FLOOR LIGHTING MODULE

RU2026115898APending Publication Date: 2026-09-07QBD QS IP
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Patent Information

Application Number
RU2026115898
Authority / Receiving Office
RU · RU
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-10-26
Filing Date
2024-10-25
Publication Date
2026-09-07

AI Technical Summary

Technical Problem

Existing analysis systems face challenges in adapting to brightfield microscopy, particularly due to the 'lens effect' caused by fluid surface tension, which distorts images and reduces analysis repeatability and effectiveness.

Method used

A module comprising at least one radiation emitter and a diffuser, spaced from the emitter by a spacer, is disposed relative to the array of assay sites such that the radiation path extends in an oblique direction, reducing the lens effect and enabling easy adaptation of analysis systems to brightfield microscopy with minimal hardware changes.

Benefits of technology

The solution allows for simple and quick adaptation of analysis systems to brightfield microscopy, reducing image distortion and enhancing the repeatability and effectiveness of assay analysis by providing a homogeneous radiation distribution and minimizing the lens effect.

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Abstract

A method of adapting an analysis system to use brightfield microscopy to analyse an array of assay sites, the method comprising: providing a module comprising at least one radiation emitter and a diffuser spaced from the at least one radiation emitter by a spacer; disposing the module relative to the array of assay sites such that a radiation path extends from the at least one radiation emitter, through the diffuser and onto the array of assay sites; wherein the at least one radiation emitter is arranged such that the radiation path extends in a direction oblique to a plane defined by the array of assay sites.
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Description

[0001] BRIGHTFIELD ILLUMINATION MODULE

[0002] FIELD

[0003] The present disclosure relates to a method of adapting an assay analysis system to brightfield microscopy. Also disclosed is an assay analysis system adapted to brightfield microscopy using the method.

[0004] BACKGROUND

[0005] Analysis systems are available for automating the analysis of chemical, biochemical or immunological assays. Such assays can be performed in a regular array of print areas that are configured to hold reactants and a test sample. Such assays generally test for the presence or level of an analyte in the test sample. A response, often in the form of a change in degree of opacity, colour, size or other detectable change, is associated with the presence or level of the analyte. The analysis system is provided with a sensor, typically a digital camera, for identifying the response in each print in the array. In this way, for example, the digital camera image can be reviewed and the response (e.g. degree of change in colour or opacity) can be identified in order to determine the presence or level of analyte in any given print area.

[0006] Typically, analysis systems will use either darkfield or brightfield illumination techniques in combination with the sensor to enable the analysis system to detect the response in the test samples. Darkfield illumination is a technique in optical microscopy that eliminates scattered light from the image collected by the sensor. This yields an image with a ‘dark’ background around the test sample. This is particularly beneficial for analysis of live cellular samples which cannot be stained or samples which have not gone through the staining process. However, using darkfield illumination techniques can produce images with low light levels, meaning that the sample may have to be strongly illuminated, potentially causing damage to the sample. Although darkfield microscopy can produce images with increased contrast, this may come at the cost of reduced sensitivity, resulting in relatively darker features of the image being difficult to detect and / or analyse. In brightfield illumination, radiation (e.g. light) propagates through the sample, and is imaged by the sensor, which is positioned on the opposite side of the sample from the light source. Contrast in the image is caused by attenuation of the transmitted light in dense areas of the sample, as denser samples absorb more light. Brightfield illumination is an extremely simple technique which allows greater sensitivity to smaller features and improved precision and repeatability of the analysis process.

[0007] It is therefore an aim of at least one embodiment of at least one aspect of the present disclosure to provide a means for easily adapting an analysis system to use brightfield microscopy.

[0008] SUMMARY

[0009] Various aspects of the present invention are defined in the independent claims. Some preferred features are defined in the dependent claims.

[0010] According to a first aspect of the present disclosure there is provided a method of adapting an analysis system to use brightfield microscopy to analyse an array of assay sites.

[0011] The method may comprise providing a module comprising at least one radiation emitter and a diffuser spaced from the at least one radiation emitter by a spacer.

[0012] The method may comprise disposing the module relative to the array of assay sites such that a radiation path extends from the at least one radiation emitter, through the diffuser and onto the array of assay sites.

[0013] In some examples, the at least one radiation emitter may be arranged such that the radiation path extends in a direction oblique to a plane defined by the array of assay sites.

[0014] Advantageously, by providing a module which incorporates at least one radiation emitter e.g. at least one light emitting diode (LED) or the like, any pre-existing emitters in the analysis system may not need to be used but may be physically retained in the system to more easily allow the adaption to be reversed by removing the module. This provides a module that may enable a user to simply and quickly adapt an analysis system to brightfield microscopy with minimal hardware changes, and may also allow the adaption to be easily reversed.

[0015] During the assay process one or more fluids may be introduced into the array of assay sites e.g. diluents, antigens, reagents or the like, which may not be easily and / or completely removable before analysis without damaging or influencing the result of the assay. Due in part to surface tension, the fluid may form a convex shape (e.g. a convex lens shape) on the surface of the array of assay sites which may refract the radiation projected thereon. This may result in distortion of the image captured by an imaging device configured or configurable to collect images of the array of assay sites, reducing the repeatability and effectiveness of the resulting analysis results. This consequence may be referred to as a “lens effect” throughout this disclosure.

[0016] By arranging the radiation emitter(s) such that the radiation path between each radiation emitter and the array of assay sites is not perpendicular to a plane defined by the array of assay sites (i.e. at an oblique angle to the plane), the lens effect may be reduced or entirely eliminated.

[0017] It will be appreciated that the term “array of assay sites" may also be known in the art as an “array” or a “microarray”. The term “microarray” may also refer to a plurality of arrays of assay sites. The “array” may comprise only one assay site or may comprise a plurality of assay sites with one or more or each of the plurality of assay sites analysed using the analysis system. These terms may be used interchangeably within the present disclosure.

[0018] The term “diffuser” used in the present disclosure may refer to any of: a holographic diffuser; a white diffusing glass diffuser; a ground glass diffuser; or any other diffuser arrangement which increases the homogeneity of radiation incident on the diffuser which propagates through the diffuser. The diffuser may comprise a combination of diffuser elements.

[0019] The term “radiation emitter” used in the present disclosure may refer to any device configured to emit electromagnetic radiation. The emitted radiation may have a single peak wavelength or broad bandwidth combing a plurality of wavelengths. The emitted radiation may be within or beyond the visible light spectrum. The radiation may be emitted from a single face, side, aperture of the radiation emitter or emitted in multiple directions.

[0020] The method may further comprise spacing the diffuser relative to the at least one radiation emitter such that a substantially homogeneous distribution of radiation is incident upon the array of assay sites.

[0021] By disposing the diffuser(s) to create a substantially homogeneous distribution of radiation on the assay sites, cheap, widely available ‘point’ sources of light, such as LEDs, may be used in the module to illuminate the assay sites for analysis by the analysis system.

[0022] With the expression “substantially homogeneous distribution of radiation”, it is meant that the intensity and / or wavelengths of radiation incident on any point on the array of assay sites is substantially the same as the intensity of radiation incident on any other point on the array of assay sites, in other words the homogeneity of the incident radiation is high. The difference between the maximum and minimum intensity of radiation incident at all points may provide a measurement of the homogeneity and may be referred to as the “gradient” throughout this disclosure.

[0023] It will be appreciated that the array of assay sites may have a region of interest (ROI) which comprises the area occupied by a plurality of assay sites to be analysed within the array of assay sites. The homogeneity of the radiation incident on the ROI may be referred to as the ROI gradient throughout the disclosure.

[0024] The gradient and / or ROI gradient may be minimised by increasing or decreasing the distance between the radiation emitter(s) and the diffuser(s) by disposing the diffuser(s) at different positions within the spacer. The distance may be based on the number, position and / or orientation of the radiation emitter(s). The distance may be based on the peak wavelength of the radiation emitted by the radiation emitter(s). The distance may be based on the number, thickness, material or other parameter of the diffuser(s). The distance may be based on the expected residual volume of fluid remaining in the array of assay sites following the assay process. The module may comprise a plurality of radiation emitters.

[0025] Advantageously by providing more than one radiation emitter the intensity and directionality of the emitted radiation may be increased. This may allow more control over the imaging parameters of individual assay sites, depending on the assay performed, improving the performance of the adapted analysis system.

[0026] By using a plurality of identical radiation emitters, redundancy is created such that if it one of the plurality of radiation emitters fails or degrades during the assay imaging process one of the other of the plurality of radiation emitters may be used to complete the assay imaging process without disturbing the assay sites, which may damage or unduly influence the result of the assay.

[0027] At least two of the plurality of radiation emitters may be configured to emit radiation at different peak wavelengths.

[0028] Following the assay process some features of the resulting test sample may only be visible when illuminated by certain wavelengths of radiation (e.g. infrared, ultraviolet or the like). By providing radiation emitters which are configured to emit different wavelengths of radiation multiple assay sites and / or features of test samples comprised within each assay site may be more easily detected without having to repeat the assay process and / or exchange the installed radiation emitters.

[0029] The spacer may comprise an adapter plate configured to releasably receive the at least one radiation emitter.

[0030] The adapter plate may be comprised in or attached to the spacer at the opposite end to the array of assay sites. The emitters may be installed into apertures in the spacer using a temporary fixing (e.g. a screw, nut, bolt), a releasable adhesive or the like.

[0031] Advantageously, by providing a releasable means of installing the radiation emitter(s) into the module, faulty or damaged emitters may be removed and / or replaced without requiring replacement of the whole module. Furthermore, the radiation emitter(s) may be exchanged for emitters having increased / decreased intensity or emitters configured to emit radiation at different peak wavelengths. In this way the hardware configuration of the analysis system may be quickly and easily adapted to optimise the assay analysis for different assay processes and results.

[0032] The spacer may comprise a frame configured to releasably receive the diffuser.

[0033] By providing a releasable means of installing the diffuser(s) into the spacer, the configuration of the module and the analysis system into which it is disposed may be quickly and consistently tailored to particular assay analysis e.g. based on the number and / or radiation peak wavelength of the radiation emitter(s). The diffuser(s) may also be easily removed for cleaning, repair and / or replacement.

[0034] The frame may be further configured to releasably receive the adapter plate.

[0035] A plurality of adapter plates may be available or supplied or purchased each with a different configuration of radiation emitters or the same configuration of radiation emitters.

[0036] By providing a releasable means of installing the adapter plate the configuration of the radiation emitter(s) e.g. number, position, orientation of each radiation emitter, can be quickly and consistently tailored to a particular assay analysis. The adapter plate may also be easily removed for repair, exchange and / or replacement of radiation emitters.

[0037] The spacer may be an enclosure configured to enclose the diffuser. At least a part of an internal surface of the enclosure may be substantially non-reflective to the peak wavelength of the radiation emitted by the at least one radiation emitter.

[0038] The internal surface may comprise, or be coated in, a material which is substantially non-reflective to the radiation emitted by the radiation emitter(s). The internal surface may comprise a layer or coating comprising a material which is substantially non- reflective to the radiation emitted by the radiation emitter(s).

[0039] In examples, the enclosure may be a cube or cuboid box. The enclosure may be four, five or six sided. The enclosure may be selectively closable. Two or more of walls of the enclosure, e.g. sidewalls, may comprise a plurality of slots or indents or projections or the like for supporting the diffuser(s). The plurality of slots or indents or projections may be configured to support the diffuser(s) substantially parallel to the array of assay sites. The plurality of slots or indents or projections may be configured to support the diffuser(s) at a plurality of distances from the radiation emitter(s). The enclosure may have one or more removable walls or hatches for allowing the diffuser(s) to be inserted into, and removed from, the enclosure. Alternatively, the enclosure may be open at one or both or all sides which do not support the diffuser(s).

[0040] The enclosure may comprise one or more apertures. The one or more apertures may accommodate the radiation emitter(s) or the adapter plate and / or the array of assay sites. Alternatively, the enclosure may be open on the side that accommodates the array of assay sites, in use e.g. the module may be disposed such that the radiation emitted by the radiation emitter(s) propagates through the diffuser(s) and out of the open side of the box so as to be incident on the array of assay sites.

[0041] In examples where the internal surface of the enclosure at least in part comprises or is coated in a material which is substantially non-reflective to the radiation emitted by the radiation emitter(s), the enclosure may act to improve the homogeneous nature of the radiation projected onto the assay sites of the array of assay sites, for example by reducing or eliminating internal reflections within the enclosure before, during and after propagation of the radiation through the diffuser(s).

[0042] The method may further comprise implementing a computer program on the analysis system comprising instructions that, when implemented on the analysis system, cause the analysis system to analyse the array of assay sites using brightfield microscopy.

[0043] In some examples, the method may comprise configuring the at least one radiation emitter to emit radiation towards the array of assay sites following asymmetric optical pathways (herein interchangeably referred to as radiation paths or radiation pathways). For example, in a method wherein a plurality of radiation emitters are implemented, a first radiation emitter of the plurality of radiation emitters may emit radiation towards the array of assay sites along a first radiation path, and a second radiation emitter of the plurality of radiation emitters may emit radiation towards the array of assay sites along a second radiation path. The first radiation path and the second radiation path may be asymmetric. For example, a length of the first radiation path may be different from a length of the second radiation path.

[0044] By implementing such an optical system having asymmetric optical pathways, e.g. wherein radiation propagation paths (hereafter ‘radiation paths’) may differ in geometrical characteristics, a unique optical behaviour of dispersion and generation of optimal illumination may be achieved.

[0045] That is, the methods and systems described herein may relate to use of such geometrically asymmetric paths, e.g. paths having different widths and / or heights and / or cross-sectional shapes, sizes or the like. Such asymmetry may advantageously provide differing radiation propagation characteristics, thereby enabling selective light routing.

[0046] In the applications and use-cases described herein, such an ability to disperse light differently across the optical pathways may ensure more uniform and targeted illumination of a scene (e.g. of microarray wells). This may improve contrast and focus on certain regions, such as in a region of interest in said microarray wells.

[0047] Such a combination of geometric and optical design principles may provide a versatile platform for achieving high levels of control over light propagation, dispersion, and routing. Use of such asymmetric optical pathways may optimize the systems and methods described herein for specific illumination patterns, which may enhance sensing capabilities, and thus subsequent signal processing.

[0048] According to a second aspect of the present disclosure there is provided an analysis system for analysing one or more assays performed at respective assay sites of an array of assay sites, adapted to use brightfield microscopy by performing the method of the first aspect.

[0049] The analysis system may comprise a test instrument, such as a “MosaiQ™” test instrument. The MosaiQ™ test instrument may be an instrument primarily designed to analyse test samples using darkfield microscopy. By providing a module which allows adaption of the test instrument to analyse test samples using brightfield microscopy, the instrument may be used to analyse the result of assays which require brightfield illumination with minimal hardware changes to the test instrument. This may also allow the test instrument to be readily adapted back to darkfield microscopy if and when required.

[0050] According to a third aspect of the present disclosure there is provided an analysis system adapted to use brightfield microscopy to analyse an array of assay sites, the analysis system comprising: an array of assay sites; a module comprising: at least one radiation emitter configured to emit radiation; and a diffuser spaced from the at least one radiation emitter by a spacer; wherein: the module is disposed relative to the array of assay sites such that a radiation path extends from the at least one radiation emitter, through the diffuser and onto the array of assay sites; and the at least one radiation emitter is arranged such that the radiation path extends in a direction oblique to a plane defined by the array of assay sites.

[0051] The at least one image may comprise one or more images of all of the plurality of assay sites or a collection of images that individually may cover one or some of the plurality of assay sites but collectively cover all of the plurality of assay sites.

[0052] The analysis system may further comprise an imaging device configured or configurable to collect at least one image of the array of assay sites.

[0053] The radiation emitter(s) may be arranged on or beyond the edge of the field of view of the imaging device. By arranging the radiation emitter(s) in this way the diffuser is more easily able to diffuse the emitted radiation to produce the substantially homogeneous distribution of radiation incident upon the array of assay sites and the radiation emitter is not ‘visible’ in the field of view of the imaging device.

[0054] It will be appreciated that the analysis system may comprise a plurality of imaging devices, e.g. two or more imaging devices. Each imaging device may be configured to collect an image of a different array of assay sites or the same array of assay sites. The analysis system may further comprise a processing system comprising at least one processing device, data storage and a communications system for receiving the at least one image and outputting an indication of an extent of a reaction at an assay site of the array of assay sites. The imaging device may be further configured to communicate the at least one image to the processing system.

[0055] The analysis system may further comprise an output device configured to receive the indication of an extent of a reaction at the assay site from the processing system and to output the indication of an extent of a reaction at the assay site.

[0056] The spacer may comprise an enclosure configured to enclose the diffuser.

[0057] At least a part of an internal surface of the enclosure may be substantially non- reflective to a peak wavelength of the radiation emitted by the at least one radiation emitter.

[0058] The at least a part of the internal surface may be provided with at least one layer or coating comprising a material substantially non-reflective to at least the peak wavelength of radiation emitted by the at least one radiation emitters.

[0059] The at least one radiation emitter may be configured to emit radiation toward the array of assay sites following asymmetric optical pathways.

[0060] The at least one radiation emitter may comprise a plurality of radiation emitters.

[0061] A first radiation emitter of the plurality of radiation emitters may be configured to emit radiation towards the array of assay sites along a first radiation path.

[0062] A second radiation emitter of the plurality of radiation emitters may be configured to emit radiation towards the array of assay sites along a second radiation path.

[0063] The first radiation path and second radiation paths may be asymmetric. A width and / or length and / or cross-section and / or shape and / or size of the first radiation path may be different from a width and / or length and / or cross-section and / or shape and / or size of the second radiation path.

[0064] The method may comprise providing the at least one radiation emitter configured to emit radiation toward the array of assay sites following asymmetric radiation paths. The method may comprise configuring the at least one radiation emitter configured to emit radiation toward the array of assay sites following asymmetric radiation paths.

[0065] The at least one radiation emitter may comprise a plurality of radiation emitters.

[0066] The method may further comprise configuring a first radiation emitter of the plurality of radiation emitters to emit radiation towards the array of assay sites along a first radiation path. The method may further comprise configuring a second radiation emitter of the plurality of radiation emitters to emit radiation towards the array of assay sites along a second radiation path. The first radiation path and second radiation path may be asymmetric. A width and / or length and / or cross-section and / or shape and / or size or the first radiation path is different from that of the second radiation path.

[0067] The method may further comprise providing a first radiation emitter of the plurality of radiation emitters configured to emit radiation towards the array of assay sites along a first radiation path. The method may further comprise providing a second radiation emitter of the plurality of radiation emitters configured to emit radiation towards the array of assay sites along a second radiation path. The first radiation path and second radiation path may be asymmetric. A width and / or length and / or cross-section and / or shape and / or size or the first radiation path is different from that of the second radiation path.

[0068] The processing system may be configured to receive at least one image of the assay sites of the array. The processing system may be configured to, for each of the assay sites, process the at least one image to determine at least one metric representative of the extent or degree of reaction at that assay site. The processing system may be configured to, for each of the assay sites, determine one or more parameters for that assay site, wherein the parameters for at least one of the assay sites of the array are different from the parameters for at least one other of the assay sites of the array. The processing system may be configured to, for each of the assay sites, determine an extent of the reaction at that assay site from the at least one metric for that assay site and the one or more parameters for that assay site.

[0069] The processing system may comprise data storage. The processing system may comprise a communications module. The processing system may comprise one or more output devices. The processing system may comprise one or more input devices.

[0070] The processing system may comprise one or more processors, which may be single or multi-core processors. The one or more processors may comprise one or more central processing units, graphics processing units, maths co-processors, tensor processing units, and / or the like. The data storage may comprise solid state memory, magnetic memory, optical memory, and / or the like. The communications unit may be configured to communicate via wired and / or wireless communications and may be configured to communicate with remote and / or local systems, e.g. via a network such as a LAN, a WAN, the internet, one or more cellular networks, an Ethernet network, a fibre optic network, and / or the like. The at least one output device may comprise a display or other visual output device, an audio output device, and / or a haptic output device.

[0071] The at least on input device may comprise a keyboard, a touchscreen, a trackball, a touchpad, a joystick, a speech recognition based input device, and / or the like. The input device may comprise a machine readable data device such as a barcode or QR code or other machine readable code scanner, a RFID tag reader, an optical tag reader, and / or the like.

[0072] The analysis system may further comprise a computer program product comprising instructions that, when implemented on the processing system, cause the processing system to analyse the array of assay sites using brightfield microscopy.

[0073] According to a fourth aspect of the disclosure, there is provided a method of adapting an analysis system to use brightfield microscopy to analyse an array of assay sites, method comprises: providing a module comprising at plurality of radiation emitters and a diffuser spaced from the plurality of radiation emitters by a spacer; disposing the module relative to the array of assay sites such that a radiation path extends from each radiation emitter of the plurality of radiation emitters, through the diffuser and onto the array of assay sites; wherein the plurality of radiation emitter are configured to emit radiation toward the array of assay sites following asymmetric radiation paths.

[0074] The plurality of radiation emitters may be arranged such that the radiation paths extends in directions oblique to a plane defined by the array of assay sites.

[0075] The spacer may comprise an enclosure configured to enclose the diffuser. At least a part of an internal surface of the enclosure may be substantially non-reflective to a peak wavelength of the radiation emitted by the at least one radiation emitter. The at least a part of the internal surface may be provided with at least one layer or coating comprising a material substantially non-reflective to at least the peak wavelength of radiation emitted by the plurality of radiation emitters.

[0076] According to a fifth aspect of the disclosure, there is provided an analysis system for analysing one or more assays performed at respective assay sites of an array of assay sites, adapted to use brightfield microscopy by performing the method of the fourth aspect.

[0077] According to a fifth aspect of the disclosure, there is provided an analysis system adapted to use brightfield microscopy to analyse an array of assay sites, the analysis system comprising: an array of assay sites; a module comprising: a plurality of radiation emitters configured to emit radiation; and a diffuser spaced from the plurality of radiation emitters by a spacer; wherein: the module is disposed relative to the array of assay sites such that radiation paths extend from the plurality of radiation emitters, through the diffuser and onto the array of assay sites; wherein the plurality of radiation emitter are configured to emit radiation toward the array of assay sites following asymmetric radiation paths.

[0078] The plurality of radiation emitters may be arranged such that the radiation paths extends in directions oblique to a plane defined by the array of assay sites.

[0079] The spacer may comprise an enclosure configured to enclose the diffuser. At least a part of an internal surface of the enclosure may be substantially non-reflective to a peak wavelength of the radiation emitted by the at least one radiation emitter. The at least a part of the internal surface may be provided with at least one layer or coating comprising a material substantially non-reflective to at least the peak wavelength of radiation emitted by the plurality of radiation emitters.

[0080] The above summary is intended to be merely exemplary and non-limiting. The disclosure includes one or more corresponding aspects, embodiments or features in isolation or in various combinations whether or not specifically stated (including claimed) in that combination or in isolation. It should be understood that features defined above in accordance with any aspect of the present disclosure or below relating to any specific embodiment of the disclosure may be utilized, either alone or in combination with any other defined feature, in any other aspect or embodiment or to form a further aspect or embodiment of the disclosure.

[0081] BRIEF DESCRIPTION OF THE DRAWINGS

[0082] These and other aspects of the present disclosure will now be described, by way of example only, with reference to the accompanying Figures, in which:

[0083] Figure 1 is a flowchart showing a method of adapting an analysis system to use brightfield microscopy according to an example embodiment of the present disclosure.

[0084] Figure 2 is a perspective view of an illustration of a module according to an example embodiment of the present disclosure.

[0085] Figure 3 is a perspective view of the example module of Figure 2 with the sidewalls and adapter plate of the module removed.

[0086] Figure 4 is an exploded perspective view of the example module of Figure 2.

[0087] Figure 5 is an expanded exploded perspective view of a portion of the adapter plate of the example module of Figure 2.

[0088] Figures 6 is an expanded perspective view of an alternative adapter plate according to an example embodiment of the present disclosure. Figure 7 is a side view of an illustration of the module of Figure 2 disposed relative to an array of assay sites.

[0089] Figure 8 is a schematic illustration of an analysis system adapted to use brightfield microscopy according to an example embodiment of the present disclosure.

[0090] Figure 9a is an image of an empty array of assay sites captured by an imaging device of an analysis system according to an example embodiment of the present disclosure.

[0091] Figure 9b is an example illumination profile of the image of Figure 9a.

[0092] Figures 10a is an example illumination profile from an analysis system adapted to use brightfield microscopy.

[0093] Figures 10b is a further example illumination profile from an analysis system adapted to use brightfield microscopy.

[0094] Figure 11 is a plan, side and perspective view of an example module frame comprising an adapter plate aperture according to an embodiment of the present disclosure.

[0095] In the figures, like parts are denoted by like reference numerals.

[0096] It will be appreciated that the drawings are for illustration purposes only and are not drawn to scale.

[0097] DETAILED DESCRIPTION OF THE DRAWINGS

[0098] Figure 1 is a flowchart summarising a method 100 of adapting an analysis system to use brightfield microscopy to analyse an array of assay sites. The analysis system may be for analysing one or more assays performed at respective assay sites of an array of assay sites for which brightfield microscopy is the preferred method of analysis as would be apparent to a person skilled in the art. The method comprises, at step S110, providing a module comprising at least one radiation emitter and a diffuser spaced from the at least one radiation emitter by a spacer. Then, at step S120, the module is disposed into the analysis system, relative to an array of assay sites, such that a path of radiation emitted from the radiation emitter(s) extends from the radiation emitter(s) through the diffuser and is incident on the array of assay sites.

[0099] The radiation emitter(s) are arranged in or on the module such that the radiation path extends in a direction oblique to a plane defined by the array of assay sites. In other words, the radiation path is not perpendicular to surface of the array of assay sites e.g. the radiation emitter(s) are not arranged directly above the array of assay sites.

[0100] Figures 2 to 5 illustrate an example embodiment of a module 200 which may be used in the method 100 of Figure 2 to adapt an analysis system to use brightfield microscopy.

[0101] Figure 2 is a perspective view of an illustration of a module 200 disposed on a base 300. The base 300 is configured to fit into a particular area within an analysis system in order to allow the module 200 to be disposed relative to an array of assay sites comprised in the analysis system to adapt the analysis system to use brightfield microscopy to analyse the assays performed at the assay sites.

[0102] The module 200 comprises a frame 210. The frame 210 comprises two walls 212 and an upper surface 214 extending between, and connecting to each of the two walls 212 at their upper edge to form an arch like structure. The upper surface 214 comprises an aperture 235 configured to releasably receive an adapter plate 230. The adapter plate 230 comprises two apertures 222 (as shown in Figure 5) configured to releasably receive two radiation emitters 220. The radiation emitters 220 are orientated such that the emitting face of the radiation emitters 220 is directed into the frame 210 i.e. in the downward direction as shown in Figure 2. The module 200 further comprises two selectively removable sidewalls 240 disposed on the open sides of the frame 210. The frame 210, adapter plate 230, radiation emitters 220 and sidewalls 240 collectively form an enclosure open at a side opposite the aperture 235.

[0103] The internal surface (not visible) of the module 200, i.e. the internal surfaces of the frame 210, sidewalls 240 and adapter plate 230, are coated (e.g. painted, powder coated, sprayed or the like) such that they are substantially non-reflective to the peak wavelength of the radiation emitted by the radiation emitters 220. This reduces unwanted internal reflections within the module 200, allowing more precise control over the radiation incident on an array of assay sites. Alternatively, one or more or each of the frame 210, sidewalls 240 and adapter plate 230 may be manufactured from a material which is substantially non-reflective to the peak wavelength of the radiation emitted by the radiation emitters 220.

[0104] In this example the module 200 comprises two radiation emitters 220 each emitting radiation having the same peak wavelength (e.g. UV light). However, it would be understood that the number of radiation emitters 220, and the peak wavelength of the radiation emitted, may depend on the analysis system, number of arrays of assay sites to be analysed, type of analysis to be performed or other relevant parameter or property of the analysis or analysis system. The radiation emitters 220 may be removed and / or replaced in the adapter plate 230 (for example as described below with reference to Figure 5). Alternatively, the adapter plate 230 comprising the radiation emitters 220 may be removed and / or replaced with an alternative adapter plate 230 comprising a different number of radiation emitters 220, an adapter plate 230 comprising radiation emitters 220 in an alternative arrangement or configured to emit radiation with a different peak wavelength, or a combination thereof. This provides a highly flexible and customisable module 200 which can be easily and quickly adapted to a particular analysis or analysis system.

[0105] Alternatively, the adapter plate 230 may be omitted from the module 200. In this case the upper surface 214 may comprise a number of apertures, each aperture configured to releasably receive a radiation emitter 220.

[0106] The radiation emitters 220, adapter plate 230 and / or sidewalls 240 may be secured to the frame 210 and / or each other using friction fit, magnetic closures, mechanical fixings (e.g. screws, nuts and bolts or the like) or any other suitable securing method. Alternatively, the radiation emitters 220, adapter plate 230 and sidewalls 240 may be permanently secured to the frame 210 and / or each other using adhesive or welds. Alternatively, the frame 210 may be manufactured with one or more of the sidewalls 240 and / or the adapter plate 230 integrated into the frame 210. Alternatively, one or more of the sidewalls 240 may be omitted.

[0107] Figure 3 is a perspective view of the module 200 illustrated in Figure 2 in which the sidewalls 240 and adapter plate 230 (comprising the radiation emitters 220) have been removed to reveal the inside of the module 200. The internal surface of each of the walls 212 comprises a plurality of projections 260 configured to releasably receive a diffuser 250. As shown in figure 3, the projections 260 form two identical columns of irregularly distributed projections 260 arranged along each of the outside edges on the internal surface of each of the walls 212. The projections 260 are configured to dispose the diffuser 250 in a plane spaced from, and generally parallel to, a plane defined by the top surface 214 of the frame 210. The top surface 214 comprises an aperture 235 configured to releasably receive the adapter plate 230 as described above with reference to Figure 2.

[0108] In this example the module 200 comprises a single diffuser 250 which, in use, is spaced from the radiation emitters 220 by disposing the diffuser 250 into the frame 210. However, it would be understood that the number, and spacing of diffusers 250 may depend on the number of radiation emitters 220, the peak wavelength of the radiation emitted, the analysis system, the number of arrays of assay sites to be analysed, the type of analysis to be performed or any other relevant parameter or property of the analysis or analysis system.

[0109] In this example the diffuser 250 comprises a 1.5mm thick glass diffuser. However, it would be understood that the thickness and construction of the diffuser may depend on the number of radiation emitters 220, the peak wavelength of the radiation emitted, the analysis system, the number of arrays of assay sites to be analysed, the type of analysis to be performed or any other relevant parameter or property of the analysis or analysis system. Alternatively, the diffuser may be a holographic diffuser, a white diffusing glass diffuser, a ground glass diffusers or any other diffuser arrangement which increases the homogeneity of radiation incident on the diffuser which propagates through the diffuser or a combination thereof.

[0110] It would be appreciated the projections 250 are only an example method of releasably receiving the diffuser 250. Alternatively / additionally, the internal surface of the walls 212 may comprise slots, indents, holes or other suitable means for supporting the diffuser at the predetermined space from the radiation emitters 220. Alternatively, the internal surface of the wall 212 may comprise a single set of projections, slots, indents, holes or the like to provide a single spacing configuration of the diffuser 250 and radiation emitters 220. Figure 4 is an exploded perspective view of the module 200 of Figure 2. This illustrates the elements of the module 200 which may be selectively removable from the frame 210 in order to repair, clean, replace and / or substitute the removed elements. This provides a module 200 which can be easily maintained and / or quickly adapted to a particular analysis application. Additionally, as described below with reference to Figure 5, the radiation emitters 220 are selectively removable from the adapter plate 230. The radiation emitters 220 are also selectively removable when the adapter plate 230 is disposed into the frame 210 as shown in Figure 2.

[0111] Figure 5 is an enlarged exploded partial perspective view of the adapter plate 230 and one radiation emitter 220 of Figure 2. In order to releasably receive each of the radiation emitters 220, the adapter plate 230 comprises an aperture 222 configured to receive the radiation emitter 220 and a recessed circumferential lip 225 configured to support the outside edge of the radiation emitter 220. The lip 225 prevents the radiation emitter 220 from passing entirely through the aperture 222. The adapter plate 230 further comprises a plurality of smaller apertures 226 (in this example two smaller aperture 226) each configured to receive a mechanical fixing (not shown) such as a bolt which is secured using a nut. Alternatively, the smaller apertures 226 are internally threaded to accommodate a threaded bolt or screw or the like.

[0112] In use, the radiation emitter 220 is disposed into the aperture 222 such that the emitting face of the radiation emitter 220 is directed away from the adapter plate 230 i.e. in the upward direction as shown in Figure 5. A bolt is inserted into the smaller aperture 226 until the head of the bolt engages with the emitting face of the radiation emitter 220. A nut is then secured to the shaft of the bolt to secure the radiation emitter 220 into the adapter plate 230. The adapter plate 230 is then inserted into the aperture 235 (as shown in Figures 2 and 3) such that the emitting face of the radiation emitter 220 is directed into the frame 210 i.e. in the downward direction as shown in Figure 2.

[0113] Figure 6 is an enlarged partial perspective view of a radiation emitter 220 disposed into an alternative adapter plate 230. In this example, the adapter plate comprises an additional portion 232 which is disposed onto the adapter plate 230 at an oblique angle to the surface of the adapter plate 230. In this example, the smaller apertures 226 (not visible) extend through the adapter plate 230 at the oblique angle such that when the radiation emitter 220 and additional part 232 are disposed into the adapter plate 230 the radiation path of the radiation emitted by the radiation emitter 220 is inclined from the surface of the adapter plate by the oblique angle. This arrangement allows further control over the angle of the radiation path with respect to the array of assay sites of the analysis system which the module 200 is disposed into or onto.

[0114] Figure 7 is a side view of an illustration of an example analysis system 1000 comprising a module 700 (which may be the module 100 of Figures 2 to 5) disposed relative to a microarray 770 comprising two arrays of assay sites 772. The module 700 comprises a frame 710, an adapter plate 730 disposed into an aperture on the top surface of the frame 710 and two radiation emitters 720a, 720b disposed into apertures on the adapter plate 730. The frame 710 further comprises a plurality of slots 760 extending partially into the internal surface of the sides of the frame 710. A diffuser 750 is disposed into the lowest slots 760, spacing the diffuser 750 from the radiation emitters by distance d1, and spacing the diffuser 750 from the upper surface 775 of the microarray 770 by distance d2.

[0115] The analysis system 1000 further comprises an imaging device 780 comprising a field of view depicted by dashed lines 785a, 785b and configured to collect at least one image of at least one of the arrays of assay sites 772. In the example of Figure 7 the imaging device is a digital camera, however, the image collection devices may take other forms as would be appreciated by a person skilled in the art. By arranging the radiation emitters 720a, 720b on the outer extremity of the field of view 785a, 785b of the imaging device 780 the gradient and in particular the ROI gradient is significantly reduced.

[0116] Following and / or during an assay procedure a volume of fluid 777 remains within each array of assay sites 772 which cannot easily be removed prior to analysis without damaging or influencing the result of the analysis and / or assay. As shown in Figure 7 the fluid 777 forms a convex lens shape protruding from the upper surface 775 of the microarray 770. By arranging the radiation emitters 720a, 720b such that a radiation path extends from the radiation emitters through the diffuser 750, through the array of assay sites 772 and incident on the imaging device 780 in a direction oblique to a plane defined by the upper surface 775 of the microarray, any distortion of the image captured by the imaging device 780 due to the lens effect is significantly reduced. Furthermore, the gradient and in particular the ROI gradient is further reduced.

[0117] Although not depicted in Figure 7, it will be understood that in some examples, the radiation emitters 720a, 720b may be configured to emit radiations toward the microarray 770, e.g. towards the array of assay sites 772, following asymmetric radiation paths. That is, in an example, a first radiation emitter 720a of the plurality of radiation emitters may configured to emit radiation towards the array of assay 772 sites along a first radiation path depicted by first dashed line 785a, and a second radiation 720b emitter of the plurality of radiation emitters may configured to emit radiation towards the array of assay 772 sites along a second radiation path depicted by corresponding second dashed line 785b. In some examples, the first radiation path 785a and the second radiation path 785b may be asymmetric. For example, a width and / or length and / or cross-section and / or shape and / or size or the first radiation path 785s may be different from that of the second radiation path 785b.

[0118] Figure 8 shows an assay analysis system 1000 for analysing assays carried out in a microarray 870, such as a multiplexed micro-array or hybridized array, that comprises a plurality of assay sites, wherein an individual assay can be performed at each assay site. The system 1000 comprises 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 only one camera 880 is shown in Figure 8, more than one camera 880 could be provided. The camera 880 in this example is configured to capture images of the whole of the microarray 870, e.g. the field of view defined by dashed lines 885 of the camera 880 encompasses the whole of the microarray 870, or at least all of the assay sites of the microarray 870. However, the camera 880 could be configured to capture images of only some of the assay sites of the microarray 870, or different cameras 880 could be configured to capture images of different subsets of assay sites of the microarray 870 or to capture the microarray 870 from different angles. The system 1000 comprises an analysis instrument 890 that receives the images collected by the camera 880 and is configured to analyse the images to determine states of reaction in specific assay sites of the microarray 870.

[0119] The analysis system 1000 comprises a processing system 892, data storage 894, a communications module 896, one or more output devices 898 and one or more user input devices 899. The processing system 892 comprises one or more processors, which could be single core or multi-core processors. The one or more processors include one or more central processing units, and optionally also one or more graphics processing units, maths co-processors, tensor processing units, and / or the like. The data storage 894 could comprise solid state memory, magnetic memory, optical memory, and / or the like. The communications unit 896 can be configured to communicate via wired and / or wireless communications. In this example, the communications unit 896 is configured to communicate with remote and / or local systems, e.g. via a network such as a LAN, a WAN, the internet, one or more cellular networks, an Ethernet network, a fibre optic network, and / or the like. The at least one output device 898 could comprise a display or other visual output device, an audio output device, and / or a haptic output device. The at least on input device 899 could comprise one or more of: a keyboard, a touchscreen, a trackball, a touchpad, a joystick, a speech recognition based input device, an RFID tag reader, a barcode or QR code reader, and / or the like.

[0120] The analysis system 1000 has been adapted to use brightfield microscopy to analyse the array of assay sites comprised in the microarray 870 by providing a module comprising two radiation emitters 820 and a diffuser 850 spaced from the radiation emitters 820 and disposing 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 radiation emitters 820 are arranged such that the radiation path extends in a direction oblique to a plane defined by the microarray 870.

[0121] Figure 9a and 9b illustrate an example method of determining the homogeneity of the radiation incident on an array of assay sites comprised in an analysis system adapted to use brightfield microscopy.

[0122] Figure 9a is a grayscale image 900 of an empty array of assay sites captured by an imaging device of an analysis system adapted to use brightfield microscopy such as the analysis system 1000 of Figure 8. The proficiency of the analysis system to use brightfield microscopy is highly dependent on the homogeneity of the radiation incident on the array of assay sites. Therefore, an objective measure of the homogeneity of the radiation incident on the array of assay sites when different parameters of the module disposed in the analysis system are changed is required. The gradient and / or ROI gradient was used by the inventors to assess the homogeneity of the radiation incident on the array of assay sites.

[0123] As shown in Figure 9a a straight horizontal line 910 is drawn through the centre of the captured image 900. The ‘gray value’ of each point or pixel along the line 910 is determined where a value of “0” represents black and a value of “255” represents white and intermediate values representing shades of gray in-between. The gray value of the image 900 as function of the length along the line 910 is shown in figure 9b. This plot is also referred to as the “illumination profile” and this term may be used to refer to such a plot within the present disclosure.

[0124] As shown in figure 9b the gray value is at or around 0 on the portions of the line 910 which are outside the array of assay sites. An average of the gray value between the dashed lines marked “BEG” in figure 9b is determined and similarly an average of the gray value between the dashed lines marked “END” is determined. The absolute difference between the END average and the BEG average is referred to as the gradient or full line gradient which is a measure of the homogeneity of the radiation incident on the array of assay sites including the areas outside the area comprising the assay sites.

[0125] Alternatively, an average of the gray value between the solid lines marked “BEG ROI” in figure 9b is determined and similarly an average of the gray value between the solid lines marked “END ROI” is determined. The absolute difference between the END ROI average and the BEG ROI average is referred to as the ROI gradient which is a measure of the homogeneity of the radiation incident on the array of assay sites including only the areas comprising the assay sites. Using this measure of gradient and ROI gradient the effect of disposing the diffuser and / or radiation emitters in different positions within the adaption module can be calculated.

[0126] Figures 10a and 10b show illumination profiles 960 and 970 which illustrate the effect on the homogeneity of the radiation incident on the array of assay sites of changing the position of the diffuser and the radiation emitters within the frame of the module 200 of Figure 2. Figure 10a shows the illumination profile resulting from the use of a module comprising a single radiation emitter with a diffuser disposed close to the single radiation emitter, for example in the uppermost slot 760 of the module 700 of Figure 7. Plot 962 represents the illumination profile when the single radiation emitter is arranged to the right of the centre line of the top surface of the frame. As shown in Figure 10a the gray value is greater at the side of the array of assay sites corresponding to the radiation emitter position for plot 962. Similarly plot 964 represents the illumination profile when the single radiation emitter is arranged to the left of the centre line of the top surface of the frame. As shown in Figure 10a the gray value is greater at the side of the array of assay sites corresponding to the radiation emitter position for plot 964. This results in a high gradient and ROI gradient which would not produce accurate assay analysis results.

[0127] Figure 10b shows the illumination profile resulting from the use of a module comprising a single radiation emitter with a diffuser disposed far from the single radiation emitter, for example in the lowermost slot 760 of the module 700 of Figure 7. Similar to plots 962 and 964, corresponding plots 972 and 974 represent the illumination profile when the single radiation emitter is arranged to the right and left respectively. As shown in figure 10b when compared to figure 10a the gradient and in particular the ROI gradient is significantly reduced, improving the performance of the analysis system.

[0128] In this way it would be appreciated by a person skilled in the art that the optimum position, number, orientation etc. of the diffuser and radiation emitter(s) can be determined for a particular analysis system, assay, test sample or required analysis procedure. The features of the disclosed module and method of disposing the disclosed module provide a flexible, highly adjustable technique for adapting an analysis system to use brightfield microscopy.

[0129] Figure 11 shows an example frame 210 used in the module 200 of Figures 2 to 5. The frame 210 has, for purposes of a non-limiting example only, a length X1 of 95±5mm, a width Y1 of 20±5mm and a depth Z1 of 65±5mm. The frame 210 comprises an elongate aperture 235 on the upper planar surface of the frame 210. The aperture 235 has a length X2 of 65±5mm and a width Y2 of 15±5mm. However, these dimension ranges should not be construed as limiting the scope of the claimed subject matter. One of skill in the art will appreciate that these dimension ranges are provided for purposes of example only to give a general indication of the order of the sizes and other dimensions could be used depending on the application and equipment used. It would be appreciated that the dimensions of the frame 210 and aperture 235 are particular to the module 200 of figures 2 to 5, which may be particular to the analysis system and the desired properties of the resulting assay analysis. That is, in other examples of the disclosed frame 210, said dimensions may be substantially different. For example, frames 210 falling within the scope of the disclosure may be substantially larger, smaller and / or may comprise dimensions in different proportions to the example provided herein.

[0130] Although the disclosure has been described in terms of preferred embodiments as set forth above, it should be understood that these embodiments are illustrative only and that the claims are not limited to those embodiments. Those skilled in the art will be able to make modifications and alternatives in view of the disclosure which are contemplated as falling within the scope of the appended claims. Each feature disclosed or illustrated in the present specification may be incorporated in the disclosure, whether alone or in any appropriate combination with any other feature disclosed or illustrated herein.

Claims

1. A method for adapting an analysis system to use bright-field microscopy for the analysis of a matrix of sample cells, comprising the steps of: provide a module comprising at least one emitter and a diffuser separated from the at least one emitter by a spacer; positioning the module relative to the matrix of sample cells such that the radiation path passes from at least one emitter through the diffuser to the matrix of sample cells; wherein at least one emitter is positioned in such a way that the radiation path passes in an inclined direction relative to the plane defined by the matrix of sample cells.

2. The method according to claim 1, wherein the spacer comprises a housing configured to accommodate the diffuser.

3. The method of claim 2, wherein at least a portion of the inner surface of the housing is substantially non-reflective for the peak wavelength of radiation emitted by the at least one emitter.

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

5. A method according to any one of the preceding claims, comprising the step of configuring at least one emitter to emit radiation towards the array of sample cells along asymmetric radiation paths.

6. The method of claim 5, wherein at least one emitter comprises a plurality of emitters, and wherein the method further comprises the steps of: configuring a first emitter of the plurality of emitters to emit radiation toward the array of sample cells along a first radiation path; and configuring a second emitter of the plurality of emitters to emit radiation in the direction of the array of sample cells along a second radiation path, wherein the first radiation path and the second radiation path are asymmetrical.

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

8. The method according to any one of the preceding claims, further comprising the step of creating a distance between the diffuser and the at least one emitter such that a substantially uniform distribution of radiation is incident on the matrix of sample cells.

9. The method according to any of the preceding claims, wherein the module comprises a plurality of emitters.

10. The method according to any one of the preceding claims, wherein at least two of the plurality of emitters are configured to emit radiation with different peak wavelengths.

11. A method according to any one of the preceding claims, wherein the spacer comprises an adapter plate configured to allow for the removable installation of at least one emitter.

12. A method according to any of the preceding claims, wherein the spacer comprises a frame adapted to detachably mount the diffuser.

13. The method according to claim 12, dependent on claim 11, in which the frame is additionally configured to allow for the removable installation of an adapter plate.

14. The method of any one of the preceding claims, further comprising the step of implementing a computer program on the analysis system containing instructions that, when executed on the analysis system, cause the analysis system to analyze the sample cell matrix using brightfield microscopy.

15. An assay system for assaying one or more assays performed in respective sample cells of a matrix of sample cells, adapted for use with brightfield microscopy by performing the method of any one of claims 1 to 14.

16. An analysis system adapted to use bright field microscopy for the analysis of a matrix of sample cells, wherein the analysis system comprises: sample cell matrix; module containing: at least one emitter configured to emit radiation; and a diffuser separated from at least one emitter by a spacer; in this case: the module is positioned relative to the matrix of sample cells such that the radiation path extends from at least one emitter through the diffuser onto the matrix of sample cells; and at least one emitter is positioned such that the radiation path passes in an inclined direction relative to the plane defined by the matrix of sample cells.

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

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

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

20. An analysis system according to any one of claims 16 to 19, comprising configuring at least one emitter to emit radiation towards the array of sample cells via asymmetric radiation paths.

21. The analysis system of any one of paragraphs 16-20, wherein at least one emitter comprises a plurality of emitters, and wherein: a first emitter of a plurality of emitters is configured to emit radiation in the direction of the matrix of sample cells along a first radiation path; and the second emitter of the plurality of emitters is configured to emit radiation in the direction of the matrix of sample cells along a second radiation path, wherein the first radiation path and the second radiation path are asymmetrical.

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 differ 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 16-22, further comprising a visualization device configured or configured to collect at least one image of the matrix of sample cells.

24. The analysis system according to any one of claims 16-23, further comprising a processing system comprising at least one processing device, a data storage device and a communication system for receiving at least one image and outputting an indicator of the extent of reaction in a sample cell of an array of sample cells, wherein the visualization device is further configured to transmit at least one image to the processing system.

25. The analysis system according to any one of claims 16-24, further comprising an output device configured to receive an indicator of the extent of reaction in the sample cell from the processing system and output said indicator of the extent of reaction in the sample cell.

26. The analysis system of any one of claims 16-25, further comprising a computer program product containing instructions that, when executed on the processing system, cause the processing system to analyze the sample cell matrix using brightfield microscopy.

27. A method for adapting an analysis system to use bright field microscopy for the analysis of a matrix of sample cells, comprising the steps of: provide a module comprising a plurality of emitters and a diffuser separated from the plurality of emitters by a spacer; the module is positioned relative to the matrix of sample cells in such a way that the radiation path passes from each emitter of the set through the diffuser onto the matrix of sample cells; wherein the plurality of emitters are configured to emit radiation in the direction of the matrix of sample cells along asymmetric radiation paths.

28. The method of claim 27, wherein the plurality of emitters are arranged such that the radiation paths extend in an inclined direction relative to the plane defined by the matrix of sample cells.

29. The method according to claim 27 or 28, wherein the spacer comprises a housing configured to accommodate the diffuser.

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

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

32. An assay system for assaying one or more assays performed in respective sample cells of a matrix of sample cells, adapted for use with brightfield microscopy by performing the method of any one of claims 27 to 31.

33. An analysis system adapted to use bright field microscopy for the analysis of a matrix of sample cells, wherein the analysis system comprises: sample cell matrix; module containing: a plurality of emitters configured to emit radiation; and a diffuser separated from a plurality of emitters by a spacer; in this case: the module is positioned relative to the matrix of sample cells in such a way that radiation paths pass from the plurality of emitters through the diffuser onto the matrix of sample cells; wherein the plurality of emitters are configured to emit radiation in the direction of the matrix of sample cells along asymmetric radiation paths.

34. The system of claim 33, wherein the plurality of emitters are arranged such that the radiation paths extend in an inclined direction relative to the plane defined by the matrix of sample cells.

35. The system according to claim 33 or 34, in which the spacer comprises a housing configured to accommodate a diffuser.

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

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