System and method for inexpensive hyperspectral imaging of point-of-care biosensors

Abstract

A system and method for a low-cost point-of-care imaging system with high spectral and spatial resolution. The emissions from a sensor are passed through a lens, passing through or reflecting from a diffraction grating, and then focused by another lens onto a detector. The design of the system allows low-cost detectors, such as a photodiode linear array or CMOS camera image sensor, to be used, allowing the imaging system to be of low enough cost to be deployed in point-of-care situations. The imaging system can achieve spectral resolution in the hyperspectral range (<20nm), and sufficient spatial resolution particularly in 1D, with no temporal delay, and in a cost-effective manner.

Description

SYSTEM AND METHOD FOR INEXPENSIVE HYPERSPECTRAL IMAGING OF POINT-OF-CARE BIOSENSORSCross Reference to Related Applications

[0001] The application claims priority and the benefit of US Provisional Patent Application Serial No. 63 / 627216, entitled "SYSTEM AND METHOD FOR INEXPENSIVE HYPERSPECTRAL IMAGING OF POINT-OF- CARE BIOSENSORS" filed on January 31, 2024, the disclosure of which is incorporated herein by reference in its entirety.Background

[0002] The field of this disclosure relates to point-of-care blood testing.

[0003] Point-of-care (POC) diagnosis and monitoring has become a solution for many hospitals, clinics, patients, and physicians who need quick and reliable test results for various biomarkers. In addition to the fast and reliable data, POC offers low cost and low maintenance solutions, which reduce the financial burden of the health care system. The low cost affords multiple periodic tests for particular patients, such as those with chronic disease, allowing them and their physicians to make informed decisions about viable treatment options with hard data, in the form of measured biomarker concentrations.

[0004] It is desirable in the art of optical sensing, including optical sensing for POC applications, to achieve spectral or spatial resolution, and ideally both. Achieving both typically involves the use of a multi- or hyper-spectral camera, which in practice is excessively expensive for many optical sensing applications, including point-of-care (POC) diagnostics using fluorescence emission from a sensor, or spectral transmission / absorption of a sensor, to quantify biomarker concentrations.

[0005] Sufficient spectral resolution is often achieved with a spectrometer. These can reach spectral resolutions of lOnm or better and come in conveniently small packages, for a few hundred dollars each. However, they have no spatial resolution, i.e., they capture any light entering their numerical aperture, effectively making them a single-point imager in length space. If one wanted to quantify the electromagnetic spectrum at different points in space, an individual spectrometer could be used for each point - or external motorized optics could be used in combination with a single spectrometer to scan various points in space. Both solutions come with disadvantages, including increased cost and complexity, as well as reduced reliability. In the case of scanning optics, time resolution is also an issue, e.g., the timetaken to acquire spectra at each required point in space could place a severe limitation on quantifying time-sensitive, transient phenomena in spectral or spatial space.

[0006] Good spatial resolution, in 2D (x and y), is often achieved with an image sensor, such as those found in off-the-shelf digital cameras. However, these generally only have three broadband spectral filters - in the red, green, and blue regions - so spectral information is limited to one reading in red, one in blue, and one in green for each 'pixel', such that the spectral resolution is poor, i.e., 3 wide bands with each on order of 100 nanometres in wavelength. Multispectral imaging has recently been used to improve spectral resolution - typically increasing the number of spectral bands to between 4 and 15, while reducing the width of these bands. Again, multispectral imaging is generally achieved with filters, either on the imaging chip itself or with an external tunable filter, such as a filter wheel, placed in front of the imaging chip. While improving spectral resolution, multispectral imaging comes with a number of disadvantages, including: increased cost of filters, particularly when deposited in a custom pattern directly on the imaging chip; resolution, or spectral bandwidth, that is still insufficient to quantify common phenomena, such as distinguishing between oxygenated and deoxygenated hemoglobin in blood; often non-contiguous spectral bands; and temporal delay in the case of tunable filters - reducing the ability to quantify transient phenomena.

[0007] Hyperspectral imagers have many more, and sometimes substantially contiguous, spectral bands - so better spectral resolution, of typically 10-20nm - and, while they may sacrifice some spatial resolution, this is still generally sufficient for most applications. However, due to their complexity, they often cost tens of thousands of dollars. This is excessively expensive for many optical sensing applications and particularly those intended for widespread use, such as point-of-care (POC) diagnostics using, for example, fluorescence emission or electromagnetic absorption by a sensor to quantify biomarker concentrations.

[0008] POC diagnostic systems for the home, rather than professional use, have even greater cost constraints. For this application, multi- and hyper-spectral camera systems are approximately two orders of magnitude too expensive ($10,000+, when a cost of $100 or less is desired).

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

[0010] A system and method for a low-cost point-of-care imaging system with high spectral and spatial resolution. The emissions from a sensor are passed through a lens, passing through or reflecting from a diffraction grating, and then focused by another lens onto a detector. The design of the system allows low-cost detectors, such as a photodiode linear array or CMOS camera image sensor, to be used, allowing the imaging system to be of low enough cost to be deployed in point-of-care situations. The imaging system can achieve spectral resolution in the hyperspectral range (<20nm), and sufficient spatial resolution particularly in ID, with no temporal delay, and in a cost-effective manner.Brief Description of the Drawings

[0011] FIG. 1 is an exemplar system modelled with ray-tracing software.

[0012] FIG. 2 is a plot of various wavelengths emitted from the biosensor, in the visible range, and their corresponding spots on the detector / image plane.

[0013] FIG. 3 is a plot of various wavelengths emitted from three different biosensors, in the visible range, and their corresponding spots on the detector / image plane.

[0014] FIG. 4 is exemplary output of the embodiment shown in FIG. 1, on a CMOS monochrome 2D camera sensor.

[0015] FIG. 5 is the spectrum of the exemplary central emitter output from FIG. 4, as quantified within the indicated rectangle on FIG. 4.

[0016] FIG. 6 shows the transmissivity of various exemplary filters used to characterize the embodiment of the system in FIG. 1.

[0017] FIG. 7 shows the exemplary output of the embodiment of the system shown in FIG. 1, with a green filter over each emitter.

[0018] FIG. 8 shows the exemplary output of the embodiment of the system shown in FIG. 1, with an OG515 filter over each emitter.

[0019] FIG. 9 shows the exemplary output of the embodiment of the system shown in FIG. 1, with an OG550 filter over each emitter.

[0020] FIG. 10 shows the exemplary output of the embodiment of the system shown in FIG. 1, with an OG570 filter over each emitter.

[0021] FIG. 11 shows the intensities of filtered emission, quantified within the rectangular region ofFIG. 4 and normalized to the emitter spectrum shown in FIG. 5.

[0022] FIG. 12 is a line diagram of an exemplary embodiment of the disclosed system.

[0023] FIG. 13a is an illustration of an overhead view of the cartridge, showing three 0.5-mm sensor spots in a line.

[0024] FIG. 13b is an illustration of an overhead view of the cartridge, showing eight 0.5-mm sensor spots not all in a line.

[0025] FIG. 14a is a side view of a constructed exemplary embodiment of the disclosed system.

[0026] FIG. 14b is an illustration of an exemplary embodiment of the disclosed system.

[0027] FIG. 15 shows the exemplary output of the embodiment of the system shown in FIG. 14b of a single white LED apertured to 0.5 mm and shone through an optically clear cuvette (i.e. reference measurement), prior to introduction of a human blood sample.

[0028] FIG. 16 shows the exemplary output of the embodiment of the system shown in FIG. 14b under the same conditions as FIG. 15 but after introduction of a human blood sample.

[0029] FIG. 17 shows the absorption spectrum of the blood sample calculated from the images in FIG. 15 and FIG. 16, demonstrating the characteristic absorbance of oxygenated hemoglobin.

[0030] FIG. 18 is a diagram illustrating an exemplary large sensor.Detailed Description

[0031] It is the object of this disclosure to provide a system and method for inexpensive hyperspectral imaging which may be used in a point-of-care imaging system.

[0032] A point-of-care imaging system comprises a lens to collimate the emissions from one or more sensors, a diffraction grating, another lens to focus the emissions onto a detector, a detector, and a housing to contain and hold in place these elements.

[0033] In one embodiment, there may be a sensor platform made as part of the housing, which platform holds the at least one sensor and is formed to allow sensors to be inserted into, and removed from, the imaging system. In one embodiment, there may be a computer or control system contained within the housing and connected to the detector, which system takes data from the detector and processes it. This processing may consist of simply passing the data out to an external computer system,or the processing may be more extensive on the point-of-care imaging device, ranging from basic display of the data detected by the detector to a full analysis of the nature of the one or more sensors based on the data from the detector. In one embodiment, the processing may additionally comprise detecting a faulty or imperfectly positioned sensor. In one embodiment, an automated system may be used to insert sensors into, remove sensors from, or position sensors within, the imaging system.

[0034] FIG. 1 is an exemplar system modelled with ray-tracing software. Referring to FIG. 1, showing the exemplar system 100, the case of a single optical emitter 120, a fluorescent biosensor 0.5mm in diameter, is modelled here - with excitation source omitted for clarity. An initial lens 130, in this example a / i diameter achromatic doublet lens, is used to collimate electromagnetic emisison 125 from the sensor, in this example visible light ranging from 450nm to 600nm, which light is then reflected off, or transmitted through, a diffraction grating 140 to separate constituent wavelengths. In this example, diffraction grating 140 is a 1200 lines / mm reflective grating, but could be a transmissive grating in other embodiments. A second lens 135, in this examplediameter achromatic doublet lens, then focuses these spatially-separated wavelengths onto the detector 115, in this example forming a 450nm emission convergence spot 110 and a 600nm emission convergence spot 105. Detector 115 may be a 1-dimensional detector, such as a linear photodiode array, or a 2-dimensional detector, such as a Complementary Metal- Oxide-Semiconductor (CMOS) or other known camera sensor technology. The doublet lens 135 between the diffraction element and the detector is a fixed focusing element, which can stay in a fixed position. It is preferably a lens which minimizes wavelength- and position-dependent distortion, such as an achromatic lens.

[0035] In one embodiment, the lenses are identical and configured for 1:1 magnification so the spot on the detector, or image plane, is also approximately 0.5mm diameter. In other embodiments, the lenses may be of different kinds and sizes.

[0036] FIG. 2 is a plot of various wavelengths emitted from the biosensor, in the visible range, and their corresponding spots on the detector / image plane. Note the separation of these spots, which imparts spectral resolution.

[0037] According to FIG. 2, in this example, the 7mm spread in wavelengths on the detector / image plane shown here achieves a spectral resolution of approximately 20nm, as can be seen from the separation of image spots for 512 and 530nm. Furthermore, the linear spread (7mm) can easily be expanded for better wavelength resolution or reduced to suit smaller photodetector arrays, at the expense of wavelength resolution.

[0038] Resolution in length and spectral space can also be modified by adjusting the apparent size of the optical emitter. In this example, it is a circular spot of 0.5 mm diameter, which produces spots corresponding to individual wavelengths on the detector that are correlated in size with the emitter. If the spot size is reduced — for example, by externally illuminating a smaller portion of the corresponding object, by aperturing, or by making the emitter itself smaller — then the spot size in wavelength space on the detector becomes smaller, permitting greater separation between wavelengths and improved resolution, as long as the pixel density on the image sensor is sufficient. The opposite is true if the emitter size is increased.

[0039] The spot diagram in FIG. 2 shows the convergence of rays traced from a 0.5mm object. The corresponding optical system shown in FIG. 1 is simple, using achromatic doublet lenses, and due to a non-optimized optical system, significant aberrations are present. As such, the circular 0.5mm object that is imaged by the lenses appears in the image plane slightly blurry with a spot size averaging approximately 0.6 mm in diameter. This reduces resolution since the larger spot formed at the detector will overlap with adjacent wavelengths. Better resolution can be achieved if the optical system is designed such that the spot size in the image plane represents that of the object (emitter) as best as possible. In the example, gains in resolution can particularly be made at longer wavelengths, where the spots are farther off the axis of the lens and thus more affected by aberrations. For example, as seen in FIG. 2, the 600nm spot is clearly larger than the 450nm spot.

[0040] Smaller spots sizes on the detector can also be achieved through demagnification of the object. Optimization of the optical system may also include adjusting magnification such that object size is reduced by some factor in the image plane (i.e., magnification, as defined here, is less than 1). In the simple system shown in FIG. 1, the ratio of the focal lengths of the lenses determines magnification. If the lens between the grating and the image plane is changed to a shorter focal length, the magnification is reduced and each spot formed on the detector will be smaller. However, the spacing between the diffracted spots, which a function of the line density of the grating (and proportional to resolution), will not be increased. Therefore, the effect of demagnifying the emitter will be to increase the dynamic range of the system, i.e. the wavelength range of the system will be increased since the diffracted image will be smaller and, given the same size 2D sensor, more of the spectra will fit on the detector.

[0041] The wavelength range of the system is determined by a number of 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 (vertically in the above example) willenable a larger wavelength range. Similarly, the length range of the system is dependent on similar factors, and a larger detector would enable a larger length range.

[0042] If the detector array is two-dimensional, e.g., a CMOS camera image sensor, spectra can be improved by techniques such as averaging pixels corresponding to a given narrow range of wavelengths; eliminating pixels corresponding to a substantial portion of the edge of the emitter (e.g., if there are unwanted edge effects of a biosensor emitter, such as a difference relative to emission at the central region due to a meniscus at the edge); or eliminating pixels at the edges of the spots above that are only partially illuminated. Similar results could be achieved with a ID photodetector array, e.g., a linear photodiode array, with both averaging and physical detector masking (where masking is also a possibility with a 2D array).

[0043] FIG. 3 is a plot of various wavelengths emitted from three different emitters, or biosensors, in the visible range, and their corresponding spots on the detector / image plane. The separation of spots in the vertical direction imparts spectral resolution, while separation in the horizontal direction imparts spatial resolution required to distinguish one sensor from another, or regions of one or more larger sensors from one another.

[0044] The current disclosure is primarily driven by a need, in various fields, to obtain spectral information from a series of point emitters, or a continuous array of emitters— which can be imaged as a series of distinct emitters by techniques mentioned above (aperture, illumination)— that are arranged predominantly in a line. In a preferred embodiment, this line of emitter(s) is oriented predominantly perpendicular to the diffraction axis of the grating.

[0045] In the example of a series of discrete biosensors in a straight microfluidic channel on a diagnostics cartridge, changes in fluorescence emission and / or transmission / absorbance, before and after exposure of the sensor to a biofluid in the microfluidic channel, could be indicative of the concentration of the analytes detected by the biosensors.

[0046] Prior to this disclosure, a typical approach— to avoid the high cost of multiple spectrometers— was to select a narrow band of wavelengths that was most indicative of each sensor's change in spectral emission with changing analyte concentration. This would typically correspond to a single spectral peak. A bandpass optical filter would then be selected to match the wavelengths of this peak, then coupled with a single photodiode or other photodetector. There are a number of problems with this approach, chief among which are an inability to capture a much broader spectrum, allowing more precise signal transduction with the additional data collected, e.g., by using Al to determine additional features in thesedata to more precisely convert spectral changes to concentration changes; and effectively freezing the design of a field instrument such that new sensors / emitters can only be quantified at the chosen wavelengths for each detector, which places significant restrictions on design or precision of new sensors.

[0047] In the disclosed system, if there are multiple light emitters, or in this case biosensors, they can be distinguished from one another spatially, along the horizontal direction, while maintaining their respective spectral resolution. This effectively permits the hyperspectral imaging required for multisensor optical detection with no delay, and thus with the ability to quantify rapidly changing phenomena.

[0048] Furthermore, the zeroth order of the diffraction grating, which corresponds to the illumination, or source light, itself (e.g., broadband light for absorbing emitters and narrowband for fluorescing emitters) can be sent to a detector array, which could be adjacent to the emitters or directly opposing the emitters, in the cases of a reflective or transmissive diffraction grating. This can permit selfcalibration, e.g., if any changes in the source occur, they can be processed at the same time as other spots they illuminate. Similar self-calibration could also be achieved in the first-order diffraction by imaging only the source light, e.g., with no biosensor in that particular area.

[0049] While only three emitters are shown in the system embodiment presented here, it is clear that many more can be characterized simultaneously. Just by reducing the space between emitters, at least 10 could be characterized in this embodiment with no other changes. Furthermore, for example, altering magnification, lens characteristics and number, and detector characteristics and number could allow the imaging of tens or even hundreds of emitters in single or multiple images, at a single point or multiple points in time. Multiple orders of diffraction could also be imaged, rather than just the first -order diffraction imaged here, as alluded to above. Additionally, multiple gratings with different characteristics could also be placed adjacent to one another, allowing different emitters to be imaged with different spectral resolution and range.

[0050] Some overlap of emitters in length space can be permitted. Ideally, the overlap is limited to an extent that one or more pixels across length space is unique to each emitter.

[0051] Beyond the physical horizontal separation of the biosensors— which, here, are arranged in a line— the individual biosensors can be further separated by interrogating just one at a time. For instance, if each is a fluorescence biosensor, requiring excitation, the biosensors could be excited one at a time. This could allow them to be quite close together even if the spatial resolution is not sufficient to otherwise distinguish one from another. This would sacrifice time resolution, as the image would no longer be a single, rapid snapshot.

[0052] FIG. 4 is exemplary output of the embodiment shown in FIG. 1, on a CMOS monochrome 2D camera sensor (but a standard colour camera could just as easily be used). FIG. 4 shows example output of the system in FIG. 1 on a CMOS monochrome 2D camera sensor, with three 0.5mm emitters, each separated by 2mm at the emitter plane. In this example output, each of the 3 emitters is a broadband LED light source, with the image of the bottom one slightly obscured by a screw head in the optical path. Using image analysis, taking a vertical pixel average within the white rectangle in FIG. 4, i.e., across pixels corresponding to the same wavelength(s), yields the spectrum in FIG. 5, which closely matches the LED spectrum as measured using a commercial spectrometer, albeit in pixel space rather than wavelength (converting to the latter requires characterization of the system, as discussed below). FIG. 5 is the spectrum of the exemplary central emitter output from Figure 4, as quantified within the indicated rectangle on FIG. 4.

[0053] At this stage, the wavelength(s) corresponding to individual pixels is unknown. The system must be calibrated to find a pixel to wavelength conversion in nm. This can be done by applying known wavelength characteristics, such as placing coloured glass filters of known transfer function between the emitters and the detector. Example filters are shown in FIG. 6. FIG. 6 shows the transmissivity of various exemplary filters used to characterize the embodiment of the system in FIG. 1, as measured with a commercial spectrometer. Furthermore, Figures 7-10 show the system output when each of these is applied to each emitter. FIG. 7 shows the exemplary output of the embodiment of the system shown in FIG. 1, with a green filter over each emitter. FIG. 8 shows the exemplary output of the embodiment of the system shown in FIG. 1, with an OG515 filter over each emitter. FIG. 9 shows the exemplary output of the embodiment of the system shown in FIG. 1, with an OG550 filter over each emitter. Finally, FIG. 10 shows the exemplary output of the embodiment of the system shown in FIG. 1, with an OG570 filter over each emitter.

[0054] Using the same linear averaging technique mentioned above— in a rectangular area— the intensities vs pixel are quantified. When normalized to the source spectrum in FIG. 5, a pixel to wavelength conversion algorithm can be ascertained by comparison to the transfer functions of the filters in FIG. 6. Other embodiments, algorithms or techniques may be used to calibrate and quantify the intensity at each pixel, and to convert pixels to corresponding wavelengths.

[0055] FIG. 11 shows intensities quantified for each filter, and then normalized to the emitter / source spectrum in FIG. 5. FIG. 11 demonstrates the ability for this system to reproduce the output of a commercial grade spectrometer (FIG. 6) with a high degree of accuracy. While thecomponents of this system added to a cost of $250, this can clearly be reduced by choosing different components and by purchasing in volume.

[0056] FIG. 12 is an illustration of an exemplary embodiment of the disclosed system. According to FIG. 12 an embodiment of the disclosed system 1200, showing the CMOS camera sensor module 1210, lenses 1215 and diffraction grating 1220 is disclosed. Also shown is the emitter plane 1205, which is the cartridge with 3 sensor spots viewed from the edge.

[0057] FIG. 13a shows the cartridge viewed from the top, showing three 0.5-mm sensor spots. FIG. 13b shows a similar cartridge viewed from the top, but showing sensor spots not in a line. The disclosed system does not require all sensors to be arranged in a line, but a linear arrangement is preferable. The example arrangement in FIG. 13b causes the sensors to tend towards a smaller spectral range if a uniform optical system is used for all sensors - however this is not necessary, as mentioned above.

[0058] FIG. 14a shows a constructed embodiment of the disclosed system 1400, showing emitter plane 1410 and a USB interface to the camera module 1415. External light source 1405 is added for transmission / absorbance measurements of sensors. An appropriate light source 1405 could also do fluorescence excitation, preferably off-axis, and preferably with a beam dump feature.

[0059] FIG. 14b is an illustration of an exemplary embodiment of the disclosed system. According to FIG. 14b, an exemplary setup for measuring hemoglobin absorbance is shown having cartridge 1420 with optically transparent cuvette 1430 at the emitter plane 1410, being illuminated by external white LED source 1405. Cartridge 1420 is shown to be blood-filled.

[0060] FIG. 15 shows the exemplary output of the embodiment of the system shown in FIG. 14b of a transmission measurement through an optically transparent cuvette prior to blood sample introduction. FIG. 16 shows the exemplary output of the embodiment of the system shown in FIG. 14b of a transmission measurement through the same cuvette after blood sample injection.

[0061] Two characteristic hemoglobin absorbance peaks can be seen in FIG. 16 (i.e., the two dark areas along the line). FIG. 17 Is the absorbance spectrum of the blood sample, calculated from the spectra obtained from FIG. 15 and FIG. 16. This demonstrates the ability for the system to distinguish between oxygenated and deoxygenated hemoglobin. The same blood sample was also measured with a medical grade blood-gas instrument to be 99% oxygenated hemoglobin. According to the disclosure, the system demonstrates the two characteristic absorption peaks of oxy-hemoglobin (at 540nm and 578nm), as opposed to the single absorption peak of deoxy-hemoglobin at 555nm. Improving the system resolution,by means described here, would particularly improve the ability to resolve the sharper oxy-hemoglobin absorption peak at 578nm.

[0062] According to the disclosure, the cartridge may comprise of one or more sensors. The one or more sensor may include multiple individual sensors shown in FIG. 13a and 13b. In further embodiments, the sensor can be one or more large sensors as shown in FIG 18. FIG. 18 is a diagram illustrating an exemplary large sensor. According to FIG. 18, a large sensor is shown which may be non-uniform in emissions or response. The large sensor has different spot areas to look for uniformity of response (i.e., 3 different spots).

[0063] According to the disclosure, the sensors, or more generally the emitters, would change their spectrum in a manner imparting some information. For example, their spectra would change when in contact with an analyte in a biological sample, in a way that's indicative of the concentration or mere presence of the analyte.

[0064] According to the disclosure, the ways the spectra would change include:• change in the spectra they emit when illuminated by narrow-band light (i.e., fluorescence or luminescence sensor),• change in the how much of difference wavelengths of broadband illumination they absorb (i.e., absorbance sensor),• change in both ways whereby they could either be measured by fluorescence or absorbance.

[0065] According to the disclosure, an example sensor is a polyvinyl chloride (PVC) based film deposited in a microfluidic channel and containing a nile blue-based "chromoionophore" that changes both absorbance and fluorescence emission spectra when a particular analyte is transported into the sensor film.

[0066] According to the disclosure, other types of sensors can also be use. For example, the sensor may include "colour-change" sensors, lateral flow sensors (i.e., pregnancy tests) and / or skin patches that change colour with analyte detection. The later flow sensors may include multiple analytes simultaneously (i.e., also known as "multiplexing").Alternate Embodiments

[0067] Currently, similar imaging is done with an electromagnetic source and detector setup that includes filters and beam-splitters; one example would be epifluorescence imaging of a fluorescent biosensor. This setup is more expensive and less flexible. The filters and dichroic beam-splitters are expensive, may be difficult to source, and place design constraints on future sensors. These designs also effectively limit imaging to a single pixel.

[0068] If the detector is a photodiode, only a single intensity value is returned. The photodiode is normally preceded by a bandpass filter so this intensity corresponds to a relatively narrow band of known wavelengths.

[0069] If the detector is a spectrometer, then an emission spectrum is returned. However, the detector images a single area in space, meaning that no spatial resolution is available. Additionally, spectrometers are expensive and one would be needed for each sensor.

[0070] Another current approach uses a diffraction grating, or a number of filters on a spinning wheel in front of the 2D detector, in the imaging, to try to reproduce a multi- or hyper-spectral image. However, these tend to be more complex systems. One example is a computed tomography imaging spectrometer. These may be classified as non-scanning hyperspectral imagers.

[0071] These solutions try to reproduce an image with as high a spatial resolution as possible. In the system disclosed herein, only enough spatial resolution is needed to distinguish the emission from one sensor from that of the sensor next to it, or one illuminated part of a large sensor to an adjacent illuminated part. Some imaging capability is sacrificed to know just which light is coming from which sensor, and get the spectrum from each.

[0072] One additional advantage of the system disclosed herein is that any sensor may be placed in any position and lit up, and the resulting emission data collected, without having defined 'channels' for each sensor specified by the filter elements, which restricts future sensors in the same position to the same imaging characteristics (filter cut-offs, etc.). Ideally the detector's pixel array is dense enough, and dispersion from the grating large enough with sufficient line density, that sufficient wavelength resolution is obtained.

[0073] It should be noted that the grating system described in FIG. 1, though simple, may be modified to further reduce system cost. Cost reductions to the FIG. l's design could include moving to plastic injection molded parts, which provide much lower costs at quantity. Additionally, the components shownin FIG. 1 could employ state-of-the-art technology to further reduce the cost, size, weight, and effort required to assemble a unit. The diffraction grating in FIG. 1 serves to separate the incoming light into its spectral components and may be a traditional grating with ruled lines or grooves, or may instead be made by holographic techniques. The lenses required to collimate the light from the emitter and focus it onto the detector may be redesigned as diffractive elements themselves (i.e. diffractive optical elements, or DOE). A DOE can transform lenses shown in FIG. 1 into a flat piece of injection molded plastic with precise and carefully designed microstructure features that focus, correct for aberrations, and achromatize the light passing through it. With current modelling software and available fabrication techniques, that if the entire optical system between the emitter and image plane were considered for a DOE design transformation, it could become a single monolithic element performing all the functions of the system shown in FIG. 1, which sits atop the detector and provides an ultra-compact and very low-cost system, improving on .

[0074] / / hereGeneral Considerations

[0075] While some embodiments or aspects of the present disclosure may be implemented in fully functioning mechanical, electrical and electrical-mechanical systems, other embodiments may be considered.

[0076] The methods disclosed herein comprise one or more steps or actions for achieving the described method. The method steps and / or actions may be interchanged with one another without departing from the scope of the claims. In other words, unless a specific order of steps or actions is required for proper operation of the method that is being described, the order and / or use of specific steps and / or actions may be modified without departing from the scope of the claims.

[0077] The specific embodiments described above have been shown by way of example and understood is that these embodiments may be susceptible to various modifications and alternative forms. Further understood is that the claims are not intended to be limited to the forms disclosed, but 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 one of ordinary skill to make and use what is considered presently to be the best mode thereof, those of ordinary skill will understand and appreciate the existence of variations, combinations, and equivalents of the specific embodiment, method, and examples herein. The system should therefore not be limited by the above-described embodiment, method, and examples, but by all embodiments and methods within the scope and spirit of the system.Thus, the present disclosure is not intended to be limited to the implementations shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

[0078] Information as herein shown and described in detail is fully capable of attaining the abovedescribed object of the present disclosure, the presently preferred embodiment of the present disclosure, and is, thus, representative of the subject matter which is broadly contemplated by the present disclosure. The scope of the present disclosure fully encompasses other embodiments which may become obvious to those skilled in the art, and is to be limited, accordingly, by nothing other than the appended claims, wherein any reference to an element being made in the singular is not intended to mean "one and only one" unless explicitly so stated, but rather "one or more." All structural and functional equivalents to the elements of the above-described preferred embodiment and additional embodiments as regarded by those of ordinary skill in the art are hereby expressly incorporated by reference and are intended to be encompassed by the present claims.

[0079] Moreover, no requirement exists for a system or method to address each problem sought to be resolved by the present disclosure, for such to be encompassed by the present claims. Furthermore, no element, component, or method step in the present disclosure is intended to be dedicated to the public regardless of whether the element, component, or method step is explicitly recited in the claims. However, various changes and modifications in form, material, workpiece, and fabrication material detail may be made, without departing from the spirit and scope of the present disclosure, as set forth in the appended claims, as may be apparent to those of ordinary skill in the art, are also encompassed by the present disclosure.

Claims

ClaimsWhat is claimed is:

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

2. The system of claim 1, wherein the diffraction grating and second lens are enabled to focus light into spatially-separated, wavelength-dependent spots 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 CMOS image sensor or an optical camera.

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

6. The system of claim 1, wherein the one or more sensors is selected from a list consisting of a PVC- based film, a colour-change sensor, a lateral flow sensor, or skin patches that change colour with analyte detection.

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

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

9. The system of claim 8 wherein the diffraction grating is a 1200 lines / 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 0.5 inch diameter doublet lens.

12. The system of claim 1, wherein the second lens focuses spatially-separated wavelengths onto the detector, thereby forming a 450nm emission convergence spot and a 600nm emission convergence spot.

13. The system of claim 1 wherein the second lens is a doublet lens, configured as a fixed focusing element that can stay in a fixed position.

14. The system of claim 13 wherein the second lens is an achromatic lens.

15. The system of claim 1 wherein the first and second lenses are identical and configured for 1:1 magnification so the spot on the detector or image plane is 0.5mm diameter.

16. A point-of-care imaging system, configured to image a cartridge specimen, the imaging system comprising: a housing; a camera module; an emitter plane; a first lens to receive light from the camera module; a second lens to transmit light to the emitter plane; a diffraction grating to diffract light from the first lens to the second lens; and wherein the emitter plane is further configured to receive the cartridge specimen and image and view multiple sensor spots on the cartridge specimen.

17. The system of claim 16 further comprising a USB interface configured to connected to the camera module.

18. The system of claim 16, further comprising an external light source configured for transmission and absorbance measurements of light from the camera module.

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

20. The system of claim 18 wherein the fluorescence excitation supports a beam dump feature.

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