Apparatus for detecting an analyte

JP2024534932A5Pending Publication Date: 2025-08-27NANOPATH INC
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Patent Information

Application Number
JP2024514617
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2021-09-07
Filing Date
2022-09-06
Publication Date
2025-08-27

AI Technical Summary

Technical Problem

Existing technologies face challenges in efficiently detecting specific nucleotide sequences from primary patient samples with high accuracy, sensitivity, and ease of use in clinical settings.

Method used

A device utilizing optical spectroscopy with immobilized metal nanoparticles on a surface to detect nucleotide sequences by measuring wavelength shifts when analytes bind to these nanoparticles, incorporating a stage, light source, spectrometer, and lens assembly for precise data collection and analysis.

Benefits of technology

Enables rapid, accurate detection of nucleotide sequences, facilitating clinical diagnosis by observing optical peak shifts and refractive index changes due to surface plasmon resonance, enhancing diagnostic efficiency.

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Abstract

Provided herein is an apparatus for detecting an analyte. In some embodiments, the analyte to be detected comprises a nucleotide sequence. In some embodiments, the analyte is detected in a liquid solution. In some embodiments, the apparatus includes a stage, a light source, a spectrometer, and a lens assembly.
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Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 241,356, filed September 7, 2021, which is incorporated by reference in its entirety.

[0002] Field The present disclosure relates generally to the detection or sensing of various materials, including biological and chemical substances. More specifically, provided herein are devices and methods for detecting nucleic acids. [Background technology]

[0003] 2. Description of Related Art In biomedical research, clinical diagnostics, environmental testing, and other related fields, it is beneficial to have devices and systems for detecting analytes, such as biomolecules and chemicals, with high accuracy, sensitivity, specificity, reproducibility, and ease of use. For example, having a fast, rapid, and accurate test for detecting specific analytes in a biological sample can be useful in clinical diagnostic situations and aid physicians in determining optimal treatment regimens.

[0004] One class of biomolecules that shares a strong causal relationship with disease states is nucleotides, and detection of a particular nucleotide sequence may suggest or support a clinical diagnosis. However, observing, detecting, or otherwise analyzing nucleotides or nucleotide sequences in an efficient manner from primary patient samples has been hindered in clinical settings for a variety of reasons. Therefore, an easily operable analyte detection system or device would be of great benefit in the clinical environment. Summary of the Invention

[0005] Disclosed herein are devices for use in detecting various constituent analytes, such as biomolecules and chemicals within a sample, for example polynucleotides within a liquid sample.

[0006] Each of the systems, devices, kits, and methods disclosed herein has several aspects, no one of which is solely responsible for their desirable attributes. Without limiting the scope of the claims, several prominent features are described herein. Numerous other examples are contemplated, including examples with fewer, additional, and / or different components, steps, features, objects, benefits, and advantages. The components, aspects, and steps may also be arranged and ordered differently. It is understood that any features of the devices and / or apparatuses disclosed herein may be combined together in any desired manner and / or configuration. It is further understood that any features of the methods of using the devices may be combined together in any desired manner. It is further understood that any combination of features of the methods and / or devices and / or arrays may be used together and / or combined with any of the examples disclosed herein. Still further, it is understood that any features or combinations of features of any of the devices and / or arrays, and / or any of the methods may be combined together in any desired manner and / or combined with any of the examples disclosed herein.

[0007] In some embodiments, provided herein is an apparatus for spectroscopically determining the presence of a target analyte. The apparatus comprises a stage, a light source, a spectrometer, and a lens assembly. The stage comprises an actuator arm and a sample holder. In some embodiments, the sample holder is configured to receive a microscope slide. In some embodiments, the microscope slide is 25 mm x 75 mm. In some embodiments, the microscope slide is 1 mm thick. In some embodiments, the slide is further characterized by a 1-2 mm thick PDMS layer having a well. In some embodiments, the microscope slide is further characterized by a coverslip. In some embodiments, the coverslip is about 170 μm. In some embodiments, the sample holder is configured to receive a microfluidic device, including, but not limited to, a cartridge, cassette, or module designed to process fluid or solid samples. In some embodiments, a plurality of sensor sites are present on a surface of the microfluidic device or devices, the plurality of sensor sites comprising a population of immobilized metal nanoparticles. In some embodiments, the actuator arm has one or more degrees of articulation. In some embodiments, the light source is configured to emit a particular wavelength. In some embodiments, the light source is configured to emit a series of particular wavelengths. In some embodiments, the light source is configured to emit a series of specific wavelengths at various intensities and durations. In some embodiments, the light source is configured to emit white light. In some embodiments, the lens assembly comprises a focusing element, an optical element, and at least one mirror. In some embodiments, the mirror or mirrors can be a concave mirror. In some embodiments, the mirror or mirrors can be a parabolic surface. In some embodiments, the focusing element adjusts the focal plane of the optical element. In some embodiments, the light emitted by the light source is reflected by the mirror or mirrors. In some embodiments, the optical path of the device is determined in whole or in part by the orientation of the mirror or mirrors. In some embodiments, the spectrometer is configured to block the light emitted by the light source.In some embodiments, the spectrometer is configured to collect data related to absorbance. In some embodiments, the spectrometer is configured to collect data related to transmittance. In some embodiments, the spectrometer is configured to collect data related to extinction. In some embodiments, the spectrometer is configured to collect data including a complete spectrum at a defined wavelength when the target analyte binds to the metal nanoparticles. In some embodiments, the spectrometer is configured to collect data including a wavelength shift when the target analyte binds or associates with the metal nanoparticles, including gold nanoparticles. In some embodiments, the spectrometer is configured to collect data related to a physical property of the nanoparticles. In some embodiments, the wavelength range of the spectrometer is between 500 nm and 1000 nm. In some embodiments, the stage and lens assembly interact to optimize sample positioning and collection, including moving the sample or sensor spot to a position of intersection with the light beam. In some embodiments, the spectrometer moves to optimize sample or sensor spot positioning and collection.

[0008] In some embodiments, the device is configured to generate an output. In some embodiments, the output is determined by absorbance, transmittance, or extinction measured by a spectrometer. In some embodiments, the spectrometer measures any wavelength shift due to binding of the metal nanoparticles to any number of analyte species. In some embodiments, binding of the metal nanoparticles to any number of analyte species changes the refractive index. In some embodiments, the change in refractive index is the result of surface plasmon resonance or other resonant vibrational events. In some embodiments, the output includes absorbance, transmittance, or extinction data from preset wavelengths. In some embodiments, the output includes absorbance, transmittance, or extinction data from a set of preset wavelengths.

[0009] In some embodiments of the present disclosure, a user configures the device using a graphical user interface (GUI). In some embodiments, the output of the device is displayed to the user using the GUI. In some embodiments, a user can configure the device to determine the spectrometer integration time, measurement location, and algorithm settings.

[0010] It should be understood that all combinations of the foregoing concepts, and the additional concepts described in more detail below, are contemplated as being part of the inventive subject matter disclosed herein and may be used to achieve the benefits and advantages described herein. [Brief description of the drawings]

[0011] Features of embodiments of the present disclosure will become apparent by reference to the following detailed description and the drawings in which like reference numbers correspond to similar, if not identical, components. For purposes of brevity, features having a reference number or functionality previously described may or may not be described in conjunction with the other drawings in which they appear.

[0012] [Figure 1] 1 illustrates an embodiment of the present disclosure. [Diagram 2] 1 shows the wavelengths and intensities of embodiments of light sources. [Diagram 3] 1 illustrates actuator positions in an embodiment of the present disclosure. [Figure 4] 1 illustrates actuator positions relative to a spectrometer sensor of the present disclosure. [Diagram 5] 1 illustrates GUI inputs and prompts along with device states in an embodiment of the present disclosure. [Figure 6] 1 illustrates GUI inputs and prompts along with device states in an embodiment of the present disclosure. [Figure 7] 1 illustrates a progression of GUI screens according to an embodiment of the present disclosure. [Figure 8] 1 illustrates a cable input according to an embodiment of the present disclosure. [Figure 9] 1 illustrates a light source and a spectrometer according to an embodiment of the present disclosure. [Figure 10] 1 illustrates an optical path and sensor assembly according to an embodiment of the present disclosure. [Figure 11] 1 illustrates a sample cassette and sample tip according to an embodiment of the present disclosure. [Figure 12] 1 illustrates a GUI menu according to an embodiment of the present disclosure. [Figure 13] 1 illustrates a GUI menu according to an embodiment of the present disclosure. [Figure 14] 1 illustrates a GUI menu according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] All patents, applications, published applications and other publications mentioned herein are incorporated by reference herein for the material referenced and in their entirety. If a term or phrase is used herein in a sense that is contrary to or otherwise inconsistent with the definition set forth in the patents, applications, published applications and other publications incorporated herein by reference, the use herein takes precedence over the definition incorporated herein by reference.

[0014] definition All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs unless clearly indicated otherwise.

[0015] As used herein, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a sequence" can include a plurality of such sequences, and so forth.

[0016] The terms comprising, including, containing, and various forms of these terms are synonymous with each other and are intended to be similarly broad. Moreover, unless expressly stated to the contrary, an example of comprising, including, or having an element or elements having a particular characteristic can include the additional elements, regardless of whether the additional elements have that characteristic.

[0017] As used herein, a spectrometer refers to any scientific instrument used to separate and measure the spectral components of a physical phenomenon. In the context of an optical spectrometer, an optical spectrometer can measure the spectrum of light, measuring the intensity of that light as a function of wavelength or frequency. The light detected by a spectrometer can consist of a continuous spectrum, an emission spectrum, a transmission spectrum, an extinction spectrum, or an absorption spectrum.

[0018] introduction The present disclosure generally relates to devices and systems for analyzing samples using optical spectroscopy. In particular, the present disclosure can analyze a series of samples, possibly liquid samples, and detect the presence or absence of various analytes based on the wavelength shift that occurs when the target analytes interact or bind with the metal nanoparticles. In some embodiments, the metal nanoparticles are immobilized on a surface, and a specific population of metal nanoparticles is present at a given spot or sensor on the surface. Based on the specific wavelength shifts generated and measured by the spectrometer according to various embodiments of the present disclosure, the presence of a specific nucleotide sequence corresponding to a specific or several disease states can be detected.

[0019] In some embodiments, provided herein is an apparatus for spectroscopically determining the presence of a target analyte. The apparatus comprises a stage, a light source, a spectrometer, and a lens assembly. The stage comprises an actuator arm and a sample holder. In some embodiments, the sample holder is configured to receive a microscope slide. In some embodiments, the microscope slide is 25 mm x 75 mm. In some embodiments, the microscope slide is 1 mm thick. In some embodiments, the slide is further characterized by a 1-2 mm thick PDMS layer having a well. In some embodiments, the microscope slide is further characterized by a coverslip. In some embodiments, the coverslip is about 170 μm. In some embodiments, the sample holder is configured to receive a microfluidic device, including, but not limited to, a cartridge, cassette, or module designed to process fluid or solid samples. In some embodiments, a plurality of sensor sites are present on a surface of the microfluidic device or devices, the plurality of sensor sites comprising a population of immobilized metal nanoparticles. In some embodiments, the actuator arm has one or more degrees of articulation. In some embodiments, the light source is configured to emit a particular wavelength. In some embodiments, the light source is configured to emit a series of particular wavelengths. In some embodiments, the light source is configured to emit a series of specific wavelengths at various intensities and durations. In some embodiments, the light source is configured to emit white light. In some embodiments, the lens assembly comprises a focusing element, an optical element, and at least one mirror. In some embodiments, the mirror or mirrors can be a concave mirror. In some embodiments, the mirror or mirrors can be a parabolic surface. In some embodiments, the focusing element adjusts the focal plane of the optical element. In some embodiments, the light emitted by the light source is reflected by the mirror or mirrors. In some embodiments, the optical path of the device is determined in whole or in part by the orientation of the mirror or mirrors. In some embodiments, the spectrometer is configured to block the light emitted by the light source.In some embodiments, the spectrometer is configured to collect data related to absorbance. In some embodiments, the spectrometer is configured to collect data related to transmittance. In some embodiments, the spectrometer is configured to collect data related to extinction. In some embodiments, the spectrometer is configured to collect data including a complete spectrum at a defined wavelength when the target analyte binds to the metal nanoparticles. In some embodiments, the spectrometer is configured to collect data including a wavelength shift when the target analyte binds or associates with the metal nanoparticles, including gold nanoparticles. In some embodiments, the spectrometer is configured to collect data related to a physical property of the nanoparticles. In some embodiments, the wavelength range of the spectrometer is between 500 nm and 1000 nm. In some embodiments, the stage and lens assembly interact to optimize sample positioning and collection, including moving the sample or sensor spot to a position of intersection with the light beam. In some embodiments, the spectrometer moves to optimize sample or sensor spot positioning and collection.

[0020] In some embodiments, presented herein is an apparatus for detecting one or more analytes in one or more sensors. The apparatus includes a light source, a spectrometer, and a lens assembly, the lens assembly including a light collecting element and a mirror, the light source configured to excite electrons in the one or more sensors, and the spectrometer configured to detect surface plasmon resonance events. In some embodiments, the spectrometer is configured to detect one or more analytes. In some embodiments, the one or more analytes include nucleic acids, cell-free nucleic acids, DNA, RNA, miRNA, oligonucleotides, peptide nucleic acids, proteins, or cells. In some embodiments, each sensor of the one or more sensors includes metal nanoparticles. In some embodiments, the metal nanoparticles bind to one or more analytes. In some embodiments, the binding of the metal nanoparticles to the one or more analytes results in a change in refractive index. In some embodiments, the change in refractive index is due to surface plasmon resonance (SPR). In some embodiments, the apparatus further includes one or more mirrors for directing the path of light emitted by the light source. In some embodiments, the apparatus further comprises a stage and an articulating arm, the articulating arm being mechanically coupled to the stage, the articulating arm being configured to move the stage in multiple dimensions to intersect the optical path at one or more predetermined points in space. In some embodiments, the metal nanoparticles are immobilized on a surface. In some embodiments, the surface is on the stage. In some embodiments, the surface is within a sample holding device, including but not limited to a cartridge, cassette, or module designed to process fluid or solid samples. In some embodiments, the surface is transparent.

[0021] In some embodiments, a method for detecting one or more analytes in one or more samples is described. In some embodiments, the method includes the steps of mounting one or more samples on a surface that includes one or more sensors, and then placing the surface in an apparatus that includes a stage, a light source, and a spectrometer, where the one or more samples are on one or more surfaces, and each surface of the one or more surfaces includes one or more sensors that include immobilized metal particles. The method further includes irradiating the surface with light from a light source of a series of wavelengths and measuring absorbance, transmittance, or extinction data of the immobilized metal particles. After irradiating the surface with light from the light source, the method also includes measuring absorbance, transmittance, or extinction data of the immobilized metal particles, and comparing the absorption, transmittance, or extinction spectrum of the immobilized metal particles before and after irradiation of the analyte of interest.

[0022] In some embodiments, the one or more analytes include nucleic acids, cell-free nucleic acids, DNA, RNA, miRNA, oligonucleotides, peptide nucleic acids, proteins, or cells. In some embodiments, the one or more samples, the one or more analytes, or the surface are first exposed to a thermal, mechanical, chemical, or biological treatment to lyse cells. In some embodiments, the analytes are concentrated through a concentration or filtration step. In some embodiments, the filtration step may include any number of tangential flow or ultrafiltration steps. In some embodiments, the concentration step may pool multiple cell populations or material derived from cell populations. In some embodiments, the one or more analytes include bacteria, viruses, human cells, and / or the genetic material of each of the foregoing. In some embodiments, the comparing step includes observing an optical peak shift when bacteria, viruses, human cells, or their respective genetic material are present.

[0023] In some embodiments, a method for detecting one or more analytes at a plurality of sensors is described. The method includes mounting the plurality of sensors to an apparatus that includes a stage, a light source, an articulating arm, and a spectrometer, each of the plurality of sensors includes a surface that includes immobilized metal particles, and each sensor in the plurality of sensors is physically isolated from all other sensors in the plurality of sensors. In some embodiments, the method further includes moving the stage by the articulating arm so that a sensor in the plurality of sensors intersects a beam path emanating from the light source. The method then includes irradiating the sensor surface with a series of wavelengths of light from the light source, the light traveling along the beam path, and acquiring absorbance, transmittance, or extinction data of the surface by the spectrometer. The method further includes comparing the absorption, transmittance, or extinction spectrum of the sensor to a reference spectrum.

[0024] In some embodiments, the one or more analytes include nucleic acids, cell-free nucleic acids, DNA, RNA, miRNA, oligonucleotides, peptide nucleic acids, proteins, or cells. In some embodiments, the one or more samples, the one or more analytes, or the surface are first exposed to a thermal, mechanical, chemical, or biological treatment to lyse cells. In some embodiments, the analytes are concentrated through a concentration or filtration step. In some embodiments, the filtration step may include any number of tangential flow or ultrafiltration steps. In some embodiments, the concentration step may pool multiple cell populations or material derived from cell populations. In some embodiments, the one or more analytes include bacteria, viruses, human cells, and / or the genetic material of each of the foregoing. In some embodiments, the comparing step includes observing an optical peak shift when bacteria, viruses, human cells, or their respective genetic material are present.

[0025] operation FIG. 1 illustrates an embodiment of an apparatus for detecting an analyte described in this disclosure, showing the optical path and optical design of light emitted by light source 10. In this embodiment, light is emitted by light source 10, reflects off mirror 20, and reflects off precision mirror 30. The light that passes through precision mirror 30 then passes through stage 50, where it is then reflected by mirror 40 and directed to fiber optic cable 70, with the optical path terminating at spectrometer 80. In some embodiments, translation arm 60 is configured to move nest 50 to extend the stage to load a sample or to change the particular sample or location analyzed by the spectrometer. In some embodiments, precision mirror 30 is further configured with optical elements configured to focus and direct the light beam emitted by light source 10. These additional embodiments include two lenses in the optical stage, one to focus and condition the light before it hits the sample, and the other to focus the light that passes through the spectrometer onto the sample. Light passing through a sample mounted on stage 50 produces absorbance data that is collected by spectrometer 80. The wavelength shift that occurs when an analyte binds to a metal nanoparticle can also be collected.

[0026] FIG. 2 shows an embodiment of a light source comparison in terms of intensity as a function of wavelength. In some embodiments, the light source may be referred to as a lamp. It may be advantageous to have a light source capable of emitting a broader range of light outside of the standard visible spectrum. In some embodiments, a collection of absorbance characteristics at higher near infrared and infrared wavelengths is provided.

[0027] 3 and 4 show embodiments of the present disclosure, where the articulating arm is operatively connected to the stage. In some embodiments, the stage may further include a sample region. In FIG. 3, the articulating arm extends the stage to a position outside the assembly housing to load a sample onto the stage and sample region. Once loaded, the articulating arm retracts and the stage and sample region move within the housing. FIG. 4 shows the sample region and stage within the device. In some embodiments, the sample region is positioned between the optical paths generated in some embodiments of the present disclosure. In some embodiments, the articulating arm is capable of moving the stage to position the sample region within the optical path. In some embodiments, multiple samples are loaded onto the sample region. In some embodiments, the movement of the sample region allows a new sample to be placed in the optical path.

[0028] FIG. 5 illustrates an embodiment of a GUI of the present disclosure, which is a graphic user interface (GUI) that allows a user to input settings and select options to modify the instrument's automated sample processing and analysis algorithms. Step 1 illustrates the splash screen of the present disclosure. Step 2 allows the user to select whether to run a test or select individual parameters based on the experimental design. Setup 1 allows the user to select and input the coordinates of relevant samples and controls. Setup 2 sets the integration time for the spectrometer measurement, while Setup 3 allows the user to manually input parameters associated with the peak detection algorithm. Finally, Setup 4 allows the user to save or load settings from a file.

[0029] FIG. 6 illustrates an embodiment of the present disclosure in which a user selects desired settings for a device, runs the device to generate output, and views the output results.

[0030] FIG. 7 illustrates an embodiment of the present disclosure where user menu options direct to subsequent or previous menu screens based on user input. In some embodiments, screen 1 advances to screen 2, which can load either screen 3 or screen 8 depending on whether the user selects "Test" or "Setup". The user at screen 3 can advance to either screen 4 or screen 8 depending on which menu option is selected. Screen 4 advances to screen 5, where the user can then abort and return to screen 4 or allow the test to run to completion and view the results on screen 6. Screen 6 allows details of the run to be viewed on screen 7.

[0031] FIG. 8 shows a series of cable inputs in an embodiment of the present disclosure. These cable inputs may include a power input and at least one data output port. In some embodiments, there may be multiple data output ports. FIG. 9 shows the light source and spectrometer assembly of the present disclosure. Additionally, FIG. 10 shows the optical path and light path according to the present disclosure.

[0032] FIG. 11 illustrates the placement of a sample cassette and a sample chip on a stage of an apparatus of the present disclosure. A sample, such as a biological or environmental sample, is introduced to the sample chip. The sample chip includes a region having a plasmonic nanomaterial, such as metal nanoparticles, configured to bind to at least one analyte to be detected. Once the sample chip and sample cassette are placed on the stage, the stage is stored within a housing of the analyte detection device. An absorption spectrum is collected while directing a light path through the plasmonic nanoparticle region.

[0033] The unique physical properties of plasmonic nanomaterials, such as metal nanoparticles, allow for the convenient detection of specific analytes through surface plasmon resonance (SPR) or localized surface plasmon resonance (LSPR). Analysis of the absorbance of an analyte when bound to the plasmonic nanoparticles can rapidly and effectively diagnose certain disease conditions.

[0034] In some embodiments, provided herein are methods for detecting analytes. In some embodiments, the methods include loading a sample into an apparatus that includes a stage, a light source, a spectrometer, and a lens assembly, where the sample includes a surface that includes immobilized metal particles and analyte complexes. Light is then emitted by the light source, where the light is configured to excite electrons at a specific wavelength, and the wavelength shift is obtained by the spectrometer to generate absorbance, transmittance, or extinction data, where the apparatus is configured to direct the light to follow the optical path.

[0035] 12-14 show a series of GUI menu, setup, measurement, and output displays of the present disclosure.

[0036] Although specific examples have been described, these examples are presented as examples only and are not intended to limit the scope of the present disclosure. Indeed, the novel methods and systems described herein may be embodied in other various forms. Furthermore, various omissions, substitutions, and modifications in the systems and methods described herein may be made without departing from the spirit of the present disclosure. The appended claims and their equivalents are intended to cover such forms or modifications as fall within the scope and spirit of the present disclosure.

[0037] It should be understood that features, materials, properties, or groups described in connection with a particular embodiment or example are also applicable to any other embodiment or example described in this section or elsewhere in this specification, except to the extent inconsistent therewith. All of the features disclosed in this specification (including any of the accompanying claims, abstract, and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. Protection is not limited to the details of any of the foregoing examples. Protection extends to any novel, or any novel combination of, features disclosed in this specification (including any of the accompanying claims, abstract, and drawings), or any novel, or any novel combination of steps of any method or process so disclosed.

[0038] Moreover, certain features described in this disclosure in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features described in the context of a single implementation can also be implemented separately in multiple implementations or in any suitable subcombination. Furthermore, although features may be described above as acting in a particular combination, in some cases, one or more features from a claimed combination can be excluded from the combination, and the combination may be claimed as a subcombination or a variation of the subcombination.

[0039] Furthermore, although operations may be shown in the figures or described in the specification in a particular order, such operations need not be performed in the particular order shown, or in any sequential order, to achieve the desired results, nor do all operations need to be performed. In particular, GUI elements or elements presented in connection with display to a user may be presented in any particular order to achieve the desired results. Other operations not shown or described may be incorporated into the illustrated methods and processes. For example, one or more additional operations may be performed before, after, simultaneously with, or between any of the described operations. Furthermore, operations may be reordered or reordered in other implementations. Those skilled in the art will appreciate that in some examples, the steps actually performed in the illustrated and / or disclosed processes may differ from those shown in the figures. In some examples, some of the above steps may be removed or other steps may be added. Furthermore, the features and attributes of the specific examples disclosed above may be combined in different ways to form additional examples, all of which are within the scope of the present disclosure. Also, the separation of the various system components in the above implementations should not be understood as requiring such separation in all implementations, and it should be understood that the described components and systems may generally be integrated together in a single product or packaged together in multiple products. For example, any of the components for the optical path systems described herein may be provided separately or integrated together (e.g., packaged together or attached together) to form an analyte analysis system.

[0040] For the purpose of this disclosure, certain aspects, advantages, and novel features are described herein.Not all such advantages can be achieved according to any particular example.Thus, for example, a person skilled in the art will recognize that the present disclosure can be embodied or carried out in a manner that achieves one advantage or group of advantages as taught herein, without necessarily achieving other advantages as taught or suggested herein.

[0041] Conditional language such as "can," "could," "might," or "may" is typically intended to convey that certain features, elements, and / or steps are included in a particular example and not in other examples, unless specifically stated to mean otherwise and unless understood to mean otherwise in the context in which it is used. As such, such conditional language is typically not intended to imply that the features, elements, and / or steps are required in any way in one or more examples, nor is it intended to imply that one or more examples necessarily include logic for determining, with or without user input or prompting, whether those features, elements, and / or steps are included in or performed in any particular example.

[0042] Conjunctive language, such as the phrase "at least one of X, Y, and Z," unless specifically stated otherwise, is understood in its ordinary context to convey that an item, term, etc., can be either X, Y, or Z. As such, such conjunctive language is not normally intended to imply that a particular example requires the presence of at least one of X, at least one of Y, and at least one of Z.

[0043] Language indicating degree as used herein, such as the terms "approximately," "about," "typically," and "substantially," refers to a value, amount, or characteristic that approximates a stated value, amount, or characteristic and that would perform a desired function or achieve a desired result if that value, amount, or characteristic were assumed.

[0044] The scope of the present disclosure is not intended to be limited by the specific disclosure of preferred examples in this section or elsewhere herein, but may be defined by the claims presented in this section or elsewhere herein, or presented in the future. The claim language should be interpreted broadly based on the language employed in the claims, and not limited to the examples described in this specification or during the prosecution of this application, which examples should be interpreted as non-exclusive.

[0045] Although the above invention has been described with respect to certain preferred embodiments, other embodiments will be apparent to those skilled in the art. Furthermore, other combinations, omissions, substitutions and modifications will be apparent to those skilled in the art in view of the disclosure herein. Therefore, the present invention is not intended to be limited by the description of the preferred embodiments, but is instead defined by reference to the appended claims. All references cited herein are incorporated by reference in their entirety.

[0046] The terminology used in the description presented herein is not intended to be interpreted in any limiting or restrictive manner, and refers to its ordinary meaning as understood by those skilled in the art in light of the present specification, unless otherwise indicated. Moreover, an embodiment may include, consist of, or consist essentially of several novel features, no single one of which is considered to be the sole cause of its desirable attributes or essential to carrying out the embodiments described herein. As used herein, the section headings are for organizational purposes only and should not be construed as limiting the described subject matter in any way. All literature and similar materials cited in this application, including but not limited to patents, patent applications, papers, books, treatises, and Internet web pages, are expressly incorporated by reference in their entirety for all purposes. In the event that the definition of a term in the incorporated references differs from the definition provided in the present teachings, the definition provided in the present teachings shall prevail. It will be understood that there is an implied "about" before the temperatures, concentrations, times, etc. discussed in the present teachings, such that minor and insubstantial deviations are within the scope of the present teachings herein.

[0047] While the present disclosure is in the context of certain embodiments and examples, those skilled in the art will understand that the present disclosure extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses of the embodiments, as well as obvious modifications and equivalents thereof. Moreover, while several variations of the embodiments have been shown and described in detail, other modifications that are within the scope of the present disclosure will be readily apparent to those skilled in the art based on the present disclosure. It is also contemplated that various combinations or subcombinations of specific features and aspects of the embodiments may be made and still fall within the scope of the present disclosure. It should be understood that various features and aspects of the disclosed embodiments may be combined with or substituted for one another to form various modes or embodiments of the present disclosure. Thus, it is intended that the scope of the present disclosure disclosed herein should not be limited by the specific disclosed embodiments described above.

Claims

1. 1. An apparatus for detecting one or more analytes in one or more sensors, comprising: A light source and a spectrometer; Lens assembly and wherein the lens assembly comprises a focusing element and a mirror, the light source is configured to excite electrons in the one or more sensors, and the spectrometer is configured to detect surface plasmon resonance events.

2. The apparatus of claim 1 , wherein the spectrometer is configured to detect the one or more analytes.

3. 10. The device of claim 1, wherein the one or more analytes comprise a nucleic acid, a cell-free nucleic acid, DNA, RNA, miRNA, an oligonucleotide, a peptide nucleic acid, a protein, or a cell.

4. The apparatus of claim 1 , wherein each sensor of the one or more sensors further comprises metal nanoparticles.

5. The device of claim 4 , wherein the metal nanoparticles bind to the one or more analytes.

6. The apparatus of claim 1 , wherein the apparatus further comprises one or more mirrors for directing the path of light emitted by the light source.

7. further comprising a stage and an articulated arm mechanically coupled to the stage; The apparatus of claim 6 , wherein the articulating arm is configured to move the stage in multiple dimensions to intersect the optical path at one or more predetermined points in space.

8. The device of claim 4 , wherein the metal nanoparticles are immobilized on a surface.

9. The device of claim 8 , wherein the surface is transparent.

10. 1. A method for detecting one or more analytes in one or more samples, comprising: mounting the one or more samples on a surface including one or more sensors; placing the surface in an apparatus comprising a stage, a light source, and a spectrometer, wherein the one or more samples are on one or more surfaces, each surface of the one or more surfaces comprising one or more sensors comprising immobilized metal particles; illuminating the surface with light from the light source at a range of wavelengths; measuring absorbance, transmittance, or extinction data of the immobilized metal particles; comparing the absorption, transmission, or extinction spectra of the immobilized metal particles before and after irradiation of the analyte of interest; A method comprising:

11. 11. The method of claim 10, wherein the one or more analytes comprise a nucleic acid, a cell-free nucleic acid, DNA, RNA, miRNA, an oligonucleotide, a peptide nucleic acid, a protein, or a cell.

12. 11. The method of claim 10, wherein the one or more samples, one or more analytes, or the surface are first exposed to a thermal, mechanical, chemical, or biological treatment to lyse cells.

13. The method of claim 11 , wherein the analyte is concentrated through a concentration or filtration step.

14. The method of claim 10 , wherein the one or more analytes comprise bacteria, viruses, human cells, and / or their respective genetic material.

15. The method of claim 10 , wherein the comparing step comprises observing an optical peak shift in the presence of bacteria, viruses, human cells, and / or their respective genetic material.

16. 1. A method for detecting one or more analytes in a plurality of sensors, comprising: mounting the plurality of sensors on an apparatus comprising a stage, a light source, an articulating arm, and a spectrometer, each of the plurality of sensors comprising a surface comprising immobilized metal particles, each sensor in the plurality of sensors being physically isolated from every other sensor in the plurality of sensors; moving the stage with the articulated arm so that a sensor in the plurality of sensors intersects a beam path emitted from the light source; emitting a series of wavelengths of light from the light source onto the sensor surface, the wavelengths traveling along the beam path; acquiring absorbance, transmittance, or extinction data for the surface with the spectrometer; comparing the absorption, transmission, or extinction spectrum of the sensor with a reference spectrum; A method comprising:

17. 17. The method of claim 16, wherein the one or more analytes comprise a nucleic acid, a cell-free nucleic acid, DNA, RNA, miRNA, an oligonucleotide, a peptide nucleic acid, a protein, or a cell.

18. The method of claim 16, wherein one or more analytes or the surface are first exposed to a thermal, mechanical, chemical, or biological treatment to lyse cells.

19. 17. The method of claim 16, wherein the analyte is concentrated via a concentration or filtration step.

20. 17. The method of claim 16, wherein the reference spectrum is baseline data of the metal particles acquired by the spectrometer before exposure and incubation with a target analyte.

21. 17. The method of claim 16, wherein the one or more analytes comprise bacteria, viruses, human cells and / or their respective genetic material.

22. 17. The method of claim 16, wherein the comparing step comprises observing an optical peak shift in the presence of bacteria, viruses, human cells, and / or their respective genetic material.