic chip.

[0098] FIG.40 shows an example of a decoder architecture.

[0099] FIG.41 shows an example experimental setup for obtaining images of flowing cells.

[0100] FIG.42 shows an example of pixel evolution over time for images of a flowing cell.

[0101] FIG.43 shows a sample of simulated particles for use in training machine learning models.

[0102] FIG.44 shows two examples of labeling complexes using circularized RNA with single and multiple fluorescent moiety conjugation.

[0103] FIG.45 shows an example of circularizing linear RNA.

[0104] FIG.46 shows an example of oligonucleotides tagged with fluorescent moieties.

[0105] FIG.47 shows an example of a labeling complex comprising an antibody, circularized RNA, and oligonucleotides conjugated to fluorescent moieties.

[0106] FIG.48 shows a number of embodiments of flow channels.

[0107] FIG.49 shows a non-uniform engineered slow-down structure for use in a flow channel.

[0108] FIG.50 shows a chip containing an application specific integrated circuit.

[0109] FIG.51 shows a diagram of a transformer processing a series of images of an analyte.

[0110] FIG.52 shows two detection rate versus false positive cell detection curves.

[0111] FIG.53 shows a diagram of moving cells being analyzed.WSGR Reference No.64149-703.601 INCORPORATION BY REFERENCE

[0112] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. DESCRIPTION

[0113] While various embodiments of the invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed.

[0114] The present disclosure provides devices, methods, and systems for high resolution imaging and high throughput analyte identification, under mild conditions within a flow channel. The present disclosure provides a platform for multi-omics analysis including genome, epigenome, transcriptome, and proteome studies. Devices provided herein can perform comprehensive, accurate assessments of populations of analytes and cells, including the heterogeneity of cells. An embodiment of the present invention comprises the integration or coupling of independent elements of analyte detection systems. An embodiment of the present invention comprises the integration or coupling of independent elements of analyte detection systems into high resolution imaging and high throughput analyte identification devices and methods. There are many challenges to achieving high throughput analyte detection using devices, methods, and systems comprising a photodetector array, a microfluidic channel, and one or more excitation sources integrated together. For some embodiments, the device comprises a photodetector array, a microfluidic channel, one or more excitation sources, and one or more light scattering control systems integrated together to yield the precision and scale of the device. For another example, one or more photodetectors may be coupled with one or more flow channels, and one or more light scattering control elements. The light scattering control systems disclosed herein can be used to reduce unwanted noise during imaging of biological entities within a flow channel. For example, dichroic optical elements may reduce optical signal transmitted between a cellular substrate and one or more photodetectors. For some embodiments, the device comprises a chip comprising an integrated photodetector array, a microfluidic channel, and one or more excitation sources integrated together.WSGR Reference No.64149-703.601

[0115] The devices and methods provided herein may provide rapid, high-throughput, parallel, multiplexable genetic, protein, and other cellular analyses down to single-molecule or single-cell level and can be used for several applications including but not limited to the isolation and detection of immune cells, circulating tumor cells (CTCs), cell-free nucleic acids and exosomes, cancer initiating cells, cell drug interaction and resistance, cell-cell communication in tumor microenvironments, and the analysis of genomes and epigenomes using single-cell next- generation imaging technologies. In order to yield the information for such analysis, delicate imaging techniques are implemented with an analyte while also having the precision to accurately characterize said analytes. In some embodiments of the methods and devices disclosed herein achieves the precision and sensitivity through an arrangement of photodetection and light modifying materials. The resulting optical communication along the optical path between the one or more photodetectors reduces signal interference by noise during imaging. The effect on sensitivity, error rate of identification, and false positive rate can be observed in FIG.9A, FIG.9B, and FIG.10A. The resulting analyte processing device can achieve measurement precision at the nanometer scale, as well as achieving the capacity to efficiently and rapidly sort analytes upon imaging and characterization. An important feature of the analyte processing device is its ability to perform high throughput analysis while also featuring low levels of shear stress on analytes and cells. The viability rate, for example, of the resulting analyzed cells after imaging is thus superior to other imaging methods with harsher conditions. Cell tolerability also means more sophisticated imaging methods are possible with otherwise unstable cell types. Furthermore, the throughput of analysis possible with the analyte processing device described herein is improved over existing technology, with the possibility of thousands of cells or analytes to be processed, imaged, or distributed in short periods of time. FIG.1A, FIG.1B, FIG.1C, FIG.1D, FIG.1E, and FIG.1F show some aspects of the device described herein. FIG.2 shows the imaging modality and how it provides a mechanism to perform time of flight imaging via a photodetector array within a flow channel. FIG.3, FIG.4, FIG.5, and FIG.6 show depictions of cells moving with a microfluidic device described herein. FIG.4 shows the effect of acoustophoresis on cells within a microfluidic channel described herein. FIG.7 show an example of a microfluidic device comprising an integrated circuit, including the layers of the microfluidic device. FIG.8 shows an example of a consumable chip and its layers, including an acoustic transducer layer, a microfluidic chamber layer, a photonics integrated circuit layer, and a CMOS imager layer. Analyte processing deviceWSGR Reference No.64149-703.601

[0116] An aspect of the present disclosure provides an analyte processing device for detecting a presence or absence of an analyte in a solution. In some embodiments, provided herein is an analyte processing device, comprising: one or more flow channels, wherein at least one flow channel of the one or more flow channels comprise an analyte processing area; one or more excitation sources in optical communication with the analyte processing area and comprising an optical path from the one or more excitation sources to the analyte processing area; and one or more photodetectors in optical communication with the analyte processing area, wherein the optical path comprises a light scattering control system. In some embodiments, provided herein is an analyte processing device, comprising: one or more flow channels, wherein at least one flow channel of the one or more flow channels comprise an analyte processing area; one or more excitation sources in optical communication with the analyte processing area and comprising an optical path from the one or more excitation sources to the analyte processing area; and one or more photodetectors in optical communication with the analyte processing area, wherein the optical path comprises a light scattering control system, wherein (i), (ii), (iii), or any combination thereof are integrated monolithically, system-in-package, heterogeneously, three- dimensionally integrated, or a combination thereof. In some embodiments, provided herein is an analyte processing device, comprising: one or more flow channels, at least one flow channel of the one or more flow channels comprising an analyte processing area; one or more excitation sources in optical communication with the analyte processing area; and one or more photodetectors in optical communication with the analyte processing area, the one or more photodetectors being configured to perform detection of a surface of one or more analytes in fluid motion, wherein the one or more photodetectors are configured to collect one or more two- dimensional images of one or more analytes, wherein the one or more two-dimensional images undergo processing to produce a three-dimensional structure of the one or more analytes.

[0117] In other embodiments, the analyte processing device measures an analytes size, texture, surface area, or other physical property. During cellular analysis, the analyte processing device may be used to determine organelle size, cell membrane size, mitochondrial count, organelle count, or other physical parameters of biological systems. The methods and devices of the present disclosure may also be used to detect, analyze, or quantify, a plurality of analytes present in an aqueous sample. The geometric arrangement, material, and circuitry of the analyte processing device may vary for imaging performance under flow channel conditions.

[0118] In some embodiments, the analyte processing device comprises one or more of the following: SiO2, TiN, Ti, Si3N4, glass, or other similar material. In some embodiments, the analyte processing device comprises a series of layers. In some embodiments, the analyteWSGR Reference No.64149-703.601 processing device comprises one or more light scattering control elements. In some embodiments the analyte processing device comprises one or more light scattering control elements forming one or more layers. In some embodiments, the analyte processing device comprises an acoustophoretic layer. In some embodiments, the analyte processing device comprises a flow channel layer. In some embodiments, the analyte processing device comprises a microfluidic channel layer. In some embodiments, the analyte processing device comprises a photonics circuit layer comprising one or more excitation sources or one or more optical circuits. In some embodiments, the analyte processing device comprises an analyte processing area. In some embodiments, the analyte processing device comprises one or more analyte processing areas. In some embodiments, the analyte processing device comprises a substrate, element, or membrane to manipulate the scattering of light. In some embodiments, the analyte processing device comprises a substrate, element, or membrane to manipulate the propagation of light.

[0119] In some embodiments, the analyte processing device comprises a chip. In some embodiments, the analyte processing device comprises a cartridge. In some embodiments, the analyte processing device comprises a replaceable cartridge. In some embodiments, the analyte processing device comprises a replaceable or consumable element. In some embodiments, the chip is integrated with one or more photodetectors, the one or more excitation sources, one or more flow channels, one or more light scattering control elements, or any combination thereof. In some embodiments, the analyte processing device comprises a semiconductor chip. In some embodiments, the analyte processing device comprises a photonics chip. In some embodiments, the chip is integrated with one or more light modifying elements. In some embodiments, the chip is integrated with one or more light scattering control systems. In some embodiments, the analyte processing device comprises one or more stacked layers. In some embodiments, the one or more stacked layers are integrated with a chip. In some embodiments, the analyte processing device comprises one or more stacked layers integrated with a chip. In some embodiments, the chip may comprise several layers including but not limited to: an acoustophoresis layer, a microfluidic chamber layer, a microfluidic channel layer, a flow channel layer, a light modifying membrane layer, a photodetector layer, an excitation source layer, an optical circuit layer, a photonics circuit layer, or a light modifying substrate layer. In some embodiments, the optical circuit comprises one or more light entry sections, one or more optical dividers, a light delivery section, or any combination thereof. In some embodiments, the analyte processing device comprises an energy source. In some embodiments, the energy source is a battery. In some embodiments, the energy source is integrated with the analyte processing device. In some embodiments, the device comprises one or more excitation sources. In some embodiments, theWSGR Reference No.64149-703.601 one or more excitation sources provide excitation energy to the flow channel to yield the first optical signal, the second optical signal, or the third optical signal.

[0120] In some embodiments, provided herein is a chip comprising one or more flow channels, wherein the one or more flow channels comprise one or more light scatter control elements adjacent to one or more analyte processing areas. In some embodiments, the chip comprises an application specific integrated circuit. In some embodiments, the chip comprises an integrated circuit. In some embodiments, the chip is integrated with one or more other aspects of the analyte processing device, including but not limited to: one or more flow channels, one or more light scattering control elements, a power source, one or more photodetectors, one or more excitation sources, or one or more displacement / phoresis elements, one or more circuits, or one or more chips. In some embodiments, the chip comprises an optical circuit. In some embodiments, readout circuitry may be operatively coupled to the analyte processing device, wherein the readout circuitry is configured to transmit the data from the analyte processing device to memory. In some embodiments, the chip comprises at least 20 flow channels. In some embodiments, the chip comprises at least 100 flow channels. In some embodiments, the chip is integrated with a circuit. In some embodiments, the chip is integrated with a microfluidic circuit. In some embodiments, the chip is integrated with an electrical circuit. In some embodiments, the chip is integrated with a photonic circuit. In some embodiments, the chip is configured to connect to an analyte processing device disclosed herein. Analyte imaging device

[0121] An aspect of the present disclosure provides an analyte imaging device for detecting a presence or absence of an analyte in a solution. In some embodiments, provided herein is an analyte imaging device comprising: a light modifying substrate; one or more photodetectors, wherein the one or more photodetectors is adjacent to the light modifying substrate; and one or more flow channels, wherein the one or more flow channels is adjacent to a surface of the light modifying substrate, and wherein a cross sectional dimension of the one or more flow channels is configured to allow the passage of a single cell. In other embodiments, the analyte imaging device measures an analyte’s size, texture, surface area, or other physical property. During cellular analysis, the analyte imaging device may be used to determine organelle size, cell membrane size, mitochondrial count, organelle count, or other physical parameters of biological systems. The methods and devices of the present disclosure may also be used to detect, analyze, or quantify, a plurality of analytes present in an aqueous sample. The geometric arrangement, material, and circuitry of the analyte imaging device may vary for imaging performance under flow channel conditions. analyte imaging deviceWSGR Reference No.64149-703.601

[0122] In some embodiments, the analyte imaging device comprises one or more of the following: SiO2, TiN, Ti, Si3N4, glass, or other similar material. In some embodiments, the analyte imaging device comprises one or more of the following: SiO2, TiN, Ti, Si3N4, and glass. In some embodiments, the analyte imaging device comprises one or more of layers. In some embodiments, the analyte imaging device comprises one or more light scattering control elements. In some embodiments the analyte imaging device comprises one or more light scattering control elements forming one or more layers. In some embodiments, the analyte imaging device comprises an acoustophoretic layer. In some embodiments, the analyte imaging device comprises a flow channel layer. In some embodiments, the analyte imaging device comprises a microfluidic channel layer. In some embodiments, the analyte imaging device comprises a photonics circuit layer comprising one or more excitation sources or one or more optical circuits. In some embodiments, the analyte imaging device comprises an analyte processing area. In some embodiments, the analyte imaging device comprises one or more analyte processing areas. In some embodiments, the analyte imaging device comprises a substrate, element, or membrane to manipulate the scattering of light. In some embodiments, the analyte imaging device comprises a substrate, element, or membrane to manipulate the propagation of light.

[0123] In some embodiments, the analyte imaging device comprises a chip. In some embodiments, the analyte processing device comprises a cartridge. In some embodiments, the analyte imaging device comprises a replaceable cartridge. In some embodiments, the analyte imaging device comprises a replaceable or consumable element. In some embodiments, the chip is integrated with one or more photodetectors, the one or more excitation sources, one or more flow channels, one or more light scattering control elements, or any combination thereof. In some embodiments, the analyte processing device comprises a semiconductor chip. In some embodiments, the analyte processing device comprises a photonics chip. In some embodiments, the chip is integrated with one or more light modifying elements. In some embodiments, the chip is integrated with one or more light scattering control systems. In some embodiments, the analyte imaging device comprises one or more stacked layers. In some embodiments, the one or more stacked layers are integrated with a chip. In some embodiments, the analyte imaging device comprises one or more stacked layers integrated with a chip. In some embodiments, the chip may comprise several layers including but not limited to: an acoustophoresis layer, a microfluidic chamber layer, a microfluidic channel layer, a flow channel layer, a light modifying membrane layer, a photodetector layer, an excitation source layer, an optical circuit layer, a photonics circuit layer, or a light modifying substrate layer. In some embodiments, the optical circuit comprises one or more light entry sections, one or more optical dividers, a light deliveryWSGR Reference No.64149-703.601 section, or any combination thereof. In some embodiments, the analyte imaging device comprises an energy source. In some embodiments, the energy source is a battery. In some embodiments, the energy source is integrated with the analyte imaging device. In some embodiments, the device comprises one or more excitation sources. In some embodiments, the one or more excitation sources provide excitation energy to the flow channel to yield the first optical signal, the second optical signal, or the third optical signal. In some embodiments, the chip comprises an application specific integrated circuit. In some embodiments, the chip comprises an integrated circuit. In some embodiments, the chip is integrated with one or more other aspects of the analyte imaging device, including but not limited to: one or more flow channels, one or more light scattering control elements, a power source, one or more photodetectors, one or more excitation sources, or one or more displacement / phoresis elements, one or more circuits, or one or more chips. In some embodiments, the chip comprises an optical circuit. In some embodiments, readout circuitry may be operatively coupled to the analyte imaging device, wherein the readout circuitry is configured to transmit the data from the analyte imaging device to memory. In some embodiments, the flow channel is configured to result in displacement of the analyte. In some embodiments, the displacement is electrical. In some embodiments, the displacement is magnetic. In some embodiments, the analyte displacement is thermal. In some embodiments, the one or more photodetectors is configured for spectral range. In some embodiments, the one or more photodetectors is configured for photon intensity. In some embodiments, the one or more photodetectors is configured for photon wavelength. In some embodiments, the one or more photodetectors comprises a pinned photodiode. In some embodiments, the one or more photodetectors comprises a single photon avalanche diode. In some embodiments, the processing comprises time of flight processing. Dimensions

[0124] A dimension of an object or analyte may be the subject of processing or analysis by devices disclosed herein. In some embodiments, the dimension comprises the volume. In some embodiments, the dimension comprises the shape. In some embodiments, the dimension comprises the position. In some embodiments, the dimension comprises the depth. In some embodiments, the dimension comprises the circumference. In some embodiments, the dimension comprises the thickness. In some embodiments, the dimension comprises the voltage. In some embodiments, the dimension comprises the velocity. In some embodiments, the dimension comprises the temperature. In some embodiments, the dimension comprises the frequency. In some embodiments, the processing is performed using Artificial Intelligence (AI). In someWSGR Reference No.64149-703.601 embodiments, the three-dimensional structure of the analyte comprises stretched representations of the analyte while the analyte passes through the space-constrained tube. In some embodiments, the stretched representations of the analyte are differently stretched. In some embodiments, the stretched representations of the analyte are identically stretched. In some embodiments, the stretched representations of the analyte determine elasticity. In some embodiments, the stretched representations of the analyte determine granularity. Analytes

[0125] The devices described herein may be used to evaluate, identify, or process a wide variety of analytes of interest. In some embodiments, the analyte is a cell. In some embodiments, the analyte comprises an emulsion. In some embodiments, the analyte comprises a peptide. In some embodiments, the analyte comprises a small molecule. In some embodiments, the analyte comprises a conjugate molecule. In some embodiments, the analyte comprises a fluorescent molecule. In some embodiments, the analyte comprises an antigen. In some embodiments, the analyte comprises a lipid. In some embodiments, the analyte comprises a gaseous compound.

[0126] In some embodiments, the analyte comprises a biological sample. In some embodiments, the analyte comprises at least one cell. In some embodiments, the analyte is a population of cells. In some embodiments, the at least one cell is a mammalian cell, a eukaryotic cell, a yeast cell, a bacterial cell, a primary cell, an immortalized cell, a cancer cell, a hybrid cell, or a derivative or an engineered form thereof. In some embodiments, the analyte is blood. In some embodiments, the analyte is plasma. In some embodiments, the analyte is cerebrospinal fluid. In some embodiments, the analyte is lymph tissue. In some embodiments, the analyte is a specific type of cell from a subject. In some embodiments, the analyte is a specific type of cell that is from the brain, liver, heart, intestine, colon, muscle, kidney, pancreas, or other organ. In some embodiments, the analyte comprises skin cells, heart cells, immune system cells such as B- cells, lymphocytes, T-cells, kidney cells, liver cells, muscle cells, nervous system cells such as astral cells, glial cells, neuronal cells, bacterial cells, or peripheral blood mononuclear cells.

[0127] In some embodiments, the analyte is in the liquid phase. In some embodiments, the analyte is in the gas phase. In some embodiments, the analyte is an aqueous solution. In some embodiments, the analyte is solvated in an organic solution (e.g., acetone, methanol, acetonitrile, tetrahydrofuran, or other organic solvent). In some embodiments, the analyte is at least one of a gas or a vapor, wherein said gas or vapor analyte is dissolved in an aqueous solution. In some embodiments the analyte is a gas in at least one of an aqueous solution or a fluid. In some embodiments, the analyte comprises one or more cells. In some embodiments, the analyte is at least partially aerosolized. In some embodiments, the analyte is an aerosol. In someWSGR Reference No.64149-703.601 embodiments, the analyte motion is laminar motion. In some embodiments, the analyte motion is turbulent. In some embodiments, the analyte comprises one or more additional solutes. In some embodiments, the analyte further comprises a solvent that is phosphate buffered saline (PBS).

[0128] In some embodiments, the analyte is processed prior to analysis. In some embodiments, the analyte is chemically modified prior to analysis. In some embodiments, the analyte is reacted with a fluorophore, dye, labeling agent, or other similar chemical reagent. In some embodiments, the analyte is centrifuged prior to analysis. In some embodiments, the analyte is heated prior to analysis. In some embodiments, the analyte is cooled prior to analysis. In some embodiments, the analyte is frozen, or flash frozen, prior to analysis. In some embodiments, the analyte is a suspension. In some embodiments, the analyte is homogenous. In some embodiments, the analyte is heterogenous. In some embodiments, the analyte may be labelled with a fluorophore, a fluorescent molecule, a dye, or other similar moiety. In some embodiments, the analyte is at least one cell that may be labelled with a fluorophore or expresses a fluorescent molecule. In some embodiments, the analyte comprises at least once cell that may express a molecule including, but not limited, to a fluorescent molecule, a phosphorescent molecule, a chemiluminescent molecule, or a bioluminescent molecule. In some embodiments, the analyte comprises fluorophores that can be used as labels for specific target analytes, in applications where the targets can be chemically modified to incorporate a TGF fluorophore. Examples include, but are not limited to, Northern blots, Southern blots, DNA microarrays, quantitative Polymerase Chain Reaction (PCR), digital PCR, and diagnostic assays. Cartridge

[0129] Another aspect of the analyte processing device is the inlet configured to receive a container comprising a sample analyte. One example embodiment of the analyte processing device is show in FIG.28. In some embodiments, said sample analyte comprises a biological sample. In some embodiments the inlet configured to receive a container comprising a biological sample comprises the received container in an upside-down (inverted) position relative to the device. Said upside down position is nonconventional and allows the sample to flow into the device using only a mild vacuum and the force of gravity. Using a mild vacuum instead of the stronger vacuum needed in the devices currently available can (1) reduce cost (2) reduce power / energy usage and (3) reduce the size of the vacuum pump needed, therefore the size of the device overall. In some embodiments, the inlet configured to receive a container upside-down relative to the device comprises a vacuum source providing mild pressure because of the utilization of the force of gravity. In some embodiments, the method used to operate the analyteWSGR Reference No.64149-703.601 processing device comprising the inlet configured to receive said container upside down requires mild vacuum pressure to force the analyte into the processing.

[0130] In some embodiments, the device for processing an analyte in a biological sample, comprises, an inlet configured to receive a container comprising the biological sample, wherein the received container is an upside-down position relative to the device; a first chamber in fluidic communication with the inlet, wherein the first chamber comprises a filter configured to remove contaminants from the biological sample; a second chamber comprising one or more reagents for configuring the analyte for optical detection, wherein the second chamber is in fluidic communication with the first chamber; and a microfluidic chip in fluidic communication with the second chamber. In some embodiments the microfluidic chip comprises one or more channels, wherein the channel of the one or more channels comprises a plurality of detection zones, wherein the device is configured to be received by a housing in electrical communication with a detector. In some embodiments the device for processing an analyte comprising an inlet configured to receive a container comprising the biological sample further comprises one or more valves, wherein the one or more valves is configured to open when the device is received by the housing. In some embodiments the one or more valves are disposed between at least one of the inlets and the first chamber; the first chamber and the second chamber; or the second chamber and the microfluidic chip. In some embodiments the one or more valves are disposed between a combination of at least two of: the inlet and the first chamber; the first chamber and the second chamber; or the second chamber and the microfluidic chip. In some embodiments, the device wherein one or more valves is configured to open when the device is received by the housing further comprises a third chamber in fluidic communication with the second chamber, the microfluidic device, or both, and wherein the third chamber is configured to collect the analyte. In some embodiments, the device wherein one or more valves is configured to open when the device is received by the housing further comprises one or more reagent reservoirs. In some embodiments, the device wherein one or more valves configured to open when the device is received by the housing further comprises said second chamber, wherein said second chamber comprises the one or more reagents dried and coupled to an inner surface of the second chamber. In some embodiments, the one or more reagents dried and coupled to the inner surface of the second chamber comprise an antibody configured to bind to the analyte. In some embodiments, the device further comprises a first reagent reservoir in fluidic communication with the second chamber, wherein the first reagent reservoir comprises one or more reagents configured to facilitate binding of the analyte and the antibody configured to bind to the analyte. In some embodiments, the device further comprises a first reagent reservoir in fluidic communication with the microfluidic chip, wherein the second reagent reservoir comprises one or more reagentsWSGR Reference No.64149-703.601 configured to facilitate transport of the analyte through the one or more channels. In some embodiments, the device further comprises a lysis reagent reservoir in fluidic communication with the first chamber. In some embodiments, the device further comprises a cooling unit in communication with the second chamber. In some embodiments, the device is configured to align the one or more detection zones with one or more optical paths of the detector such that the one or more detection zones are in optical communication with the detector upon the housing receiving the detector. In some embodiments, said inlet comprises one or more protrusions or prongs, wherein the one or more protrusions or prongs comprise one or more channels in fluidic communication with the first chamber. In some embodiments, the one or more protrusions or prongs are configured to collect the analyte and facilitate transport of the analyte to the first chamber. In some embodiments, the one or more protrusions or prongs are configured to couple to the container comprising the biological sample and to form a sealed coupling to the container. In some embodiments, the device for processing an analyte in a biological sample comprising said first chamber, said second chamber, said third chamber, and said microfluidic chip is in fluidic communication with one or more waste reservoirs. In some embodiments, the fluidic communication with one or more waste reservoirs is with any possible combination of the first, second, third chambers, and microfluidic chip. In some embodiments, the one or more reagents dried and coupled to the inner surface of the second chamber are lyophilized. In some embodiments, the device comprising the first reagent reservoir further comprises one or more reagents for fluorescent-activation cell sorting (FACS) analysis of the analyte. In some embodiments, the device comprising the second reagent reservoir further comprises one or more surfactants. In some embodiments the device comprising the microfluidic chip further comprises one or more single photon avalanche diode (SPAD) arrays.

[0131] In some embodiments, the analyte processing device simplifies and automates sample preparation for imaging (e.g., imaging with a CMOS SPAD array). In some embodiments, the analyte processing device may be a disposable cartridge. In some embodiments, the analyte processing device may be used for blood processing. In some embodiments, the analyte processing device comprises a tube connection mechanism (e.g., a blood tube), a separation chamber for filtering out components of the sample (e.g., red blood cells, lymphocytes), a mixing chamber which may be used to combine the sample with a buffer (e.g., a FACS buffer which may prepare the sample for analysis), an incubation chamber for reacting the sample with a reagent (e.g., antibody staining, attachment of dyes to the sample, conjugation of antibodies to a target on a cell, etc.), or a microfluidic chip for SPAD analysis. In some embodiments, the tube may remain outside of the analyte processing device after insertion. In some embodiments, theWSGR Reference No.64149-703.601 sample may flow through one or more channels of a chip of the analyte processing device for FACS analysis.

[0132] In some embodiments, the tube may be attached to the analyte processing device. One example of the attachment of the tube to the analyte processing device is shown in FIG.29. In some embodiments, one or more prongs may be disposed on the analyte processing device to pierce a rubber stopper of a conventional EDTA-blood tube. In some embodiments, the analyte processing device forms a seal with the tube. In some embodiments, the prongs may be used to regulate the flow of a sample (e.g., blood) into the analyte processing device. In some embodiments, the prongs may comprise a channel allowing the sample to flow from the tube into the analyte processing device. In some embodiments, the diameter of the channel may be used to control the rate of flow of the sample from the tube into the analyte processing device.

[0133] In some embodiments, the tubes may be labeled with a unique patient identifier amenable to automated processing (e.g., barcode, QR code). One example of a labeled tube is shown in FIG.30. In some embodiments, the labeled tubes may be compatible with automated data tracking systems or methods such that patient samples may be processed at the site of sample procurement. In some embodiments, the analyte processing device may comprise an integrated camera to read the label. In some embodiments, the label reading and sample processing by the analyte processing device may be integrated with electronic health record or electronic medical record systems, where the integration may reduce the risk of losing patient samples, improperly indexing patient samples, or losing patient data. Flow channel

[0134] Another aspect of the analyte processing device is the flow channel. In some embodiments, the analyte processing device comprises more than one flow channel. In some embodiments, the analyte processing device comprises more than two, more than four, more than eight, or more than 16 flow channels. In some embodiments, the analyte processing device comprises more than two, more than 64, more than 128, or more than 256 flow channels. In some embodiments, the flow channel comprises at least one outlet, at least two outlets, at least three outlets, or at least four outlets. In some embodiments, the flow channel comprises at least 16 outlets, at least 64 outlets, at least 128 outlets, at least 256 outlets, at least 1028 outlets. In some embodiments, the flow channel comprises at least one inlet, at least two inlets, at least three inlets, or at least four inlets. In some embodiments, the flow channel comprises at least 16 inlets, at least 64 inlets, at least 128 inlets, at least 256 inlets, at least 1028 inlets. In some embodiments, the flow channel is rectangular. In some embodiments, the flow channel is curved, indented, or similarly modified. In some embodiments, the flow channel is integratedWSGR Reference No.64149-703.601 with the analyte processing device. In some embodiments, the flow channel is configured to generate electrophoresis such as acoustophoresis, electrophoresis, or magnetophoresis. In some embodiments, the flow channel is configured to displace analytes within the flow channel. In some embodiments, the flow channel comprises one or more pumps. In some embodiments, the flow channel comprises one or more double-sided indents. In some embodiments, the flow channel comprises one or more single sided indents. In some embodiments, the flow channel comprises one or more single sided pinches. In some embodiments, the flow channel comprises one or more double sided pinches. In some embodiments, the flow channel comprises one or more curves. In some embodiments, the flow channel comprises one or more posts. In some embodiments, the flow channel comprises one or more bisections. In some embodiments, the flow channel comprises one or more intersections. In some embodiments, the flow channel comprises one or more convergence sections. In some embodiments, the flow channel comprises one or more bumps. In some embodiments, the flow channel comprises one or more posts. In some embodiments, the flow channel comprises one or more surface acoustic wave sources. In some embodiments, the flow channel comprises one or more flow channels. In some embodiments, the one or more flow channels comprise more than one analyte processing area. In some embodiments, the one or more excitation sources are integrated with the analyte processing device. In some embodiments, the one or more photodetectors are layered below the one or more flow channels. In some embodiments, the one or more flow channels are configured to rotate a cell on an axis. In some embodiments, the one or light scatter control elements comprise one or more diffractive optic layers. In some embodiments, the one or light scatter control elements comprise one or more light scattering control elements. In some embodiments, the one or light scatter control elements are integrated with the chip. In some embodiments, the flow channel comprises one or more features configured to displace the cell. In some embodiments, the flow channel comprises one or more chemical functionalizations. In some embodiments, the one or more chemical functionalizations are configured to interact with one or more analytes. In some embodiments, the one or more flow channels is configured to receive an acoustic wave, wherein the acoustic wave is configured to rotate the cell on an axis. In some embodiments, the flow channel comprises one or more features configured to rotate the cell on an axis. In some embodiments, the one or more flow channels are configured to contact a light scattering control system. In some embodiments, the one or more flow channels have a width configured to pass one cell at a time. In some embodiments, the width of the one or more flow channels is 100 nanometers.

[0135] In some embodiments, the flow channel comprises a gate. In some embodiments, the flow channel comprises one or more gates. In some embodiments, the flow channel comprises aWSGR Reference No.64149-703.601 sorting junction. In some embodiments, the flow channel comprises one or more sorting junction. In some embodiments, the flow channel comprises a series of sorting junctions. In some embodiments, the flow channel comprises one or more chambers. In some embodiments, the flow channel comprises more than five, more than 10, more than 50, or more than 100 chambers. In some embodiments, the flow channel comprises a fluid reservoir. In some embodiments, the flow channel comprises more than one fluid reservoir. In some embodiments, the flow channel comprises one or more pneumatically driven valves. In some embodiments, the flow channel comprises one or more fluid reservoirs. In some embodiments, the flow channel further comprises one or more peristaltic pumps. In some embodiments, the flow channel comprises Polydimethylsiloxane (PDMS). In some embodiments, the microfluidic channel comprises Polydimethylsiloxane (PDMS). In some embodiments, the flow channel comprises glass. In some embodiments, the microfluidic channel comprises glass. In some embodiments, the flow channel comprises plastic. In some embodiments, the microfluidic channel comprises plastic. In some embodiments, the flow channel comprises PMMA. In some embodiments, the microfluidic channel comprises PMMA. In some embodiments, the flow channel comprises polycarbonate. In some embodiments, the microfluidic channel comprises polycarbonate. In some embodiments, the microfluidic channel comprises a width of between about 10 μm to about 100 μm. In some embodiments, the microfluidic channel comprises a width of between about 10 μm to about 30 μm. In some embodiments, the microfluidic channel comprises a width of between about 1 μm to about 10 μm. In some embodiments, the microfluidic channel comprises a width of between about 0.1 μm to about 1.0 μm. In some embodiments, the microfluidic channel comprises a width of between about 0.01 μm to about 0.1 μm. In some embodiments, the microfluidic channel comprises a width of between about 0.001 μm to about 0.01 μm. In some embodiments, the microfluidic channel comprises a width of between about 0.001 μm to about 1.0 μm. In some embodiments, the microfluidic channel comprises a height of between about 10 μm to about 100 μm. In some embodiments, the microfluidic channel comprises a height of between about 10 μm to about 30 μm. In some embodiments, the microfluidic channel comprises a height of between about 1 μm to about 10 μm. In some embodiments, the microfluidic channel comprises a height of between about 0.1 μm to about 1.0 μm. In some embodiments, the microfluidic channel comprises a height of between about 0.01 μm to about 0.1 μm. In some embodiments, the microfluidic channel comprises a height of between about 0.001 μm to about 0.01 μm. In some embodiments, the microfluidic channel comprises a height of between about 0.001 μm to about 1.0 μm. In some embodiments, the microfluidic channel comprises a length of between about 10 μm to about 100 mm. In some embodiments, the microfluidic channel comprises a length of between about 10 μm to about 10WSGR Reference No.64149-703.601 mm. In some embodiments, the microfluidic channel comprises a length of between about 1 μm to about 10 μm. In some embodiments, the microfluidic channel comprises a length of between about 0.1 μm to about 1.0 mm. In some embodiments, the microfluidic channel comprises a length of between about 0.01 μm to about 0.1 mm. In some embodiments, the microfluidic channel comprises a length of between about 0.001 μm to about 0.01 mm. In some embodiments, the microfluidic channel comprises a length of between about 0.001 μm to about 1.0 mm. In some embodiments, the one or more flow channels comprise multiple single inlets and a single outlet. In some embodiments, the one or more flow channels comprise multiple single inlets and a doublet outlet. In some embodiments, the one or more flow channels comprise a single inlet and multiple outlets.

[0136] In some embodiments, the flow channel comprises a feedback loop. In some embodiments, the flow channel comprises an inline pump. In some embodiments, the flow channel comprises a pump. In some embodiments, the flow channel comprises a cell injector. In some embodiments, the flow channel comprises a cell cartridge. In some embodiments, the flow channel comprises a cell collector. In some embodiments, the flow channel comprises a buffer reservoir. In some embodiments, the flow channel may branch in an 1xN pattern, where N is an integer greater than one. In some embodiments, the flow channel may branch in a series of 1xN patterns, where N is an integer greater than one.

[0137] In some embodiments, the analyte processing device comprises a substrate, element, or membrane to manipulate the scattering of light. In some embodiments, the analyte processing device comprises a substrate, element, or membrane to manipulate the propagation of light. In some embodiments, the flow channel comprises a light modifying system. In some embodiments, the flow channel comprises a light modifying substrate. In some embodiments, the flow channel comprises a light modifying element. In some embodiments, the light modifying element may be a dichroic optical component, a mirror, a membrane, a concentrator, a lens, a blocker, optical grating, a reflector, vertical couplers, lateral couplers, a filter, or a light entry section. In some embodiments, the analyte processing device comprises a light entry section. In some embodiments, the light entry section is a pinhole. In some embodiments, the light entry section comprises vertical couplers. In some embodiments, the light entry section comprises lateral couplers. In some embodiments, the light entry section comprises optical grating. In some embodiments, the light entry section comprises one or more dichroic optical components. In some embodiments, the filter is a dielectric material. In some embodiments, the filter is a metallic material. In some embodiments, the filter is a semiconductor material. In some embodiments, the filter is a combination of a dielectric, metallic, or semiconductor material, orWSGR Reference No.64149-703.601 combination thereof. In some embodiments, the filter comprises more than layer of filters. In some embodiments, the blocker comprises a layer of absorptive material configured to absorb specific light wavelengths. In some embodiments, the blocker comprises a layer of material configured to transmit specific wavelengths of light. In some embodiments, the blocker comprises a layer of material configured to transmit specific ranges of wavelengths of light. In some embodiments, the blocker comprises a layer of material configured to absorb specific ranges of wavelengths of light. In some embodiments, a blocker increases the signal to noise ratio by a factor of two. In some embodiments, a blocker increases the signal to noise ratio by a factor of at least two, at least 10, at least 100, at least 1,000, or at least 10,000. In some embodiments, the concentrator comprises a lens. In some embodiments, the lens is a microlens, a flat lens, a diffractive lens, an absorptive lens, or a non-absorptive lens. In some embodiments, the concentrator is a dielectric block. In some embodiments, the dielectric block is at least 100 nanometers thick. In some embodiments, dielectric block is at least 1 micrometer thick. In some embodiments, the mirror is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the reflector is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the mirror is configured to improve the coupling efficiency of lateral couplers. In some embodiments, the reflector is configured to improve the coupling efficiency of lateral couplers. In some embodiments, the one or more flow channels is configured to generate a displacement effect on an analyte located in the at least one flow channel, thereby selectively displacing the analyte in the one or more analyte processing areas. In some embodiments, the displacement is acoustical. In some embodiments, the displacement is electrical. In some embodiments, the displacement is magnetic. In some embodiments, the displacement is caused by a fluid wave. In some embodiments, the displacement is caused by a structure of a flow channel. In some embodiments, the displacement is caused by a density wave. In some embodiments, the displacement is via droplet displacement. In some embodiments, the one or more flow channels further comprises a gate. In some embodiments, the one or more flow channels further comprises a sealable chamber. In some embodiments, the one or more flow channels further comprises one or more pneumatically driven valves. In some embodiments, the one or more flow channels further comprises one or more fluid reservoirs. In some embodiments, the one or more flow channels further comprises one or more peristaltic pumps. In some embodiments, the one or more flow channels are a space-constrained tube relative to the analyte. Excitation sourcesWSGR Reference No.64149-703.601

[0138] Several arrangements are possible to yield an excitation within the context of the analyte processing device described herein. In some embodiments, the device comprises one excitation source. In some embodiments, the device comprises more than one, more than two, more than three, more than four, or more than five excitation sources. In some embodiments, the device comprises at least 10, at least 20, at least 30, or at least 40 excitation sources. In some embodiments, the device comprises one or more excitation sources integrated with the device. In some embodiments, the device comprises one or more excitation sources integrated with a chip. In some embodiments, the one or more excitation sources comprises a photon array. In some embodiments, the one or more excitation sources comprises one or more photon arrays. In some embodiments, the one or more excitation sources comprises a waveguide. In some embodiments, the one or more excitation sources are configured to yield specific wavelengths of lights. In some embodiments, the one or more excitation sources comprises an interposer. In some embodiments, the one or more excitation sources comprises a transducer. In some embodiments, the one or more excitation sources comprises a laser. In some embodiments, the one or more excitation sources comprises an integrated circuit. In some embodiments, the one or more excitation sources comprises an interposer. In some embodiments, the excitation source comprises a transducer. In some embodiments, the excitation source comprises an interposer. In some embodiments, the excitation source comprises more than one interposer. In some embodiments, the excitation source comprises a transducer. In some embodiments, the excitation source comprises one or more transducers. In some embodiments, the excitation source comprises a laser. In some embodiments, the excitation source comprises more than one laser, more than 10 lasers, more than 100 lasers, or more than 1,000 lasers. In some embodiments, the laser is a bonded laser. In some embodiments, the laser is an external laser. In some embodiments, the laser is a continuous laser. In some embodiments, the laser is a pulsed laser. In some embodiments, the one or more lasers are a tunable laser. In some embodiments, the one or more excitation sources is configured to generate a light wavelength between 300 nm and 1,200 nm. In some embodiments, the one or more excitation sources is configured to generate a light with a height between at least 80 nm and at most 200 nm. In some embodiments, the one or more excitation sources is configured to generate light intensity of at least 1 μW / μm2. In some embodiments, the one or more excitation sources generates a light intensity of less than 101 μW / μm2. In some embodiments, at least one of the one or more excitation sources is a reference excitation source. In some embodiments, the one or more excitation sources is integrated with the analyte processing device. In some embodiments, the one or more photodetectors is integrated with the analyte processing device. In some embodiments, the one or more excitation sources further comprise a waveguide.WSGR Reference No.64149-703.601

[0139] In some embodiments, the one or more lasers are integrated with a chip. In some embodiments, the excitation source is integrated with a chip. In some embodiments, the chip is integrated with one flow channel. In some embodiments, the chip is integrated with more than one flow channel. In some embodiments, the chip is integrated with a phoresis mechanism. In some embodiments, the chip is integrated with one or more excitation sources. In some embodiments, the chip is integrated with one or more microfluidic channels. In some embodiments, the chip is integrated with one or more micro-optics components. In some embodiments, the chip is integrated with one or more photonic circuits. In some embodiments, the chip is integrated with one or more CMOS photodetectors. In some embodiments, the chip is integrated with one or more photodetectors. In some embodiments, the chip is integrated with one or more light scattering control elements. In some embodiments, the semiconductor chip comprises a power source, one or more controllers, one or more readouts, and one or more photodetector pixels.

[0140] In some embodiments, the excitation source comprises a waveguide. In some embodiments, the excitation source comprises an optical waveguide. In some embodiments, the optical waveguide may branch in an 1xN pattern, where N is an integer greater than one. In some embodiments, the optical waveguide comprises more than one branching point. In some embodiments, the optical waveguide may comprise one or more 1x2 branching points. In some embodiments, the excitation source is configured to excite light at specific wavelengths. In some embodiments, the excitation source is configured to excite light at specific ranges of light wavelengths. In some embodiments, the excitation source is configured to excite light in the ultraviolet range. In some embodiments, the excitation source is configured to excite light in the deep ultraviolet range. In some embodiments, the excitation source is configured to excite light in the UVA range. In some embodiments, the excitation source is configured to excite light in the UVB range. In some embodiments, the excitation source is configured to excite light in the UVC range. In some embodiments, the excitation source is configured to excite light with a wavelength of between about 100 nm and about 400 nm, between about 100 nm and about 300 nm, between about 315 nm and about 400 nm, between about 280 nm and about 315 nm, between about 100 nm and about 280 nm, between about 280 nm and about 400 nm, or between about 100 nm and about 315 nm. In some embodiments, the excitation source is configured to excite light with a wavelength of less than about 400nm, about 350 nm, about 315 nm, about 300 nm, about 280 nm, about 250 nm, about 200 nm, or about 100 nm. In some embodiments, the excitation source is configured to excite light in the microwave range. In some embodiments, the excitation source is configured to excite light in the IR to visible light range. In some embodiments, the excitation source is configured to excite light up to about 50 mW, about 100WSGR Reference No.64149-703.601 mW, about 150 mW, about 200 mW, about 250 mW, about 300 mW, about 350 mW, about 400 mW about 450 mW, about 500 mW, about 550 mW, about 600 mW, about 650 mW, about 700 mW, about 750 mW, about 800 mW, about 900 mW, or about 1000 mW peak power. In some embodiments, the excitation source is configured to excite light at a repetition rate of about 1 MHz, 2 MHz, 3 MHz, 4 MHz, 5 MHz, 6 MHz, 7 MHz, 8 MHz, 9 MHz, 10 MHz, 11 MHz, 12 MHz, 13 MHz, 14 MHz, 15 MHz, 20 MHz, 25 MHz, 30 MHz, 35 MHz, 40 MHz, 45 MHz, 50 MHz, 60 MHz, 70 MHz, 80 MHz, 90 MHz, or 100 MHz. In some embodiments, the excitation source comprises a pinhole for light entry. In some embodiments, the excitation source comprises an optical circuit. In some embodiments, the optical circuit comprises one or more light entry sections.

[0141] In some embodiments, the excitation source is programmed to generate an evanescent light field. In some embodiments, the excitation source is programmed to generate a superposition of light fields. In some embodiments, the excitation sources are programmed to synchronize with other elements of the analyte processing device sources. In some embodiments, the one or more excitation sources are programmed to synchronize with other excitation sources. In some embodiments, the one or more excitation sources further comprise an interposer. In some embodiments, the one or more excitation sources further comprise a transducer. In some embodiments, the transducer is integrated into the chip. In some embodiments, the transducer is external to the chip. In some embodiments, the one or more excitation sources comprise one laser. In some embodiments, the one or more excitation sources comprises one or more light emitting diodes (LED). In some embodiments, the LED is a micro- LED. In some embodiments, the one or more excitation sources comprise multiple lasers. In some embodiments, the one or more excitation sources comprise external lasers. In some embodiments, the one or more excitation sources comprise bonded lasers. In some embodiments, the one or more excitation sources comprise at least one continuous laser. In some embodiments, the one or more excitation sources comprise at least one pulsed laser. In some embodiments, the one or more excitation sources comprise at least one tunable laser. In some embodiments, the one or more excitation sources comprise at least one laser tuned to near IR to visible range wavelengths of light. Photodetectors

[0142] In some aspects of the disclosure herein, the analyte processing area is configured to enable photodetectors to yield high resolution images of an analyte. In some embodiments, the resolution of the images is at least about 2000 nm, at least about 1500 nm, at least about 1000 nm, at least about 900 nm, at least about 800 nm, at least about 700 nm, at least about 600 nm, atWSGR Reference No.64149-703.601 least about 500 nm, at least about 400 nm, at least about 300 nm, at least about 200 nm, at least about 100 nm, at least about 90 nm, at least about 80 nm, at least about 70 nm, at least about 60 nm, at least about 50 nm, at least about 40 nm, at least about 30 nm, at least about 20 nm, or at least about 10 nm. In some cases, the analyte processing device comprises one photodetector. In some cases, the analyte processing device comprises more than one photodetector, more than two photodetectors, more than four photodetectors, more than eight photodetectors, or more than 16 photodetectors. In some cases, the analyte processing device comprises more than 32 photodetector, more than 64 photodetectors, more than 128 photodetectors, more than 256 photodetectors, or more than 512 photodetectors. In some embodiments, the photodetector comprises a semiconductor imager. In some embodiments, the photodetector comprises one or more semiconductor imagers. In some embodiments, the photodetector comprises a pixel. In some embodiments, the photodetector comprises more than one pixel. In some embodiments, the photodetector comprises more than 10, more than 100, more than 1,000 or more than 10,000 pixels. In some embodiments, the photodetectors are positioned 10 microns apart from each other. In some embodiments, the photodetectors are positioned 15 microns apart from each other. In some embodiments, the photodetectors are positioned 20 microns apart from each other. In some embodiments, the photodetectors are positioned at least 5 microns apart from each other. In some embodiments, the photodetectors are positioned at least 10 microns apart from each other. In some embodiments, the photodetectors are positioned at least 20 microns apart from each other. In some embodiments, the photodetector comprises one or more pixels. In some embodiments, the photodetector pixel size is 10 microns by 10 microns. In some embodiments, the photodetector pixel size is 20 microns by 10 microns. In some embodiments, the photodetector pixel size is 20 microns by 20 microns. In some embodiments, a photodetector may comprise a camera or camera-like detector with a square, rectangular, or linear array of pixels. In some embodiments, the photodetector may be spatially arranged in a specific manner. In some embodiments, the analyte processing device comprises one photodetector station. In some embodiments, the analyte processing device comprises at least 2, at least 4, at least 8, at least 16, or at least 64 photodetector stations. In some embodiments, the analyte processing device comprises at least 128, at least 512, or at least 1028 photodetector stations. In some embodiments, the one or more photodetectors comprise a single photodetector pixel. In some embodiments, the one or more photodetector pixels are 10 microns by 10 microns in size. In some embodiments, the one or more photodetector pixels are 20 microns by 20 microns in size. In some embodiments, the one or more photodetector pixels are 20 microns by 10 microns in size. In some embodiments, the analyte processing device comprises two or more photodetectors, wherein the two or more photodetectors are positioned 20 microns apart fromWSGR Reference No.64149-703.601 one another. In some embodiments, the one or more excitation sources in optical communication with the analyte processing area comprises an optical path from the one or more excitation sources to the analyte processing area, the optical path comprising a light scattering control system.

[0143] In some cases, one or more photodetectors are located on the bottom of the flow channel. In some cases, one or more photodetectors are located on the side of the flow channel. In some cases, one or more photodetectors are located on the top of the flow channel. In some embodiments, one or more photodetectors covers a section of the flow channel surface. In some embodiments, the photodetector comprises a complementary metal oxide sensor (CMOS) imager. In some embodiments, the photodetector comprises one or more complementary metal oxide sensor (CMOS) imagers. In some embodiments, the photodetector comprises a CMOS imager configured to flush electrons generated with scattered light upon excitation. In some embodiments, the photodetector comprises a spectral CMOS imager. In some embodiments, the photodetector comprises a CMOS imager configured for photon wavelength. In some embodiments, the photodetector comprises a CMOS imager configured for photon intensity. In some embodiments, the photodetector comprises a pinned photodiode CMOS imager. In some embodiments, the photodetector comprises a single-photon avalanche diode CMOS imager. In some embodiments, the one or more photodetectors comprise a complementary metal oxide sensor (CMOS) imager. In some embodiments, the CMOS imager is configured to flush electrons generated with scattered light upon excitation. In some embodiments, the CMOS imager is spectral. In some embodiments, the CMOS imager is configured for photon intensity. In some embodiments, the CMOS imager is configured for photon wavelength. In some embodiments, the CMOS imager is a pinned photodiode. In some embodiments, the CMOS imager is a single photon avalanche diode array. In some embodiments, the CMOS imager comprises one or more arrays of single photon avalanche diodes. In some embodiments, the CMOS imager further comprises one or more event cameras. In some embodiments, the CMOS imager further comprises one or more time-delay integration (TDI) camera.

[0144] In some embodiments, the one or more photodetectors forms an optical path with the analyte processing area. In some embodiments, the one or more photodetectors forms an optical path with one or more analyte processing areas. In some embodiments, the one or more photodetectors forms one or more optical paths with the analyte processing area. In some embodiments, the optical path comprises light modifying substrates, layers, or elements. In some embodiments, the optical path comprises a light entry section, an optical circuit, optical grating, a reflector, vertical couplers, lateral couplers, a filter, a blocker, a concentrator, a mirror, or anWSGR Reference No.64149-703.601 optical membrane. In some embodiments, the optical path comprises one or more light modifying substrates, layers, or elements. In some embodiments, the one or more photodetectors are configured to simultaneously collect the one or more two-dimensional images. In some embodiments, the one or more photodetectors are configured to simultaneously collect the one or more two-dimensional images. In some embodiments, the one or more photodetectors are configured to collect the one or more two-dimensional images without the use of markers or labels. In some embodiments, the one or more photodetector(s) comprises at least one of: a spectral detector, an emissions detector, or a scattering detector. In some embodiments, the analyte processing device comprises at least one emissions detector and at least one scattering detector. In some embodiments, the one or more two-dimensional images determines the absolute or relative size of the analyte. In some embodiments, the three-dimensional structure of the analyte maps the surface of the analyte. In some embodiments, the three-dimensional structure of the analyte comprises deformed representations of the analyte. In some embodiments, the deformed representations of the same analyte represent different deformations. In some embodiments, the deformed representations of the analyte represent an unchanged deformation.

[0145] In some embodiments, the one or more photodetectors comprises one or more single- photon avalanche diode (SPAD) arrays. In some embodiments, the one or more photodetectors comprise a single-photon avalanche diodes (SPAD) array. In some embodiments, the one or more photodetectors comprise one or more silicon photomultipliers (SiPM). In some embodiments, the one or more two-dimensional images comprises 1 pixel. In some embodiments, the one or more two-dimensional images has a 1:1 aspect ratio of the analyte. In some embodiments, the one or more two-dimensional images each depict an area on a surface of the analyte having a length of from 0.5 microns to 100 microns and a width from 0.5 microns to 100 microns, and a width being equal to or smaller than the length. In some embodiments, the one or more two-dimensional images having the 1:1 aspect ratio are combined with separate two-dimensional images of the same analyte with the same aspect ratio to produce the three- dimensional structure of an analyte. In some embodiments, the aspect ratios from the one or more two-dimensional images with the 1:1 aspect ratio are combined with separate two- dimensional images with different aspect ratios when producing the three-dimensional structure of one or more analytes. In some embodiments, the three-dimensional structure depicts a holistic distribution of surface markers of the one or more analytes. In some embodiments, the holistic distribution of surface markers can be defined as localized or partial. In some embodiments, the holistic distribution of surface markers can be defined as random. In some embodiments, the holistic distribution of surface markers can determine a parameter of a chemical or biologicalWSGR Reference No.64149-703.601 test. In some embodiments, a defined stretch or a deformation can determine a false positive for a chemical or biological test. In some embodiments, the parameter of a chemical or biological test can separate a false positive from a true positive. In some embodiments, the light scattering control system is configured to improve signal to noise ratio by at least a factor of five relative to photodetecting only unscattered or specular light. Analyte processing area

[0146] The analyte processing area may comprise multiple individual sections or elements to optimize imaging under specific circumstances. The analyte processing area may also be geometrically arranged to optimize imaging under a useful circumstance. In some embodiments, the analyte processing device comprises one or more analyte processing areas. In some embodiments, the analyte processing area forms an optical path with the one or more excitation sources. In some embodiments, the analyte processing area forms an optical path with the one or more photodetectors. In some embodiments, the analyte processing area may be between a sorting junction and a gate. In some embodiments, the analyte processing area may be between more than one sorting junction or more than one gate. In some embodiments, the analyte processing area comprises a light scattering control system. In some embodiments, the analyte processing area comprises a light scattering control element. In some embodiments, the analyte processing area comprises one or more light scattering control elements. In some embodiments, the analyte processing area comprises an optical membrane. In some embodiments, the analyte processing area comprises a light modifying substrate or light modifying element. In some embodiments, the analyte processing area comprises an optical membrane. In some embodiments, the analyte processing area comprises a layer of light modifying substrates. In some embodiments, the flow channel comprises an analyte processing area. In some embodiments, the flow channel comprises one or more analyte processing areas. In some embodiments, the analyte processing area is at the bottom surface. In some embodiments, the analyte processing area is at the top surface. In some embodiments, the analyte processing area is on the side of the surface. In some embodiments, the analyte processing area comprises one or more diffractive optic layers. In some embodiments, the analyte processing area is adjacent to one or more diffractive optic layers. In some embodiments, the analyte processing area is adjacent to a diffractive optic layer. In some embodiments, the analyte processing area is above one or more photodetectors. In some embodiments, the analyte processing area is above one or more light modifying substrates. In some embodiments, the analyte processing area is located at a bottom surface of one or more flow channels.WSGR Reference No.64149-703.601

[0147] In some embodiments, the microfluidic channel is arranged as shown in FIG.22. In some embodiments, the microfluidic channel is arranged as shown in Type I of FIG.22. In some embodiments, the microfluidic channel is arranged as shown in Type II of FIG.22. In some embodiments, the microfluidic channel is arranged as shown in Type III of FIG.22. In some embodiments, the analyte processing area comprises a photomultiplier tube. Analytes

[0148] In some embodiments, the analyte comprises multiple analytes comprising at least one of: small molecules, polymers, cellular structures, or surface markers. In some embodiments, the multiple analytes comprise materials from biological systems. In some embodiments, the materials from biological systems comprise cells or internal cell organelles. In some embodiments, the multiple analytes comprise free floating or secreted proteins. In some embodiments, the multiple analytes comprise a nucleotide. In some embodiments, the multiple analytes comprise or are contained within exosomes. In some embodiments, the multiple analytes comprise or are contained within neutrophils. In some embodiments, the multiple analytes comprise nucleotides. In some embodiments, the multiple analytes are extravesicular. In some embodiments, the multiple analytes comprise at least one of microorganisms or microbes. In some embodiments, the three-dimensional structures of each of the multiple analytes is analyzed individually. In some embodiments, the three-dimensional structure of each of the multiple analytes may produce a new three-dimensional structure of an additional, larger analyte. In some embodiments, structural integrity of the multiple analytes is preserved after displacement in the one or more flow channels. In some embodiments, the surface markers comprise cell surface markers. Many analytes of interest may be characterized by the analyte processing device. In some embodiments, the analyte is singular. In some embodiments, the analyte comprises a population. In some embodiments, the analyte is an inorganic chemical. In some embodiments, the analyte is an organic chemical. In some embodiments, the analyte is a peptide, small molecule, drug molecule, drug-conjugate molecule, dye molecule, dye-conjugate molecule, fluorescent molecule, or any other organic chemicals of interest.

[0149] In some embodiments, the analyte can comprise a biological sample. In some embodiments, the analyte comprises at least one cell. In some embodiments, the analyte is a population of cells. In some embodiments, the at least one cell may be a mammalian cell, a eukaryotic cell, a yeast cell, a bacterial cell, a primary cell, an immortalized cell, a cancer cell, a hybrid cell, or a derivative or an engineered form thereof. In some embodiments, the analyte is blood. In some embodiments, the analyte is plasma. In some embodiments, the analyte is cerebrospinal fluid. In some embodiments, the analyte is lymph tissue. In some embodiments,WSGR Reference No.64149-703.601 the analyte is a specific type of cell from a subject. In some embodiments, the specific type of cell is from the brain, liver, heart, intestine, colon, muscle, kidney, pancreas, or other organ. In some embodiments, the analyte comprises skin cells, heart cells, immune system cells such as B- cells, lymphocytes, T-cells, kidney cells, liver cells, muscle cells, nervous system cells such as astral cells, glial cells, neuronal cells, bacterial cells, or peripheral blood mononuclear cells.

[0150] In some embodiments, the analyte is in the liquid phase. In some embodiments, the analyte is in the gas phase. In some embodiments, the analyte is an aqueous solution. In some embodiments, the analyte is solvated in an organic solution (e.g., acetone, methanol, acetonitrile, tetrahydrofuran, or other organic solvent). In some embodiments, the analyte is at least partially aerosolized. In some embodiments, the analyte is an aerosol. In some embodiments, the motion of the analyte is laminar. In some embodiments, the analyte motion is turbulent. In some embodiments, the analyte comprises one or more additional solutes. In some embodiments, the solvent is phosphate buffered saline (PBS). In some embodiments, the analyte motion is laminar. In some embodiments, the analyte motion is turbulent. In some embodiments, the analyte is not in motion. In some embodiments, the analyte is an aerosol. In some embodiments, the analyte is in the gas phase. In some embodiments, the analyte is in the liquid phase. In some embodiments, the analyte is an aqueous solution. In some embodiments, the analyte comprises one or more cells. In some embodiments, the analyte comprises blood. In some embodiments, the analyte comprises lymph. In some embodiments, the analyte comprises a cell line. In some embodiments, the analyte comprises a cell culture. In some embodiments, the analyte is membrane-bound. In some embodiments, the membrane of the membrane-bound analyte is intact after analysis. In some embodiments, the analyte comprises a cell. In some embodiments, the cell is viable after analysis. In some embodiments, the analyte comprises a cell. In some embodiments, the cell is viable after analysis as indicated by a viability stain. In some embodiments, the viability stain can be tryphan blue, methylene blue, or SYTOX®. In some embodiments, the cell is not stained by tryphan blue, methylene blue, or SYTOX® after analysis. In some embodiments, the cell is able to divide after analysis. In some embodiments, the cell membrane of the cell is intact after analysis. In some embodiments, the cell is not lysed after analysis. In some embodiments, the cell is not undergoing apoptosis after analysis. In some embodiments, the cell is able to generate ATP after analysis. In some embodiments, the analyte comprises a human cell. In some embodiments, the analyte comprises a bacterial cell. In some embodiments, the analyte comprises urine. In some embodiments, the analyte comprises bodily fluids. In some embodiments, the analyte comprises feces. In some embodiments, the analyte comprises peritoneal cavity fluid. In some embodiments, the analyte comprises bone marrow fluid. In some embodiments, the analyte comprises cerebrospinal fluid. In some embodiments,WSGR Reference No.64149-703.601 the analyte comprises cells purified from a subject’s blood sample. In some embodiments, the analyte comprises blood serum or plasma.

[0151] In some embodiments, the analyte is processed prior to analysis. In some embodiments, the analyte is reacted with a fluorophore, dye, labeling agent, or other similar chemical reagent. In some embodiments, the analyte is centrifuged prior to analysis. In some embodiments, the analyte is heated prior to analysis. In some embodiments, the analyte is cooled prior to analysis. In some embodiments, the analyte is frozen, or flash frozen, prior to analysis. In some embodiments, the analyte is a suspension. In some embodiments, the analyte is homogenous. In some embodiments, the analyte is heterogenous. In some embodiments, the analyte may be labelled with a fluorophore, a fluorescent molecule, a dye, or other similar moiety. In some embodiments, at least one cell may be labelled with a fluorophore or expresses a fluorescent molecule. In some embodiments, at least once cell may express a molecule including, but not limited, to a fluorescent molecule, a phosphorescent molecule, a chemiluminescent molecule, or a bioluminescent molecule. In some embodiments, fluorophores can be used as labels for specific target analytes, in applications where the targets can be chemically modified to incorporate a TGF fluorophore. Examples includes, but are not limited to, Northern blots, Southern blots, DNA microarrays, quantitative Polymerase Chain Reaction (PCR), digital PCR, and diagnostic assays. Optical paths

[0152] Acquisition of optical signals is possible by optical communication within the analyte processing device described herein. Optical communication may be partially characterized by the optical path between an analyte of interest and one or more photodetectors. In some embodiments, optical communication comprises an optical path between an analyte of interest, one or more excitation sources, and one or more photodetectors. In some embodiments, optical communication comprises an optical path between one or more analytes of interest, one or more excitation sources, and one or more photodetectors. In some embodiments, the optical path is configured to yield an evanescent light beam from the one or more excitation sources.

[0153] In some embodiments, the analyte processing device comprises an optical path. In some embodiments, the optical path is formed between one or more excitation sources and an analyte. In some embodiments, the optical path is formed between one or more photodetectors and the analyte processing area. In some embodiments, the optical path is formed between one or more photodetectors, one or more excitation sources, and an analyte. In some embodiments, the optical path is formed between one or more photodetectors and the analyte processing area. In some embodiments, the optical path comprises a light scattering control element. In someWSGR Reference No.64149-703.601 embodiments, the light scattering control element comprises a layer of material. In some embodiments, the material comprises one or more of the following: SiO2, TiN, Ti, Si3N4, silicon oxynitride (SiOxNy), TaO, HfO, Si, glass, or other similar material or oxide.

[0154] In some embodiments, the optical path between the photodetector and the analyte processing area comprises a light scattering control element. In some embodiments, the optical path comprises a lens, concentrator, dielectric, dichroic, reflector, or mirror. In some embodiments, the optical path comprises elements configured to redirect scattered light distal from a photodetector. In some embodiments, the optical path comprises elements configured to redirect scattered light distal from one or more photodetectors. In some embodiments, the optical path comprises more than one element configured to redirect scattered light distal from a photodetector. In some embodiments, the optical path comprises a dichroic optical component configured to redirect scattered light distal from one or more photodetectors. In some embodiments, the optical path comprises more than one membrane. In some embodiments, the optical path comprises a light modifying membrane. In some embodiments, the optical path comprises an angle relative to an analyte. In some embodiments, the optical path comprises an angle relative to the light modifying element. In some embodiments, the optical path comprises an angle relative to the light modifying substrate. In some embodiments, the optical path comprises an angle relative to the light modifying layer. In some embodiments, the light scattering control element comprises one or more layers of the following: SiO2, TiN, Ti, Si3N4, silicon oxynitride (SiOxNy), TaO, HfO, Si, glass, or other similar material or oxide. In some embodiments, the light modifying substrate comprises one or more layers of the following: SiO2, TiN, Ti, Si3N4, silicon oxynitride (SiOxNy), TaO, HfO, Si, glass, or other similar material or oxide. In some embodiments, the optical path forms an angle of at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, or at least 90 degrees with the one or more light scattering control elements. Light scattering control system

[0155] In order to diversify approaches to imaging analytes, the analyte processing device may comprise a particular light scattering control system. In some embodiments, the light scattering control system comprises an optical membrane comprising a polarizer, waveplate, absorber, filter, blocker, concentrator, reflector, or mirror. In some embodiments, the one or more photodetectors comprise a shutter configured to reduce overexposure of light. In some embodiments, the light scattering control system is configured to optimize signal to noise ratio of an analyte. In some embodiments, the light scattering control system is configured to optimize light propagation. In some embodiments, the light scattering control system isWSGR Reference No.64149-703.601 configured to optimize evanescent light propagation. In some embodiments, the light scattering control system is configured to propagate evanescent light. In some embodiments, the light scattering control system is configured to shutter excess light excitation within the analyte processing device. In some embodiments, the light scattering control system is configured to reduce excess light propagation. In some embodiments, the light scattering control system is configured to optimize angular light propagation. In some embodiments, the light scattering control system comprises a light modifying element. In some embodiments, the light scattering control system comprises one or more light modifying elements.

[0156] The light scattering control systems are capable of increasing the sensitivity of imaging. In some embodiments, the measurement sensitivity achieved through the light scatter control system is at least a factor of two. In some embodiments, the sensitivity increase is at least a factor of 10, at least a factor of 100, at least a factor of 1,000, at least a factor of 10,000, or at least a factor 100,000. In some embodiments, the light scattering control systems increase the signal to noise ratio by at least a factor of two, a factor of five, a factor of 10, a factor of 100, a factor of 1,000, or a factor of 10,000. In some embodiments, the signal to noise ratio is improved by reducing excess electrons. In some embodiments, the signal to noise ratio is improved by signal correlation between more than two or more photodetectors. In some embodiments, signal to noise ratio is improved by an evanescent light field. In some embodiments, signal to noise ratio is improved by imaging modality. In some embodiments, the noise is reduced from light scattering within a waveguide. In some embodiments, the noise is reduced from light scattering due to photonics structure. In some embodiments, the noise is reduced from light scattering due to an integrated circuit. In some embodiments, the noise is reduced from light scattering due to an application specific integrated circuit. In some embodiments, the noise is reduced from light scattering due to light scattering from one or more analytes. In some embodiments, the noise is reduced from light scattering due to flow channel structure. In some embodiments, the noise is reduced from light scattering due to microfluidic channel walls. In some embodiments, the noise is reduced from light scattering due to photodetector structure. In some embodiments, the light scattering control system comprises a dichroic optical component configured to redirect scattered light distal from the one or more photodetectors. In some embodiments, the light scattering control system is configured to improve signal to noise ratio by at least a factor of five. In some embodiments, the filter is comprised of at least one layer of dielectric material configured to absorb unwanted light wavelengths and improve signal to noise ratio by a factor of at least five. In some embodiments, the filter is comprised of at least one layer of semiconductor material configured to absorb unwanted light wavelengths and improve signal to noise ratio by a factor of at least five. In some embodiments, the filter is comprised of at least one layer ofWSGR Reference No.64149-703.601 metallic material configured to absorb unwanted light wavelengths and improve signal to noise ratio by a factor of at least five. In some embodiments, the filter is comprised of at least two layers of dielectric, semiconductor, or metallic material configured to absorb unwanted light wavelengths and improve signal to noise ratio by a factor of at least 5. In some embodiments, the blocker comprises a layer of absorptive material configured to transmit specific wavelengths. In some embodiments, the blocker is tuned to absorb specific photonic wavelength ranges. In some embodiments, the filter is comprised of at least two layers of dielectric, semiconductor, or metallic material configured to absorb unwanted light wavelengths and improve signal to noise ratio. In some embodiments, the filter is comprised of a polarizing light filter. In some embodiments, the blocker comprises a layer of absorptive material configured to transmit specific wavelengths of light. In some embodiments, the blocker is tuned to absorb specific photonic wavelength ranges. In some embodiments, the concentrator is a microlens concentrator. In some embodiments, the concentrator comprises a flat lens concentrator. In some embodiments, the concentrator comprises a diffractive lens. In some embodiments, the concentrator comprises an absorptive lens. In some embodiments, the concentrator comprises a non-absorptive lens. In some embodiments, the concentrator comprises a polarization sensitive lens. In some embodiments, the concentrator comprises a dielectric. In some embodiments, the concentrator comprises a dielectric block. In some embodiments, the concentrator comprises a dielectric block at least 100 nanometers thick. In some embodiments, the concentrator comprises a dielectric block at least one micrometer thick. In some embodiments, the one or more excitation sources comprise an optical circuit comprising one or more light entry sections, one or more optical dividers, and a light delivery section. In some embodiments, the light delivery section further comprises one or more dichroic optical components configured to redirect scattered light away from the light delivery section. In some embodiments, the light entry section comprises vertical couplers. In some embodiments, the light entry section comprises optical grating. In some embodiments, the light entry section further comprises a lateral coupler. In some embodiments, the light entry section is a pinhole. In some embodiments, the reflector is configured to improve the coupling efficiency of the vertical couplers. In some embodiments, the mirror is configured to improve the coupling efficiency of vertical couplers. Light scattering control elements

[0157] Light scattering control elements can individually and synergistically yield a favorable effect on physical characterization of analytes in a flow channel. In some embodiments, the analyte processing device comprises a light scattering control element, which may form part of a broader light scattering control system. In some embodiments, the analyte processing deviceWSGR Reference No.64149-703.601 comprises one or more light scattering control systems. In some embodiments, the analyte processing device comprises one or more light scattering control elements. In some embodiments, the optical path comprises a light scattering control element. In some embodiments, the optical path comprises one or more light scattering control elements. In some embodiments, the light scattering control element comprises a lens, a concentrator, mirror, reflector, optical grating, blocker, coupler, or absorptive material. In some embodiments, the light scattering control element comprises a micro-interferogram element (MIE). In some embodiments, the one or more light scatter control elements reduces the signal to noise ratio of one or more optical signals emitted from the chip by at least a factor of 10.

[0158] In some embodiments, the one or more light scattering control elements comprise a light entry section. In some embodiments, the light entry section is a pinhole. In some embodiments, the light entry section comprises vertical couplers. In some embodiments, the light entry section comprises lateral couplers. In some embodiments, the light entry section comprises optical grating. In some embodiments, the light entry section comprises one or more dichroic optical components. In some embodiments, the filter is a dielectric material. In some embodiments, the filter is a metallic material. In some embodiments, the filter is a semiconductor material. In some embodiments, the filter is a combination of a dielectric, metallic, or semiconductor material, or combination thereof. In some embodiments, the filter comprises more than layer of filters. In some embodiments, the blocker comprises a layer of absorptive material configured to absorb specific light wavelengths. In some embodiments, the blocker comprises a layer of material configured to transmit specific wavelengths of light. In some embodiments, the blocker comprises a layer of material configured to transmit specific ranges of wavelengths of light. In some embodiments, the blocker comprises a layer of material configured to absorb specific ranges of wavelengths of light. In some embodiments, a blocker increases the signal to noise ratio by a factor of two. In some embodiments, a blocker increases the signal to noise ratio by a factor of at least two, at least 10, at least 100, at least 1,000, or at least 10,000. In some embodiments, the concentrator comprises a lens. In some embodiments, the lens is a microlens, a flat lens, a diffractive lens, an absorptive lens, or a non-absorptive lens. In some embodiments, the concentrator is a dielectric block. In some embodiments, the dielectric block is at least 100 nanometers thick. In some embodiments, dielectric block is at least 1 micrometer thick. In some embodiments, the mirror is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the reflector is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the mirror is configured to improve the coupling efficiency of lateral couplers. In some embodiments, the reflector is configured to improve the coupling efficiency of lateral couplers. In someWSGR Reference No.64149-703.601 embodiments, the light scattering control elements are integrated with the analyte processing device. In some embodiments, the light scattering control elements are adjacent to one or more photodetectors. In some embodiments, the light scattering control elements are on a surface on one or more flow channels. In some embodiments, the light scattering control elements comprise a diffractive optic layer. In some embodiments, the light scattering control elements are between one or more photodetectors and one or more flow channels. In some embodiments, the one or more flow channels is above the one or more light scattering control elements. In some embodiments, the light scattering control elements are configured to send and receive one or more photons to and from the one or more flow channels. In some embodiments, the diffractive optic layer is configured to send and receive one or more photons to and from the one or more flow channels. In some embodiments, one or more photodetectors is configured to receive one or more photons from the diffractive optic layer. In some embodiments, the one or more photodetectors is configured to receive one or more photons from the light scattering control elements. In some embodiments, the flow channels are configured to receive one or more photons from the light scattering control elements. In some embodiments, the light modifying substrate is displaced between the one or more photodetectors and the one or more flow channels. In some embodiments, the light modifying substrate comprises a diffractive optic layer. In some embodiments, the light modifying substrate is displaced between the one or more photodetectors and the one or more flow channels. In some embodiments, a diffractive optic layer is displaced between the one or more photodetectors and the one or more flow channels. In some embodiments, the one or more flow channels are displaced on or above the diffractive optic layer. In some embodiments, the light modifying substrate is configured to send and receive one or more photons to and from the one or more flow channels. In some embodiments, the diffractive optic layer is configured to send and receive one or more photons to and from the one or more flow channels. In some embodiments, the one or more photodetectors is configured to receive one or more photons from the light modifying substrate. In some embodiments, the one or more photodetectors is configured to receive one or more photons from the diffractive optic layer. Chips In some embodiments, disclosed herein are chips, which may be separate structures from the analyte imaging device or analyte processing device. In some embodiments, the chip forms a layer of an analyte imaging device or analyte processing device. In some embodiments, provided herein is a chip comprising one or more flow channels, wherein the one or more flow channels comprise one or more light scatter control elements adjacent to one or more analyte processingWSGR Reference No.64149-703.601 areas. In some embodiments, the one or more flow channels are configured to rotate a cell on an axis. In some embodiments, the one or light scatter control elements comprise one or more diffractive optic layers. In some embodiments, the one or light scatter control elements comprise one or more light scattering control elements. In some embodiments, the one or light scatter control elements are integrated with the chip. In some embodiments, the flow channel comprises one or more features configured to displace the cell. In some embodiments, the flow channel comprises one or more chemical functionalizations. In some embodiments, the one or more chemical functionalizations are configured to interact with one or more analytes. In some embodiments, the one or more flow channels is configured to receive an acoustic wave, wherein the acoustic wave is configured to rotate the cell on an axis. In some embodiments, the flow channel comprises one or more features configured to rotate the cell on an axis. In some embodiments, the one or more flow channels are configured to contact a light scattering control system. In some embodiments, the one or more flow channels have a width configured to pass one cell at a time. In some embodiments, the width of the one or more flow channels is 100 nanometers. In some embodiments, the chip comprises at least 20 flow channels. In some embodiments, the chip comprises at least 100 flow channels. In some embodiments, the chip is integrated with a circuit. In some embodiments, the chip is integrated with a microfluidic circuit. In some embodiments, the chip is integrated with an electrical circuit. In some embodiments, the chip is integrated with a photonic circuit. In some embodiments, the chip is configured to connect to an analyte processing device disclosed herein. Engineering

[0159] Some disclosed embodiments analyze a liquid or gaseous analyte that is not fixed but remains in fluid motion. In some embodiments, the analyte is an aerosol. In some embodiments, the analyte comprises or is a cell. The analyte retains structural integrity in time as it passes through the apparatus and is not sacrificed or damaged when analyzed. In some embodiments, spatial information is preserved. In some embodiments the spatial information is preserved exactly, and the aspect ratio or pixelation from the original two- dimensional image is maintained in the final three-dimensional image.

[0160] Some disclosed embodiments record primary source data of the analyte in solution or suspension. The analyte is imaged two dimensionally as a static image while in fluid motion, with its size and position in space preserved. The fluid motion reveals multiple perspective views of the same analyte to the fixed imaging apparatus. The apparatus may be simple or complex. In some embodiments, the two-dimensional images are ultimatelyWSGR Reference No.64149-703.601 combined algorithmically to create a three-dimensional image of the analyte or multiple analytes.

[0161] In the disclosed embodiments, the preservation of spatial information allows for precise imaging or screening of an analyte. In some embodiments, this spatial information is used to map the surface of an analyte. In some embodiments, this spatial information is used to determine relative or absolute size. In some embodiments this spatial information is used to ascertain the position of an analyte or multiple analytes within an enclosed or infinite space. In some embodiments this spatial information is used to map analytes relative to other analytes. In some embodiments the pixel orientation information of each image can be preserved during instantaneous imaging of the same analyte from different perspectives. In some embodiments the original pixel orientation information for each analyte is preserved when the original images are combined algorithmically.

[0162] In certain disclosed embodiments, the analyte passes through a space-constrained tube during the imaging process. In certain disclosed embodiments, the analyte passes through a space-constrained tube during a screening process. In some embodiments, the space-constrained tube comprises a slow-down region. In some embodiments, the tube is a channel. In some embodiments, the channel comprises an inlet and an outlet. In some embodiments the channel comprising an inlet and outlet ranges in width from 100 micrometers to 2000 micrometers and ranges in height from 8 micrometers to 50 micrometers. In some embodiments, the channel comprising an inlet and outlet comprises a widened channel. In some embodiments, the channel comprising an inlet and outlet with width ranging from 1000 to 2000 micrometers and a height from 8 micrometers to 50 micrometers comprises a widened channel. In some embodiments, the channel comprising an inlet and an outlet additionally comprises at least one S-bend channel shape. In some embodiments, said channel with at least one S-bend channel shape comprises a width from 10 micrometers to 100 micrometers and a height from 8 micrometers to 50 micrometers. In some embodiments, the channel comprising an inlet and an outlet is configured as an exosome channel. In some embodiments, the exosome channel ranges from 100 nanometers to 1 micrometer and ranges in height from 100 nanometers to 1 micrometer. In some embodiments, the channel bifurcates completely from a single channel into at least two separate individual channels. In some embodiments where the channel bifurcates completely from a single channel into at least two separate individual channels, the width of the single channel is 100 micrometers to 2000 micrometers and the width of the two separate individual channels is 30 micrometers each. In some embodiments the channelWSGR Reference No.64149-703.601 bifurcates completely from a single channel into at least two separate individual channels. . In some embodiments where the channel bifurcates completely from a single channel into at least two separate individual channels, the single channel narrows before bifurcating into two individual channels. In some embodiments where the channel bifurcates completely from a single channel into at least two separate individual channels, the single channel narrows to a width of 30 micrometers before bifurcating into two individual channels.

[0163] In some embodiments, the tube is closed at one end. In some embodiments, the tube is closed at both ends. In some embodiments, the analyte is a particle. In some embodiments, the particle is subjected to flow in the channel. In some embodiments, the particle is subjected to flow in the channel, and the orientation of the particle is manipulated at least once in a single pass of the particle along the channel. In some embodiments, the method of screening a particle comprises, subjecting the particle to flow in the channel, providing a first light beam diffracted into at least a second light beam and a third light beam, wherein the second light beam exposes a first location on the channel and the third light beam exposes a second location on the channel, and wherein the particle has a first orientation in the first location and a second orientation at the second location, thereby generating a first photon from the first location and a second photon from the second location; and detecting the first photon and the second photon using a single photon avalanche diode (SPAD) array in proximity of the channel. In some embodiments, the first photon is emitted from a first region on a surface of the particle and the second photon is emitted from a second region on the surface. In some embodiments, the channel is part of a microfluidic device. In some embodiments, the microfluidic device is part of an integrated system, wherein the system further comprises the SPAD array. In some embodiments, the integrated system further comprises an inlet. In some embodiments, the integrated system further comprises a filtration module. In some embodiments, the integrated system further comprises a sample preparation module configured to prepare the particle for screening. In some embodiments, the sample preparation module is configured to enrich the particle, stain the particle with a dye, add a reagent onto the particle, perform an assay on the particle, inject a reagent inside the particle, or any combination thereof. In some embodiments, said reagent comprises a fluorescent entity. In some embodiments, said reagent comprises a fluorescent dye, a fluorophore, a quantum dot, an antibody, a nucleic acid molecule, or any combination thereof, wherein the reagent is excitable by a light to emit the first photon, the second photon, or both.

[0164] In some embodiments, the system further comprises a photonics circuit configured to diffract the first light beam into the second and the third light beams. In some embodiments, theWSGR Reference No.64149-703.601 channel comprises a physical bump configured to manipulate the orientation of the particle, as shown in the example of FIG.31. In some embodiments the channel comprises a surface acoustic wave (SAW) source configured to generate one or more acoustic waves, wherein the one or more acoustic waves manipulate the orientation of the particle, as shown in the example of FIG.32. In some embodiments, the channel comprises a plurality of SAW sources. In some embodiments, the first location and the second location are spatially separate detection regions separated by at least one re-orientation region configured to manipulate the orientation of the cell. In some embodiments, the re-orientation region comprises a segment with a different channel width, where the segment has a width greater than the width of the channel at sample entry, as shown in the example of FIG.33. In some embodiments, the re-orientation region comprises at least one of: a bump, a surface acoustic wave source (SAW), a channel segment with a different channel width compared to the channel, or any combination thereof. In some embodiments, the re-orientation region comprises a relaxation segment of the channel having a width wider that the width of the channel, and wherein the particle relaxes and re-orients as it passes through the relaxation segment. In some embodiments, the channel comprises one or more pillars, one or more ridges, or both, as shown in an example in FIG.49.

[0165] In some embodiments, the analyte may undergo structural changes as a result of passage through a tube with a narrower segment as compared to the width of the channel at sample entry, as shown in FIG.34. The analyte may deform, stretch, and / or exhibit varying degrees of elasticity. In some embodiments, the imaging apparatus(es) can detect these structural changes and use them as stand-alone characteristic information about analyte. In some embodiments, the imaging apparatus(es) can detect the time passed during each structural change or lack thereof by taking multiple images. In some embodiments the multiple images used to detect the time passed during each structural change can be timed to reveal different structural changes or lack thereof. In some embodiments, the imaging apparatus(es) can use a single analyte’s structural changes in comparison with the structural changes occurring in another analyte or multiple other analyte(s). In some embodiments, the structural changes can reveal different aspects of the same or different surface features of an analyte or multiple analytes and contribute to information used for surface mapping. In some embodiments, the structural changes can reveal different aspects of the same or different surface features of an analyte or multiple analytes and contribute to information used algorithmically for surface mapping.

[0166] The method of screening a particle disclosed herein comprises subjecting the particle to flow in a channel, wherein the orientation of the particle is manipulated at least once in a singleWSGR Reference No.64149-703.601 pass of the particle along the channel; providing a first light beam diffracted into at least a second light beam and a third light beam, wherein the second light beam exposes a first location on the channel and the third light beam exposes a second location on the channel, and wherein the particle has a first orientation in the first location and a second orientation at the second location, thereby generating a first photon from the first location and a second photon from the second location; and detecting the first photon and the second photon using a single photon avalanche diode (SPAD) array in proximity of the channel. In some embodiments, the method of screening a particle comprises the first location and the second location as spatially separate detection regions separated by at least one re-orientation region configured to manipulate the orientation of the cell. In some embodiments, the re-orientation region comprises a constriction segment having a width narrower that the width of the channel, and wherein the particle stretches and re-orients as it passes through the constriction segment. In some embodiments, the channel comprises a serpentine channel, a spiral channel, or both. One example of a serpentine channel and a spiral channel is shown in FIG.35.

[0167] In some embodiments, a channel may comprise the structures shown in the examples of FIG.48. In some embodiments, the channel may comprise a width of 1000 micrometers to 2000 micrometers. In some embodiments, the channel may comprise an s-bend with a width of 10 micrometers to 100 micrometers. In some embodiments, the channel may comprise an exosome channel with a width of 100 nanometers to 1 micrometer. In some embodiments, the channel may comprise a bifurcated channel. In some embodiments, the bifurcated channel may comprise a portion of width 1000 micrometers to 2000 micrometers, a portion of width 30 micrometers, a valve between the portion of width 30 micrometers and a bifurcated channel with two portions of width 30 micrometers. In some embodiments the channel comprises an inlet and one or more outlet portions.

[0168] In some embodiments, the width of a channel or of one or more portions of the channel is about 0.001 micrometers to about 10,000 micrometers. In some embodiments, the width of a channel is about 0.001 micrometers to about 0.01 micrometers, about 0.001 micrometers to about 0.1 micrometers, about 0.001 micrometers to about 1 micrometer, about 0.001 micrometers to about 10 micrometers, about 0.001 micrometers to about 100 micrometers, about 0.001 micrometers to about 1,000 micrometers, about 0.001 micrometers to about 10,000 micrometers, about 0.01 micrometers to about 0.1 micrometers, about 0.01 micrometers to about 1 micrometer, about 0.01 micrometers to about 10 micrometers, about 0.01 micrometers to about 100 micrometers, about 0.01 micrometers to about 1,000 micrometers, about 0.01 micrometers to about 10,000 micrometers, about 0.1 micrometers to about 1 micrometer, about 0.1WSGR Reference No.64149-703.601 micrometers to about 10 micrometers, about 0.1 micrometers to about 100 micrometers, about 0.1 micrometers to about 1,000 micrometers, about 0.1 micrometers to about 10,000 micrometers, about 1 micrometer to about 10 micrometers, about 1 micrometer to about 100 micrometers, about 1 micrometer to about 1,000 micrometers, about 1 micrometer to about 10,000 micrometers, about 10 micrometers to about 100 micrometers, about 10 micrometers to about 1,000 micrometers, about 10 micrometers to about 10,000 micrometers, about 100 micrometers to about 1,000 micrometers, about 100 micrometers to about 10,000 micrometers, or about 1,000 micrometers to about 10,000 micrometers. In some embodiments, the width of a channel is about 0.001 micrometers, about 0.01 micrometers, about 0.1 micrometers, about 1 micrometer, about 10 micrometers, about 100 micrometers, about 1,000 micrometers, or about 10,000 micrometers. In some embodiments, the width of a channel is at least about 0.001 micrometers, about 0.01 micrometers, about 0.1 micrometers, about 1 micrometer, about 10 micrometers, about 100 micrometers, or about 1,000 micrometers. In some embodiments, the width of a channel is at most about 0.01 micrometers, about 0.1 micrometers, about 1 micrometer, about 10 micrometers, about 100 micrometers, about 1,000 micrometers, or about 10,000 micrometers.

[0169] In some embodiments, the width of a channel or of one or more portions of the channel is about 100 micrometers to about 1,000 micrometers. In some embodiments, the width of a channel is about 100 micrometers to about 200 micrometers, about 100 micrometers to about 300 micrometers, about 100 micrometers to about 400 micrometers, about 100 micrometers to about 500 micrometers, about 100 micrometers to about 600 micrometers, about 100 micrometers to about 700 micrometers, about 100 micrometers to about 800 micrometers, about 100 micrometers to about 900 micrometers, about 100 micrometers to about 1,000 micrometers, about 200 micrometers to about 300 micrometers, about 200 micrometers to about 400 micrometers, about 200 micrometers to about 500 micrometers, about 200 micrometers to about 600 micrometers, about 200 micrometers to about 700 micrometers, about 200 micrometers to about 800 micrometers, about 200 micrometers to about 900 micrometers, about 200 micrometers to about 1,000 micrometers, about 300 micrometers to about 400 micrometers, about 300 micrometers to about 500 micrometers, about 300 micrometers to about 600 micrometers, about 300 micrometers to about 700 micrometers, about 300 micrometers to about 800 micrometers, about 300 micrometers to about 900 micrometers, about 300 micrometers to about 1,000 micrometers, about 400 micrometers to about 500 micrometers, about 400 micrometers to about 600 micrometers, about 400 micrometers to about 700 micrometers, about 400 micrometers to about 800 micrometers, about 400 micrometers to about 900 micrometers, about 400 micrometers to about 1,000 micrometers, about 500 micrometers to about 600WSGR Reference No.64149-703.601 micrometers, about 500 micrometers to about 700 micrometers, about 500 micrometers to about 800 micrometers, about 500 micrometers to about 900 micrometers, about 500 micrometers to about 1,000 micrometers, about 600 micrometers to about 700 micrometers, about 600 micrometers to about 800 micrometers, about 600 micrometers to about 900 micrometers, about 600 micrometers to about 1,000 micrometers, about 700 micrometers to about 800 micrometers, about 700 micrometers to about 900 micrometers, about 700 micrometers to about 1,000 micrometers, about 800 micrometers to about 900 micrometers, about 800 micrometers to about 1,000 micrometers, or about 900 micrometers to about 1,000 micrometers. In some embodiments, the width of a channel is about 100 micrometers, about 200 micrometers, about 300 micrometers, about 400 micrometers, about 500 micrometers, about 600 micrometers, about 700 micrometers, about 800 micrometers, about 900 micrometers, or about 1,000 micrometers. In some embodiments, the width of a channel is at least about 100 micrometers, about 200 micrometers, about 300 micrometers, about 400 micrometers, about 500 micrometers, about 600 micrometers, about 700 micrometers, about 800 micrometers, or about 900 micrometers. In some embodiments, the width of a channel is at most about 200 micrometers, about 300 micrometers, about 400 micrometers, about 500 micrometers, about 600 micrometers, about 700 micrometers, about 800 micrometers, about 900 micrometers, or about 1,000 micrometers.

[0170] In some embodiments, the width of a channel or of one or more portions of the channel is about 100 nanometers to about 1,000 nanometers. In some embodiments, the width of a channel is about 100 nanometers to about 200 nanometers, about 100 nanometers to about 300 nanometers, about 100 nanometers to about 400 nanometers, about 100 nanometers to about 500 nanometers, about 100 nanometers to about 600 nanometers, about 100 nanometers to about 700 nanometers, about 100 nanometers to about 800 nanometers, about 100 nanometers to about 900 nanometers, about 100 nanometers to about 1,000 nanometers, about 200 nanometers to about 300 nanometers, about 200 nanometers to about 400 nanometers, about 200 nanometers to about 500 nanometers, about 200 nanometers to about 600 nanometers, about 200 nanometers to about 700 nanometers, about 200 nanometers to about 800 nanometers, about 200 nanometers to about 900 nanometers, about 200 nanometers to about 1,000 nanometers, about 300 nanometers to about 400 nanometers, about 300 nanometers to about 500 nanometers, about 300 nanometers to about 600 nanometers, about 300 nanometers to about 700 nanometers, about 300 nanometers to about 800 nanometers, about 300 nanometers to about 900 nanometers, about 300 nanometers to about 1,000 nanometers, about 400 nanometers to about 500 nanometers, about 400 nanometers to about 600 nanometers, about 400 nanometers to about 700 nanometers, about 400 nanometers to about 800 nanometers, about 400 nanometers to about 900 nanometers, about 400 nanometers to about 1,000 nanometers, about 500 nanometers to about 600 nanometers, about 500WSGR Reference No.64149-703.601 nanometers to about 700 nanometers, about 500 nanometers to about 800 nanometers, about 500 nanometers to about 900 nanometers, about 500 nanometers to about 1,000 nanometers, about 600 nanometers to about 700 nanometers, about 600 nanometers to about 800 nanometers, about 600 nanometers to about 900 nanometers, about 600 nanometers to about 1,000 nanometers, about 700 nanometers to about 800 nanometers, about 700 nanometers to about 900 nanometers, about 700 nanometers to about 1,000 nanometers, about 800 nanometers to about 900 nanometers, about 800 nanometers to about 1,000 nanometers, or about 900 nanometers to about 1,000 nanometers. In some embodiments, the width of a channel is about 100 nanometers, about 200 nanometers, about 300 nanometers, about 400 nanometers, about 500 nanometers, about 600 nanometers, about 700 nanometers, about 800 nanometers, about 900 nanometers, or about 1,000 nanometers. In some embodiments, the width of a channel is at least about 100 nanometers, about 200 nanometers, about 300 nanometers, about 400 nanometers, about 500 nanometers, about 600 nanometers, about 700 nanometers, about 800 nanometers, or about 900 nanometers. In some embodiments, the width of a channel is at most about 200 nanometers, about 300 nanometers, about 400 nanometers, about 500 nanometers, about 600 nanometers, about 700 nanometers, about 800 nanometers, about 900 nanometers, or about 1,000 nanometers.

[0171] In some embodiments, the width of a channel or one or more portions of the channel is about 1 nanometer to about 100 nanometers. In some embodiments, the width of a channel is about 1 nanometer to about 20 nanometers, about 1 nanometer to about 30 nanometers, about 1 nanometer to about 40 nanometers, about 1 nanometer to about 50 nanometers, about 1 nanometer to about 60 nanometers, about 1 nanometer to about 70 nanometers, about 1 nanometer to about 80 nanometers, about 1 nanometer to about 90 nanometers, about 1 nanometer to about 100 nanometers, about 20 nanometers to about 30 nanometers, about 20 nanometers to about 40 nanometers, about 20 nanometers to about 50 nanometers, about 20 nanometers to about 60 nanometers, about 20 nanometers to about 70 nanometers, about 20 nanometers to about 80 nanometers, about 20 nanometers to about 90 nanometers, about 20 nanometers to about 100 nanometers, about 30 nanometers to about 40 nanometers, about 30 nanometers to about 50 nanometers, about 30 nanometers to about 60 nanometers, about 30 nanometers to about 70 nanometers, about 30 nanometers to about 80 nanometers, about 30 nanometers to about 90 nanometers, about 30 nanometers to about 100 nanometers, about 40 nanometers to about 50 nanometers, about 40 nanometers to about 60 nanometers, about 40 nanometers to about 70 nanometers, about 40 nanometers to about 80 nanometers, about 40 nanometers to about 90 nanometers, about 40 nanometers to about 100 nanometers, about 50 nanometers to about 60 nanometers, about 50 nanometers to about 70 nanometers, about 50WSGR Reference No.64149-703.601 nanometers to about 80 nanometers, about 50 nanometers to about 90 nanometers, about 50 nanometers to about 100 nanometers, about 60 nanometers to about 70 nanometers, about 60 nanometers to about 80 nanometers, about 60 nanometers to about 90 nanometers, about 60 nanometers to about 100 nanometers, about 70 nanometers to about 80 nanometers, about 70 nanometers to about 90 nanometers, about 70 nanometers to about 100 nanometers, about 80 nanometers to about 90 nanometers, about 80 nanometers to about 100 nanometers, or about 90 nanometers to about 100 nanometers. In some embodiments, the width of a channel is about 1 nanometer, about 20 nanometers, about 30 nanometers, about 40 nanometers, about 50 nanometers, about 60 nanometers, about 70 nanometers, about 80 nanometers, about 90 nanometers, or about 100 nanometers. In some embodiments, the width of a channel is at least about 1 nanometer, about 20 nanometers, about 30 nanometers, about 40 nanometers, about 50 nanometers, about 60 nanometers, about 70 nanometers, about 80 nanometers, or about 90 nanometers. In some embodiments, the width of a channel is at most about 20 nanometers, about 30 nanometers, about 40 nanometers, about 50 nanometers, about 60 nanometers, about 70 nanometers, about 80 nanometers, about 90 nanometers, or about 100 nanometers.

[0172] In some embodiments, the analyte comprises a plurality of particles. In some embodiments, the plurality of particles can be a plurality of cells or a plurality of molecules. In some embodiments, the channel can accommodate the plurality of particles at the same time. In some embodiments, the width of the channel can accommodate the plurality of particles at the same time. In some embodiments, the height of the channel can accommodate the plurality of particles at the same time. In some embodiments, the channel can accommodate at least 1, at least 2, at least 3, at least 4, at least 4, at least 5, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 120, at least 140, at least 160, at least 180, at least 200, at least 300, at least 400, or at least 500 particles of the plurality of particles at the same time. In some embodiments, the width of the channel can accommodate at least 1, at least 2, at least 3, at least 4, at least 4, at least 5, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 120, at least 140, at least 160, at least 180, at least 200, at least 300, at least 400, or at least 500 particles of the plurality of particles at the same time. In some embodiments, the height of the channel can accommodate at least 1, at least 2, at least 3, at least 4, at least 4, at least 5, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 120, at least 140, at least 160, at least 180, at least 200, at least 300, at least 400, or at least 500 particles of the plurality of particles at the same time. In some embodiments, the width and / or the height of the channel can accommodate at least 1, at least 2, at least 3, at least 4, at least 4, at least 5, at leastWSGR Reference No.64149-703.601 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 120, at least 140, at least 160, at least 180, at least 200, at least 300, at least 400, or at least 500 particles of the plurality of particles at the same time. In some embodiments, the particles of the plurality of particles have freedom of motion. In some embodiments, the freedom of motion is perpendicular to the direction of flow though the channel.

[0173] In some embodiments, a channel may comprise a slowdown structure comprising one or more of one or more bumps, one or more SAWs, one or more ridges, one or more pillars, one or more wider portions, one or more narrower portions, one or more serpentine portions, or one or more spiral portions.

[0174] In some embodiments, any of the imaging methods disclosed herein further comprise characterizing a surface of the particle and generating a topographic map of the surface. In some embodiments, any of the screening methods disclosed herein further comprise characterizing a surface of the particle and generating a topographic map of the surface. In some embodiments, the topographic map comprises a location map of one or more markers, an intensity map of one or more markers, a density map of one or more markers, or any combination thereof. In some embodiments, the analyte comprises or is a cell and the topographic map is a topographic map of a cell surface marker. In some embodiments, the particle comprises or is a cell isolated from a clinical sample of a subject. In some embodiments wherein the particle comprises or is a cell isolated from a clinical sample of a subject, further comprising diagnosing the subject with a condition or disease. In some embodiments the diagnosis of the subject with a condition or disease further comprises classifying the cell into one or more classifications, providing one or more insights about the condition of the subject, or both.

[0175] In some embodiments, the method of any of the methods of screening a particle disclosed herein may further comprise an analyte sorting module. In some embodiments, the analyte sorting module is configured to sort the analyte based on a classification of the one or more classifications. In some embodiments, the analyte sorting module comprises a valve.

[0176] In some embodiments, the method of any of the methods of screening a particle disclosed herein may further comprise a plurality of spatially separate detection regions, wherein a detection region comprises a vortex, wherein the particle is trapped in the vortex for a duration of time and screened. In some embodiments, the channel of any of the channels disclosed as part of a device disclosed herein, wherein the channel comprises an inlet connect to a sample reservoir containing the particle. In some embodiments, the particle is stirred, mixed, vortexed,WSGR Reference No.64149-703.601 rotated, or any combination thereof in the sample reservoir to prevent the sedimentation of the particle in the sample reservoir.

[0177] In some embodiments, a system of any one of the systems described herein comprises a screening module comprising a plurality of layers, wherein the plurality of layers comprise: a first layer comprising a microfluidic device, wherein the microfluidic device comprises a flow channel configured to flow a particle therein, wherein the flow channel comprises a plurality of detection regions therein; a second layer adjacent to the first layer comprising a photonic circuit configured to diffract a single beam into two or more diffracted beams, wherein the two or more diffracted beams expose the plurality of detection regions, thereby generating a plurality of photons from the particle; and, a third layer comprising a single photon avalanche diode (SPAD) array configured to detect the plurality of photons. In some embodiments, the plurality of detection regions is spatially separated. In some embodiments, the plurality of detection regions each comprise a vortex, wherein the particle is trapped in the vortex. In some embodiments, the flow channel comprises a bump or a surface acoustic wave (SAW) source between a first detection region and a second detection region of the plurality of detection regions, wherein the bump or the SAW source is configured to re-orient the particle. In some embodiments, the flow channel comprises a serpentine channel, a spiral channel, or both.

[0178] In some embodiments, the flow channel further comprises a re-orientation region comprising at least one of: a bump, a surface acoustic wave source (SAW), a relaxation region wider than the flow channel, a constriction region narrower than the flow channel, or any combination thereof. In some embodiments, the microfluidic device further comprises an inlet. In some embodiments, the system further comprises a filtration module configured to filter the particle prior to entering the microfluidic device. In some embodiments, the system further comprises a sample preparation module configured to prepare the particle for screening. In some embodiments, the sample preparation module is configured to enrich the particle, stain the particle with a dye, add a reagent onto the particle, perform an assay on the particle, inject a reagent inside the particle, or any combination thereof. In some embodiments, the reagent comprises a fluorescent entity. In some embodiments, the reagent comprises a fluorescent dye, a fluorophore, a quantum dot, an antibody, a nucleic acid molecule, or any combination thereof, wherein the reagent is excitable by a light to emit the first photon, the second photon, or both. In some embodiments, the system further comprises a sample barcode reader configured to detect and record a barcode associated with a sample comprising the particle. In some embodiments, the system further comprises a processor configured to analyze data generated by the system. InWSGR Reference No.64149-703.601 some embodiments, the processor further comprises a processor configured to link a sample barcode to data generated by the system.

[0179] In disclosed embodiments, surface markers can identify a measurable quality of a molecule or particle. In some embodiments, a measurable quality is determined by the density or pattern of binding sites on the surface of the molecule. Markers bind to these sites and the resulting marker density determines whether or not the measurable quality exists. In some embodiments, if the density is localized or partial, the measurable quality does not exist. In some embodiments, if the pattern of markers is random, the measurable quality does not exist.

[0180] In some embodiments, the system described above may circulate the particle (e.g., analyte, target) a number of times to obtain a larger dataset for analyzing the particle. In some embodiments, the circulation of the particle may comprise the use of one or more traps that leverage aspects of the particle (e.g., biophysical properties if the particle is a cell, microorganism, etc.). In some embodiments, the number of times may be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1,000, 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, or more times. In some embodiments, the traps may be engineered to capture particles of interest based on size (e.g., cancer cells larger than platelets, blood cells). In some embodiments, the traps may be used to filter out particles that are not of interest into waste. In some embodiments, the trap may use a vortex to filter out particles of interest as shown in an example in FIG.36. In some embodiments, the trap may use one or more constricted or narrower channels to trap particles of interest as shown in an example in FIG.37.

[0181] In some embodiments, the system may comprise an input module for the input of unprocessed sample (e.g., blood, breast milk) into the system, wherein the unprocessed sample comprises the particle discussed above. In some embodiments, the system may comprise a filtration module which may remove particles from the unprocessed sample based on one or more metrics comprising size, shape, density, mechanical properties, or electrical properties. In some embodiments, the filtration module may use an array of posts or physical structures (e.g., a slowdown structure), deterministic lateral displacement, vortex-enabled microfluidic structures, or dielectrophoresis. In some embodiments, the system may further comprise a sample processing module, wherein the unprocessed sample may be enriched (before or after exposure to the filtering module). In some embodiments, the enriched sample may have only particles of interest or tagged particles. In some embodiments, the processing module may comprise staining the particle, which may provide the benefit of reduced human error (e.g., no human pre- processing). In some embodiments, the enrichment of the sample may be by an array of posts,WSGR Reference No.64149-703.601 deterministic lateral displacement, vortex-enabled microfluidic channels, or dielectrophoresis. In some embodiments, the tagged particles may comprise a plurality of particles of the sample conjugated with one or more tags, wherein the one or more tags may comprise a fluorescent dye, a fluorophore, a quantum dot, an antibody, or a nucleic acid molecule. In some embodiments, the system may further comprise a sensing module, wherein the sensing module is configured to obtain one or more images of the sample. In some embodiments, the sensing module may obtain one or more metrics of the sample, wherein the one or more metrics comprise signal intensity (e.g., fluorescent intensity) or signal lifetime (e.g., fluorescent lifetime). In some embodiments, the system further comprises a particle sorting module, where the particle sorting module may remove a portion of the sample via a microfluidic valve. In some embodiments, the system may further comprise a collection module, where the collection module may collection a portion of the sample of interest or waste, where the sample of portion of interest may be retained for post- processing. In some embodiments, the modules described herein may be disposed in sequence as shown in an example in FIG.38. In some embodiments, the modules may be in a different sequence or one or more modules may be in parallel to one another.

[0182] In some embodiments, the unprocessed sample may be delivered to the system as either an integral or peripheral component. In some embodiments, the unprocessed sample may be delivered to the system in a manner to prevent sedimentation and minimize dead volume for interfacing samples with the system. In some embodiments, the manner comprises, as shown in various examples in FIG.39, a spinning magnet, an orbiting tube, a syringe upside down with syringe pump, a hole in the bottom of a vial, a tubing cut at an angle to prevent sealing of the tubing against a container of the unprocessed sample, or sprung tubing to ensure contact of the sprung tubing with the bottom of the container of the unprocessed sample. In some embodiments, the chip of FIG.39 comprises the system described elsewhere herein. ASIC SPAD Array

[0183] In some embodiments disclosed herein is a chip with a layered architecture comprising a plurality of layers, where a first layer comprises one or more flow channels, where the one or more layers comprise an analyte processing area. In some embodiments, the first layer is in optical communication with a second layer, wherein the second layer comprises one or more excitation sources and an optical path to the analyte processing area. In some embodiments, a third layer is in optical communication with the analyte processing area of the first layer and comprises an array of one or more photodetectors and an application specific integrated circuit (ASIC). In some embodiments, the optical path comprises a light scattering control system. In some embodiments, the third layer comprises at least one SPAD. In some embodiments, theWSGR Reference No.64149-703.601 third layer comprises a plurality of SPAD pixels. In some embodiments, each of the plurality of SPAD pixels is surrounded at least in part by circuitry. In some embodiments, the area of the third layer comprises the plurality of SPAD pixels, where the plurality of SPAD pixels is optionally surrounded at least in part by circuitry. In some embodiments, the space between a first SPAD pixel and another SPAD pixel is engineered to reduce cross-talk between the first SPAD pixel and the another SPAD pixel. In some embodiments, the first layer is engineered to enable the detection of one or more morphological characteristics. In some embodiments, the one or more morphological characteristics comprises a dataset used for assessment of a chemical or a biological test. In some embodiments the one or more morphological characteristics comprises a dataset used for improvement of a chemical or a biological test. In some embodiments, the array and the ASIC creates free space on the third layer. In some embodiments, the free spaces comprise one or more additional lasers bonded to the third layer. In some embodiments, the one or more excitation sources comprises at least one laser or the one or more additional lasers bonded to the third layer. In some embodiments, the array comprises a CMOS SPAD array.

[0184] An example of the chip with the layered architecture is shown in FIG.50. In some embodiments, the array (e.g., of SPAD pixels) is not packed and is engineered according to the parameters of the first layer (e.g., the one or more flow channels). In some embodiments, one or more optical waveguides may be oriented parallel to the one or more flow channels. In some embodiments, the one or more additional layers may be in optical communication with the one or more optical waveguides. In some embodiments, the one or more excitation sources of the second layer may comprise lasers disposed in an array about the chip. In some embodiments, the ASIC may enable a smaller chip size relative to a chip with an equal number of SPAD array pixels without the ASIC. In some embodiments, the circuitry of the ASIC may partially or completely surround each pixel of the SPAD pixels. In some embodiments, one or more of the first, second, or third layers may be combined into a single layer. Methods of analysis

[0185] The analyte processing device of the disclosure herein can be used to conduct biological and chemical analysis useful for many types of scientific experiments. In some embodiments, the analyte processing device is used to determine important biochemical and physiological details of a sample or analyte. In some embodiments, provided herein is a method for analyzing an analyte, comprising: providing a device comprising (i) a flow channel and (ii) one or more photodetectors in optical communication with the flow channel, wherein the one or more photodetectors comprises a light scattering control element; using the one or moreWSGR Reference No.64149-703.601 photodetectors to acquire an optical signal from the analyte flowing through the flow channel; and processing the optical signal to identify a presence of the cell in the fluid flowing through the flow channel.

[0186] In some embodiments, provided herein is a method for analyzing an analyte, comprising: providing a device comprising (i) a flow channel comprising the analyte, and (ii) one or more photodetectors in optical communication with the flow channel; using the one or more photodetectors to acquire a first optical signal from the flow channel at a first position within the flow channel at a first time point; using the one or more photodetectors to acquire a second optical signal from the flow channel at a second position within the flow channel at a second time point subsequent to the first time point, wherein the second position is downstream of the first position; and processing the first optical signal and the second optical signal to identify the analyte flowing through the flow channel. In some embodiments, the method further comprises using the one or more photodetectors to acquire a third optical signal at a third position within the flow channel. In some embodiments, the third position is downstream from the second position. In some embodiments, the first position, the second position, and the third position are equidistant from one other. In some embodiments, the difference between the second time point and the first time point is substantially equal to a difference between the third time point and the second time point.

[0187] In some embodiments, the method of analysis disclosed herein may vary with detection technology. Detection technology may be suited to the analytic procedure of the analyte processing device. In some embodiments, the detection technology comprises uncorrelated time lapse microscopy. In some embodiments, the detection technology comprises time of flight imaging. In some embodiments, the detection technology comprises a time-of-flight camera. In some embodiments, the detection technology comprises time of flight methods. In some embodiments, the detection technology comprises time correlated single photon counting (TCSCP). In some embodiments, the detection technology comprises uncorrelated time lapse microscopy (UTLM). In some embodiments, the detection technology comprises uncorrelated time lapse imaging (UTLI). In some embodiments, the method of analysis may comprise one or more detection technologies. In some embodiments, the method of analysis may comprise one or more detection algorithms. In some embodiments, the method of analysis comprises signal processing. In some embodiments, the method of analysis comprises data processing. In some embodiments, the method of analysis comprises a classification algorithm.

[0188] In some aspects, the methods of analyzing an analyte comprise providing a device comprising a flow channel and one or more photodetectors in optical communication with saidWSGR Reference No.64149-703.601 flow channel, wherein said one or more photodetectors comprises one or more light scattering control elements, using said one or more photodetectors to acquire an optical signal from said analyte flowing through said flow channel, computer processing said optical signal to identify a presence of said cell in said fluid flowing through said flow channel. In some embodiments, the method of analysis comprises acquiring a light scattering spectra. In some embodiments, the method of analysis comprises acquiring an angular light scattering pattern. In some embodiments, the method of analysis comprises repeatedly detecting one or more beams of light.

[0189] In some aspects, the disclosure herein includes methods of analyzing an analyte comprising imaging an analyte. In some embodiments, the method of analysis comprises more than one optical signal. In some embodiments, the method of analysis comprises more than two, more than three, more than four, more than five, or more than ten optical signals. In some embodiments, the method of analysis comprises acquiring more than 10, more than 100, more than 1,000, or more than 10,000 optical signals. In some embodiments, the method of analysis comprises acquiring an optical signal at one time point. In some embodiments, the method of analysis comprises more than one, more than two, more than three, more than four, or more than five time points. In some embodiments, the method of analysis comprises acquiring optical signals at more than 10, more than 100, more than 1,000, or more than 10,000 time points. In some embodiments, the method of analysis comprises circulating an analyte within the one or more flow channels N times. In some embodiments, the method of analysis comprises imaging an analyte at least M times across a section of the one or more flow channels. In some embodiments, the method of analyzing comprises generating an N x M time of flight data for an analyte, wherein M is a number greater than one. In some embodiments, the method of analyzing comprises generating an N x M time of flight data for an analyte, wherein M is a number greater than one.

[0190] In some embodiments, the method of analysis comprises acquiring optical signals at equal time intervals. In some embodiments, the method of analysis comprises acquiring optical signals at unique time intervals. In some embodiments, the method of analysis comprises acquiring optical signals at equal spatial intervals. In some embodiments, the method of analysis comprises acquiring optical signals at unique time intervals. In some embodiments, the method of analysis comprises acquiring optical signals at a downstream position with respect to an initial optical signal. In some embodiments, the method of analysis comprises acquiring optical signals at equidistant spatial intervals. In some embodiments, the method of analysis comprises acquiring optical signals at unique spatial intervals.WSGR Reference No.64149-703.601

[0191] In some embodiments, the method of analysis comprises acquiring one or more optical signals using a single photodetector. In some embodiments, the method of analysis comprises acquiring at least two, at least three, at least five, at least 10, at least 100, at least 1,000 or at least 1,000 optical signals using a single photodetector. In some embodiments, the method of analysis comprises acquiring one or more optical signals using more than one photodetector. In some embodiments, the method of analysis comprises acquiring at least two, at least three, at least five, at least 10, at least 100, at least 1,000 or at least 1,000 optical signals using more than one photodetector.

[0192] In some embodiments, the method of analysis comprises using a second photodetector or sensor that is configured to detect two or more optical signals (e.g., images) for each of a plurality of one or more analytes. In some embodiments, the two or more optical signals (e.g., images) detected by the second photodetector comprise the second signal from the second point of detection. In some embodiments, the two or more images for each of the plurality of target droplets may comprise a signal generated by a modulated or pulsed light source configured to provide repetitive short illumination of light energy. In some embodiments, the modulated or pulsed light source may optionally comprise one or more lasers or laser-like sources configured to provide stroboscopic illumination. In some embodiments, the first photodetector or sensor may comprise a fast-response optical detector. The fast-response optical detector may comprise a photomultiplier tube (PMT), a photodiode, an avalanche photodiode detector (APD), or a hybrid detector (HyD). In some embodiments, a photodetector may comprise a camera or camera-like detector with a square, rectangular, or linear array of pixels. In some embodiments, the photodetector may be spatially arranged in a specific manner. In some embodiments, the one or more excitation sources comprises at least one continuous wave laser. In some embodiments, the one or more excitation sources comprises at least one pulsed laser. In some embodiments, the one or more excitation sources comprises at least one tunable laser. In some embodiments, the one or more excitation sources comprises a laser tuned to near IR to visible wavelengths. In some embodiments, the one or more excitation sources comprises a single laser. In some embodiments, the one or more excitation sources comprises multiple lasers. In some embodiments, the one or more excitation sources comprises bonded lasers. In some embodiments, the one or more excitation sources comprises external lasers. In some embodiments, the one or more photodetectors comprise a single pixel photodetector. In some embodiments, the flow channel is on a substrate. In some embodiments, the photodetectors are on the substrate. In some embodiments, the flow channel and the one or more photodetectors are on layers on the substrate.WSGR Reference No.64149-703.601

[0193] In some embodiments, the method of analysis comprises providing an analyte processing device that comprises a substrate, element, or membrane to manipulate the scattering of light. In some embodiments, the method of analysis comprises an analyte processing device that comprises one or more substrates, elements, or membranes to manipulate the propagation of light.

[0194] In some embodiments, the method of analysis comprises providing an analyte processing device that measures an analyte’s size, texture, surface area, or other physical property. Using methods of cellular analysis, the analyte processing device may be used to determine organelle size, cell membrane size, mitochondrial count, organelle count, or other physical parameters of biological systems. In some embodiments, the analyte processing device comprises one or more of the following: SiO2, TiN, Ti, Si3N4, silicon oxynitride (SiOxNy), TaO, HfO, Si, glass, or other similar material or oxide. In some embodiments, an analyte processing device comprises a series of layers. In some embodiments, the analyte processing device comprises one or more light scattering control elements. In some embodiments, the method of analysis comprises providing an analyte processing device that comprises one or more light scattering control elements forming one or more layers. In some embodiments, the analyte processing device comprises an acoustophoretic layer. In some embodiments, the analyte processing device comprises a flow channel layer. In some embodiments, the analyte processing device comprises a microfluidic channel layer. In some embodiments, the analyte processing device comprises a photonics circuit layer comprising one or more excitation sources or one or more optical circuits. In some embodiments, the analyte processing device comprises an analyte processing area. In some embodiments, the method of analysis comprises providing an analyte processing device that comprises one or more analyte processing areas.

[0195] In some embodiments, the method of analysis comprises providing an analyte processing device comprises a chip. In some embodiments, the analyte processing device comprises a cartridge. In some embodiments, the analyte processing device comprises a replaceable cartridge. In some embodiments, the method of analysis comprises an analyte processing device comprises a replaceable or consumable element. In some embodiments, the method of analysis comprises a chip that is integrated with one or more photodetectors, one or more excitation sources, one or more flow channels, one or more light scattering control elements, or any combination thereof. In some embodiments, the method of analysis comprises an analyte processing device that comprises a semiconductor chip. In some embodiments, the method of analysis comprises an analyte processing device that comprises a photonics chip. In some embodiments, the method of analysis comprises a chip is integrated with one or more lightWSGR Reference No.64149-703.601 modifying elements. In some embodiments, the method of analysis comprises a chip that is integrated with one or more light scattering control systems. In some embodiments, the method of analysis comprises providing an analyte processing device that comprises one or more stacked layers. In some embodiments, the method of analysis comprises an analyte processing device comprising one or more layers of material that are integrated with a chip. In some embodiments, the method of analysis comprises providing an analyte processing device that comprises one or more stacked layers integrated with a chip. In some embodiments, the method of analysis comprises a chip that comprises several layers including but not limited to: an acoustophoresis layer, a microfluidic chamber layer, a microfluidic channel layer, a flow channel layer, a light modifying membrane layer, a photodetector layer, an excitation source layer, an optical circuit layer, a photonics circuit layer, or a light modifying substrate layer. In some embodiments, the method of analysis comprises an analyte processing device that comprises an optical circuit that comprises one or more light entry sections, one or more optical dividers, a light delivery section, or any combination thereof. In some embodiments, the method of analysis comprises an analyte processing device that comprises an energy source. In some embodiments, the method of analysis comprises an analyte processing device that comprises a battery. In some embodiments, the method of analysis comprises an analyte processing device that comprises an energy source is integrated with the analyte processing device.

[0196] In some embodiments, the method of analysis comprises a chip that comprises an application specific integrated circuit. In some embodiments, the method of analysis comprises a chip that comprises an integrated circuit. In some embodiments, the method of analysis comprises a chip that is integrated with one or more other aspects of the analyte processing device, including but not limited to: one or more flow channels, one or more light scattering control elements, a power source, one or more photodetectors, one or more excitation sources, or one or more phoresis elements, one or more circuits, or one or more chips. In some embodiments, the method of analysis comprises a chip that comprises an optical circuit. In some embodiments, the method of analysis comprises an analyte processing device wherein a readout circuitry may be operatively coupled to the analyte processing device, wherein the readout circuitry is configured to transmit the data from the analyte processing device to memory.

[0197] In some embodiments, the method of analysis comprises an analyte processing device that comprises more than one flow channel. In some embodiments, the method of analysis comprises an analyte processing device that comprises more than two, more than four, more than eight, or more than 16 flow channels. In some embodiments, the method of analysis comprises an analyte processing device that comprises more than two, more than 64, more thanWSGR Reference No.64149-703.601 128, or more than 256 flow channels. In some embodiments, the method of analysis comprises providing a flow channel that comprises at least one outlet, at least two outlets, at least three outlets, or at least four outlets. In some embodiments, the method of analysis comprises providing a flow channel that comprises at least 16 outlets, at least 64 outlets, at least 128 outlets, at least 256 outlets, at least 1028 outlets. In some embodiments, the method of analysis comprises providing a flow channel that comprises at least one inlet, at least two inlets, at least three inlets, or at least four inlets. In some embodiments, the method of analysis comprises providing a flow channel that comprises at least 16 inlets, at least 64 inlets, at least 128 inlets, at least 256 inlets, at least 1028 inlets. In some embodiments, the method of analysis comprises providing a flow channel that is rectangular. In some embodiments, the method of analysis comprises providing a flow channel that is curved, indented, or similarly modified. In some embodiments, the method of analysis comprises providing a flow channel that is integrated with the analyte processing device. In some embodiments, the method of analysis comprises providing a flow channel that is configured to generate electrophoresis such as acoustophoresis, electrophoresis, or magnetophoresis. In some embodiments, the method of analysis comprises providing a flow channel that is configured to displace analytes within the flow channel. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more pumps. In some embodiments, the method of analysis comprises providing a flow channel comprises one or more double-sided indents. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more single sided indents. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more single sided pinches. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more double sided pinches. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more curves. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more posts. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more bisections. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more intersections. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more convergence sections.

[0198] In some embodiments, the method of analysis comprises providing a flow channel that comprises a gate. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more gates. In some embodiments, the method of analysis comprises providing a flow channel that comprises a sorting junction. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more sortingWSGR Reference No.64149-703.601 junction. In some embodiments, the method of analysis comprises providing a flow channel that comprises a series of sorting junctions. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more chambers. In some embodiments, the method of analysis comprises providing a flow channel that comprises more than five, more than 10, more than 50, or more than 100 chambers. In some embodiments, the method of analysis comprises providing a flow channel that comprises a fluid reservoir. In some embodiments, the method of analysis comprises providing a flow channel that comprises more than one fluid reservoir.

[0199] In some embodiments, the method of analysis comprises providing a flow channel that comprises a feedback loop. In some embodiments, the method of analysis comprises providing a flow channel that comprises an inline pump. In some embodiments, the method of analysis comprises providing a flow channel that comprises a pump. In some embodiments, the method of analysis comprises providing a flow channel that comprises a cell injector. In some embodiments, the method of analysis comprises providing a flow channel that comprises a cell cartridge. In some embodiments, the method of analysis comprises providing a flow channel that comprises a cell collector. In some embodiments, the method of analysis comprises providing a flow channel that comprises a buffer reservoir. In some embodiments, the method of analysis comprises providing a flow channel that may branch in an 1xN pattern, where N is an integer greater than one. In some embodiments, the method of analysis comprises providing a flow channel that may branch in a series of 1xN patterns, where N is an integer greater than one. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more pneumatically driven valves. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more fluid reservoirs. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more peristaltic pumps.

[0200] In some embodiments, the method of analysis comprises providing an analyte processing device that comprises a substrate, element, or membrane to manipulate the scattering of light. In some embodiments, the method of analysis comprises providing an analyte processing device that comprises a light scattering control system. In some embodiments, the method of analysis comprises providing a flow channel that comprises a light modifying system. In some embodiments, the method of analysis comprises providing a flow channel that comprises a light modifying substrate. In some embodiments, the method of analysis comprises providing a flow channel that comprises a light modifying element. In some embodiments, the light scattering control system comprises a light modifying element that may be a dichroicWSGR Reference No.64149-703.601 optical component, a mirror, a membrane, a concentrator, a lens, a blocker, optical grating, a reflector, vertical couplers, lateral couplers, a filter, or a light entry section. In some embodiments, the method of analysis comprises providing an analyte processing device that comprises a light entry section. In some embodiments, the light scattering control system comprises a light entry section that is a pinhole. In some embodiments, the light scattering control system comprises a light entry section that comprises vertical couplers. In some embodiments, the light scattering control system comprises a light entry section that comprises lateral couplers. In some embodiments, the method of analysis comprises a light entry section that comprises optical grating. In some embodiments, the light scattering control system comprises a light entry section that comprises one or more dichroic optical components. In some embodiments, the method of analysis comprises a filter that is a dielectric material. In some embodiments, the light scattering control system comprises a filter that is a metallic material. In some embodiments, the light scattering control system comprises a filter is a semiconductor material. In some embodiments, the filter is a combination of a dielectric, metallic, or semiconductor material, or combination thereof. In some embodiments, the filter comprises more than layer of filters. In some embodiments, the light scattering control system comprises a blocker that comprises a layer of absorptive material configured to absorb specific light wavelengths. In some embodiments, the blocker comprises a layer of material configured to transmit specific wavelengths of light. In some embodiments, the blocker comprises a layer of material configured to transmit specific ranges of wavelengths of light. In some embodiments, the blocker comprises a layer of material configured to absorb specific ranges of wavelengths of light. In some embodiments, the blocker increases the signal to noise ratio by a factor of two. In some embodiments, the blocker increases the signal to noise ratio by a factor of at least two, at least 10, at least 100, at least 1,000, or at least 10,000. In some embodiments, the light scattering control system comprises a concentrator that that comprises a lens. In some embodiments, the light scattering control system comprises a lens that is a microlens, a flat lens, a diffractive lens, an absorptive lens, a non-absorptive lens, or any combination thereof. In some embodiments, the light scattering control system comprises a concentrator that that is a dielectric block. In some embodiments, the dielectric block is at least 100 nanometers thick. In some embodiments, the dielectric block that is at least 1 micrometer thick. In some embodiments, the light scattering control system comprises a mirror that is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the light scattering control system comprises a reflector that is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the light scattering control system comprises a mirror that is configured to improve the couplingWSGR Reference No.64149-703.601 efficiency of lateral couplers. In some embodiments, the light scattering control system comprises a reflector that is configured to improve the coupling efficiency of lateral couplers.

[0201] In some embodiments, the method of analysis comprises providing a device that comprises one excitation source. In some embodiments, the device comprises more than one, more than two, more than three, more than four, or more than five excitation sources. In some embodiments, the device comprises at least 10, at least 20, at least 30, or at least 40 excitation sources. In some embodiments, the device comprises one or more excitation sources integrated with the device. In some embodiments, the device comprises one or more excitation sources integrated with a chip. In some embodiments, the device comprises one or more excitation sources that comprises a photon array. In some embodiments, the device comprises one or more excitation sources that comprises one or more photon arrays. In some embodiments, the device comprises one or more excitation sources that comprises a waveguide. In some embodiments, the device comprises one or more excitation sources that are configured to yield specific wavelengths of lights. In some embodiments, the device comprises one or more excitation sources that comprises an interposer. In some embodiments, the device comprises one or more excitation sources that comprises a transducer. In some embodiments, the device comprises one or more excitation sources that comprises a laser. In some embodiments, the device comprises one or more excitation sources that comprises an integrated circuit. In some embodiments, the device comprises one or more excitation sources that comprise an interposer. In some embodiments, the device comprises an excitation source that comprises a transducer. In some embodiments, the device comprises an excitation source comprises an interposer. In some embodiments, the device comprises an excitation source that comprises more than one interposer. In some embodiments, the device comprises an excitation source comprises a transducer. In some embodiments, the device comprises an excitation source that comprises one or more transducers. In some embodiments, the device comprises an excitation source that comprises a laser. In some embodiments, the device comprises an excitation source that comprises more than one laser, more than 10 lasers, more than 100 lasers, or more than 1,000 lasers. In some embodiments, the device comprises a laser that is a bonded laser. In some embodiments, the device comprises a laser that is an external laser. In some embodiments, the device comprises a laser is a continuous laser. In some embodiments, the device comprises a laser that is a pulsed laser. In some embodiments, the device comprises one or more lasers that are tunable lasers. In some embodiments, the device comprises one or more excitation sources that is configured to generate a light wavelength between 300 nm and 1,200 nm. In some embodiments, the device comprises one or more excitation sources that is configured to generate a light with a height between at least 80 nm and at most 200 nm. In some embodiments, theWSGR Reference No.64149-703.601 device comprises one or more excitation sources that is configured to generate light intensity of at least 1 μW / μm2. In some embodiments, the device comprises one or more excitation sources that generates a light intensity of less than 101 μW / μm2. In some embodiments, the device comprises one or more lasers are integrated with a chip. In some embodiments, the one or more lasers comprises an excitation source that is integrated with a chip. In some embodiments, the device comprises a chip that is integrated with one flow channel. In some embodiments, the device comprises a chip that is integrated with more than one flow channel. In some embodiments, the device comprises a chip that is integrated with a phoresis mechanism. In some embodiments, the device comprises a chip that is integrated with one or more excitation sources. In some embodiments, the device comprises a chip that is integrated with one or more microfluidic channels. In some embodiments, the device comprises a chip that is integrated with one or more micro-optics components. In some embodiments, the device comprises a chip that is integrated with one or more photonic circuits. In some embodiments, the device comprises a chip that is integrated with one or more CMOS photodetectors. In some embodiments, the device comprises a chip that is integrated with one or more photodetectors. In some embodiments, the device comprises a chip that is integrated with one or more light scattering control elements. In some embodiments, the device comprises a semiconductor chip that comprises a power source, one or more controllers, one or more readouts, and one or more photodetector pixels. In some embodiments, the device comprises an excitation source that comprises a waveguide. In some embodiments, the device comprises an excitation source that comprises an optical waveguide. In some embodiments, the device comprises an optical waveguide may branch in an 1xN pattern, where N is an integer greater than one. In some embodiments, the device comprises an optical waveguide comprises more than one branching point. In some embodiments, the device comprises an optical waveguide may comprise one or more 1x2 branching points. In some embodiments, the device comprises an excitation source that is configured to excite light at specific wavelengths. In some embodiments, the device comprises an excitation source that is configured to excite light at specific ranges of light wavelengths. In some embodiments, the device comprises an excitation source that is configured to excite light in the ultraviolet range. In some embodiments, the excitation source is configured to excite light in the deep ultraviolet range. In some embodiments, the excitation source is configured to excite light in the UVA range. In some embodiments, the excitation source is configured to excite light in the UVB range. In some embodiments, the excitation source is configured to excite light in the UVC range. In some embodiments, the excitation source is configured to excite light with a wavelength of between about 100 nm and about 400 nm, between about 100 nm and about 300 nm, between about 315 nm and about 400 nm, betweenWSGR Reference No.64149-703.601 about 280 nm and about 315 nm, between about 100 nm and about 280 nm, between about 280 nm and about 400 nm, or between about 100 nm and about 315 nm. In some embodiments, the excitation source is configured to excite light with a wavelength of less than about 400nm, about 350 nm, about 315 nm, about 300 nm, about 280 nm, about 250 nm, about 200 nm, or about 100 nm. In some embodiments, the device comprises an excitation source that is configured to excite light in the microwave range. In some embodiments, the device comprises an excitation source that is configured to excite light in the IR to visible light range. In some embodiments, the excitation source is configured to excite light up to about 50 mW, about 100 mW, about 150 mW, about 200 mW, about 250 mW, about 300 mW, about 350 mW, about 400 mW about 450 mW, about 500 mW, about 550 mW, about 600 mW, about 650 mW, about 700 mW, about 750 mW, about 800 mW, about 900 mW, or about 1000 mW peak power. In some embodiments, the excitation source is configured to excite light at a repetition rate of about 1 MHz, 2 MHz, 3 MHz, 4 MHz, 5 MHz, 6 MHz, 7 MHz, 8 MHz, 9 MHz, 10 MHz, 11 MHz, 12 MHz, 13 MHz, 14 MHz, 15 MHz, 20 MHz, 25 MHz, 30 MHz, 35 MHz, 40 MHz, 45 MHz, 50 MHz, 60 MHz, 70 MHz, 80 MHz, 90 MHz, or 100 MHz. In some embodiments, the device comprises an excitation source that comprises a pinhole for light entry. In some embodiments, the device comprises an excitation source that comprises an optical circuit. In some embodiments, the device comprises an optical circuit comprises one or more light entry sections. In some embodiments, the device comprises an excitation source that is programmed to generate an evanescent light field. In some embodiments, the device comprises an excitation source that is programmed to generate a superposition of light fields. In some embodiments, the device comprises an excitation source that’s programmed to synchronize with other elements of the analyte processing device sources. In some embodiments, the device comprises one or more excitation sources are programmed to synchronize with other excitation sources. In some embodiments, the device comprises an analyte processing area that is configured to enable photodetectors to yield high resolution images of an analyte. In some embodiments, the resolution of the images is at least about 2000 nm, at least about 1500 nm, at least about 1000 nm, at least about 900 nm, at least about 800 nm, at least about 700 nm, at least about 600 nm, at least about 500 nm, at least about 400 nm, at least about 300 nm, at least about 200 nm, at least about 100 nm, at least about 90 nm, at least about 80 nm, at least about 70 nm, at least about 60 nm, at least about 50 nm, at least about 40 nm, at least about 30 nm, at least about 20 nm, or at least about 10 nm. In some embodiments, the device comprises an analyte processing device that comprises one photodetector. In some embodiments, the device comprises an analyte processing device that comprises more than one photodetector, more than two photodetectors, more than four photodetectors, more than eight photodetectors, or more than 16 photodetectors. In some cases, the analyte processing deviceWSGR Reference No.64149-703.601 comprises more than 32 photodetector, more than 64 photodetectors, more than 128 photodetectors, more than 256 photodetectors, or more than 512 photodetectors. In some embodiments, the device comprises a photodetector that comprises a semiconductor imager. In some embodiments, the device comprises a photodetector that comprises one or more semiconductor imagers. In some embodiments, the device comprises a photodetector that comprises a pixel. In some embodiments, the device comprises a photodetector that comprises more than one pixel. In some embodiments, the device comprises a photodetector that comprises more than 10, more than 100, more than 1,000 or more than 10,000 pixels. In some embodiments, the device comprises a photodetector that’s positioned 10 microns apart from each other. In some embodiments, the device comprises a photodetector that’s positioned 15 microns apart from each other. In some embodiments, the device comprises a photodetector that’s positioned 20 microns apart from each other. In some embodiments, the device comprises a photodetector that’s positioned at least 5 microns apart from each other. In some embodiments, the device comprises a photodetector that’s positioned at least 10 microns apart from each other. In some embodiments, the device comprises a photodetector that’s positioned at least 20 microns apart from each other. In some embodiments, the device comprises a photodetector that comprises one or more pixels. In some embodiments, the device comprises a photodetector that pixel size is 10 microns by 10 microns. In some embodiments, the device comprises a photodetector that pixel size is 20 microns by 10 microns. In some embodiments, the device comprises a photodetector that pixel size is 20 microns by 20 microns. In some embodiments, the device comprises a, a photodetector may comprise a camera or camera-like detector with a square, rectangular, or linear array of pixels. In some embodiments, the device comprises a photodetector that may be spatially arranged in a specific manner. In some embodiments, the device comprises providing an analyte processing device that comprises one photodetector station. In some embodiments, the device comprises providing an analyte processing device that comprises at least 2, at least 4, at least 8, at least 16, or at least 64 photodetector stations. In some embodiments, the device comprises providing an analyte processing device that comprises at least 128, at least 512, or at least 1028 photodetector stations. In some cases, one or more photodetectors are located on the bottom of the flow channel. In some cases, one or more photodetectors are located on the side of the flow channel. In some cases, the device comprises one or more photodetectors that are located on the top of the flow channel. In some embodiments, the device comprises one or more photodetectors covers a section of the flow channel surface. In some embodiments, the device comprises a photodetector that comprises a complementary metal oxide sensor (CMOS) imager. In some embodiments, the device comprises a photodetector that comprises one or more complementary metal oxide sensorWSGR Reference No.64149-703.601 (CMOS) imagers. In some embodiments, the device comprises a photodetector that comprises a CMOS imager configured to flush electrons generated with scattered light upon excitation. In some embodiments, the device comprises a photodetector that comprises a spectral CMOS imager. In some embodiments, the device comprises a photodetector that comprises a CMOS imager configured for photon wavelength. In some embodiments, the device comprises a photodetector that comprises a CMOS imager configured for photon intensity. In some embodiments, the device comprises a photodetector that comprises a pinned photodiode CMOS imager. In some embodiments, the device comprises a photodetector that comprises a single- photon avalanche diode CMOS imager. In some embodiments, the device comprises one or more photodetectors that form an optical path with the analyte processing area. In some embodiments, the device comprises one or more photodetectors forms an optical path with one or more analyte processing areas. In some embodiments, the device comprises one or more photodetectors forms one or more optical paths with the analyte processing area. In some embodiments, the device comprises an optical path that comprises light modifying substrates, layers, or elements. In some embodiments, the device comprises an optical path that comprises a light entry section, an optical circuit, optical grating, a reflector, vertical couplers, lateral couplers, a filter, a blocker, a concentrator, a mirror, or an optical membrane. In some embodiments, the device comprises an optical path comprises one or more light modifying substrates, layers, or elements. In some embodiments, the methods comprise an analyte processing area that comprises multiple individual sections or elements to optimize imaging under specific circumstances. In some embodiments, the device comprises an analyte processing device that comprises one or more analyte processing areas. In some embodiments, the device comprises an analyte processing area that forms an optical path with the one or more excitation sources. In some embodiments, the device comprises an analyte processing area that forms an optical path with the one or more photodetectors. In some embodiments, the device comprises an analyte processing area that may be between a sorting junction and a gate. In some embodiments, the device comprises an analyte processing area that is be between more than one sorting junction or more than one gate. In some embodiments, the device comprises an analyte processing area that comprises a light scattering control system. In some embodiments, the device comprises an analyte processing area that comprises a light scattering control element. In some embodiments, the device comprises an analyte processing area that comprises one or more light scattering control elements. In some embodiments, the device comprises an analyte processing area that comprises an optical membrane. In some embodiments, the device comprises an analyte processing area that comprises a light modifying substrate or light modifying element. In some embodiments, the device comprises an analyte processing area thatWSGR Reference No.64149-703.601 comprises an optical membrane. In some embodiments, the device comprises an analyte processing area that comprises a layer of light modifying substrates. In some embodiments, the method of analysis comprises providing a flow channel that comprises an analyte processing area. In some embodiments, the method of analysis comprises providing a flow channel that comprises one or more analyte processing areas. In some embodiments, the device comprises an analyte processing area that is at the bottom surface. In some embodiments, the device comprises an analyte processing area that is at the top surface. In some embodiments, the device comprises an analyte processing area that is on the side of the surface.

[0202] In some embodiments, the method of analysis comprises an analyzing an analyte that is singular. In some embodiments, the analyte comprises a population. In some embodiments, the analyte is an inorganic chemical. In some embodiments, the analyte is an organic chemical. In some embodiments, the analyte is a peptide, small molecule, drug molecule, drug-conjugate molecule, dye molecule, dye-conjugate molecule, fluorescent molecule, or any other organic chemicals of interest.

[0203] In some embodiments, the method of analysis comprises analyzing an analyte that comprises a biological sample. In some embodiments, the method of analysis comprises an analyte that comprises at least one cell. In some embodiments, the method of analysis comprises an analyte that is a population of cells. In some embodiments, the analyte comprises at least one cell that may be a mammalian cell, a eukaryotic cell, a yeast cell, a bacterial cell, a primary cell, an immortalized cell, a cancer cell, a hybrid cell, or a derivative or an engineered form thereof. In some embodiments, the analyte is blood. In some embodiments, the analyte is plasma. In some embodiments, the analyte is cerebrospinal fluid. In some embodiments, the analyte is lymph tissue. In some embodiments, the analyte is a specific type of cell from a subject. In some embodiments, the analyte is a specific type of cell that is from the brain, liver, heart, intestine, colon, muscle, kidney, pancreas, or other organ. In some embodiments, the analyte comprises skin cells, heart cells, immune system cells such as B-cells, lymphocytes, T-cells, kidney cells, liver cells, muscle cells, nervous system cells such as astral cells, glial cells, neuronal cells, bacterial cells, or peripheral blood mononuclear cells.

[0204] In some embodiments, the method of analysis comprises analyzing an analyte that is in the liquid phase. In some embodiments, the method of analysis comprises analyzing an analyte that is in the gas phase. In some embodiments, the analyte is an aqueous solution. In some embodiments, the analyte is solvated in an organic solution (e.g., acetone, methanol, acetonitrile, tetrahydrofuran, or other organic solvent). In some embodiments, the analyte is at least partially aerosolized. In some embodiments, the analyte is an aerosol. In some embodiments, the analyteWSGR Reference No.64149-703.601 motion is a laminar motion. In some embodiments, the analyte motion is turbulent. In some embodiments, the analyte comprises one or more additional solutes. In some embodiments, the analyte comprises a solvent that is phosphate buffered saline (PBS).

[0205] In some embodiments, the method of analysis comprises analyzing an analyte that is processed prior to analysis. In some embodiments, the method of analysis comprises an analyte that is reacted with a fluorophore, dye, labeling agent, or other similar chemical reagent. In some embodiments, the method of analysis comprises an analyte that is centrifuged prior to analysis. In some embodiments, the method of analysis comprises an analyte is heated prior to analysis. In some embodiments, the method of analysis comprises an analyte that is cooled prior to analysis. In some embodiments, the method of analysis comprises an analyte that is frozen, or flash frozen, prior to analysis. In some embodiments, the method of analysis comprises an analyte that is a suspension. In some embodiments, the method of analysis comprises an analyte that is homogenous. In some embodiments, the method of analysis comprises an analyte is heterogenous. In some embodiments, the method of analysis comprises an analyte that may be labelled with a fluorophore, a fluorescent molecule, a dye, or other similar moiety. In some embodiments, the method of analysis comprises an analyte that is at least one cell that may be labelled with a fluorophore or expresses a fluorescent molecule. In some embodiments, the method of analysis comprises at least once cell that may express a molecule including, but not limited, to a fluorescent molecule, a phosphorescent molecule, a chemiluminescent molecule, or a bioluminescent molecule. In some embodiments, the method of analysis comprises fluorophores that can be used as labels for specific target analytes, in applications where the targets can be chemically modified to incorporate a TGF fluorophore. Examples include, but are not limited to, Northern blots, Southern blots, DNA microarrays, quantitative Polymerase Chain Reaction (PCR), digital PCR, and diagnostic assays.

[0206] In some embodiments, the method of analysis comprises optical communication that comprises an optical path between an analyte of interest, one or more excitation sources, and one or more photodetectors. In some embodiments, the method of analysis comprises optical communication that comprises an optical path between one or more analytes of interest, one or more excitation sources, and one or more photodetectors.

[0207] In some embodiments, the method of analysis comprises an analyte processing device that comprises an optical path. In some embodiments, the method of analysis comprises an optical path is formed between one or more excitation sources and an analyte. In some embodiments, the method of analysis comprises an optical path that is formed between one or more photodetectors and the analyte processing area. In some embodiments, the method ofWSGR Reference No.64149-703.601 analysis comprises an optical path that is formed between one or more photodetectors, one or more excitation sources, and an analyte. In some embodiments, the method of analysis comprises an optical path that is formed between one or more photodetectors and the analyte processing area. In some embodiments, the method of analysis comprises an optical path that comprises a light scattering control element. In some embodiments, the method of analysis comprises a light scattering control element that comprises a layer of material. In some embodiments, the method of analysis comprises a light scattering control element that comprises a material that comprises one or more of the following: SiO2, TiN, Ti, Si3N4, silicon oxynitride (SiOxNy), TaO, HfO, Si, glass, or other similar material or oxide. In some embodiments, the method of analysis comprises an optical path that forms an angle of at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, or at least 90 degrees with the one or more light scattering control elements.

[0208] In some embodiments, the method of analysis comprises providing a device comprising an optical path between the photodetector and the analyte processing area that comprises a light scattering control element. In some embodiments, the method of analysis comprises an optical path that comprises a lens, concentrator, dielectric, dichroic, reflector, or mirror. In some embodiments, the method of analysis comprises an optical path that comprises elements configured to redirect scattered light distal from a photodetector. In some embodiments, the method of analysis comprises an optical path that comprises elements configured to redirect scattered light distal from one or more photodetectors. In some embodiments, the method of analysis comprises an optical path that comprises more than one element configured to redirect scattered light distal from a photodetector. In some embodiments, the method of analysis comprises an optical path that comprises a dichroic optical component configured to redirect scattered light distal from one or more photodetectors. In some embodiments, the method of analysis comprises an optical path that comprises more than one membrane. In some embodiments, the method of analysis comprises an optical path comprises a light modifying membrane. In some embodiments, the method of analysis comprises an optical path that comprises an angle relative to an analyte. In some embodiments, the method of analysis comprises an optical path that comprises an angle relative to the light modifying element. In some embodiments, the method of analysis comprises an optical path that comprises an angle relative to the light modifying substrate. In some embodiments, the method of analysis comprises an optical path that comprises an angle relative to the light modifying layer.

[0209] In some embodiments, the method of analysis comprises providing a device that comprises a light scattering control system that is configured to optimize signal to noise ratio ofWSGR Reference No.64149-703.601 an analyte. In some embodiments, the method of analysis comprises a light scattering control system that is configured to optimize light propagation. In some embodiments, the method of analysis comprises a light scattering control system that is configured to optimize evanescent light propagation. In some embodiments, the method of analysis comprises a light scattering control system that is configured to propagate evanescent light. In some embodiments, the method of analysis comprises a light scattering control system that is configured to shutter excess light excitation within the analyte processing device. In some embodiments, the method of analysis comprises a light scattering control system that is configured to reduce excess light propagation. In some embodiments, the method of analysis comprises a light scattering control system that is configured to optimize angular light propagation. In some embodiments, the method of analysis comprises a light scattering control system that comprises a light modifying element. In some embodiments, the method of analysis comprises a light scattering control system that comprises one or more light modifying elements.

[0210] In some embodiments, the method of analysis comprises a measurement sensitivity achieved through the light scatter control system that is at least a factor of two. In some embodiments, the method of analysis comprises a sensitivity increase is at least a factor of 10, at least a factor of 100, at least a factor of 1,000, at least a factor of 10,000, or at least a factor 100,000. In some embodiments, the method of analysis comprises a light scattering control system that increases the signal to noise ratio by at least a factor of two, a factor of five, a factor of 10, a factor of 100, a factor of 1,000, or a factor of 10,000. In some embodiments, the method of analysis comprises a signal to noise ratio that is improved by reducing excess electrons. In some embodiments, the method of analysis comprises a signal to noise ratio that is improved by signal correlation between more than two or more photodetectors. In some embodiments, the method of analysis comprises a signal to noise ratio that is improved by an evanescent light field. In some embodiments, the method of analysis comprises a signal to noise ratio that is improved by an imaging modality. In some embodiments, the method of analysis comprises reducing noise from light scattering within a waveguide. In some embodiments, the method of analysis comprises reducing noise from light scattering due to photonics structure. In some embodiments, the method of analysis comprises reducing noise from light scattering due to an integrated circuit. In some embodiments, the method of analysis comprises reducing noise from light scattering due to an application specific integrated circuit. In some embodiments, the method of analysis comprises a noise is reduced from light scattering due to light scattering from one or more analytes. In some embodiments, the method of analysis comprises reducing noise from light scattering due to flow channel structure. In some embodiments, the method of analysis comprises reducing noise from light scattering due to microfluidic channel walls. InWSGR Reference No.64149-703.601 some embodiments, the method of analysis comprises reducing noise from light scattering due to photodetector structure.

[0211] In some embodiments, the method of analysis comprises providing an analyte processing device that comprises a light scattering control element, which may form a broader light scattering control system. In some embodiments, the analyte processing device comprises one or more light scattering control systems. In some embodiments, the analyte processing device comprises one or more light scattering control elements. In some embodiments, the analyte processing device comprises an optical path that comprises a light scattering control element. In some embodiments, the analyte processing device comprises an optical path that comprises one or more light scattering control elements. In some embodiments, the analyte processing device comprises a light scattering control element that comprises a lens, a concentrator, mirror, reflector, optical grating, blocker, coupler, or absorptive material. In some embodiments, the method of analysis comprises a light scattering control element that comprises a micro-interferogram element (MIE). In some embodiments, the analyte processing device comprises one or more light scattering control elements comprise a light entry section. In some embodiments, the analyte processing device comprises a light entry section that is a pinhole. In some embodiments, the analyte processing device comprises a light entry section that comprises vertical couplers. In some embodiments, the analyte processing device comprises a light entry section that comprises lateral couplers. In some embodiments, the analyte processing device comprises a light entry section comprises optical grating. In some embodiments, the analyte processing device comprises a light entry section comprises one or more dichroic optical components. In some embodiments, the analyte processing device comprises a filter that is a dielectric material. In some embodiments, the analyte processing device comprises a filter that is a metallic material. In some embodiments, the analyte processing device comprises a filter that is a semiconductor material. In some embodiments, the analyte processing device comprises a filter that is a combination of a dielectric, metallic, or semiconductor material, or combination thereof. In some embodiments, the analyte processing device comprises a filter that comprises more than layer of filters. In some embodiments, the analyte processing device comprises a blocker that comprises a layer of absorptive material configured to absorb specific light wavelengths. In some embodiments, the analyte processing device comprises a blocker that comprises a layer of material configured to transmit specific wavelengths of light. In some embodiments, the analyte processing device comprises a blocker that comprises a layer of material configured to transmit specific ranges of wavelengths of light. In some embodiments, the analyte processing device comprises a blocker that comprises a layer of material configured to absorb specific ranges of wavelengths of light. In some embodiments, the analyte processingWSGR Reference No.64149-703.601 device comprises a, a blocker increases the signal to noise ratio by a factor of two. In some embodiments, the analyte processing device comprises a blocker that increases the signal to noise ratio by a factor of at least two, at least 10, at least 100, at least 1,000, or at least 10,000. In some embodiments, the analyte processing device comprises a concentrator that comprises a lens. In some embodiments, the analyte processing device comprises a lens that is a microlens, a flat lens, a diffractive lens, an absorptive lens, or a non-absorptive lens. In some embodiments, the analyte processing device comprises a concentrator that is a dielectric block. In some embodiments, the analyte processing device comprises a dielectric block that is at least 100 nanometers thick. In some embodiments, the analyte processing device comprises a dielectric block that is at least 1 micrometer thick. In some embodiments, the analyte processing device comprises a mirror that is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the analyte processing device comprises a reflector that is configured to improve the coupling efficiency of vertical couplers. In some embodiments, the analyte processing device comprises a mirror that is configured to improve the coupling efficiency of lateral couplers. In some embodiments, the analyte processing device comprises a reflector that is configured to improve the coupling efficiency of lateral couplers. In some embodiments, the analyte processing device comprises light scattering control elements that are integrated with the analyte processing device.

[0212] In some embodiments, provided herein is a method of imaging an analyte in motion, comprising: providing a flow channel adjacent to one or more photodetectors, wherein the flow channel comprises an analyte processing area configured for one or more photodetection events; providing conditions sufficient for the analyte to travel along a path in the flow channel; using the one or more photodetectors to probe the analyte in motion N times within the analyte processing area, wherein N is a number greater than one; repeating the first through third operation (i-iii) M times to generate an N x M time of flight (TOF) data for the analyte in motion, wherein M is a number greater than one; and using the N x M TOF data to classify the analyte in motion at an accuracy greater than 80 %.

[0213] In some embodiments, using the N x M TOF data classifies the analyte in motion at an accuracy greater than 90 %. In some embodiments, using the N x M TOF data classifies the analyte in motion at an accuracy greater than 95 %. In some embodiments, using the N x M TOF data classifies the analyte in motion at an accuracy greater than 98 %. In some embodiments, using the N x M TOF data classifies the analyte in motion at an accuracy greater than 99 %. In some embodiments, the analyte in motion is probed at spatially separate locations along the analyte processing area. In some embodiments, the flow channel further comprises one or moreWSGR Reference No.64149-703.601 pneumatically driven valves. In some embodiments, the flow channel further comprises one or more fluid reservoirs. In some embodiments, the flow channel further comprises one or more peristaltic pump valves. In some embodiments, the flow channel further comprises one or more peristaltic pump valves. In some embodiments, the classification confirms a biotherapeutic analytical characterization. In some embodiments, the classification comprises classifying a cellular phenotype. In some embodiments, the classification comprises using a machine learning algorithm. In some embodiments, the machine learning algorithm is a convolutional neural network. In some embodiments, the machine learning algorithm is a generational neural network. In some embodiments, the convolutional neural network is a 1D neural network trained using a training data set comprising at least 100 data sets. In some embodiments, the machine learning algorithm classifies cells as cancerous or non-cancerous. In some embodiments, the machine learning algorithm classifies at least 100,000 cells per second. In some embodiments, the machine learning algorithm classifies with a false negative rate of less than one in one billion. In some embodiments, the machine learning algorithm classifies with a false positive rate of less than one in one billion. In some embodiments, the machine learning algorithm classifies with a true positive rate of at least 99.9 percent.

[0214] In some embodiments, provided herein is a method of determining a dimension of an analyte or a cell, the method comprising subjecting the analyte or the cell to flow along a flow channel; and repeatedly detecting one or more beams of light, wherein the one or more beams of light are scattered by the analyte or the cell, and wherein the one or more beams of light comprise an angular light scattering pattern, wherein the angular light scattering pattern identifies the dimension of the analyte or the cell. In some embodiments, provided herein is a method of determining a dimension of an analyte or a cell, the method comprising subjecting the analyte or the cell to flow along a flow channel; and repeatedly detecting one or more beams of light, wherein the one or more beams of light are scattered by the particle or the cell, and wherein the one or more beams of light comprise a light scattering spectral pattern, wherein the light scattering spectral pattern identifies the dimension of the analyte or the cell. In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting a signal from the cell to identify the cellular size at an accuracy of at least 10-9m in a time period of at most 10 minutes. In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting a signal from the cell to identify the cellular organelle size at an accuracy of at least 10-9m in a time period of at most 10 minutes. In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b)WSGR Reference No.64149-703.601 detecting a signal from the cell to identify a number of cellular mitochondria at an accuracy of at least 95 percent in a time period of at most 10 minutes. In some embodiments, provided herein is a method for processing or analyzing a cell, comprising (a) subjecting the cell to flow along a flow channel and (b) detecting a signal from the cell to identify a population of at least 1,000 cells in a time period of at most 10 minutes. In some embodiments, provided herein is a method of imaging a surface of a cell, the method comprising: providing a fluidic microchannel configured to receive the cell, wherein the fluidic microchannel comprises at least two detection zones along a length of the fluidic microchannel, wherein each of the at least two detection zones comprise an imager, and wherein the microfluidic channel comprises a feature adjacent to the at least two detection zones, wherein the feature is configured to induce a rotation along an axis of the cell upon contact with the cell; disposing the cell in the fluidic microchannel; providing a force adjacent to the fluidic microchannel, thereby traversing the cell across the length of the fluidic microchannel, wherein the feature does not terminate the traversing of the cell across the length of the fluidic microchannel; and capturing at least two, two dimensional images of the cell.

[0215] In some embodiments, the at least two, two dimensional images of the cell are at least super-resolution. In some embodiments, the method further comprises generating a three- dimensional structure of the cell derived from the at least two, two dimensional images of the cell. In some embodiments, provided herein is a method of imaging a surface of a cell in three dimensions, the method comprising: a. providing a flow channel configured to receive the cell, wherein the flow channel comprises at least a first detection zone and a second detection zone along a length of the flow channel, wherein the first detection zone, the second detection zone, or both, comprises an imager, and wherein the microfluidic channel comprises a feature adjacent to the first detection zone or the second detection zone, wherein the feature is configured to induce a rotation along an axis of the cell upon contact with the cell; (b) disposing the cell in the flow channel; (c) subjecting the cell to flow through the flow channel; (d) capturing one or more images of the cell as the cell passes the first detection zone and the second detection zone; and (e) generating a three-dimensional structure of the cell derived from the one or more images of the cell. In some embodiments, the feature does not terminate the flow of the cell through the fluidic microchannel. In some embodiments, the three-dimensional structure comprises an atlas of the cell. In some embodiments, the three-dimensional structure of the cell is at least super- resolution. In some embodiments, the three-dimensional structure comprises a classification of one or more membrane bound structures of the cell. In some embodiments, the three- dimensional structure comprises a morphometric classification of the cell. In some embodiments, the three-dimensional structure comprises a topography map of one or moreWSGR Reference No.64149-703.601 membrane bound structures of the cell. In some embodiments, the three-dimensional structure comprises a map comprising a location of the one or more membrane bound structures on the surface of the cell. In some embodiments, the three-dimensional structure further comprises a motion dynamic characterization of the cell. In some embodiments, the detection comprises a spatial density map of one or more analytes. In some embodiments, the three-dimensional structure comprises one or more dynamic topographical data of the cell. In some embodiments, the cell is a single cell of a population of cells, and wherein the method further comprises repeating (b)-(e) for a second cell of the population of cells. In some embodiments, the steps (b)- (e) for the second cell of the population of cells occurs simultaneously to the first cell. In some embodiments, the repeating (b)-(e) for the second cell of the population of cells occurs subsequent to the first cell. In some embodiments, the first cell is a single cell of a population of cells, and wherein the method further comprises repeating (b)-(e) for a hundredth cell of the population of cells. In some embodiments, the repeating (b)-(e) for the hundredth cell of the population of cells occurs simultaneously to the first cell. In some embodiments, the repeating (b)-(e) for the hundredth cell of the population of cells occurs subsequent to the first cell. In some embodiments, provided herein is a method of analyzing a subject’s blood comprising connecting a subject’s blood flow to a device or analyte processing device disclosed herein. In some embodiments, the analysis comprises cancer cell detection. In some embodiments, the analysis comprises preparation of a subject’s blood prior to analysis. In some embodiments, the analysis further comprises removal of cancer cells. In some embodiments, the analysis comprises intermittent sampling of the subject’s blood. In some embodiments, provided herein is a method of spatially identifying one or more markers on an analyte surface, comprising: subjecting the analyte to flow through a flow channel; subjecting the analyte to one or more excitation sources, wherein the one or more excitation sources generates a light scattering pattern of the analyte surface; processing the light scattering pattern algorithmically to generate a topographic map of the analyte surface. In some embodiments, the topographic map comprises a location map of one or more markers. In some embodiments, the topographic map comprises an intensity map of one or more markers. In some embodiments, the topographic map comprises a density map of one or more markers.

[0216] In some embodiments, provided herein is a method for analyzing an analyte, comprising: providing a device comprising (i) a flow channel comprising the analyte, and (ii) one or more photodetectors in optical communication with the one or more flow channels; using the one or more photodetectors to acquire a first optical signal from the one or more flow channels at a first time point; using the one or more photodetectors to acquire a second optical signal from the one or more flow channels at a second time point subsequent to the first timeWSGR Reference No.64149-703.601 point; and processing the first optical signal and the second optical signal to identify the analyte flowing through the one or more flow channels, collecting one or more two-dimensional images of the analyte, wherein the one or more two-dimensional images are combined and optimized algorithmically to produce a three-dimensional structure of the analyte, wherein the analyte in fluid motion is imaged as if it were static.

[0217] In some embodiments, the method further comprises using the one or more photodetectors to acquire a third optical signal at a third time point within the one or more flow channels. In some embodiments, the device further comprises one or more excitation sources in optical communication with the analyte processing area. In some embodiments, the method further comprises processing the three-dimensional structures to improve analyte analysis. In some embodiments, the method further comprises using the three-dimensional structure to determine analyte characteristics for a chemical or biological test. In some embodiments, the analyte characteristics reduce the number of false positives. In some embodiments, the analyte characteristics of multiple analytes is used to determine analyte characteristic distribution of a population of analytes. In some embodiments, the reduced number of false positives results in a change in a treatment protocol. In some embodiments, the method further comprises using the three-dimensional structure to separate false positive cancer tests from true cancer positives, wherein the results are used to create an individualized cancer treatment plan. In some embodiments, the analyte characteristic distribution of a population of analytes indicates the severity of multiple myeloma for a subject. In some embodiments, the characterization of the population of analytes can be used to extrapolate a causal factor of multiple myeloma present in the subject.

[0218] In some embodiments, provided herei...

Claims

WSGR Reference No.64149-703.601 CLAIMS What is claimed is:

1. A method of morphological reconstruction of an analyte in-motion, the method comprising: a. subjecting the analyte to flow through a channel; b. subjecting the analyte to a light from one or more excitation sources, wherein the light is interacted with by the analyte, thereby emitting a plurality of photons from the analyte; c. detecting the plurality of photons using an image sensor placed in proximity of the channel, thereby generating an image; d. repeating (b) and (c) to generate a plurality of images; and e. processing the plurality of images using a machine learning model to generate a morphological reconstruction of the analyte, wherein the machine learning model is configured to perform operations including: i. segmenting the plurality of images to identify the pixels corresponding to the analyte, and / or ii. using the machine learning model to generate the morphological reconstruction of the analyte.

2. The method of claim 1, wherein the machine learning model is further configured perform operations including cropping the plurality of images to center the analyte in each of the plurality of images.

3. The method of claim 1, wherein the morphological reconstruction generated by the machine learning model is a higher resolution than the plurality of images generated from the detection of the plurality of photons by the image sensor.

4. The method of claim 1, wherein the morphological reconstruction generated by the machine learning model is at least one two-dimensional image, wherein the at least one two- dimensional image is a higher resolution than the plurality of images generated from the detection of the plurality of photons by the image sensor.

5. The method of claim 1, wherein the morphological reconstruction generated by the machine learning model is at least one three-dimensional image, wherein the at least one three-WSGR Reference No.64149-703.601 dimensional image is a higher resolution than the plurality of images generated from the detection of the plurality of photons by the image sensor.

6. The method of claim 1, wherein the morphological reconstruction generated by the machine learning model is optimized in comparison to the plurality of images generated from the detection of the plurality of photons by the image sensor.

7. The method of claim 6, wherein the optimized morphological reconstruction undergoes differentiable optimization comprising one optimization per interference and does not require training data.

8. The method of claim 6, wherein the optimized morphological reconstruction occurs only at the forward pass and requires training data.

9. The method of claim 1, wherein the deep neutral network simulates training data using a physical process for which the parameters are defined.

10. The method of claim 1, further comprising applying a machine learning classifier to obtain one or more characteristics of the analyte from the morphological reconstruction of the analyte.

11. The method of claim 10, wherein the one or more characteristics of the analyte comprise an analyte size, an analyte length, an analyte thickness, an analyte roughness, an analyte type, an analyte morphology, or an analyte shape.

12. The method of claim 11, wherein the analyte shape comprises a round shape, a cubic shape, an oval shape, or a tangled shape.

13. The method of claim 10, wherein the machine learning classifier comprises a neural network.

14. The method of claim 10, wherein the machine learning classifier is initially trained on a library of data comprising one or both of a plurality of synthetic analytes or a plurality of simulated analytes.

15. The method of claim 1, wherein the machine learning model is initially trained on a library of data comprising one or both of a plurality of synthetic analytes or a plurality of simulated analytes.

16. The method of claims 14 or 15, wherein the plurality of synthetic analytes have a diameter of about 800 nm to about 5000 nm.WSGR Reference No.64149-703.601 17. The method of claim 1, wherein the machine learning model comprises at least one of a convolutional neural network (CNN), a long-short-term-memory (LSTM) network, a recurrent neural network (RNN), a transformer, or an encoder-decoder network.

18. The method of claim 17, wherein the encoder-decoder network comprises a pre-trained VGG19 encoder network.

19. The method of claim 1, further comprising performing the method on a population of analytes to obtain an analyte size distribution.

20. The method of claim 1, further comprising performing the method on multiple analytes.

21. The method of claim 1, further comprising performing the method on a population of analytes to obtain for a plurality of the population of analytes one or more metrics comprising an analyte size, an analyte length, an analyte roughness, an analyte type, an analyte morphology, or an analyte shape.

22. The method of claim 1, wherein the operations of (e) further include applying a confidence threshold to the detection of the analyte.

23. The method of claim 1, wherein the operations of (e) further include up-sampling the morphological reconstruction of the analyte.

24. The method of claim 1, wherein the light from one or more excitation sources comprises an intensity-modulated laser light.

25. The method of claim 24, wherein the intensity-modulated laser light is split into a plurality of laser light beams.

26. The method of claim 1, wherein the light from one or more excitation sources comprises a discrete laser light.

27. The method of claim 1, wherein the plurality of images is generated at a rate of at least 1 KHz.

28. The method of claim 1, wherein the plurality of images is generated at a rate of at least 5 KHz.

29. The method of claim 1, wherein the plurality of images is generated at a rate of at least 10 KHz.WSGR Reference No.64149-703.601 30. The method of claim 1, wherein the image sensor comprises a complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) array.

31. The method of claim 1, wherein the image sensor comprises a confocal microscope or a high- speed camera.

32. The method of claim 1, wherein the analyte comprises an aerosol.

33. The method of claim 1, wherein the channel is one of a plurality of channels.

34. The method of claim 1, wherein the channel is a microfluidic device channel.

35. The method of claim 1, wherein the morphological reconstruction comprises a topographic map of the analyte.

36. The method of claim 1, wherein the light is diffracted into one or more beams exposing a plurality of separate locations along the channel, thereby exciting the analyte repeatedly in one pass of the analyte along the channel, wherein the excitation of the analyte emits one or more photons of the plurality of photons.

37. The method of claim 1, wherein the morphological reconstruction comprises a surface of the analyte.

38. The method of claim 1, wherein the flow is from about 1 cell per second to about 10,000 cells per second.

39. A device for processing an analyte in a biological sample, the device comprising: a. an inlet configured to receive a container comprising the biological sample; b. a first chamber in fluidic communication the inlet, wherein the first chamber comprises a filter configured to remove contaminants from the biological sample; c. a second chamber comprising one or more reagents for configuring the analyte for optical detection, wherein the second chamber is in fluidic communication with the first chamber; and d. a microfluidic chip in fluidic communication with the second chamber, wherein the microfluidic chip comprises: i. one or more channels, wherein a channel of the one or more channels comprises a plurality of detection zones,WSGR Reference No.64149-703.601 wherein the device is configured to be received by a housing in electrical communication with a detector.

40. The device of claim 39, wherein the received container is in an inverted position relative to the device.

41. The device of claim 39 or claim 40, wherein the received container is configured to provide the biological sample using a mild vacuum.

42. The device of any one of claims 39-41, wherein the device further comprises one or more valves disposed between: a. the inlet and the first chamber; b. the first chamber and the second chamber; c. the second chamber and the microfluidic chip; or d. any combination thereof; wherein the one or more valves is configured to open when the device is received by the housing.

43. The device of any one of claims 39-42, wherein the device further comprises a third chamber in fluidic communication with the second chamber, the microfluidic device, or both, and wherein the third chamber is configured to collect the analyte.

44. The device of any one of claims 39-43, wherein the device further comprises one or more reagent reservoirs.

45. The device of any one of claims 39-44, wherein the second chamber comprises one or more reagents dried and coupled to an inner surface of the second chamber.

46. The device of any one of claims 39-45, wherein the one or more reagents dried and coupled to the inner surface of the second chamber comprise an antibody configured to bind to the analyte.

47. The device of any one of claims 39-46, wherein the device further comprises a first reagent reservoir in fluidic communication with the second chamber, wherein the first reagent reservoir comprises one or more reagents configured to facilitate binding of the analyte and the antibody configured to bind to the analyte.WSGR Reference No.64149-703.601 48. The device of any one of claims 39-47, wherein the device further comprises a second reagent reservoir in fluidic communication with the microfluidic chip, wherein the second reagent reservoir comprises one or more reagents configured to facilitate transport of the analyte through the one or more channels.

49. The device of any one of claims 39-48, wherein the device further comprises a lysis reagent reservoir in fluidic communication with the first chamber.

50. The device of any one of claims 39-49, wherein the device further comprises a cooling unit in communication with the second chamber.

51. The device of any one of claims 39-50, wherein the device is configured to align the one or more detection zones with one or more optical paths of the detector such that the one or more detection zones are in optical communication with the detector upon the housing receiving the detector.

52. The device of any one of claims 39-51, wherein the inlet comprises one or more protrusions or prongs, wherein the one or more protrusions or prongs comprise one or more channels in fluidic communication with the first chamber.

53. The device of any one of claims 39-52, wherein the one or more protrusions or prongs are configured to couple to the container comprising the biological sample and to form a sealed coupling to the container.

54. The device of any one of claims 39-53, wherein the one or more protrusions or prongs are configured to collect the analyte and facilitate transport of the analyte to the first chamber.

55. The device of any one of claims 39-54, wherein the first chamber, the third chamber, the microfluidic chip, or any combination thereof, is in fluidic communication with one or more waste reservoirs.

56. The device of any one of claims 39-55, wherein the one or more reagents are dried and coupled to the inner surface of the second chamber are lyophilized.

57. The device of any one of claims 39-56, wherein the first reagent reservoir comprises one or more reagents for fluorescent-activation cell sorting (FACS) analysis of the analyte.

58. The device of any one of claims 39-57, wherein the second reagent reservoir comprises one or more surfactants.WSGR Reference No.64149-703.601 59. The device of any one of claims 39-58, wherein the microfluidic chip comprises one or more single photon avalanche diode (SPAD) arrays.

60. A chip with a layered architecture, comprising: a. a first layer comprising one or more flow channels, wherein at least one flow channel of the one or more flow channels comprises an analyte processing area; b. a second layer comprising one or more excitation sources in optical communication with the first layer and an optical path from the one or more excitation sources to the analyte processing area; and c. a third layer comprising an array of one or more photodetectors in optical communication with the analyte processing area and an application specific integrated circuit (ASIC), wherein the optical path comprises a light scattering control system.

61. The chip of claim 60, wherein the third layer comprises at least one single-photon avalanche diodes (SPAD).

62. The chip of claim 60 or 61, wherein the array comprises a plurality of SPAD pixels, wherein the array is in optical communication with the first layer.

63. The chip of claim 62, wherein the array is engineered to allow space in between each of the plurality of SPAD pixels, wherein the space permits circuitry to surround at least a portion of each of the plurality of SPAD pixels.

64. The chip of claim 63, wherein a total area of the array and the circuitry comprises an area of the third layer.

65. The chip of claims 63 or 64, wherein the space between each of the plurality of pixels reduces the cross-talk between pixels.

66. The chip of claim 60, wherein the first layer is engineered to detect one or more morphological characteristic.

67. The chip of claim 66, wherein the one or more morphological characteristic comprises a dataset used for assessment of a chemical or a biological test.

68. The chip of claim 66, wherein the one or more morphological characteristic comprises a dataset used for improvement of a chemical or a biological test.WSGR Reference No.64149-703.601 69. The chip of claim 60, wherein the array and the ASIC creates free space on the third layer.

70. The chip of claim 69, wherein the free space comprises one or more additional lasers bonded to the third layer.

71. The chip of claim 60, wherein the one or more excitation sources comprises at least one laser.

72. The chip of claim 60, wherein the array comprises a complementary metal-oxide semiconductor (CMOS) SPAD array.

73. The chip of claim 60, wherein at least two of the three layers are combined into a single layer.

74. The chip of claim 60, wherein all three layers are combined into a single layer.

75. A method of screening a particle, the method comprising: a. subjecting the particle to flow in a channel, wherein the orientation of the particle is manipulated at least once in a single pass of the particle along the channel; b. providing a first light beam diffracted into at least a second light beam and a third light beam, wherein the second light beam exposes a first location on the channel and the third light beam exposes a second location on the channel, and wherein the particle has a first orientation in the first location and a second orientation at the second location, thereby generating a first photon from the first location and a second photon from the second location; and c. detecting the first photon and the second photon using a single photon avalanche diode (SPAD) array in proximity of the channel.

76. The method of claim 75, wherein the first photon is emitted from a first region on a surface of the particle and the second photon is emitted from a second region on the surface.

77. The method of claim 75, wherein the channel is part of a microfluidic device.

78. The method of claim 77, wherein the microfluidic device is part of an integrated system, and wherein the system further comprises the SPAD array.

79. The method of claim 78, wherein the system further comprises a photonics circuit configured to diffract the first light beam into the second and the third light beams.

80. The method of claim 75, wherein the channel comprises a physical bump configured to manipulate the orientation of the particle.WSGR Reference No.64149-703.601 81. The method of claim 75, wherein the channel comprises a surface acoustic wave (SAW) source configured to generate one or more acoustic waves, wherein the one or more acoustic waves manipulate the orientation of the particle.

82. The method of claim 81, wherein the channel comprises a plurality of SAW sources.

83. The method of claim 75, wherein the first location and the second location are spatially separate detection regions separated by at least one re-orientation region configured to manipulate the orientation of the cell.

84. The method of claim 83, wherein the re-orientation region comprises at least one of: a bump, a surface acoustic wave source (SAW), a channel segment with a different channel width compared to the channel, or any combination thereof.

85. The method of claim 83, wherein the re-orientation region comprises a relaxation segment of the channel having a width wider that the width of the channel, and wherein the particle relaxes and re-orients as it passes through the relaxation segment.

86. The method of claim 83, wherein the re-orientation region comprises a constriction segment having a width narrower that the width of the channel, and wherein the particle stretches and re-orients as it passes through the constriction segment.

87. The method of claim 75, wherein the channel comprises a serpentine channel, a spiral channel, or both.

88. The method of claim 78, wherein the integrated system further comprises an inlet.

89. The method of claim 88, wherein the integrated system further comprises a filtration module.

90. The method of claim 89, wherein the integrated system further comprises a sample preparation module configured to prepare the particle for screening.

91. The method of claim 90, wherein the sample preparation module is configured to enrich the particle, stain the particle with a dye, add a reagent onto the particle, perform an assay on the particle, inject a reagent inside the particle, or any combination thereof.

92. The method of claim 91, wherein the reagent comprises a fluorescent entity.

93. The method of claim 91, wherein the reagent comprises a fluorescent dye, a fluorophore, an antibody, a nucleic acid molecule, or any combination thereof, wherein the reagent is excitable by a light to emit the first photon, the second photon, or both.WSGR Reference No.64149-703.601 94. The method of any one of claims 75-93, further comprising characterizing a surface of the particle and generating a topographic map of the surface.

95. The method of claim 94, wherein the topographic map comprises a location map of one or more markers, an intensity map of one or more markers, a density map of one or more markers, or any combination thereof.

96. The method of any one of claims 75-95, wherein the analyte comprises or is an aerosol.

97. The method of any one of claims 75-96, wherein the analyte comprises or is a cell.

98. The method of claim 95, wherein the analyte comprises or is a cell, and wherein the topographic map is a topographic map of a cell surface marker.

99. The method of any one of claims 75-98, wherein the particle comprises or is a cell isolated from a clinical sample of a subject.

100. The method of claim 99, further comprising diagnosing the subject with a condition or disease.

101. The method of claim 99, further comprising classifying the cell into one or more classifications, providing one or more insights about the condition of the subject, or both.

102. The method of any one of claims 75-101, further comprising an analyte sorting module.

103. The method of claim 102, wherein the analyte sorting module is configured to sort the analyte based on a classification of the one or more classifications.

104. The method of claim 102 or 103, wherein the analyte sorting module comprises a valve.

105. The method of claim 75, wherein the channel comprises a plurality of spatially separate detection regions, wherein a detection region comprises a vortex, wherein the particle is trapped in the vortex for a duration of time and screened.

106. The method of any one of claims 75-105, wherein the channel comprises an inlet connect to a sample reservoir containing the particle.

107. The method of claim 106, wherein the particle is stirred, mixed, vortexed, rotated, or any combination thereof in the sample reservoir to prevent the sedimentation of the particle in the sample reservoir.

108. A system comprising a screening module comprising a plurality of layers, wherein the plurality of layers comprise:WSGR Reference No.64149-703.601 a. a first layer comprising a microfluidic device, wherein the microfluidic device comprises a flow channel configured to flow a particle therein, wherein the flow channel comprises a plurality of detection regions therein, b. a second layer adjacent to the first layer comprising a photonic circuit configured to diffract a single beam into two or more diffracted beams, wherein the two or more diffracted beams expose the plurality of detection regions, thereby generating a plurality of photons from the particle; and, c. a third layer comprising a single photon avalanche diode (SPAD) array configured to detect the plurality of photons.

109. The system of claim 108, wherein the plurality of detection regions is spatially separated.

110. The system of claim 108 or 109, wherein the plurality of detection regions each comprise a vortex, wherein the particle is trapped in the vortex.

111. The system of claim 108, wherein the flow channel comprises a bump or a surface acoustic wave (SAW) source between a first detection region and a second detection region of the plurality of detection regions, wherein the bump or the SAW source is configured to re-orient the particle.

112. The system of any one of claims 108-111, wherein the flow channel comprises a serpentine channel, a spiral channel, or both.

113. The system of 111, wherein the flow channel further comprises a re-orientation region comprising at least one of: a bump, a surface acoustic wave source (SAW), a relaxation region wider than the flow channel, a constriction region narrower than the flow channel, a slow-down structure, or any combination thereof.

114. The system of claim 108, wherein the microfluidic device further comprises an inlet.

115. The system of claim 114, wherein the system further comprises a filtration module configured to filter the particle prior to entering the microfluidic device.

116. The system of claim 115, wherein the system further comprises a sample preparation module configured to prepare the particle for screening.

117. The system of claim 116, wherein the sample preparation module is configured to enrich the particle, stain the particle with a dye, add a reagent onto the particle, perform an assay on the particle, inject a reagent inside the particle, or any combination thereof.WSGR Reference No.64149-703.601 118. The system of claim 117, wherein the reagent comprises a fluorescent entity.

119. The system of claim 118, wherein the reagent comprises a fluorescent dye, a fluorophore, an antibody, a nucleic acid molecule, or any combination thereof, wherein the reagent is excitable by a light to emit the first photon, the second photon, or both.

120. The system of any one of claims 108 to 119, further comprising a sample barcode reader configured to detect and record a barcode associated with a sample comprising the particle.

121. The system of any one of claims 108 to 120, further comprising a processor configured to analyze data generated by the system.

122. The system of claim 121, wherein the processor is further configured to link a sample barcode to data generated by the system.

123. The system of claim 108, wherein the particle comprises a biological material.

124. The system of claim 123, wherein the biological material comprises one or more cells or one or more cell organelles.

125. The system of any one of claims 108, 123, or 124, wherein the particle is contained in an exosome.

126. The system of any one of claims 108, 123, 124, or 125, wherein the particle is extravesicular.

127. The system of claim 108, wherein the particle comprises a microorganism or microbe.

128. A labelling complex comprising: a. an antibody configured to bind to an analyte; b. a circularized nucleic acid molecule, wherein the circularized nucleic acid molecule is engineered to: i. conjugate to the antibody; ii. comprise a binding site for one or more labeled oligonucleotides comprising a label, wherein the circularized nucleic acid molecule comprises a first binding site for a first labeled oligonucleotide of the one or more labeled oligonucleotides, and wherein the circularized nucleic acid molecule comprises a second binding site for a second oligonucleotide of the one or more labeled oligonucleotides; andWSGR Reference No.64149-703.601 c. the one or more labeled oligonucleotides, wherein the one or more labeled oligonucleotides are bound to the circularized nucleic acid molecule.

129. A labelling complex comprising: a. an antibody configured to bind to an analyte; b. a circularized nucleic acid molecule, wherein the circularized nucleic acid molecule is engineered to: i. conjugate to the antibody; ii. comprise one or more binding sites for one or more labeled oligonucleotides comprising a label, wherein a binding site on the circularized nucleic acid molecule is specific to a labeled oligonucleotide of the one or more labeled oligonucleotides; and c. the one or more labeled oligonucleotides, wherein the one or more labeled oligonucleotides are bound to the circularized nucleic acid molecule.

130. The labelling complex of claim 128 or claim 129, wherein the label comprises a secondary antibody conjugated to a signal-emitting moiety.

131. The labelling complex of any one of claims 128-130, wherein the signal-emitting moiety comprises a fluorescence mechanism.

132. The labelling complex of any one of claims 128-131, wherein the signal-emitting moiety comprises a fluorophore, a fluorescent dye, or a quantum dot.

133. The labelling complex of any one of claims 128-132, wherein the one or more labeled oligonucleotides comprises at least 2, 3, 4, 5, 6, or 7 labeled oligonucleotides.

134. The labelling complex of any one of claims 128-133, wherein the one or more labeled oligonucleotides comprise a length of at least about 2 bases.

135. The labelling complex of any one of claims 128-134, wherein the first binding site is located at least about 4 bases from the second binding site on the circularized nucleic acid molecule.

136. The labelling complex of any one of claims 128-135, wherein the first labeled oligonucleotide comprises at least about 2 signal-emitting moieties.

137. The labelling complex of any one of claims 128-136, wherein the circularized nucleic acid molecule comprises a length of at least about 100 bases.WSGR Reference No.64149-703.601 138. The labelling complex of any one of claims 128-137, wherein the circularized nucleic acid molecule comprises a length of at least about 40 bases.

139. The labelling complex of any one of claims 128-138, wherein the circularized nucleic acid molecule comprises a length of at least about 10 bases.

140. A method of detecting an analyte, the method comprising: a. providing an antibody configured to bind to the analyte, wherein the antibody is conjugated to a circularized nucleic acid molecule, wherein the circularized nucleic acid molecule is engineered to: i. conjugate to the antibody; ii. comprise one or more binding sites for one or more labeled oligonucleotides comprising a label, wherein a binding site on the circularized nucleic acid molecule is specific to a labeled oligonucleotide of the one or more labeled oligonucleotides; b. contacting the analyte with the antibody; and c. detecting a signal from the one or more labeled oligonucleotides.

141. A method of detecting an analyte, the method comprising: a. providing an antibody configured to bind to the analyte, wherein the antibody is conjugated to a circularized nucleic acid molecule, wherein the circularized nucleic acid molecule is engineered to: i. conjugate to the antibody; ii. comprise one or more labeled oligonucleotides, wherein the one or more labeled oligonucleotides comprises:

1. a first labeled oligonucleotide comprising a first binding site on the circularized nucleic acid molecule; and 2. a second labeled oligonucleotide comprising a second binding site on the circularized nucleic acid molecule; and b. detecting a signal from the one or more labeled oligonucleotides.WSGR Reference No.64149-703.601 142. The method of claim 140 or claim 141, wherein the one or more labeled oligonucleotides comprises at least about 2 labeled oligonucleotides.

143. The method of any one of claims 140-142, wherein the one or mor labeled oligonucleotides comprise a length of at least about 2 bases.

144. The method of any one of claims 140-143, wherein the first binding site is located at least about 2 bases from the second binding site on the circularized nucleic acid molecule.

145. The method of any one of claims 140-144, wherein the first labeled oligonucleotide comprises at least about 2 signal-emitting moieties.

146. The method of any one of claims 140-145, wherein the circularized nucleic acid molecule comprises a length of at least about 100 bases.

147. The method of any one of claims 140-146, wherein the circularized nucleic acid molecule comprises a length of at least about 40 bases.

148. The method of any one of claims 140-147, wherein the circularized nucleic acid molecule comprises a length of at least about 4 bases.

149. The method of any one of claims 140-148, wherein the method further comprises disposing one or more metal particles within proximity of the one or more labeled oligonucleotides.

150. The method of any one of claims 140-149, wherein the one or more labeled oligonucleotides are disposed no more than 15 nanometers from a labeled oligonucleotide of the one or more labeled oligonucleotides.

151. A labelling complex comprising: a. one or more antibodies engineered to bind to an analyte; and b. a hollow mesoporous silica nanoparticle engineered to: i. conjugate to the one or more antibodies, and ii. contain at least one luminescent dye.

152. The labeling complex of claim 151, wherein the at least one luminescent dye comprises a fluorescent molecule.

153. The labeling complex of claim 151, wherein the hollow mesoporous silica nanoparticle is a mesoporous fused silica nanoparticle.WSGR Reference No.64149-703.601 154. The labeling complex of claim 153, wherein the hollow mesoporous silica has a tunable pore size, where the tunable pore size is from about 2 nanometers to 50 nanometers in diameter.

155. The labeling complex of claim 153, wherein the hollow mesoporous silica has a tunable shell thickness that ranges from about 1 nanometer to about 1 micrometer.

156. The labeling complex of claim 153, wherein the hollow mesoporous silica has a tunable shell thickness of less than 1 nanometer.

157. The labeling complex of claim 151, wherein one or more parameters of the labeling complex can be altered by a change in a synthesis condition, wherein the one or more parameters comprises stability, absorption, or label loading, and wherein the synthesis condition comprises one or more of temperature, pH, or silica-to-antigen ratio.

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