Low-cost hyperspectral imaging system and method for point-of-care biosensor

Abstract

A low-cost point-of-care imaging system with high spectral and spatial resolution and a method thereof are provided. The light emitted by the sensor passes through one set of lenses, passes through or is reflected from the diffraction grating, and then is focused onto the detector by the other set of lenses. The design of the system allows the use of a low-cost detector, such as a photosensitive diode linear array or a CMOS camera sensor, so that the imaging system can be applied to the scene of the point of care with sufficiently low cost. The imaging system can reach a high spectral resolution in a high spectral range (less than 20 nanometers), and especially a sufficient spatial resolution in a one-dimensional direction, without time delay and with cost effectiveness.

Description

Related applications can be referenced together.

[0001] This application claims priority and enjoys the benefit of U.S. Provisional Patent Application Serial No. 63 / 627216, filed January 31, 2024, entitled "SYSTEM AND METHOD FOR INEXPENSIVE HYPERSPECTRALIMAGING OF POINT-OF-CARE BIOSENSORS", the entire disclosure of which is incorporated herein by reference. Background Technology

[0002] This disclosure pertains to blood testing at nursing sites.

[0003] Point-of-care (POC) diagnostics and monitoring has become a solution for many hospitals, clinics, patients, and physicians who require rapid and reliable results for various biomarkers. In addition to rapid and reliable data, POCs offer a low-cost and low-maintenance solution, reducing the financial burden on healthcare systems. The low cost allows for multiple, regular tests for specific patients, such as those with chronic diseases, enabling them and their physicians to make informed decisions about feasible treatment options based on hard data on biomarker concentrations.

[0004] This anticipates achieving spectral or spatial resolution, and ideally both, in the field of optical sensing technology, including optical sensing applications at the point of care. Achieving both typically involves using multispectral or hyperspectral cameras, which is prohibitively expensive in practice for many optical sensing applications, including using fluorescence emission from sensors or spectral transmission / absorption from sensors to quantify biomarker concentrations for point-of-care diagnostics.

[0005] Sufficient spectral resolution is typically achieved using spectrometers. These can achieve spectral resolution of 10 nanometers or better and are available in convenient small packages costing a few hundred dollars each. However, they do not provide spatial resolution, meaning they capture any light that enters their numerical aperture, effectively making them single-point imagers in length space. If you want to quantify the electromagnetic spectrum at different points in space, you can use a separate spectrometer at each point; or combine an external motorized optics unit with a single spectrometer to scan different points in space. Both solutions have drawbacks, including increased cost and complexity, and reduced reliability. In the case of scanning optics, temporal resolution is also a drawback; for example, the time required to acquire the spectrum at each desired point in space can severely limit the quantization of the spectrum or time-sensitive transients in space.

[0006] Good two-dimensional (x and y) spatial resolution is typically achieved through image sensors, such as commercially available digital cameras. However, this usually involves only three broadband spectral filters—in the red, green, and blue regions—so the spectral information is limited to one red reading, one blue reading, and one green reading per "pixel," resulting in very poor spectral resolution, i.e., three broadband bands, each with a wavelength of approximately 100 nanometers. Multispectral imaging has recently been used to improve spectral resolution—typically increasing the number of spectral bands to between four and 15 while reducing the width of these bands. Moreover, multispectral imaging is typically achieved through filters, either on the imaging chip itself or placed in front of the imaging chip along with external adjustable filters (such as filter wheels). Despite the improved spectral resolution, multispectral imaging still faces several challenges, including: increased filter costs, especially when custom-designed filters are directly deposited onto the imaging chip; insufficient filter resolution or spectral bandwidth to quantify common phenomena, such as distinguishing between oxyhemoglobin and deoxyhemoglobin in blood; often discontinuous spectral bands; and time delays in tunable filter cases—reducing the ability to quantify transient phenomena.

[0007] Hyperspectral imagers possess more, and sometimes fully continuous, spectral bands—thus achieving higher spectral resolution, typically 10–20 nanometers; and while they may sacrifice some spatial resolution, this remains generally sufficient for most applications. However, due to their complexity, they typically cost tens of thousands of dollars. This is prohibitively expensive for many optical sensing applications, especially those intended for broad applications such as point-of-care diagnostics, for example, using the fluorescence emission or electromagnetic absorption of sensors to quantify biomarker concentrations.

[0008] There are greater cost constraints for home-based point-of-care diagnostic systems intended for non-professional use. For this application, multispectral and hyperspectral imaging systems are approximately two orders of magnitude more expensive (over $10,000, while the expected cost is $100 or less).

[0009] There is a need for a low-cost point-of-care imaging system with high spectral and spatial resolution. Summary of the Invention

[0010] A low-cost point-of-care imaging system and method with high spectral and spatial resolution is disclosed. Emitted light from a sensor passes through a set of mirrors, is reflected by or through a diffraction grating, and is then focused onto a detector by another set of mirrors. The system design allows for the use of low-cost detectors, such as photodiode linear arrays or CMO camera sensors, enabling the imaging system to be applied to point-of-care settings at a sufficiently low cost. This imaging system achieves high spectral resolution in the high spectral range (less than 20 nanometers), and, particularly, sufficient spatial resolution in one dimension, with no time delay and cost-effectiveness. Attached Figure Description

[0011] Figure 1 This is an example system modeled using ray tracing software.

[0012] Figure 2 It is a map showing the various wavelengths emitted by a biosensor within the visible range and their corresponding focal points on the detector / image plane.

[0013] Figure 3 It is a map showing the various wavelengths emitted by three different biosensors within the visible range and their corresponding focal points on the detector / image plane.

[0014] Figure 4 yes Figure 1 The illustrated embodiment shows an example output on a CMOS monochrome 2D camera sensor.

[0015] Figure 5 yes Figure 4 The spectrum output by the central transmitter in the example shown is in Figure 4 Quantization is performed within the rectangular area shown.

[0016] Figure 6 Showing the characterization Figure 1 The transmittance of various example filters in the system embodiments shown.

[0017] Figure 7 Showing Figure 1 The example results of the system embodiment shown have each transmitter covered with a green filter.

[0018] Figure 8 Showing Figure 1 The example results of the system embodiment shown have each transmitter covered with an OG515 filter.

[0019] Figure 9 Showing Figure 1 The example results of the system embodiment shown have each transmitter covered with an OG550 filter.

[0020] Figure 10 Showing Figure 1The example results of the system embodiment shown have each transmitter covered with an OG570 filter.

[0021] Figure 11 Shown in Figure 4 Quantize and standardize within the rectangular area Figure 5 The emitted intensity of the emitted spectrum is shown.

[0022] Figure 12 This is a line diagram of an example embodiment of the disclosed system.

[0023] Figure 13a This is a top view of the box, showing three 0.5 mm sensor clusters arranged along a line.

[0024] Figure 13b This is a top view of the box, showing the eight 0.5 mm sensor clusters that are not all arranged in a single line.

[0025] Figure 14a This is a side view of an example embodiment of the disclosed system.

[0026] Figure 14b This is an illustration of an example embodiment of the disclosed system.

[0027] Figure 15 Showing Figure 14b The example output of the system embodiment shown shows a single white LED with an aperture of 0.5 mm illuminating an optically clear cuvette (i.e., a reference measurement) before the introduction of a human blood sample.

[0028] Figure 16 Showing Figure 14b The system embodiment shown is in relation to Figure 15 Example output under the same conditions but with human blood samples included.

[0029] Figure 17 Showing according to Figure 15 and Figure 16 The blood sample absorption spectrum calculated from the image shows the characteristic absorbance of oxyheme.

[0030] Figure 18 This is a diagram illustrating an example of a large sensor.

[0031] Detailed description

[0032] The purpose of this disclosure is to provide a low-cost hyperspectral imaging system and method that can be used in point-of-care imaging systems.

[0033] A point-of-care imaging system includes a lens for calibrating the emission of one or more sensors, a diffraction grating, another lens for focusing the emission onto a detector, a detector, and a housing for housing and securing these components.

[0034] In one embodiment, a sensor platform may be manufactured as part of a housing, accommodating at least one sensor and configured to allow insertion and removal of the sensor from the imaging system. In another embodiment, a computer or control system may be housed within the housing and connected to the detector, capable of acquiring and processing data from the detector. This processing may include simply transmitting data to an external computer system, or it may involve more extensive processing on the point-of-care imaging device, ranging from basic display of data detected by the detector to comprehensive analysis of the nature of one or more sensors based on the detector data. In one embodiment, the processing may also include detecting defective or poorly positioned sensors. In one embodiment, an automated system may be used to insert, remove, or integrate sensors into the imaging system.

[0035] Figure 1 This is an example system modeled using ray tracing software. (Reference) Figure 1 The example system 100 is shown, modeled here as a single optical emitter 120, a 0.5 mm diameter fluorescent biosensor—the excitation source is omitted for clarity. An initial lens 130, in this example a ½-inch diameter achromatic doublet, is used to calibrate the electromagnetic emission 125 from the sensor, in this example visible light in the range of 450 nm to 600 nm, which is then reflected or transmitted from a diffraction grating 140 to separate the combined wavelengths. In this example, the diffraction grating 140 is a 1200 line frets / mm reflection grating, but in other embodiments it could be a transmission grating. A second lens 135, in this example a ½-inch diameter achromatic doublet, then focuses these spatially separated wavelengths onto a detector 115, in this example forming a 450 nm emission convergence point 110 and a 600 nm emission convergence point 105. Detector 115 can be a one-dimensional detector, such as a linear photodiode array, or a two-dimensional detector, such as a complementary metal-oxide-semiconductor (CMOS) sensor or other known imaging sensor technology. The doublet lens 135 between the diffraction component and the detector is a fixed-focusing component that can be held in a fixed position. Preferably, it is a lens whose wavelength and position-dependent distortion are minimized, such as an achromatic lens.

[0036] In one embodiment, the lenses are identical and configured for 1:1 magnification, so that the diameter of the focal point on the detector or image plane is also approximately 0.5 mm. In other embodiments, the lenses may be of different types and sizes.

[0037] Figure 2 This is a map showing the various wavelengths of visible light emitted by the biosensor and their corresponding focal points on the detector / image plane. Note that the separation of these focal points provides spectral resolution.

[0038] according to Figure 2 In this example, the 7 mm wavelength scattering on the detector / image plane shown here achieves a spectral resolution of approximately 20 nm, as can be seen from the separation of the 512 nm and 530 nm image focal points. Furthermore, the linear scattering (7 mm) can be easily extended to obtain better wavelength resolution, or scaled down to fit a smaller photodetector array, but at the cost of wavelength resolution.

[0039] The length and resolution in the spectral space can also be modified by adjusting the apparent size of the optical emitter. In this example, it is a circular dot with a diameter of 0.5 mm that produces a focal point on the detector corresponding to a single wavelength, which is associated with the emitter size. If the dot size is reduced—for example, by external illumination on a smaller portion of the corresponding object, by adjusting the aperture, or by reducing the size of the emitter itself—then the focal point size in the wavelength space on the detector becomes smaller, allowing for larger wavelength spacing and improved resolution, provided the pixel density on the image sensor is sufficient. The opposite is true if the emitter size is increased.

[0040] Figure 2 The image shows the convergence of light rays traced from a 0.5 mm object. Figure 1 The corresponding optical system shown is simple, using an achromatic doublet lens, and suffers from significant aberrations due to its non-optimized optics. Therefore, a 0.5 mm circular object imaged by the lens appears slightly blurred in the image plane, with a focal point size averaging approximately 0.6 mm in diameter. This reduces resolution because the larger focal point formed on the detector overlaps with adjacent wavelengths. Better resolution can be achieved if the optical system is designed so that the focal point size in the image plane is as representative as possible of the object (emitter) size. In this example, the resolution gain is particularly noticeable at longer wavelengths, where the focal point is farther from the lens axis and therefore more susceptible to aberrations. For example, as... Figure 2 As shown, the 600 nm aggregate point is significantly larger than the 450 nm aggregate point.

[0041] A smaller focal size on the detector can also be achieved by downscaling the object. Optimization of the optical system can also include adjusting the magnification to reduce the object size in the image plane by a certain factor (i.e., a magnification less than 1 as defined here). Figure 1In the simple system shown, the ratio of the lens focal lengths determines the magnification. If the lens between the grating and the image plane is changed to a shorter focal length, the magnification decreases, and each focal point formed on the detector becomes smaller. However, the spacing between the diffraction focal points, which is proportional to the grating line density and thus the resolution, does not increase. Therefore, the effect of downscaling the emitter is to increase the dynamic range of the system; that is, the wavelength range of the system will increase because the diffraction pattern will be smaller, and given a two-dimensional sensor of the same size, more spectrum will fit into its detector.

[0042] The wavelength range of a system is determined by many factors, including the resolution, magnification, and lens characteristics (including lens size) discussed above, as well as the size of the detector. For example, a larger detector in wavelength space (vertical in the example above) will achieve a greater wavelength range. Similarly, the length range of a system depends on similar factors, with a larger detector achieving a greater length range.

[0043] If the detector array is two-dimensional, such as a CMOS camera sensor, the spectrum can be improved by averaging pixels corresponding to a given narrow wavelength range; eliminating pixels at most of the emitter edges (e.g., if unwanted biosensor emitter edge effects exist, such as differences in rays relative to the central region due to the meniscus at the edges); or eliminating pixels at the edges of the aforementioned focal points that are only partially illuminated. Similar results can be achieved using a one-dimensional optical detector array (e.g., a linear photodiode array) combined with averaging and physical detector masking (which is also possible in two-dimensional arrays).

[0044] Figure 3 It is a map showing the various wavelengths emitted by three different emitters or biosensors within the visible range and their corresponding focal points on the detector / image plane. The separation of focal points in the vertical direction gives spectral resolution, while the separation in the horizontal direction gives spatial resolution, which is needed to distinguish one sensor from another, or to distinguish one or more large sensor regions.

[0045] This disclosure is primarily driven by a need in various fields to acquire spectral information from a series of single-point emitters or a continuous array of emitters—which can be imaged as a series of independent emitters using the aforementioned techniques (pinhole, illumination)—these emitters are primarily arranged along a line. In a preferred embodiment, the emitter line is primarily perpendicular to the diffraction axis of the grating.

[0046] In an example of a series of unconnected biosensors in a linear microfluidic channel on a diagnostic box, the changes in fluorescence emission and / or transmission / absorbance of the sensor before and after exposure to the biofluid in the microfluidic channel can reflect the concentration of the analyte detected by the biosensor.

[0047] Prior to this disclosure, a typical approach—to avoid the high cost of multiple spectrometers—was to select a narrow band of emission spectrum that best reflects the variation of each sensor's emission spectrum with analyte concentration. This typically responds to a single spectral peak. A bandpass filter is then selected to match the wavelength of that peak, and a single photodiode or other photodetector is coupled in. This approach has several drawbacks, the main one being the inability to acquire a broader spectrum, which would allow for more precise signal conversion with additional data collected, such as using artificial intelligence (AI) to determine additional characteristics of this data, more accurately converting spectral changes into concentration changes. In effect, it freezes the design of field instruments, limiting new sensors / emitters to quantization only at selected wavelengths for each detector, significantly restricting the design or accuracy of new sensors.

[0048] In the disclosed system, if multiple emitters are present, or in this case, biosensors, they can be spatially distinguished from each other in the horizontal direction while maintaining their respective spectral resolution. This effectively allows for hyperspectral imaging required for real-time multi-sensor optical detection; thus, it possesses the ability to rapidly quantify changes in phenomena.

[0049] Furthermore, corresponding to the illumination or light source, the zero-order diffraction grating itself (e.g., for absorbing broadband light from the emitter and for absorbing narrow-band light from the fluorescence emitter) can be sent to the detector array, which, in the case of a reflective or transmissive diffraction grating, can be adjacent to the emitter or directly opposite it. This allows for self-calibration, for example, if any change occurs in the light source, it can be processed simultaneously with other illuminated focal points. Similar self-calibration can be achieved by imaging only its light source in the first-order diffraction (e.g., in a specific region where there are no biosensors).

[0050] Although only three emitters are shown in the system embodiment illustrated here, it is clear that many more can be characterized simultaneously. Simply by reducing the space between the emitters, at least 10 can be characterized in this embodiment without other changes. Further, for example, changing the magnification, lens characteristics and number, and detector characteristics and number, can allow for the simultaneous imaging of dozens or even hundreds of emitters, either single-point or multi-point. Imaging of multiple orders of diffraction, not just the first-order diffraction imaged here, as described above, is also possible. Furthermore, multiple gratings with different characteristics can be placed adjacent to each other, thereby allowing imaging of different emitters at different spectral resolutions and ranges.

[0051] Some overlap between emitters in the length space is permissible. Ideally, the degree of overlap should be limited such that one or more pixels across the length space for each emitter are unique.

[0052] In addition to physical separation of the linearly arranged biosensors, individual biosensors can be further separated by being queried one at a time. For example, if each is a fluorescent biosensor that needs to be excited, it can be excited one at a time. This allows them to be placed very close to each other, even if the spatial resolution is insufficient to distinguish them. This will sacrifice temporal resolution, as the image will no longer be a single, quick screenshot.

[0053] Figure 4 yes Figure 1 The illustrated embodiment shows an example output on a CMOS monochrome 2D camera sensor (but a standard color camera can also be easily used). Figure 4 Shown in Figure 1 The example system output shown is based on a CMOS monochrome 2D camera sensor and features three 0.5 mm emitters, each spaced 2 mm apart on the emission plane. In this example output, each of the three emitters is a broadband light-emitting diode (LED) light source, with the image of the bottom emitter slightly obscured in the optical path by a screw head. Image analysis is then used to... Figure 4 The vertical pixels within the white rectangle are averaged; that is, the average value is obtained by averaging across pixels of the same wavelength. Figure 5 The spectrum shown is in very good agreement with the LED spectrum measured using a commercial spectrometer, although it is in pixel space rather than wavelength space (conversion to the latter requires characterization of the system as described below). Figure 5 yes Figure 4 The spectrum output by the central transmitter in the example shown is in Figure 4 Quantization is performed within the rectangular area shown.

[0054] At this stage, the wavelength corresponding to a single pixel is unknown. The system must be calibrated to find the nanometer-scale pixel-to-wavelength conversion. This can be accomplished by applying known wavelength characteristics, such as placing a colored glass filter with known transmission capabilities between the transmitter and detector. Example filters are shown below. Figure 6 As shown. Figure 6 Showing the characterization Figure 1 The transmittance of various example filters in the illustrated system embodiment was measured using a commercial spectrometer. In addition, Figure 7-10 The system output is shown when each of these is applied to each transmitter. Figure 7 Showing Figure 1 The example output of the system embodiment shown has each transmitter covered with a green filter. Figure 8 Showing Figure 1 The example output of the system embodiment shown has each transmitter covered with an OG515 filter. Figure 9 Showing Figure 1 The example output of the system embodiment shown depicts each transmitter covered with an OG550 filter. Finally, Figure 10 Showing Figure 1 The example output of the system embodiment shown has each transmitter covered with an OG570 filter.

[0055] The relationship between intensity and pixels was quantized using the same linear averaging technique described above (within a rectangular region). When normalized to... Figure 5 When considering a spectral light source, comparison can be made between the light sources in the spectrum. Figure 6 The transmission function of each filter determines the algorithm for converting a pixel to a wavelength. Other embodiments, algorithms, or techniques can be used to calibrate and quantify the intensity of each pixel and convert the pixel to the corresponding wavelength.

[0056] Figure 11 The intensity was displayed for each filter quantized and then normalized to... Figure 5 The emitter / light source spectrum in the image. Figure 11 This demonstrates that the system can reproduce commercial-grade spectrometers with high accuracy. Figure 6 The output of the system. Although the total cost of the system components is $250, this can be significantly reduced by selecting different components and purchasing in bulk.

[0057] Figure 12 These are illustrations of example embodiments of the disclosed system. According to... Figure 12 An embodiment of system 1200 is disclosed, showing a CMOS camera module 1210, a lens 1215, and a diffraction grating 1220. An emission plane 1205 is also shown, which is a box with three sensor focal points as seen from the edge.

[0058] Figure 13a The box, viewed from above, shows three 0.5 mm sensor focal points. Figure 13b A similar box is shown as a top view, but with sensor clusters not aligned in a line. The disclosed system does not require all sensors to be aligned in a line, but linear alignment is preferred. If all sensors use a uniform optical system, Figure 13b The example arrangement in the image will cause the sensor to tend to have a smaller spectral range—however, as mentioned above, this is not necessary.

[0059] Figure 14a A constructed embodiment of the disclosed system 1400 is shown, illustrating an emission plane 1410 and a USB interface connected to a camera module 1415. An external light source 1405 is added for the sensor's transmission / absorbance measurement. A suitable light source 1405 may also preferably be used for off-axis fluorescence excitation and preferably has beam-collecting properties.

[0060] Figure 14b These are illustrations of example embodiments of the disclosed system. According to... Figure 14b The image shows an example setup for measuring heme absorbance, which has a box 1420 with an optically transparent cuvette 1430 at the emission plane 1410, illuminated by an external white LED light source 1405. The box 1420 is shown filled with blood.

[0061] Figure 15 Showing Figure 14b The example output of the system embodiment shown is a transmission measurement performed using an optically transparent cuvette before the introduction of a blood sample. Figure 16 Showing Figure 14b The example output of the system embodiment shown is a transmission measurement performed using the same cuvette after the blood sample has been injected.

[0062] Figure 16 Two characteristic heme absorbance peaks can be seen (i.e., two dark areas along the line). Figure 17 It is based on from Figure 15 and Figure 16 The obtained spectra were used to calculate the absorbance spectrum of the blood sample. This demonstrates the system's ability to distinguish between oxyheme and deoxyheme. The same blood sample was also measured using a medical-grade blood gas analyzer, yielding 99% oxyheme. According to this disclosure, the system exhibits two characteristic absorption peaks for oxyheme (at 540 nm and 578 nm), instead of the single absorption peak for deoxyheme at 555 nm. Improving the system resolution in the manner described herein will particularly enhance the ability to process the clearer absorption peak of oxyheme at 578 nm.

[0063] According to this disclosure, the box may include one or more sensors. The one or more sensors may include... Figure 13a and 13b The diagram shows multiple individual sensors. In a further embodiment, the sensors can be one or more large sensors, such as... Figure 18 As shown. Figure 18 This is a diagram illustrating an example of a large sensor. According to... Figure 18 This illustrates a large sensor that may be non-uniform in its emission or response. The large sensor has different focal point regions in an attempt to find corresponding uniformity (i.e., 3 distinct focal points).

[0064] According to this disclosure, sensors, or more generally transmitters, will emit certain information in the form of changes in their spectra. For example, their spectra may change when they come into contact with an analyte in a biological sample, indicating to some extent the concentration or mere presence of the analyte.

[0065] According to this disclosure, various modes of spectral variation include: • Changes in their emission spectrum when illuminated by narrow-band light (i.e., fluorescence or luminescence sensors). • They absorb varying amounts of different wavelengths of broadband illumination (i.e., absorbance sensors). • Changes in two ways, which can be measured by fluorescence or absorbance.

[0066] According to this disclosure, an example sensor is a polyvinyl chloride (PVC) based film deposited in a microfluidic channel, which contains a Nile blue-based chromogenic ion carrier, and the absorbance and fluorescence emission spectra of the film change when a specific analyte is delivered to the sensor film.

[0067] According to this disclosure, other types of sensors may also be used. For example, sensors may include "color-changing sensors", lateral flow sensors (i.e., pregnancy tests), and / or patches that change color as the analyte is detected. The latter flow sensors may include multiple analytes simultaneously (i.e., also known as "multiplex detection").

[0068] Alternative embodiments

[0069] Currently, similar imaging is accomplished through electromagnetic source and detector setups that include filters and beamsplitters; one example is epifluorescence imaging in fluorescence biosensors. This setup is more expensive and less flexible. Filters and dichroic beamsplitters are costly, may be difficult to procure, and impose design constraints on future sensors. These designs also effectively limit imaging to a single pixel.

[0070] If the detector is a photodiode, it only sends back an intensity value. This photodiode typically has a bandpass filter in front of it, so the intensity is a relatively narrow band corresponding to a known wavelength.

[0071] If the detector is a spectrometer, it sends back an emission spectrum. However, the detector only images a single region in space, meaning there is no spatial resolution. Furthermore, spectrometers are expensive, and each sensor requires its own spectrometer.

[0072] Another existing approach is to use diffraction gratings or multiple filters on a rotating wheel in front of a two-dimensional (2D) detector in the imaging process to attempt to reproduce multispectral or hyperspectral images. However, these tend to be more complex systems. One example is computed tomography imaging spectrometers. These can be classified as non-scanning hyperspectral imagers.

[0073] These solutions attempt to reproduce images with the highest possible spatial resolution. In the system disclosed herein, only sufficient spatial resolution is needed to distinguish the emissions of adjacent sensors, or the emissions of one illuminated portion of a large sensor from those of adjacent illuminated portions. This sacrifices some imaging capability to determine which light originates from which sensor and to acquire the spectrum of each sensor.

[0074] An additional advantage of the system disclosed herein is that any sensor can be placed anywhere and illuminated to collect the resulting emission data without requiring a "channel" specified by the filter assembly for each sensor. This would limit future sensors in the same location to having only the same imaging characteristics (filter cutoff wavelength, etc.). Ideally, the detector's pixel array is dense enough, and the grating has sufficient line density to achieve sufficiently large dispersion, thus obtaining adequate wavelength resolution.

[0075] It should be pointed out that, Figure 1 The grating system described in the paper is simple, but its cost can be further reduced by modification. Figure 1 Cost reductions in design can include shifting towards injection-molded plastic parts, which offers lower costs during mass production. Furthermore, Figure 1 The components shown can utilize state-of-the-art technology to further reduce the cost, size, weight, and workload required to assemble the unit. Figure 1 The diffraction grating in the image is used to separate the incident light into its spectral components, and can be a conventional grating with serrated lines or grooves, or alternatively, fabricated using holographic techniques. The lenses required to calibrate and focus the light from the emitter onto the detector can be redesigned as the diffraction assembly itself (i.e., a diffractive optics assembly, or a design of experiments (DOE)). The design of experiments can... Figure 1 The lens shown is converted into a flat, injection-molded plastic part with precise and meticulously designed microstructural features that focus light passing through it, correct aberrations, and decolorize. With current modeling software and available fabrication techniques, if the entire optical system between the emitter and image plane is considered in a DOE design conversion, it can be a single element performing [DOE design conversion]. Figure 1 All the functions of the system shown are provided by this single element located on top of the detector, resulting in an improved ultra-compact and extremely low-cost system.

[0076] General considerations

[0077] While some embodiments or aspects of this disclosure may be implemented in fully operational mechanical, electrical, and electromechanical systems, other embodiments may also be contemplated.

[0078] The methods disclosed herein include one or more steps or operations for implementing the methods. The method steps and / or operations may be interchanged without departing from the scope of the claims. In other words, unless the correct operation of the described method requires a specific order of steps or operations, the order and / or use of such specific steps and / or operations may be modified without departing from the scope of the claims.

[0079] The specific embodiments described above have been shown by way of example, and it will be understood that these embodiments are susceptible to various modifications and alternatives. It is further understood that the claims are not intended to limit the forms disclosed, but rather to cover all modifications, equivalents, and alternatives falling within the spirit and scope of this disclosure. While the foregoing written description of the system enables those skilled in the art to make and use what is presently considered the best mode, those skilled in the art will understand and recognize the existence of variations, combinations, and equivalents of the particular embodiments, methods, and examples herein. Therefore, the system should not be limited to the embodiments, methods, and examples described above, but should be limited to all embodiments and methods within the spirit and scope of the system. Consequently, this disclosure is not intended to be limited to the implementations shown herein, but should be given the broadest scope consistent with the principles and novel features disclosed herein.

[0080] The information shown and described in detail herein is fully capable of achieving the objectives of this disclosure and the currently preferred embodiments thereof, and therefore represents the subject matter of a broad conception of this disclosure. The scope of this disclosure fully covers other embodiments that may be apparent to those skilled in the art, and is therefore limited only by the appended claims, wherein any reference to a component in the singular is not intended to mean "one and only one," but rather "one or more," unless expressly stated otherwise. All structural and functional equivalents of the components of the foregoing preferred embodiments and the additional embodiments that would be apparent to those skilled in the art are expressly incorporated herein by reference and are intended to be covered by these claims.

[0081] Furthermore, the system or method need not solve every problem that this disclosure aims to address to be covered by these claims. Moreover, any component, element, or method step in this disclosure is not intended to be made public, whether or not it is expressly recited in the claims. However, various changes and modifications to the form, materials, workpiece, and manufacturing details may be apparent to those skilled in the art without departing from the spirit and scope of this disclosure, as described in the appended claims, and are also included in this disclosure.

Claims

1. A point-of-care imaging system configured to image a sample cartridge, the system comprising: a housing; a first lens configured to collimate emissions from one or more sensors; a diffraction grating; a detector; and a second lens configured to focus emissions onto the detector; wherein the one or more sensors are housed in or on the sample cartridge.

2. The system of claim 1, wherein the diffraction grating and second lens are configured to focus light into spatially separated, wavelength-dependent foci on the detector.

3. The system of claim 1, wherein the detector is a two-dimensional detector array.

4. The system of claim 1, wherein the detector is a complementary metal-oxide- semiconductor (CMOS) image sensor or an optical camera.

5. The system of claim 1, wherein the detector is a one-dimensional detector configured as a linear array of photosensitive diodes.

6. The system of claim 1, wherein the one or more sensors are selected from a list comprising: a plastic film, a colorimetric sensor, a lateral flow sensor, or a patch that changes color upon detection of an analyte.

7. The system of claim 1, wherein the first lens is a doublet lens having a 0.5 inch diameter and is configured to collimate light having wavelengths in a range of 450 nm to 600 nm emitted by the sensors.

8. The system of claim 1, wherein the diffraction grating is configured to reflect or transmit light.

9. The system of claim 8, wherein the diffraction grating is a 1200 line / mm reflective grating.

10. The system of claim 8, wherein the diffraction grating is a transmissive grating.

11. The system of claim 1, wherein the second lens is a doublet lens having a 0.5 inch diameter.

12. The system of claim 1, wherein the second lens focuses each spatially separated wavelength onto the detector to form a 450 nm emission focus and a 600 nm emission focus.

13. The system of claim 1, wherein the second lens is a doublet lens configured as a fixed focus assembly that can be held in a fixed position.

14. The system of claim 13, wherein the second lens is a set of achromatic lenses.

15. The system of claim 1, wherein the first and second lenses are identical and are configured for a 1:1 magnification, such that the foci on the detector or image plane are 0.5 mm in diameter.

16. A point-of-care imaging system configured to image a sample cartridge, the imaging system comprising: a housing; a camera module; an emission plane; a first lens configured to receive light from the camera module; a second lens configured to transmit light to the emission plane; a diffraction grating configured to diffract light from the first lens to the second lens; and wherein the emission plane is further configured to receive the sample cartridge and image and view a plurality of sensor points on the sample cartridge. ​ 17. The system of claim 16, further comprising a USB interface configured to connect to the camera module.

18. The system of claim 16, further comprising an external light source configured to perform a brightness measurement on light transmitted from the camera module.

19. The system of claim 18, wherein the external light source is configured for off-axis fluorescence excitation.

20. The system of claim 18, wherein the fluorescence excitation is to support a beam collection function.

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