Bright field lighting module

Abstract

A method for adapting an analysis system to analyze a detection site array using a bright-field microscope, the method comprising: providing a module including at least one radiation emitter and a diffuser, the diffuser being spaced apart from the at least one radiation emitter by a spacer; and arranging the module relative to the detection site array such that a radiation path extends from the at least one radiation emitter through the diffuser and onto the detection site array; wherein the at least one radiation emitter is arranged such that the radiation path extends in a direction inclined to a plane defined by the detection site array.

Description

Technical Field

[0001] This disclosure relates to a method for adapting a detection and analysis system to a bright-field microscope. A detection and analysis system adapted to a bright-field microscope using this method is also disclosed. Background Technology

[0002] Analytical systems can be used to automate the analysis of chemical, biochemical, or immunoassay assays. Such assays can be performed in a regular array of printed areas configured to hold reactants and test samples. Typically, such assays test for the presence or level of an analyte in the test sample. Response values ​​(typically in the form of opacity, color, size, or other detectable changes) are correlated with the presence or level of the analyte. The analytical system is equipped with sensors (typically digital cameras) to identify the response in each “print” in the array. In this way, for example, a digital camera image can be examined and the response (e.g., the degree of change in color or opacity) can be identified to determine the presence or level of the analyte in any given “print” area.

[0003] Typically, analytical systems utilize either dark-field or bright-field illumination techniques in conjunction with sensors to enable the system to detect responses in the test sample. Dark-field illumination is a technique in optical microscopy that removes scattered light from the image collected by the sensor. This produces an image with a “dark” background around the test sample. This is particularly advantageous for analyzing live cell samples that cannot be stained or samples that have not undergone a staining process. However, using dark-field illumination can produce images with lower light levels, meaning the sample may have to be strongly illuminated, potentially leading to sample damage. While dark-field microscopy can produce images with increased contrast, this can come at the cost of reduced sensitivity, making it difficult to detect and / or analyze relatively dark features in the image.

[0004] In bright-field illumination, radiation (e.g., light) propagates through the sample and is imaged by a sensor positioned on the side of the sample opposite the light source. The contrast in the image is caused by the attenuation of transmitted light in denser regions of the sample, as denser samples absorb more light. Bright-field illumination is an extremely simple technique that allows for greater sensitivity to smaller features, as well as improved accuracy and repeatability in the analytical process.

[0005] Therefore, the object of at least one embodiment of at least one aspect of this disclosure is to provide a device for easily adapting an analytical system to use a bright-field microscope. Summary of the Invention

[0006] Various aspects of the invention are defined in the independent claims. Preferred features are defined in the dependent claims.

[0007] According to a first aspect of this disclosure, a method is provided to adapt an analysis system for analyzing a detection site array using a bright-field microscope.

[0008] The method may include a providing module comprising at least one radiation emitter and a diffuser, wherein the diffuser is spaced apart from the at least one radiation emitter by a spacer.

[0009] The method may include: positioning the module relative to the detection site array such that a radiation path extends from the at least one radiation emitter through the diffuser and reaches the detection site array.

[0010] In some examples, the at least one radiation emitter is arranged such that the radiation path extends in a direction inclined to the plane defined by the array of detection sites.

[0011] Advantageously, by providing a module (which includes at least one radiation emitter, such as at least one light-emitting diode (LED)), it may be unnecessary to use any pre-existing emitter in the analysis system; instead, it can be physically maintained within the system, making it easier to reverse the fit by removing the module. This provides a module that allows the user to easily and quickly adapt the analysis system to a bright-field microscope with minimal hardware changes, and also allows for easy reversal of the fit.

[0012] During the detection process, one or more fluids (e.g., diluents, antigens, reagents, etc.) may be introduced into the detection site array. These fluids may not be easily and / or completely removed before analysis without damaging or affecting the detection results. Partly due to surface tension, the fluids can form convex shapes (e.g., convex lens shapes) on the surface of the detection site array, which can refract the radiation projected onto them. This can distort the image captured by an imaging device configured or capable of collecting images of the detection site array, thereby reducing the reproducibility and validity of the resulting analysis. Throughout this disclosure, this result can be referred to as the "lens effect."

[0013] By arranging the radiation emitters(s) such that the radiation path between each radiation emitter and the detection site array is not perpendicular to the plane defined by the detection site array (i.e., at an angle to the plane), the lensing effect can be reduced or completely eliminated.

[0014] It will be understood that, in the art, the term "detection site array" may also be referred to as "array" or "microarray." The term "microarray" may also refer to an array of multiple detection sites. The "array" may include only one detection site or may include multiple detection sites, wherein the analysis system is used to analyze one or more of the multiple detection sites, or to analyze each of the multiple detection sites. In this disclosure, these terms may be used interchangeably.

[0015] As used in this disclosure, the term "diffuser" may refer to any of the following: a holographic diffuser, a white diffuser glass diffuser, a frosted glass diffuser, or other diffuser arrangement (which increases the uniformity of radiation incident on and propagating through the diffuser). The diffuser may include an assembly of diffuser elements.

[0016] As used in this disclosure, the term "radiator" can refer to any device configured to emit electromagnetic radiation. The emitted radiation may have a single peak wavelength or a wide bandwidth combining multiple wavelengths. The emitted radiation may be within or beyond the visible spectrum. The radiation may be emitted from a single surface, side, or aperture of the emitter, or in multiple directions.

[0017] The method may further include spacing the diffuser relative to the at least one radiation emitter such that substantially uniformly distributed radiation is incident on the array of detection sites.

[0018] By setting the diffuser(s)(s) to produce substantially uniformly distributed radiation at the detection sites, inexpensive and widely available point light sources (such as LEDs) can be used in the module to illuminate the detection sites for analysis by the analysis system.

[0019] For the description of "substantially uniformly distributed radiation," this means that the intensity and / or wavelength of radiation incident at any point on the detector site array is substantially the same as the intensity of radiation incident at any other point on the detector site array; in other words, the uniformity of the incident radiation is high. The difference between the maximum and minimum intensities of the incident radiation at all points can provide a measure of said uniformity, and throughout this disclosure, said difference may be referred to as a "gradient."

[0020] It will be understood that the detection site array can have a region of interest (ROI), which includes the area occupied by the plurality of detection sites to be analyzed within the detection site array. Throughout the disclosure, the uniformity of incident radiation on the ROI can be referred to as the ROI gradient.

[0021] By positioning the diffusers(s) at different locations within the spacer, the gradient and / or ROI gradient can be minimized by increasing or decreasing the distance between the radiating emitters(s) ...

[0022] The module may include multiple radiation emitters.

[0023] Advantageously, by providing more than one radiation emitter, the intensity and directionality of the emitted radiation can be increased. This allows for greater control over the imaging parameters at each detection site, depending on the detection being performed, thereby improving the performance of the adapted analysis system.

[0024] By using multiple identical radiation emitters, redundancy is created, such that if one of the multiple radiation emitters fails or degrades during the detection imaging process, another of the multiple radiation emitters can be used to complete the detection imaging process without interfering with the detection site, which would otherwise damage or inappropriately affect the detection results.

[0025] At least two of the plurality of radiators can be configured to emit radiation at different peak wavelengths.

[0026] Following the detection process, some features of the resulting test sample may be visible only when irradiated with certain radiation wavelengths (e.g., infrared, ultraviolet, etc.). By providing a radiation emitter configured to emit radiation of different wavelengths, it is easier to detect multiple detection sites and / or features of the test sample included within each detection site, without having to repeat the detection process and / or exchange the installed radiation emitter.

[0027] The spacer may include an adapter plate configured to releasably receive the at least one radiation emitter.

[0028] The adapter plate may be included in or attached to the spacer at the end opposite to the detection site array. Temporary fasteners (e.g., screws, nuts, bolts), releasable adhesives, etc., may be used to mount the transmitter into the holes in the spacer.

[0029] Advantageously, by providing a releasable device for mounting the (multiple) radiation emitters into the module, a faulty or damaged emitter can be removed and / or replaced without replacing the entire module. Furthermore, the (multiple) radiation emitters can be interchanged with emitters that increase / decrease intensity, or with emitters configured to emit radiation at different peak wavelengths. In this way, the hardware configuration of the analysis system can be quickly and easily adapted to optimize the detection analysis for different detection processes and results.

[0030] The spacer may include a frame configured to releasably receive the diffuser.

[0031] By providing a releasable device for mounting the diffusers(s) into the spacer(s), the configuration of the module and the analysis system to which it is set can be quickly and consistently tailored for specific detection and analysis values, for example, based on the number and / or peak wavelength of the radiation emitters(s). The diffusers(s)(s) can also be easily removed for cleaning, repair, and / or replacement.

[0032] The frame can also be configured to releasably receive the adapter board.

[0033] Multiple adapter boards may be available, supplied, or purchased, each with a different configuration of radiating emitters or the same configuration of radiating emitters.

[0034] By providing a releasable device for mounting the adapter board, the configuration of the (multiple) radiation emitters (e.g., the number, location, and orientation of each radiation emitter) can be quickly and consistently customized for specific detection analyses. The adapter board can also be easily removed for repair, replacement, and / or replacement of the radiation emitters.

[0035] The spacer may be a housing configured to surround the diffuser. At least a portion of the inner surface of the housing may be substantially non-reflective for the peak wavelength of the radiation emitted by the at least one radiating emitter.

[0036] The inner surface may comprise or be coated with a material that is substantially non-reflective to the radiation emitted by the radiation emitter(s). The inner surface may include a layer or coating comprising a material that is substantially non-reflective to the radiation emitted by the radiation reflector(s).

[0037] In the example, the housing may be a cube or a cuboid. The housing may have four, five, or six sides. The housing is selectively closable. Two or more walls of the housing (e.g., sidewalls) may include multiple slots, notches, or protrusions for supporting the diffuser(s). The multiple slots, notches, or protrusions may be configured to support the diffuser(s) substantially parallel to the array of detection sites. The multiple slots, notches, or protrusions may be configured to support the diffuser(s) at multiple distances from the radiating emitter(s). The housing may have one or more removable walls or notches to allow insertion into and removal of the diffuser(s). Alternatively, the housing may be open on one, two, or all sides that do not support the diffuser(s).

[0038] The housing may include one or more openings. These openings may accommodate the radiation emitter(s), adapter plate(s), and / or the detection site array. Alternatively, the housing may be open on the side accommodating the detection site array; for example, in use, the module may be configured such that radiation emitted by the radiation emitter(s) propagates through the diffuser(s) and exits the opening side of the housing to incident on the detection site array.

[0039] In the example (where the inner surface of the housing is at least partially comprised or coated with a material that is substantially non-reflective to radiation emitted by the radiation emitter(s)(s),) the housing can be used to improve the uniformity of the radiation projected onto the detection sites of the detection site array, for example by reducing or eliminating internal reflections within the housing before, during, and after the radiation propagates through the diffuser(s).

[0040] The method may further include implementing a computer program on the analysis system, the computer program including instructions that, when implemented on the analysis system, cause the analysis system to use a bright-field microscope to analyze the detection site array.

[0041] In some examples, the method may include configuring the at least one radiation emitter to emit radiation toward the detection site array along an asymmetric optical path (which may be interchangeably referred to herein as a radiation path). For example, in a method implementing multiple radiation emitters, a first radiation emitter of the multiple radiation emitters may emit radiation toward the detection site array along a first radiation path, and a second radiation emitter of the multiple radiation emitters may emit radiation toward the detection site array along a second radiation path. The first radiation path and the second radiation path may be asymmetric.

[0042] For example, the length of the first radiation path may be different from the length of the second radiation path.

[0043] By implementing such an optical system with asymmetric optical paths (e.g., where the radiation propagation paths (hereinafter referred to as "radiation paths") can differ in geometric properties), unique optical behaviors of dispersion and generation of optimal illumination can be achieved.

[0044] In other words, the methods and systems described herein can involve the use of geometrically asymmetric paths, such as paths with different widths, and / or heights, and / or cross-sectional shapes, dimensions, etc. This asymmetry can advantageously provide different radiative propagation characteristics, thereby enabling selective ray routing.

[0045] In the applications and use cases described herein, this ability to disperse light differently across the optical path ensures more uniform and targeted illumination of a scene, such as a scene of microarray wells. This can improve contrast and focus on certain areas, such as the region of interest in the microarray wells described herein.

[0046] This combination of geometric and optical design principles provides a versatile platform for achieving a high level of control over light propagation, dispersion, and routing. Such asymmetric optical paths can be used to optimize the systems and methods described herein for specific lighting patterns, enhancing sensing capabilities and thus improving subsequent signal processing.

[0047] According to a second aspect of this disclosure, an analysis system is provided for analyzing one or more detections performed at corresponding detection sites in a detection site array, the analysis system being adapted to use a bright-field microscope by performing the methods of the first aspect.

[0048] The analysis system may include testing instruments, such as "MosaiQ". TM "Testing instruments. The MosaiQ" TMThe testing instrument may be primarily designed for analyzing test samples using dark-field microscopy. By providing a module that allows the testing instrument to be adapted for analyzing test samples using bright-field microscopy, the instrument can be used to analyze the results of tests requiring bright-field illumination, with minimal hardware changes to the testing instrument. This also allows the testing instrument to be easily adapted back to dark-field microscopy, if needed or when required.

[0049] According to a third aspect of this disclosure, an analysis system is provided, the analysis system being adapted to analyze a detection site array using a bright-field microscope, the analysis system comprising:

[0050] Detection site array;

[0051] Module, the module includes:

[0052] At least one radiation emitter, the at least one radiation emitter being configured to emit radiation; and

[0053] A diffuser, spaced apart from the at least one radiation emitter by a spacer;

[0054] in:

[0055] The module is positioned relative to the detection site array such that a radiation path extends from the at least one radiation emitter through the diffuser and reaches the detection site array; and

[0056] The at least one radiation emitter is arranged such that the radiation path extends in a direction inclined to the plane defined by the array of detection sites.

[0057] The at least one image may include one or more images or a set of images of all the plurality of detection sites, wherein the set of images may individually cover one or some of the plurality of detection sites, but collectively cover all of the plurality of detection sites.

[0058] The analysis system may also include an imaging device configured or capable of being configured to collect at least one image of the detection site array.

[0059] The radiation emitters(s) can be arranged at or outside the edge of the field of view of the imaging device. By arranging the radiation emitters(s) in this way, the diffuser can more easily diffuse the emitted radiation to produce a substantially uniform distribution of radiation incident on the array of detection sites, and the radiation emitters are not "visible" in the field of view of the imaging device.

[0060] It will be understood that the analysis system may include multiple imaging devices, such as two or more imaging devices. Each imaging device may be configured to collect images of different arrays of detection sites or images of the same array of detection sites.

[0061] The analysis system may further include a processing system, which includes at least one processing device, a data storage device, and a communication system. The communication system is used to receive the at least one image and to output an indication of the degree of response at the detection sites of the detection site array. The imaging device may also be configured to transmit the at least one image to the processing system.

[0062] The analysis system may further include an output device configured to receive, from the processing system, the indication of the degree of reaction at the detection site, and to output the indication of the degree of reaction at the detection site.

[0063] The spacer may include a housing configured to surround the diffuser.

[0064] At least a portion of the inner surface of the housing may be substantially non-reflective to the peak wavelength of radiation emitted by the at least one radiation emitter.

[0065] At least a portion of the inner surface may be provided with at least one layer or coating, the at least one layer or coating comprising a material that is substantially non-reflective with respect to at least the peak wavelength of the radiation emitted by the at least one radiation emitter.

[0066] The at least one radiation emitter can be configured to emit radiation toward the detection site array along an asymmetric optical path.

[0067] The at least one radiation emitter may include multiple radiation emitters.

[0068] The first of the plurality of radiation emitters can be configured to emit radiation toward the detection site array along a first radiation path.

[0069] The second of the plurality of radiation emitters can be configured to emit radiation toward the detection site array along a second radiation path.

[0070] The first radiation path and the second radiation path can be asymmetric.

[0071] The width, and / or length, and / or cross-section, and / or shape, and / or size of the first radiation path may differ from the width, and / or length, and / or cross-section, and / or shape, and / or size of the second radiation path.

[0072] The method may include: providing at least one radiation emitter configured to emit radiation toward the detection site array along an asymmetric radiation path. The method may also include: configuring at least one radiation emitter to emit radiation toward the detection site array along an asymmetric radiation path.

[0073] The at least one radiation emitter may include multiple radiation emitters.

[0074] The method may further include: configuring a first radiation emitter among the plurality of radiation emitters to emit radiation toward the detection site array along a first radiation path. The method may further include: configuring a second radiation emitter among the plurality of radiation emitters to emit radiation toward the detection site array along a second radiation path. The first radiation path and the second radiation path may be asymmetrical. The width, and / or length, and / or cross-section, and / or shape, and / or size of the first radiation path differs from the width, and / or length, and / or cross-section, and / or shape, and / or size of the second radiation path.

[0075] The method may further include: providing a first radiation emitter among the plurality of radiation emitters, the first radiation emitter being configured to emit radiation toward the detection site array along a first radiation path. The method may further include: providing a second radiation emitter among the plurality of radiation emitters, the second radiation emitter being configured to emit radiation toward the detection site array along a second radiation path. The first radiation path and the second radiation path may be asymmetrical. The width, and / or length, and / or cross-section, and / or shape, and / or size of the first radiation path differs from the width, and / or length, and / or cross-section, and / or shape, and / or size of the second radiation path.

[0076] The processing system can be configured to receive at least one image of the array of detection sites. The processing system can be configured to process the at least one image for each of the detection sites to determine at least one metric, the at least one metric representing the degree of response at the detection site. The processing system can be configured to determine one or more parameters for each of the detection sites, wherein the parameters for at least one detection site in the array of detection sites are different from the parameters for at least one other detection site in the array of detection sites. The processing system can be configured to determine the degree of response at the detection site for each detection site based on the at least one metric for the detection site and based on the one or more parameters for the detection site.

[0077] The processing system may include a data storage device. The processing system may include a communication module. The processing system may include one or more output devices. The processing system may include one or more input devices.

[0078] The processing system may include one or more processors, which may be single-core or multi-core processors. The one or more processors may include one or more central processing units, graphics processing units, mathematical coprocessors, tensor processing units, etc. Data storage may include solid-state memory, magnetic memory, optical memory, etc. The communication unit may be configured to communicate via wired and / or wireless communication, and may be configured to communicate with remote and / or local systems, for example, via a network (such as a LAN, WAN, the Internet, one or more cellular networks, Ethernet, fiber optic networks, etc.). The at least one output device may include a display or other visual output device, an audio output device, and / or a haptic output device.

[0079] At least one input device may include a keyboard, touchscreen, trackball, touchpad, joystick, voice recognition-based input device, etc. The input device may also include machine-readable data devices (such as barcodes or QR codes), other machine-readable code scanners, RFID tag readers, optical tag readers, etc.

[0080] The analysis system may further include a computer program product comprising instructions that, when executed on the processing system, cause the processing system to analyze the detection site array using a bright-field microscope.

[0081] According to a fourth aspect of this disclosure, a method is provided to adapt an analysis system for analyzing a detection site array using a bright-field microscope, the method comprising: providing a module including a plurality of radiation emitters and a diffuser, the diffuser being spaced apart from the plurality of radiation emitters by a spacer; and arranging the module relative to the detection site array such that a radiation path extends from each of the plurality of radiation emitters through the diffuser and onto the detection site array; wherein the plurality of radiation emitters are configured to emit radiation toward the detection site array along an asymmetric radiation path.

[0082] The plurality of radiation emitters can be arranged such that the radiation path extends in a direction inclined to the plane defined by the array of detection sites.

[0083] The spacer may include a housing configured to surround the diffuser. At least a portion of the inner surface of the housing may be substantially non-reflective to the peak wavelength of the radiation emitted by the at least one radiating emitter. At least a portion of the inner surface may be provided with at least one layer or coating comprising a material substantially non-reflective to at least the peak wavelength of the radiation emitted by the plurality of radiating emitters.

[0084] According to a fifth aspect of this disclosure, an analysis system is provided for analyzing one or more detections performed at corresponding detection sites in a detection site array, the analysis system being adapted to use a bright-field microscope by performing the methods of the fourth aspect.

[0085] According to a fifth aspect of this disclosure, an analysis system is provided adapted to analyze a detection site array using a bright-field microscope. The analysis system includes: a detection site array; and a module comprising a plurality of radiation emitters and a diffuser, the plurality of radiation emitters being configured to emit radiation, the diffuser being spaced apart from the plurality of radiation emitters by spacers; wherein: the module is positioned relative to the detection site array such that a radiation path extends from the plurality of radiation emitters through the diffuser and reaches the detection site array; wherein the plurality of radiation emitters are configured to emit radiation toward the detection site array along an asymmetric radiation path.

[0086] The plurality of radiation emitters can be arranged such that the radiation path extends in a direction inclined to the plane defined by the array of detection sites.

[0087] The spacer may include a housing configured to surround the diffuser. At least a portion of the inner surface of the housing may be substantially non-reflective to the peak wavelength of the radiation emitted by the at least one radiating emitter. At least a portion of the inner surface may be provided with at least one layer or coating comprising a material substantially non-reflective to at least the peak wavelength of the radiation emitted by the plurality of radiating emitters.

[0088] The foregoing "Summary of the Invention" is intended to be exemplary and not restrictive. Whether stated as a combination or individually specifically (including the claimed matters), this disclosure includes one or more corresponding aspects, embodiments, or features, individually or in various combinations. It should be understood that features defined above according to any aspect of this disclosure or hereinafter with respect to any specific embodiment of this disclosure may be used alone or in combination with any other defined features in any other aspect or embodiment, or features defined above according to any aspect of this disclosure or hereinafter with respect to any specific embodiment of this disclosure may be used to form another aspect or embodiment of this disclosure. Attached Figure Description

[0089] These and other aspects of this disclosure will now be described by way of example only with reference to the accompanying drawings, in which:

[0090] Figure 1 This is a flowchart illustrating a method for adapting an analysis system to use a bright-field microscope according to an exemplary embodiment of the present disclosure.

[0091] Figure 2 This is a perspective view illustrating a module according to an exemplary embodiment of the present disclosure.

[0092] Figure 3 yes Figure 2 The example module is shown in perspective, with the module's sidewalls and adapter plate removed.

[0093] Figure 4 yes Figure 2 An exploded perspective view of the example module in the example.

[0094] Figure 5 yes Figure 2 An enlarged exploded perspective view of a portion of the adapter board of the example module.

[0095] Figure 6 This is an enlarged perspective view of an alternative adapter board according to an exemplary embodiment of the present disclosure.

[0096] Figure 7 It is set relative to the detection site array. Figure 2 A side view of the module's diagram.

[0097] Figure 8 This is a schematic diagram of an analytical system suitable for use with a bright-field microscope, according to an exemplary embodiment of the present disclosure.

[0098] Figure 9a It is an image of a blank detection site array captured by the imaging apparatus of an analysis system according to an example embodiment of the present disclosure.

[0099] Figure 9b yes Figure 9a Example lighting contours in the image.

[0100] Figure 10a It is an example illumination profile based on an analytical system suitable for use with a bright-field microscope.

[0101] Figure 10b This is another example of illumination profile based on an analytical system suitable for use with a bright-field microscope.

[0102] Figure 11 These are plan views, side views, and perspective views of an example module frame including adapter board holes according to embodiments of the present disclosure.

[0103] In the accompanying drawings, similar parts are indicated by similar reference numerals.

[0104] It will be understood that the accompanying drawing is for illustrative purposes only and is not drawn to scale. Detailed Implementation

[0105] Figure 1 This is a flowchart outlining method 100, which adapts an analysis system for analyzing a detection site array using a bright-field microscope. The analysis system can be used to analyze one or more detections performed at corresponding detection sites in the detection site array, for which bright-field microscopy is the preferred analytical method, as will be apparent to those skilled in the art. The method includes: providing a module at step S110 comprising at least one radiation emitter and a diffuser, the diffuser being spaced apart from the at least one radiation emitter by a spacer. Then, at step S120, positioning the module in the analysis system relative to the detection site array such that radiation paths emitted from the radiation emitter(s) extend from the radiation emitter(s) through the diffuser and incident on the detection site array.

[0106] Multiple radiation emitters are arranged in or on the module such that the radiation path extends in a direction inclined to the plane defined by the detection site array. In other words, the radiation path is not perpendicular to the surface of the detection site array; for example, the multiple radiation emitters are not arranged directly above the detection site array.

[0107] Figures 2 to 5 An example embodiment of module 200 is shown, which can be used for Figure 2 Method 100 in the middle is used to adapt the analysis system to use a bright-field microscope.

[0108] Figure 2This is a perspective view of the module 200 mounted on the base 300. The base 300 is configured to fit into a specific area within the analysis system to allow the module 200 to be positioned relative to an array of detection sites included in the analysis system, so that the analysis system is suitable for analyzing detections performed at the detection sites using a bright-field microscope.

[0109] Module 200 includes a frame 210. The frame 210 includes two walls 212 and a top surface 214 extending between the two walls 212 and connecting to each of the two walls 212 at their upper edges to form an arched structure. The top surface 214 includes a hole 235 configured to releasably receive an adapter plate 230. The adapter plate 230 includes two holes 222 (e.g., ...). Figure 5 As shown), the two openings 222 are configured to releasably receive two radiation emitters 220. The radiation emitters 220 are oriented such that the emitting surfaces of the radiation emitters 220 are guided into the frame 210, i.e., in... Figure 2 As shown in the downward direction. Module 200 also includes two selectively removable sidewalls 240 disposed on the open side of frame 210. Frame 210, adapter plate 230, radiation emitter 220, and sidewalls 240 together form a housing that is open on the side opposite to the opening 235.

[0110] The inner surfaces (invisible) of module 200 (i.e., the inner surfaces of frame 210, sidewall 240, and adapter plate 230) are coated (e.g., painted, powder-coated, sprayed, etc.) such that the inner surfaces of module 200 are substantially non-reflective with respect to the peak wavelength of the radiation emitted by radiator 220. This reduces unwanted internal reflections within module 200, thereby allowing for more precise control of the radiation incident on the detection site array. Alternatively, one or more of frame 210, sidewall 240, and adapter plate 230, or each of them, may be made of a material that is substantially non-reflective with respect to the peak wavelength of the radiation emitted by radiator 220.

[0111] In this example, module 200 includes two radiation emitters 220, each emitting radiation (e.g., UV light) with the same peak wavelength. However, it will be understood that the number of radiation emitters 220 and the peak wavelength of the emitted radiation can depend on the analysis system, the number of detection site arrays to be analyzed, the type of analysis to be performed, or other relevant parameters or properties of the analysis or analysis system. Radiation emitters 220 can be removed and / or replaced in adapter board 230 (e.g., as referenced below). Figure 5(as described above). Alternatively, the adapter board 230 including the radiation emitter 220 can be removed, and / or replaced with an alternative adapter board 230 including a different number of radiation emitters 220, an adapter board 230 including radiation emitters 220 with an alternative arrangement or configured to emit radiation with different peak wavelengths, or a combination thereof. This provides a highly flexible and customizable module 200 that can be easily and quickly adapted to a specific analysis or analytical system.

[0112] Alternatively, the adapter board 230 can be omitted from module 200. In this case, the upper surface 214 may include a plurality of holes, each configured to releasably receive the radiation emitter 220.

[0113] The radiator 220, adapter plate 230, and / or sidewall 240 can be secured to the frame 210 and / or to each other using friction fit, magnetic closure, mechanical fasteners (e.g., screws, nuts, and bolts), or any other suitable securing method. Alternatively, the radiator 220, adapter plate 230, and sidewall 240 can be permanently secured to the frame 210 and / or to each other using adhesives or welding. Alternatively, the frame 210 can be manufactured with one or more sidewalls 240 and / or adapter plates 230 integrated into the frame 210. Alternatively, one or more sidewalls 240 can be omitted.

[0114] Figure 3 yes Figure 2 The diagram shows a perspective view of module 200, with sidewalls 240 and adapter plate 230 (including the radiation emitter 220) removed to expose the interior of module 200. The inner surface of each of the walls 212 includes a plurality of protrusions 260 configured to releasably receive the diffuser 250. Figure 3 As shown, protrusions 260 form two identical rows of irregularly distributed protrusions 260 arranged along each of the outer edges of the outer edges on the inner surface of each wall 212. The protrusions 260 are configured to align the diffuser 250 in a plane spaced apart from and substantially parallel to the plane defined by the top surface 214 of the frame 210. The top surface 214 includes a hole 235 configured to releasably receive the adapter plate 230, as referenced above. Figure 2 As stated above.

[0115] In this example, module 200 includes a single diffuser 250, which, in use, is spaced apart from the radiation emitter 220 by being positioned within frame 210. However, it will be understood that the number and spacing of the diffusers 250 can depend on the number of radiation emitters 220, the peak wavelength of the emitted radiation, the analysis system, the number of detection sites to be analyzed, the type of analysis to be performed, or any other relevant parameters or properties of the analysis or analysis system.

[0116] In this example, the diffuser 250 comprises a 1.5 mm thick glass diffuser. However, it will be understood that the thickness and construction of the diffuser can depend on the number of radiation emitters 220, the peak wavelength of the emitted radiation, the analysis system, the number of detector sites to be analyzed, the type of analysis to be performed, or any other relevant parameter or property of the analysis or analysis system. Alternatively, the diffuser can be a holographic diffuser, a white diffuse glass diffuser, a frosted glass diffuser, or any other diffuser arrangement, or a combination thereof, that increases the uniformity of radiation incident on and propagating through the diffuser.

[0117] It will be understood that the protrusion 250 is merely an example method of releasably receiving the diffuser 250. Alternatively / additionally, the inner surface of the wall 212 may include slots, notches, holes, or other suitable devices for supporting the diffuser at a predetermined distance from the radiator 220. Alternatively, the inner surface of the wall 212 may include a single set of protrusions, slots, notches, holes, etc., to provide a single spaced configuration of the diffuser 250 and the radiator 220.

[0118] Figure 4 yes Figure 2 An exploded perspective view of module 200. This shows the components of module 200, which can be selectively removed from frame 210 for repair, cleaning, replacement, and / or substitution. This provides module 200 that can be easily maintained and / or quickly adapted to specific analytical applications. See also the following references. Figure 5 As described above, the radiation emitter 220 can be selectively removed from the adapter board 230. For example... Figure 2 As shown, when the adapter board 230 is placed in the frame 210, the radiation emitter 220 can also be selectively removed.

[0119] Figure 5 yes Figure 2An enlarged exploded partial perspective view of the adapter plate 230 and a radiator 220. To releasably receive each of the radiators 220, the adapter plate 230 includes an aperture 222 and a recessed circumferential lip 225. The aperture 222 is configured to receive the radiator 220, and the recessed circumferential lip 225 is configured to support the outer edge of the radiator 220. The lip 225 prevents the radiator 220 from completely passing through the aperture 222. The adapter plate 230 also includes a plurality of smaller apertures 226 (two smaller apertures 226 in this example), each aperture 226 being configured to receive a mechanical fastener (not shown), such as a bolt secured using a nut. Alternatively, the smaller apertures 226 have internal threads to accommodate threaded bolts or screws, etc.

[0120] In use, the radiation emitter 220 is positioned within the hole 222, such that the emitting surface of the radiation emitter 220 is guided away from the adapter plate 230, i.e., in the upward direction, as... Figure 5 As shown. Insert the bolt into the smaller hole 226 until the head of the bolt engages with the emitting surface of the radiator 220. Then, secure the nut to the bolt's shaft to secure the radiator 220 to the adapter plate 230. Then, insert the adapter plate 230 into the hole 235 (as shown). Figure 2 and Figure 3 As shown), this guides the emitting surface of the radiation emitter 220 into the frame 210, i.e., in such a way... Figure 2 As shown in the downward direction.

[0121] Figure 6 This is an enlarged partial perspective view of the radiation emitter 220 disposed in the alternative adapter plate 230. In this example, the adapter plate includes an additional portion 232 disposed at an angle to the surface of the adapter plate 230. In this example, a smaller aperture 226 (not visible) extends through the adapter plate 230 at an angle such that when the radiation emitter 220 and the additional portion 232 are disposed in the adapter plate 230, the radiation path of the radiation emitted by the radiation emitter 220 is angled from the surface of the adapter plate at this angle. This arrangement allows for further control of the angle of the radiation path relative to the detection site array of the analysis system, in which the module 200 is disposed or on the detection site array.

[0122] Figure 7 This is a side view of an example analysis system 1000, which includes a module 700 positioned relative to a microarray 770 (the module 700 may be...). Figures 2 to 5Module 100 of the microarray 770 includes two detection site arrays 772. Module 700 includes a frame 710, an adapter plate 730, and two radiation emitters 720a and 720b. The adapter plate 730 is disposed in a hole on the top surface of the frame 710, and the two radiation emitters 720a and 720b are disposed in holes on the adapter plate 730. The frame 710 also includes a plurality of slots 760 that partially extend into the inner surface of the side portion of the frame 710. A diffuser 750 is disposed in the lowest slot 760, such that the diffuser 750 is spaced apart from the radiation emitters by a distance d1, and such that the diffuser 750 is spaced apart from the upper surface 775 of the microarray 770 by a distance d2.

[0123] The analysis system 1000 also includes an imaging device 780, which includes a field of view depicted by dashed lines 785a, 785b, and is configured to collect at least one image of at least one array of the detection site array 772. Figure 7 In the example, the imaging device is a digital camera; however, the image collection device may take other forms that those skilled in the art will understand. By arranging the radiation emitters 720a and 720b at the outer ends of the field of view 785a and 785b of the imaging device 780, the gradient (especially the ROI gradient) is significantly reduced.

[0124] After and / or during the detection procedure, a certain volume of fluid 777 remains within each detection site array 772, and this volume of fluid 777 cannot be easily removed before analysis without damaging or affecting the analytical results and / or detection results. Figure 7 As shown, the fluid 777 forms a convex lens shape that protrudes from the upper surface 775 of the microarray 770. By arranging the radiation emitters 720a and 720b such that the radiation path extends from the radiation emitters through the diffuser 750, through the detection site array 772, and is incident on the imaging device 780 in a direction inclined to the plane defined by the upper surface 775 of the microarray, any distortion of the image captured by the imaging device 780 due to the lensing effect is significantly reduced. Furthermore, the gradient (and particularly the ROI gradient) is further reduced.

[0125] Although not in Figure 7While depicted herein, it will be understood that in some examples, radiation emitters 720a and 720b may be configured to emit radiation toward the microarray 770 (e.g., toward the detection site array 772) along an asymmetric radiation path. That is, in the examples, a first radiation emitter 720a of a plurality of radiation emitters may be configured to emit radiation toward the detection site array 772 along a first radiation path depicted by a first dashed line 785a, and a second radiation emitter 720b of a plurality of radiation emitters may be configured to emit radiation toward the detection site array 772 along a second radiation path depicted by a corresponding second dashed line 785b. In some examples, the first radiation path 785a and the second radiation path 785b may be asymmetric. For example, the width, and / or length, and / or cross-section, and / or shape, and / or size of the first radiation path 785a may differ from the width, and / or length, and / or cross-section, and / or shape, and / or size of the second radiation path 785b.

[0126] Figure 8 A detection analysis system 1000 is shown, which is used to analyze detections performed in a microarray 870 (such as a multiplexed microarray or hybrid array) comprising multiple detection sites, wherein a separate detection can be performed at each detection site. The system 1000 includes one or more imaging devices or sensors (in this example, in the form of a digital camera 880) configured to collect images of the microarray 870. Although in Figure 8 Only one camera 880 is shown, but more than one camera 880 may be provided. In this example, camera 880 is configured to capture an image of the entire microarray 870, for example, the field of view defined by the dashed line 885 of camera 880 covers the entire microarray 870, or at least all of the detection sites of microarray 870. However, camera 880 may be configured to capture images of only some of the detection sites of microarray 870, or different cameras 880 may be configured to capture images of different subsets of the detection sites of microarray 870, or may be configured to capture microarray 870 from different angles. System 1000 includes an analysis instrument 890 that receives the image collected by camera 880 and is configured to analyze the image to determine the reaction state at a specific detection site of microarray 870.

[0127] The analysis system 1000 includes a processing system 892, a data storage 894, a communication module 896, one or more output devices 898, and one or more user input devices 899. The processing system 892 includes one or more processors, which may be single-core or multi-core processors. The one or more processors include one or more central processing units, and optionally also include one or more graphics processing units, mathematical coprocessors, tensor processing units, etc. The data storage 894 may include solid-state memory, magnetic storage, optical storage, etc. The communication unit 896 may be configured to communicate via wired and / or wireless communication. In this example, the communication unit 896 is configured to communicate with remote and / or local systems, for example, via a network (such as a LAN, WAN, the Internet, one or more cellular networks, Ethernet, fiber optic networks, etc.). The at least one output device 898 may include a display or other visual output device, an audio output device, and / or a haptic output device. At least one input device 899 may include one or more of the following: keyboard, touch screen, trackball, touchpad, joystick, voice recognition-based input device, RFID tag reader, barcode or QR code reader, etc.

[0128] By providing a module comprising two radiation emitters 820 and a diffuser 850 spaced apart from the radiation emitters 820, and by arranging the module relative to the microarray 870 such that a radiation path extends from the radiation emitters 820 through the diffuser 850 and onto the microarray 870, the analysis system 1000 is adapted to analyze an array of detection sites included in the microarray 870 using a bright-field microscope. The radiation emitters 820 are arranged such that the radiation path extends in a direction inclined to the plane defined by the microarray 870.

[0129] Figure 9a and Figure 9b An example method is shown for determining the uniformity of radiation incident on an array of detection sites included in an analytical system suitable for use with a bright-field microscope.

[0130] Figure 9a It is composed of analytical systems suitable for use with bright-field microscopes (such as...) Figure 8 The analysis system 1000 captures a grayscale image 900 of a blank detection site array using its imaging device. The proficiency of the analysis system in using a bright-field microscope is highly dependent on the uniformity of the radiation incident on the detection site array. Therefore, it is necessary to objectively measure the uniformity of the radiation incident on the detection site array as different parameters of the modules set in the analysis system change. The inventors use gradients and / or ROI gradients to evaluate the uniformity of the radiation incident on the detection site array.

[0131] like Figure 9a As shown, draw a straight horizontal line 910 through the center of the captured image 900. Determine the "grayscale value" of each point or pixel along line 910, where a value of "0" represents black, a value of "255" represents white, and intermediate values ​​represent shades of gray in between. Figure 9b The diagram shows the grayscale value of image 900 as a function of the length along line 910. This graph is also referred to as an "illumination profile," and the term can be used to refer to such a graph within this disclosure.

[0132] like Figure 9b As shown, on the portion of line 910 outside the detection site array, the grayscale value is 0 or approximately 0. This is determined in... Figure 9b The average grayscale values ​​between the dashed lines marked "BEG" are determined, and similarly, the average grayscale values ​​between the dashed lines marked "END" are determined. The absolute difference between the "END" average and the "BEG" average is called the gradient or global gradient, which is a measure of the uniformity of radiation incident on the detector site array, which includes regions located outside the regions containing the detector sites.

[0133] Alternatively, determine in Figure 9b The average grayscale values ​​between the solid lines marked "BEG ROI" are determined, and similarly, the average grayscale values ​​between the solid lines marked "END ROI" are determined. The absolute difference between the "END ROI" average and the "BEG ROI" average is called the ROI gradient, which is a measure of the uniformity of radiation incident on an array of detection sites that includes only the regions containing the detection sites. Using these measurements of the gradient and the ROI gradient, the effect of placing diffusers and / or radiation emitters at different locations within the adapter module can be calculated.

[0134] Figure 10a and Figure 10b Illumination contours 960 and 970 are shown, which illustrate: in Figure 2 Within the framework of module 200, the effect of changing the positions of the diffuser and radiation emitter on the uniformity of radiation incident on the detection site array is investigated.

[0135] Figure 10a The illustration shows the lighting profile produced by using a module comprising a single radiating emitter, wherein the diffuser is positioned close to the single radiating emitter, for example, set at... Figure 7 In the uppermost slot 760 of module 700. Curve 962 shows the lighting profile when a single radiating emitter is positioned to the right of the centerline of the top surface of the frame. (As shown...) Figure 10aAs shown, for curve 962, the grayscale value is larger on the side of the detection site array corresponding to the position of the radiating emitter. Similarly, curve 964 shows the illumination profile when a single radiating emitter is arranged to the left of the centerline of the top surface of the frame. Figure 10a As shown in curve 964, the grayscale value is larger on the side of the detection site array corresponding to the radiation emitter location. This results in a high gradient and ROI gradient, which will not produce accurate detection analysis results.

[0136] Figure 10b The illustration shows the lighting profile produced by using a module comprising a single radiating emitter, wherein the diffuser is positioned away from the single radiating emitter, for example, set at... Figure 7 In the lowest slot 760 of module 700. Similar to curves 962 and 964, corresponding curves 972 and 974 show the illumination profiles when a single radiating emitter is arranged on the right and left sides respectively. Figure 10b As shown, when with Figure 10a In comparison, the gradient, and especially the ROI gradient, is significantly reduced, thereby improving the performance of the analysis system.

[0137] In this way, those skilled in the art will understand that the optimal location, number, orientation, etc., of the diffuser and (multiple) radiation emitters can be determined for a specific analytical system, the sample being tested, or the required analytical process. The features in the disclosed module and the method of setting up the disclosed module provide a flexible, highly adjustable technique for adapting an analytical system to use a bright-field microscope.

[0138] Figure 11 It shows in Figures 2 to 5 Example frame 210 used in module 200. For non-limiting example purposes only, frame 210 has a length X1 of 95±5 mm, a width Y1 of 20±5 mm, and a depth Z1 of 65±5 mm. Frame 210 includes an elongated hole 235 on its upper flat surface. Hole 235 has a length X2 of 65±5 mm and a width Y2 of 15±5 mm. However, these dimensional ranges should not be construed as limiting the scope of the claimed subject matter.

[0139] Those skilled in the art will understand that these size ranges are provided for illustrative purposes only to give a general indication of the size levels, and that other sizes may be used depending on the application and the device used. It will be understood that for... Figures 2 to 5For module 200, the dimensions of frame 210 and aperture 235 are specific, and may be specific for the analytical system and the desired properties of the resulting detection analysis. That is, in other examples of the disclosed frame 210, the dimensions may be substantially different. For example, frames 210 falling within the scope of this disclosure may be significantly larger, smaller, and / or may include dimensions at a different scale than those provided herein.

[0140] While this disclosure has been described with reference to preferred embodiments as described above, it should be understood that these embodiments are merely illustrative and the claims are not limited to those embodiments. Modifications and substitutions will be possible for those skilled in the art based on this disclosure, and such modifications and substitutions are considered to fall within the scope of the appended claims. Each feature disclosed or illustrated in this specification may be incorporated into this disclosure, either alone or in any suitable combination with any other feature disclosed or illustrated herein.

Claims

1. A method for adapting an analysis system to analyze a detection site array using a bright-field microscope, the method comprising: A module is provided, the module comprising at least one radiation emitter and a diffuser, the diffuser being spaced apart from the at least one radiation emitter by a spacer; The module is positioned relative to the detection site array such that a radiation path extends from the at least one radiation emitter through the diffuser and reaches the detection site array; The at least one radiation emitter is arranged such that the radiation path extends in a direction inclined relative to the plane defined by the array of detection sites.

2. The method as described in claim 1, wherein, The spacer includes a housing configured to surround the diffuser.

3. The method as described in claim 2, wherein, At least a portion of the inner surface of the housing is substantially non-reflective with respect to the peak wavelength of the radiation emitted by the at least one radiation emitter.

4. The method of claim 3, wherein, The at least portion of the inner surface is provided with at least one layer or coating, the at least one layer or coating comprising a material that is substantially non-reflective with respect to at least the peak wavelength of radiation emitted by the at least one radiation emitter.

5. The method as claimed in any of the preceding claims, wherein the method comprises: The at least one radiation emitter is configured to emit radiation toward the detection site array along an asymmetric radiation path.

6. The method of claim 5, wherein, The at least one radiation emitter includes a plurality of radiation emitters, and the method further includes: A first radiation emitter of the plurality of radiation emitters is configured to emit radiation toward the detection site array along a first radiation path; and The second radiation emitter among the plurality of radiation emitters is configured to emit radiation toward the detection site array along a second radiation path. The first radiation path and the second radiation path are asymmetric.

7. The method of claim 6, wherein, The width, and / or length, and / or cross-section, and / or shape, and / or size of the first radiation path are different from the width, and / or length, and / or cross-section, and / or shape, and / or size of the second radiation path.

8. The method of any of the preceding claims, further comprising spacing the diffuser relative to the at least one radiation emitter such that substantially uniformly distributed radiation is incident on the array of detection sites.

9. The method as claimed in any of the preceding claims, wherein, The module includes multiple radiation emitters.

10. The method as claimed in any of the preceding claims, wherein, At least two of the plurality of radiators are configured to emit radiation with different peak wavelengths.

11. The method as claimed in any of the preceding claims, wherein, The spacer includes an adapter plate configured to releasably receive the at least one radiation emitter.

12. The method as claimed in any of the preceding claims, wherein, The spacer includes a frame configured to releasably receive the diffuser.

13. The method of claim 12, wherein, when subordinate to claim 11, The frame is also configured to receive the adapter board in a releasable manner.

14. The method of any preceding claim, further comprising implementing a computer program on the analysis system, the computer program including instructions that, when implemented on the analysis system, cause the analysis system to analyze the detection site array using a bright-field microscope.

15. An analysis system for analyzing one or more detections performed at corresponding detection sites in a detection site array, the analysis system being adapted to use a bright-field microscope by performing the method of any one of claims 1 to 14.

16. An analytical system adapted to analyze a detection site array using a bright-field microscope, the analytical system comprising: Detection site array; Module, the module includes: At least one radiation emitter, the at least one radiation emitter being configured to emit radiation; and A diffuser, the diffuser being spaced apart from the at least one radiation emitter by a spacer; in: The module is positioned relative to the detection site array such that a radiation path extends from the at least one radiation emitter through the diffuser and reaches the detection site array; and The at least one radiation emitter is arranged such that the radiation path extends in a direction inclined relative to the plane defined by the array of detection sites.

17. The analysis system of claim 16, wherein, The spacer includes a housing configured to surround the diffuser.

18. The analysis system of claim 17, wherein, For the peak wavelength of the radiation emitted by the at least one radiation emitter, at least a portion of the inner surface of the housing is substantially non-reflective.

19. The analysis system of claim 18, wherein, The at least portion of the inner surface is provided with at least one layer or coating, the at least one layer or coating comprising a material that is substantially non-reflective with respect to at least the peak wavelength of radiation emitted by the at least one radiation emitter.

20. The analysis system of any one of claims 16 to 19, wherein the analysis system comprises configuring the at least one radiation emitter to emit radiation toward the detection site array along an asymmetric radiation path.

21. The analysis system as described in claims 16 to 20, wherein, The at least one radiation emitter includes a plurality of radiation emitters, and wherein: The first of the plurality of radiation emitters is configured to emit radiation toward the detection site array along a first radiation path; and The second of the plurality of radiation emitters is configured to emit radiation toward the detection site array along a second radiation path. The first radiation path and the second radiation path are asymmetric.

22. The analysis system of claim 21, wherein, The width, and / or length, and / or cross-section, and / or shape, and / or size of the first radiation path are different from the width, and / or length, and / or cross-section, and / or shape, and / or size of the second radiation path.

23. The analysis system of any one of claims 16 to 22, further comprising an imaging device configured or configured to collect at least one image of the detection site array.

24. The analysis system of any one of claims 16 to 23, further comprising a processing system, the processing system including at least one processing device, a data storage device, and a communication system, the communication system being configured to receive the at least one image and output an indication of the degree of reaction at the detection sites in the detection site array, wherein, The imaging device is also configured to transmit the at least one image to the processing system.

25. The analysis system of any one of claims 16 to 24, further comprising an output device configured to receive from the processing system an indication of the degree of reaction at the detection site, and to output the indication of the degree of reaction at the detection site.

26. The analysis system of any one of claims 16 to 25, further comprising a computer program product including instructions that, when executed on the processing system, cause the processing system to analyze the detection site array using a bright-field microscope.

27. A method for adapting an analysis system to analyze an array of detection sites using a bright-field microscope, the method comprising: A module is provided, the module comprising a plurality of radiation emitters and a diffuser, the diffuser being spaced apart from the plurality of radiation emitters by spacers; The module is positioned relative to the detection site array such that a radiation path extends from each of the plurality of radiation emitters through the diffuser and reaches the detection site array; The plurality of radiation emitters are configured to emit radiation toward the detection site array along an asymmetric radiation path.

28. The method of claim 27, wherein, The plurality of radiation emitters are arranged such that the radiation path extends in a direction inclined to the plane defined by the array of detection sites.

29. The method of claim 27 or 28, wherein, The spacer includes a housing configured to surround the diffuser.

30. The method of claim 29, wherein, At least a portion of the inner surface of the housing is substantially non-reflective with respect to the peak wavelength of the radiation emitted by the at least one radiation emitter.

31. The method of claim 30, wherein, The at least portion of the inner surface is provided with at least one layer or coating, the at least one layer or coating comprising a material that is substantially non-reflective with respect to at least the peak wavelength of the radiation emitted by the plurality of radiation emitters.

32. An analysis system for analyzing one or more detections performed at corresponding detection sites in an array of detection sites, the analysis system being adapted to use a bright-field microscope by performing the method of any one of claims 27 to 31.

33. An analytical system adapted to analyze a detection site array using a bright-field microscope, the analytical system comprising: Detection site array; Module, the module includes: Multiple radiation emitters, the multiple radiation emitters being configured to emit radiation; and A diffuser, which is spaced apart from the plurality of radiation emitters by spacers; in: The module is positioned relative to the detection site array such that a radiation path extends from the plurality of radiation emitters, passes through the diffuser, and reaches the detection site array; The plurality of radiation emitters are configured to emit radiation toward the detection site array along an asymmetric radiation path.

34. The system of claim 33, wherein, The plurality of radiation emitters are arranged such that the radiation path extends in a direction inclined relative to the plane defined by the array of detection sites.

35. The system as described in claim 33 or 34, wherein, The spacer includes a housing configured to surround the diffuser.

36. The system of claim 35, wherein, At least a portion of the inner surface of the housing is substantially non-reflective with respect to the peak wavelength of the radiation emitted by the at least one radiation emitter.

37. The system of claim 36, wherein, The at least portion of the inner surface is provided with at least one layer or coating, the at least one layer or coating comprising a material that is substantially non-reflective with respect to at least the peak wavelength of the radiation emitted by the plurality of radiation emitters.

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