WO2023198395A1

WO2023198395A1 - Optical module, test assay and reader device

Info

Publication number: WO2023198395A1
Application number: PCT/EP2023/056695
Authority: WO
Inventors: Alexander Gaiduk; Boon Chong CHEAH; Sandesh CHITTOORI; Gunter Siess; Mohsen Mozaffari
Original assignee: Ams-Osram Ag
Priority date: 2022-04-12
Filing date: 2023-03-16
Publication date: 2023-10-19

Abstract

An optical module for reading a test assay (40) comprises a housing (10), the housing (10) further comprising at least one measurement unit (20), wherein each measurement unit (20) comprises a light source (21) and an optical detector (22), enclosed by the housing (10). A sample plane (11) is arranged to receive the test assay (40). Optics (32) is arranged in the housing (10) and/or on the test assay (40) and operable to provide a first optical path (31) from the light source (21) to the sample plane (11), and operable to provide a second optical path (31) from the sample plane (11) to the optical detector (22). The optics (32), light source (21) and optical detector (22) are aligned with respect to each other such that the light source (21) is operable to illuminate a dedicated target region (42) of the test assay (40), and such that the optical detector (22) is operable to detect light emitted from the dedicated target region (42), respectively. In particular, the light source (21) may comprise a micro- LED.

Description

OPTICAL MODULE, TEST ASSAY AND READER DEVICE

This disclosure relates to an optical module, a test assay and to a reader device.

Background of the disclosure

Personalized diagnostics and health test devices play an ever increasing role in society facing medical conditions such as aging and pandemic risks. Health test devices allow faster, precise and individual treatment of potential patients. However, it remains a challenge to offer such devices both for the mass market and at an affordable price. Another challenge is the wide range of possible use cases and the application flexibility of the technology and corresponding system architecture. Yet another challenge concerns sensitivity, specificity, and reliability of the provided results. Optical technology seems to offer a promising technology to overcome those challenges.

Lateral flow technology is based on a series of capillary pads, such as pieces of porous paper, micro-structured polymer, or sintered polymer. Each of these elements has the capacity to transport fluid (e.g., urine) spontaneously. The first element (the sample pad) acts as a sponge and holds an excess of sample fluid. Once soaked, the fluid migrates to the second element (conjugate pad) in which the manufacturer has stored the so-called conjugate, a dried format of bioactive particles in a salt-sugar matrix that contains everything to guarantee an optimized chemical reaction between the target molecule (e.g., an antigen) and its chemical partner (e.g. antibody) that has been immobilized on the particle's surface. While the sample fluid dissolves the salt-sugar matrix, it also mobilizes the particles and in one combined transport action the sample and conjugate mix while flowing through the porous structure. In this way, the analyte binds to the particles while migrating further through the third capillary pad. This material has one or more regions (often called stripes or lines) where a third molecule has been immobilized by the manufacturer. By the time the sample-conjugate mix reaches these strips, analyte has been bound on the particle and the third 'capture' molecule binds the complex. After a while, when more and more fluid has passed the stripes, particles accumulate and the stripe-area changes color. Typically, there are at least two regions: One (the control) that captures any particle and thereby shows that reaction conditions and technology worked fine, typically the test line appears on the test strip before the control line. The second (the test) contains a specific capture molecule and only captures those particles onto which an analyte molecule has been immobilized. This makes the diagnostic result of the test visible.

After passing these reaction regions the fluid enters the final porous material, the wick that simply acts as a waste container and also assists in controlling the flow rate. Multiple test lines can also be positioned adjacent each other with the last line on the strip being the control line. There are generally three types of lateral flow tests.

A first type relies on lateral flow tests without any electronics. A user "reads" a contrast change by naked eye, giving a yes/no answer to the user. These types of lateral flow tests are not suitable for digital diagnostic tests where digital quanti fication is required . For the identi fication of many diseases , quantitative measurements are important and these yes/no , qualitative types of tests are generally not suitable for quantitative diagnostics testing . Information that can be quanti fied could include (but not limited) include contrast , contrast levels , spatial position, wavelength/color of the response , etc .

A second type relies on lateral flow tests with an external optical readout . This type allows quantitative detection with an improved and reproducible sensitivity . In particular, quantitative measurements typically use sensing technology ( for example , absorbance , scattering in transmission and/or reflection, as well as fluorescence , luminescence signals sensing) to sense a test region of a lateral flow test strip to determine a quantitative value based on, in the simplest case , the contrast or color change in the test region . However, for this type of lateral flow test , an external reader device , for example a desktop-si zed reading apparatus is required .

A third type relies on lateral flow tests with the light source and detector assembled on, for example , a printed circuit board . An advantage of these kind of readout systems is that quanti fication is possible and an increased sensitivity can be achieved without the need for external detector hardware . However, this type of solution utili zes discrete components such as LEDs , photodiodes and various structural components assembled by a pick and place machine . Typically, the components will be secured in position by glue and/or solder . A problem of such assemblies is that there may be displacement of the components in an uncontrollable way as a result of solder or glue reflow at high temperatures applied during one or more manufacturing steps . This problem may be particularly noticeable with the larger structural components such as housings that have a heavier weight relative to the other components of the assembly and are thus more susceptible to reflow misalignment . A consequence of this unpredictable positional misalignment is that quantitative measurements provided by such assemblies are less reliable . For example , a weak detected signal from a test line may be indicative of lower analyte concentration in a sample or it may be the result of bad positional misalignment . Accordingly, such assemblies may be inaccurate and can cause unpredictable variation in quantitative measurements thereby reducing reproducibility and accuracy .

Despite the above issues , lateral flow technology is signi ficantly cheaper and easier to scale up than the central laboratory approach and other point-of-care testing approaches in part because the raw materials , reagents and equipment it relies on are more widely available and can be mass produced more easily . Moreover, i f de-centrali zed testing can be enabled or even be done by the patient themselves , logistics costs of transporting samples to a centrali zed testing facility and waiting times can be reduced .

The global Covidl 9 pandemic of 2020 has made it apparent that the central laboratory testing and specialist diagnostic equipment point-of-care testing approaches are unable to be scaled up fast enough to process the vast numbers of tests needed to meet the unprecedented explosion in global demand caused by the pandemic . Future pandemics are also likely to cause a similar sharp increase in demand for testing capacity which laboratory and specialist diagnostic equipment point- of-care testing approaches are unlikely to be able to meet . Additionally, to minimi ze the impact of a pandemic on the economy in a controlled way, determining who is and who is not immune is likely to be beneficial as those who are immune may return to work more quickly . Accordingly, immunity sel ftests on a massive scale may become a main tool in a government ' s approach to limiting the economic impact of a pandemic in a way that can be scaled up and mass-produced cheaply and quickly .

As has become apparent from above , LFT devices for quantitative digital optical signal detection frequently suf fer from low light ef ficiency ( combined on illumination and detection) . Therefore , absorption, scattering, and fluorescence signals detection remain di f ficult due to missing signal-to-noise ratio .

It is an obj ect of the present disclosure to provide an optical module , a test assay and a reader device with improved optical properties and compatible with mass production .

These obj ectives are achieved by the subj ect-matter of the independent claims . Further developments and embodiments are described in the dependent claims .

Summary of the disclosure

The following relates to an improved concept in the field of optical sensing for diagnostics-related devices . The improved concept suggests a solution which allows to combine ( 1 ) a defined biochemistry; ( 2 ) a lateral flow technology, e . g . improved design of LFT technology; and ( 3 ) an improved spectral sensing equipment . An optical module comprises one or more measurement units arranged in a housing . The measurement units comprise light sources and optical detectors . Optical performance of the measurement unit can be improved by using at least one illumination source and at least one light sensor spectrally dedicated and spatially aligned with a single area of observation ( target region) on a sample ( test assay) . The overall light ef ficiency of the measurement unit can be improved by using a light-collimation optics such as micro-optics elements and collection optics such as micro-optics elements or both light-collimation and light-collection micro-optics elements . Furthermore , dedicated optics can also be arranged on the test assay itsel f , e . g . to improve the overall optical ef ficiency for lateral flow testing, LFT , detection by using a special arrangement on the test assay . One example , involves solid immersion lenses , S IL, attached to target regions on the test assay in conj unction with mechanical openings for light path . This allows to increase collection ef ficiency and control mechanical tolerances . Another benefit in using dedicated optics attached to the test assay is to insure spatial alignment and provide mechanical reference between optical axis in the optical sensing and sample areas/volumes of the tests assay .

In at least one embodiment , an optical module for reading a test assay comprises a housing . The housing further comprises at least one measurement unit , wherein each measurement unit comprises a light source and an optical detector, which are enclosed by the housing. Furthermore, the optical module comprises a sample plane arranged to receive the test assay.

Optics are arranged in the housing. In addition, or alternatively, optics are arranged on the test assay. By a way of the arrangement of the light source and optical detector, and optics either arranged in the housing and/or the test assay, with respect to each other different optical paths are established. A first optical path is provided from the light source to the sample plane, and a second optical path is provided from the sample plane to the optical detector .

The optics, light source and optical detector are aligned with respect to each other such that, in operation of the optical module, the light source illuminates a dedicated target region of the test assay. Furthermore, the optics, light source and optical detector are aligned with respect to each other such that, in operation of the optical module, the optical detector detects light emitted from the dedicated target region, respectively.

The proposed optical module allows for modular design of an optical sensing system. Furthermore, the components of any given measurement unit, i.e. light sources and optical detectors can be placed with respect to the optics (in the housing and/or on the test assay) to design optical paths for increased optical efficiency, i.e. better illumination efficiency and, thus, excitation of compounds at the target regions, and better detection efficiency. The optics do not have to be high magnification or geometric aberration optimized imaging optics, but can be a lower cost collimation optics and lower quality imaging capabilities optics. In at least one embodiment , the housing comprises a plurality of measurement units . Each light source is operable to illuminate a single dedicated target region in the sample plane . A corresponding one of the optical detectors is operable to detect light emitted from said single dedicated target region . The optics is arranged to provide a dedicated first and second optical path . The measurement units can be manufactured as dedicated modules of the housing . Thus , the modules may be optimi zed and arranged for the test assay at hand .

In at least one embodiment , one or more of the light sources comprise a light-emitting diode , a micro light-emitting diode , and/or a resonant-cavity light emitting device . A light source may also be implemented as an array comprising a plurality of the elements listed above .

In particular, a micro light-emitting diode is also referred to as micro-LED . For example , the light source comprise a micro-LED . In case that the optical module comprises more than one light source , preferably at least one light source or all light sources comprise a micro-LED .

As a broad definition, a micro-LED could be seen as any light emitting diode ( LED) - generally not a laser - with a particularly small si ze .

As a rule - and this is a very important criterion in addition to si ze - a growth substrate is removed from microLEDs , so that typical heights of such micro-LEDs are in the range of 1 . 5 pm to 10 pm, for example . In principle , a micro-LED does not necessarily have to have a rectangular radiation emission surface . Generally, for example , an LED could have a radiation emission surface in which, in plan view of the layers of a layer stack of the micro-LED, any lateral extent of the radiation emission surface is less than or equal to 100 pm or less than or equal to 70 pm .

For example , in the case of rectangular micro-LEDs , an edge length - especially in plan view of the layers of the layer stack - smaller than or equal to 70 pm or smaller than or equal to 50 pm is often cited as a criterion .

Mostly, such micro-LEDs are provided on wafers with - for the micro-LED non-destructively - detachable holding structures .

At present , micro-LEDs are mainly used in displays . The micro-LEDs form pixels or subpixels and emit light of a defined color . Small pixel si ze and a high density with close distances make micro-LEDs suitable , among others , for small monolithic displays for AR applications , especially data glasses . In addition, other applications are being developed, in particular regarding the use in data communication or pixelated lighting applications .

Di f ferent ways of spelling micro-LED, e . g . pLED, p-LED, uLED, u-LED or micro light emitting diode can be found in the relevant literature .

In at least one embodiment , one or more of the optical detectors comprise a photodiode , an Avalanche photodiode , a charge-coupled device , and/or a CMOS photodetector . An optical detector may also be implemented as an array comprising a plurality of the elements listed above.

In at least one embodiment, the optics comprises an illumination optics and/or a detection optics. The illumination optics is operable to guide light along the first optical path and detection optics is operable to guide light along the second optical path. The optical paths guide light for the purpose of excitation (illumination) and detection (e.g., of faint fluorescence) . Using the optics, the optical module can be compact and cost efficient.

In at least one embodiment, the optics comprises one or multiple collimating optics, such as lenses or gratings, and/or one or more collecting optics, mirrors, micro-mirrors or micro-mirror array (s) .

In at least one embodiment, at least one measurement unit comprises a curved incision which is arranged in the housing. The curved incision forms a chamber with respect to the sample plane. One or more light sources are arranged along the curved incision, e.g. to form a ring. The curved incision may of spherical or parabolic shape. The curved incision provides a center point (or focal point) which can be aligned with a target region of the test assay, if attached to the sample plane. Said measurement unit further comprises a grove which is arranged in the housing, or housing body, such that an opening is formed facing the center point. One or more optical detectors are arranged inside the grove, thus facing the center point.

The proposed design, including curved incision, allows for a compact layout combined with efficient illumination and detection . The curved incision can be used to create an illumination ring ( " light ring" ) which may combine a plurality of light sources in a small space and placed in multiple positions on one or multiple circules that are parallel to the sample plane . Ef ficient illumination may translate into ef ficient light absorption or light scattering or excitation of fluorescence at a target region placed with respect to the chamber and center point . At the same time , light emitted from the center point , e . g . scattering or fluorescence , can be collected and guided towards the optical detector with a high ef ficiency .

In at least one embodiment , an illumination optics and/or a detection optics are arranged in front of the opening of the grove , respectively . The optics may collect light from the target region and guide and/or focus said light towards the optical detector .

In at least one embodiment , the grove comprises a crossshape . The cross-shape comprises branches of a cross , with end-sections and a center section . A beam-splitter is arranged at the center section . At least one optical detector is arranged at an end-section and is coaxial with an axis defined by the center point and the beam-splitter, thus , establishing a measurement path . At least one a reference detector is arranged at an end-section being perpendicular with respect to an axis defined by the center point and the optical detector, thus , establishing a reference path .

In at least one embodiment , further comprising a reference light source arranged at an end-section being coaxial with respect to an axis defined by the optical detector and the beam-splitter, thus , establishing an illumination path . In at least one embodiment, the sample plane is arranged to permanently attach or removeably attach the test assay. The optical module may, thus, we a disposable component or only the test assay may be disposable. This allows to optimize a price tag and opens up the possibility of mass production.

In at least one embodiment, a test assay comprises a carrier. One or more target regions are arranged on the carrier. Furthermore, optics attached to the carrier at the location of the target regions. For example, a dedicated optical element, such as a lens, is attached, or directly mounted to, a corresponding target region of the assay. Using optics on the test assay provides increased efficiency and mechanical stability as well as reproducibility of the optical sensing.

In at least one embodiment, the optics comprises at least one solid immersion lens, SIL. A SIL effectively increases the numerical aperture, e.g. of the first and/or second optical path. Numerical aperture indicates the range of angles over which the system can accept or emit light. This effectively increases numerical apertures and, thus, enhance detection efficiency.

In at least one embodiment, the solid immersion lens comprises a hemispherical SIL or a Weierstrass SIL.

There are two types of SIL. A hemispherical SIL which can increase the numerical aperture up to n, n being the index of refraction of the material of the lens. Another type is denoted Weierstrass SIL (or super hemispherical SIL) . Such a SIL comprises a truncated sphere which can increase the numerical aperture up to n². Both types of SIL are effective means to further increase collection ef ficiency of light to the target regions .

In at least one embodiment , the optics attached to the carrier are configured to mechanically lock into an optical module to be connected to the test assay . The optics , such as S IL, have a certain height . Thus , the test assay, in a certain sense , has a regularly structured surface which, in turn, can be used to mechanically align and lock the test assay to the optical module .

In at least one embodiment , an assay reader device comprises an optical module according to one or more of the aspects presented above . Furthermore , the optical module is mounted on a printed or flexible circuit board . The circuit board may comprises electronics to drive the light sources and/or optical detectors . For example , the circuit board comprises a micro-controller or micro-processor . Moreover, the reader device comprises a test assay comprising target regions . The test assay may be permanently attached or removeably attached to the sample plane and aligned with its target regions to the optical module .

In at least one embodiment , wherein the test assay comprises a test assay with optics according to one or more of the aspects presented above .

In at least one embodiment , the reader device further comprises means for sample flow from an opening to the test assay . The means for sample flow may comprise micro- fluidics , for example , and are attached to transport a sample to be tested to the test assay and consequently to the target regions . Further embodiments of the reader device according to the improved concept become apparent to a person skilled in the art from the embodiments of the optical module and test assay described above , and vice versa .

The following description of figures of example embodiments may further illustrate and explain aspects of the improved concept . Components and parts with the same structure and the same ef fect , respectively, appear with equivalent reference symbols . Insofar as components and parts correspond to one another in terms of their function in di f ferent figures , the description thereof is not necessarily repeated for each of the following figures .

Brief description of the drawings

In the Figures :

Figure 1 shows example embodiments of an optical module for reading a test assay,

Figure 2 shows an example embodiment of optics for an optical module ,

Figure 3 shows another example embodiment of optics for an optical module ,

Figures 4A to 4D show example embodiments of an optical module ,

Figures 5A to 5C show further example embodiments of an optical module , Figure 6 shows another example embodiment of an optical module , and

Figure 7 shows an example embodiment of a test assay .

Figure 1 shows example embodiments of an optical module for reading a test assay . The drawing shows a schematic representation of an optical module for reading a test assay, such as a lateral flow test , LFT , or lateral flow assay . For example , the optical modules depicted in the drawings can be used as LFT systems for optical sensing of absorption or scattering or fluorescence from an active bio-volume in an LFT test assay that comprises a transparent/ semi-transparent test strip ( carrier ) , such as a backing card, cellulose material for fluid flow with active bio-volume printed in cellulose .

Figure 1 shows example embodiments of an optical module for reading a test assay . The modules are only schematically depicted and represented by light source 21 , optical detector 22 and optical paths 30 , 31 . However, the drawing highlights the test assay 40 .

The first embodiment ( on the left ) relies on optics arranged in the housing 10 (not shown, optics included in the first and second optical paths 30 , 31 ) . The test assay 40 may have no additional optics . The second embodiment ( in the middle ) employs solid immersion lenses 33 , S IL, which are arranged on the test assay . This embodiment can be combined with optics such as in the first embodiment or can solely rely on the solid immersion lenses . The solid immersion lenses can be arranged on either side of the assay, i . e . facing the light source 21 and/or the optical detector 22. Alternatively, a solid immersion lens is only arranged on one side of the test assay, i.e. facing the light source or the optical detector. In a third embodiment (on the right) one side of the test assay is arranged with a solid immersion lens while the other is arranged with fluid immersion 34 instead. The SIL may either face the light source or the optical detector.

Further details will be discussed with respect to the following Figures. In general, the optical module comprises a housing 10 (not shown) which comprises one or more measurement units 20. Each measurement unit comprises at least one light source 21 and at least one optical detector 22, and are enclosed by the housing. The measurements units can be considered a modular building block of the optical module .

The measurement units 20 define individual units, or modules that can be used as building block to scale up the optical module or opto-electro-mechanical system. The measurement units 20 can have light source (s) 21, collimation optics, imaging optics (same as collimation or different) , optical detector (s) 22, single point or array detector (s) , e.g. working in coaxial arrangement with further optical components, such as polarizing, dichroic, and/or 50-50 beam splitter elements 23. Additional proximity or light condition sensors 24 can be implemented for environment and/or fluid dynamics monitoring. The measurement units 20 can be tailored to a respective target region. For example, in one target region a first substance is to be measured, while in another target region another substance is to be measured. These substances may be different and need different illumination or detection windows, e.g. to excite fluorescence and sense fluorescence light.

For easier representation, in the following measurements units 20 are shown with a single light source 21 and a single optical detector 22. The concepts shown therein can be applied for any measurement unit, including those which comprise more than a single light source and/or more than a single optical detector. In a measurement unit, the light source and optical detector are aligned with respect to each other such that optical paths 30, 31 are established. For example, a first optical path 30 optically connects the light source to a sample plane 11. A second optical path 31 optically connects the sample plane to the optical detector.

The sample plane 11 is arranged to receive the test assay 40. For example, the test assay can be permanently connected to the sample plane, e.g. as part of the housing 10 or as a test stripe which is connected to the housing. In this case, the optical module may be disposable as a whole. Alternatively, the test assay can be arranged on, or implemented as, a test stripe which can be mounted to the sample plane. In this case, only the test stripe may be disposable and the optical module can be used multiple times.

The test assay comprises a carrier 41, such as a back card or sample pad, e.g. cellulose. The assay comprises one or more target regions 42. The target regions comprise a test material, such as an active compound, e.g. bio-active particles denoted conjugates.

Optics 32 guides light along the optical paths 30, 31. With the test assay in place, the optics, light source 21 and optical detector 22 are aligned with respect to each other. As a consequence, in a measurement unit 20, if the light source emits light it thereby illuminates a dedicated target region 42 of the test assay 40. The optical detector 22 eventually detects light which is emitted from the dedicated target region. This alignment can be achieved by optics 32 which is arranged in the housing and/or on the test assay. In other words, the light source and the optical detector are aligned with respect to each other such that optical paths 30, 31 are established by means of the optics in the housing and/or are established once the optics on the test assay is in place.

The schematic representation shows three different embodiments. These embodiments differ in that the optical paths 30, 31 comprise optics 32 either in the housing and/or on the test assay. Any combination thereof is also feasible.

The proposed optical module may have a number of advantages, including, for example, increased efficiency of optical sensing reading test assays, such as for LFT-compatible devices, modular design, increased efficiency and mechanical stability and reproducibility optical design with SIL and increased performance stripes for LFT with SIL design.

The optics 32 can be divided into illumination and detection optics. The illumination optics guides light along the first optical path 30. Detection optics guides light along the second optical path 31. The optics can be miniaturized and is capable of observing a relatively small target region or multiple target regions of the test assay. Illumination is provided via the light source (s) 21, including micro-LED, LEDs, resonant-cavity light emitting device, such as VCSELs, or other types of micro-lasers, or arrays thereof. The illumination optics can use one or multiple collimating optics, such as lenses or gratings, and/or one or more collimating optics, mirrors, micro-mirrors or micro mirror array (s) . The detection is provided by optical detector (s) 22, such as a single point single color, single color multiple points, a single point multiple colors or multiple colors multiple points light detection devices, e.g. having ability for synchronization with the illumination or other user or hardware triggered actions. The optical detector (s) can be based on a photodiode, an Avalanche photodiode, a charge-coupled device, and/or a CMOS photodetector, or an array thereof. The detection optics can use one or more collimating or focusing optics elements, such as lenses. Or the detection optics can use one or more mirrors, micromirrors or micro-mirror arrays (s) .

Figure 2 shows an example embodiment of optics for an optical module. The drawing shows a schematic representation of optics 32 for light collimation and focusing. The optics can have a dual purpose and be used for both illumination and detection optics, depending on where they are located.

If the optics 32 is used for the illumination then the drawing shows a substrate 12 (as a part of test assay) and a number of optical excitation areas 22 (multiple target regions on a sample) . The structured optical elements or micro lenses 35 are arranged with the optics carrier 40, which spreads the illumination 21 over multiple areas 22 in the sample carrier 12. This way, the illumination efficiency of the target regions of the test assay is increased. If the optics is used for detection, then the structured optical elements or micro lenses 35 which are arranged with the optics carrier 40 are focusing the light from multiple sample region in the test assay 21 towards the multiple detectors 22 in the detector array 12. This way, the detection efficiency from the target regions of the test assay is increased.

Thus, the micro-lenses 35 are further arranged to focus light onto the corresponding optical detectors or sample target regions 22. For example, the array of micro-optics can be arranged, instead or additionally, at an underside of the test assay, e.g. on the side facing the optical detectors. This way, detection efficiency can be increased. The microlenses can be implemented as individual round lenses, e.g. one lens per excitation/detection area 22. Alternatively, the micro-lenses can be implemented as cylindrical lenses, e.g. spanning along several excitation/detection areas 22. Other lens form and design is possible as well, e.g. metalenses or Fresnel type lenses.

Figure 3 shows another example embodiment of optics for an optical module. The drawing shows a schematic representation of light collimation and focusing on different target regions of the test assay using a mirror 35 or a set of micro mirrors in general, and adjustable mirror system in particular. The mirror can be arranged for the purpose of illumination and increase of illumination efficiency. In addition, or alternatively, the mirror can be arranged to guide light to different sensitive areas on the optical detectors, e.g. for the purpose of detection efficiency increase. Figures 4A to 4C show example embodiments of an optical module. Figure 4A shows the housing 10 and two chambers 14, implemented by curved incisions 13, arranged therein. Furthermore, there is an opening 35 arranged in the housing to enter a (liquid) sample and transfer the sample to the sample plane 11. The two chambers are associated with two measurement units, respectively. Figures 4B, 4C and 4D illustrate possible implementations of these measurement units. Optionally, additional controlled illumination and sensors 24 can be arranged in the housing, including a sensor for dedicated proximity, or fluid flow detection, etc. The sensor can be single point sensor or line sensor or array sensor. The additional illumination and sensor 24 are to be controlled in a sequence with main illumination and sensors located in chambers 14 to avoid a possible cross talk in the optical light detection workflow.

In operation, e.g. in a reader device, the optical module is equipped with a test assay, e.g. a LFT test stripe. A sample is entered into the optical module via the opening 35. The sample flows along the sample plane and reaches dedicated target regions 42 of the test assay 40. The target regions are associated with respective measurement units 20, e.g. chambers 14. The measurement units are arranged to conduct measurements of the corresponding target regions, i.e. by way of light sources 21 and optical detectors 22.

Figure 4B shows a first embodiment of a measurement unit for an optical module. This design implements a ring-like illumination and reflex detection via optics 32 (e.g., reflection and transmission possible) . The housing has a curved incision 13 which forms a first chamber 14. For example, the curved incision has spherical or parabolic shape. In this example, two light sources 21 are arranged on the curved incision. The light sources are arranged for emission of light with a desired wavelength or a desired range of wavelengths. An emission cone of the light sources can be directed towards the sample plane 11, respectively. There could be one or multiple illumination sources placed in the curved incision in multiple positions in the shape of one or more illumination rings parallel to the sample plane 11. A first optical path 30 is established from the light source (s) to the sample plane. For example, the curved incision provides a center point (or focal point) . The emission cones can be directed towards the center point. A target region 42 of the test assay 40 can be placed at, or be aligned with, the optics for illumination, e.g. placed at or near the center point.

The collection optics 32 is arranged to pass light, which may be emitted from the direction defined by the center point. Furthermore, the optical detector 22 is arranged in the housing and faces, via the collection optics, the center point of the curved incision. Thus, a second optical path 31 is established from the sample plane 11 to the optical detector 22.

Optionally, or additionally, a collection (micro-) optics 32 can be arranged next to the curved incision 13 in the corresponding groove 16 and/or in front of an optical detector 22.

In operation, a test assay 40 comprising one or more target regions 42 is placed at the sample plane 11. For example, a target region is aligned with respect to the center point.

Furthermore, the neighboring measurement unit (see Figure 4A) has a similar center point which is aligned with another target region of the assay . In other words , the light sources 21 illuminate a dedicated target region 42 of the test assay . The light sources emit light towards the respective center point 15 , either at the same time , or in a sequence one after the other .

Eventually, a compound reaches the target region 42 , is excited and a scattering or fluorescent light is emitted . A portion of said scattering or fluorescent light is emitted towards the collection optics 32 and collected . Collected light is then guided towards the optical detector 22 . For example , the collected light is focused at the optical detector by means of the collection optics .

The operation which has been described with respect to one measurement unit can be applied in the same way to the neighboring measurement unit , or any other number of units , which may be implemented in the optical module , e . g . to read more target regions of the test assay, i f present .

Figure 4C shows a modi fication of the measurement unit for the optical module . This design adds coaxial illumination and detection ( e . g . , operation in reflection and transmission possible ) . The collection optics 32 is complemented with a beam splitter 23 , which is arranged in the housing 10 between collection optics 32 and the optical detector 22 . The beam splitter ef fectively divides the second optical path 31 into a measurement path and a coaxial illumination path . The measurement path optically connects the optical detector 22 and the collection optics 32 via the beam splitter 23 . The illumination path comprises an additional light source 21 which is located downstream the beam splitter 23 (e.g., at an angle of 90 degree) .

In operation, a test assay comprising one or more target regions 42 is placed at the sample plane 11, as discussed above. Illumination of the test assay is complemented with the illumination path and the additional light source 21. The additional light source can be located such that the target region 42 can be illuminated via the beam splitter 23.

Figure 4D shows another modification of the measurement unit for the optical module. This design allows for coaxial and ring illumination and transmission. Furthermore, the design adds the possibility of further optical detectors, e.g. two detectors, where additional one can be used for different wavelength, time delay, etc.

The measurement unit 20 is based on the one shown in Figure 4C, i.e. features the illumination path and beam splitter 23. Furthermore, a light combiner (or splitter) 26 is arranged in the housing 10 between collection optics 32, downstream the beam splitter 23 and the optical detector 22. The light combiner 26 divides the measurement path into a first and second branch. The first branch allows detection via the optical detector 22. The second branch comprises an additional optical detector 25, which is located downstream the light combiner (e.g., at an angle of 90 degree) . This additional optical detector can be used to detect different wavelength and/or a time delay and/or polarization. The light combiner can be implemented as a 50-50 beam splitter, dichroic or as a polarization beam splitter. In operation, a test assay comprising one or more target regions 42 is placed at the sample plane 11, as discussed above. Furthermore, depending on its implementation, the additional optical detector 25 can be used to gather additional data, e.g. different spectral, reference or time delay data.

Furthermore, as optional components, the optical module comprises additional sensors 24, e.g. for proximity or fluid presence monitoring. These sensors can be placed in the housing, e.g. outside the chambers 14.

The proposed optical module allows for improved illumination and detection efficiency. The module depicted in Figure 4A has two measurement units with respective chambers facing to a sample plane and a loading space for fluid (opening) that can be further carried inside the device to a sample plane under measurement units.

The module of Figure 4B features enhanced collection efficiency with respect to a test assay that can be placed or connected to sample plane. The chambers 14 in the housing 10 have a curved or illumination-equidistant mechanical shape, and can be equipped with one or multiple illumination light sources 21 (for example two, or for example three, or for example four, etc.) arranged in a pre-defined order relative to the test assay and to the first and second optical paths 30, 31 (e.g., for light collection. This implements a ring of light sources, or one or more illumination rings equipped with illumination sources of one or more types of light sources. The collection optics 32 allows to increase collection efficiency and may be corrected for optical (chromatic) aberrations. The optical detector 22 can be a single point detector or an array of single point detectors/photodiodes , or an image sensor or an array of image sensors with di f ferent color sensitivity .

The module of Figure 4C features further illumination element ( s ) for coaxial illumination that can be used for enhanced illumination ef ficiency of a sample . The beam splitter 23 , or light combiner, can be polari zation based, or color based, or a beam splitter with 50-to-50 . The optical module can be equipped with an additional sensor (not shown) that is aligned on the axis passing via coaxial illumination 21 and beamsplitter 23 and is placed after the beamsplitter 23 . Such detector can be used as a reference detector to monitor stability of the coaxial illumination unit . The detector can be single point or multiple areas of di f ferent types . The module of Figure 4D features additional data collection via additional detector 26 , e . g . di f ferent spectral , polari zation or time delay data .

There can be additional sensors 24 for sample proximity monitoring or for fluid presence monitoring . The sensor 24 can be accompanied with the dedicated illumination .

Figures 5A to 5C show further example embodiments of an optical module . The drawings show schematic illustrations of optical detection building blocks , or mechanical "bones" for a measurement unit . The housing of an optical module can be manufactured from a continuous block, such as a mold structure . However, the housing can also be built up from building blocks , which each hold a respective measurement unit . For example , a first building block is depicted in Figure 5A. This arrangement (module 1 ) can be used for ring light illumination and collimated detection as discussed with respect to Figure 4B . Double dots indicate schematically positions for illumination and detection elements , i . e . light sources and optical detectors . No optical elements are shown in the schematics . The building block comprises a body with the curved incision 13 and a groove 16 . The optical detector can be placed into the groove . Optics can be arranged with respect to the groove and the optical alignment are discussed above .

A second building block (module 2 ) is depicted in Figure 5B . This block has increasing complexity arrangement that includes positions for ring light , coaxial illumination, and multiple detectors as discussed with respect to Figure 4C . Schematic positions of optical elements are shown . The building block comprises a body with the curved incision 13 and a cross-shaped groove 17 . The optical detector can be placed into the cross-shaped groove , e . g . , at end sections 18 of the cross-shape . Optics can be arranged with respect to the cross-shaped groove and the optical alignment discussed above .

A third building block (module 3 ) is depicted in Figure 5C . This block is a more complex arrangement that includes positions for ring light , coaxial illumination and detection, and multiple detectors as discussed with respect to Figure 4D . Schematic positions of optical elements are shown . The building block comprises a body with the curved incision 13 and a double-cross-shaped groove 18 . For example , the arrangement of optical elements can be as follows : ( a ) Figure 5A as in Figure 4B, (b ) Figure 5B as in Figure 4C with a beam splitter to establish a measurement path and illumination path, and ( c ) Figure 5C as in Figure 4D, with additional light combiner and detectors arranged in divided measurement paths .

Figure 6 shows another example embodiment of an optical module . The drawing is a schematic representation that shows the optical module with two measurement units 20 ( or modules ) arranged one after another and a test assay 40 on the sample plane 11 . The test assay comprises a carrier 41 and multiple optical elements attached to the carrier . The optical elements are implemented as solid immersion lenses 33 and are directly attached to the carrier 41 and centered or aligned to dedicated target regions 42 of the assay .

A solid immersion lens 33 , or S IL for short , was originally developed for enhancing the spatial resolution of optical microscopy . There are two types of S IL . A hemispherical S IL which can increase the numerical aperture up to n, n being the index of refraction of the material of the lens . Another type is denoted Weierstrass S IL ( or super hemispherical S IL ) . Such a S IL comprises a truncated sphere which can increase the numerical aperture up to n² . Both types of S IL are ef fective means to further increase collection ef ficiency of light to the target regions .

Figure 7 shows an example embodiment of a test assay . The upper part of the drawing shows a typical lateral flow test stripe with T and C active areas ( target regions 42 ) where optical detection using the optical module takes place . The test assay 40 comprises a carrier 41 , such as a back card or sample pad, e.g. cellulose. Note that a reference area can be additionally created on the same stripe to insure reference signal and fluid presence monitoring. The separation between T and C can be varied.

The bottom part of the drawing shows a side view of the test assay, or test stripe. Two SIL lenses 33 are attached above respective target regions, e.g. two sample positions T and C. The position of a SIL element relative to the respective target region, i.e. active LFT area, can vary a little but due to optical performance of SIL the illumination and collection efficiency will be less affected by such a mechanical mismatch. For example, an optimal position with respect to shift (e.g., along the sample plane) and height (e.g., with respect to the center point of a chamber 14) may not be met due to process variations during manufacture or be changing under mechanical stress acting on the module. SIL lenses can accounted to deviations from the optimal position due to their inherent high numerical aperture.

Additionally, the height of SIL lenses will insure equal distance for both target regions (T and C channel) relative to optical detector and light source of a corresponding measurement unit. Furthermore, position deviations may also be due to imperfect placement or manufacture of the test assay. Additionally, provided low mechanical tolerances for relative positioning of SIL elements, the mechanical fit of test stripe with two (or more) SIL elements will be improved since SIL elements can act as reference point for optomechanical arrangements. It has a potential to be cost effective and with improved performance at the same time. Additionally the two or more SIL lenses can be produced as a single block being mechanically attached to each other to ensure mechanical accuracy for sample positioning in the optical path and increased reprodusibility of the illumination and/or optical signal detection.

The concept discussed above in view of several embodiments allows for several advantageous effects. For example, LFT devices, including reader devices, may provide improved signal detection and fit to detection of absorption, scattering and fluorescence signals. Thus, such a device is less dependent on the type of related biochemistry. The measurements units allow for a modular approach to system architecture and miniaturization, including a dedicated design of LFT stripes and flexible modification/ customization. The improved concept is scalable for LFT but also for other sample configurations (i.e. microfluidics, etc.) and scalable for small lab devices and table top devices (beyond disposable and semi-disposable) .

The optical modules do not need to be a perfect imaging system with highly corrected geomentrical aberrations. Optics performance can mainly be focused on optimization of chromatic information and improved spectral detection. Light sensor can be a single point device. The optical resolution and image data info may not be needed.

The improved concept may rely on lower/low cost optics if cost limits need to be met. In this respect, the optical module or LFT device can use LFT stripes with optical elements attached to the stripe itself, e.g. in the form of SIL, and defining the mechanical accuracy and providing mechanical reference. LFT stripes with build in SIL lenses allow for improved light ef ficiency and mechanical (positioning) accuracy . Optical modules have been found to have improved collimation for illumination, with an improvement by factors of 2 to 10 . Furthermore , optical modules have been found to have improved light collection ef ficiency, with an improvement by a factor of at least 2 .

While this speci fication contains many speci fics , these should not be construed as limitations on the scope of the invention or of what may be claimed, but rather as descriptions of features speci fic to particular embodiments of the invention . Certain features that are described in this speci fication in the context of separate embodiments can also be implemented in combination in a single embodiment . Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination . Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or variation of a sub-combination .

Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results . In certain circumstances , multitasking and parallel processing may be advantageous . A number of implementations have been described in the text above . Nevertheless , various modi fications may be made without departing from the spirit and scope of the invention . Accordingly, other implementations are within the scope of the claims .

This patent application claims the priority of German patent application 10 2022 108 868 . 5 the disclosure content of which is hereby incorporated by reference .

References

10 housing

11 sample plane

12 substrate

13 curved incision

14 chamber

16 groove

17 cross-shaped groove

18 end section

19 double-cross-shaped groove

20 measurement unit

21 light source

22 optical detector

23 beam splitter

24 sensor

25 additional optical detector

26 light combiner / splitter

30 first optical path

31 second optical path

32 optics ( lens or mirror )

33 solid immersion lens

34 immersion fluid

35 opening

40 test assay

41 carrier

42 target region

Claims

1. An optical module for reading a test assay (40) , comprising : a housing (10) , the housing (10) further comprising at least one measurement unit (20) , wherein each measurement unit (20) comprises a light source (21) and an optical detector (22) , enclosed by the housing (10) , a sample plane (11) arranged to receive the test assay (40) , optics (32) arranged in the housing (10) and/or on the test assay (40) and operable to provide a first optical path (31) from the light source (21) to the sample plane (11) , and operable to provide a second optical path (31) from the sample plane (11) to the optical detector (22) ; wherein the optics (32) , light source (21) and optical detector (22) are aligned with respect to each other such that :

- the light source (21) is operable to illuminate a dedicated target region (42) of the test assay (40) , and

- the optical detector (22) is operable to detect light emitted from the dedicated target region (42) , respectively, wherein the sample plane (11) is arranged to permanently attach or to removeably attach the test assay (40) .

2. The optical module according to claim 1, wherein: the housing (10) comprises a plurality of measurement units (20) , each light source (21) is operable to illuminate a single dedicated target region (42) of the sample plane (11) , a corresponding one of the optical detectors (22) is operable to detect light emitted from said single dedicated target region (42) , and the optics (32) is arranged to provide a dedicated first and second optical path (30, 31) .

3. The optical module according to claim 1 or 2, wherein one or more of the light sources (21) comprise: a light-emitting diode, a micro light-emitting diode, and/or a resonant-cavity light emitting device, or an array thereof.

4. The optical module according to one of claims 1 to 3, wherein one or more of the optical detectors (22) comprise: a photodiode, an Avalanche photodiode, a charge-coupled device, and/or a CMOS photodetector, or an array thereof.

5. The optical module according to one of claims 1 to 4, wherein the optics (32) comprises an illumination optics and/or a detection optics, wherein the illumination optics is operable to guide light along the first optical path and detection optics is operable to guide light along the second optical path.

6. The optical module according to one of claims 1 to 5, wherein the optics (32) comprises one or multiple collimating optics, such as lenses or gratings, and/or one or more collecting optics, mirrors, micro-mirrors or micro mirror array ( s ) . 7. The optical module according to one of claims 1 to 6, wherein : at least one measurement unit (20) comprises a curved incision (13) arranged in the housing (10) such that the curved incision (13) forms a chamber (14) with respect to the sample plane (11) , one or more light sources (21) are arranged along the curved incision (13) , the curved incision (13) provides a center point (15) (or focal point) to be aligned with a target region (42) of the test assay (40) , said measurement unit (20) comprises a groove (16) arranged in the housing (10) such that an opening is formed facing the center point (15) , and one or more optical detectors (22) are arranged inside the groove (16) .

8. The optical module according to claim 7, wherein an illumination optics and/or a detection optics is arranged in front of the opening of the groove (16) , respectively.

9. The optical module according to claim 7 or 8, wherein the grove (16) comprises a cross-shape comprising branches with end-sections and a center section, a beam-splitter (23) arranged at the center section, at least one optical detector (22) arranged at an endsection being coaxial with the center point (15) and the beam-splitter (23) , establishing a measurement path, and at least one a reference detector (25) arranged at an endsection being perpendicular with respect to the center point (15) and optical detector (22) , establishing a reference path. 10. The optical module according to claim 9, further comprising a reference light source (26) coaxial arranged at an end-section being coaxial with the optical detector (22) and the beam-splitter (23) , establishing an illumination path .

11. The optical module according to one of claims 1 to 10, wherein the light source (21) comprises a micro-LED.

12. A test assay, comprising: a carrier (41) , one or more target regions (42) arranged on the carrier (41) and optics (32) attached to the carrier (41) at the location of the target regions (42) .

13. The test assay according to claim 12, wherein the optics

(32) comprises at least one solid immersion lens (33) , SIL.

14. The test assay according to claim 13, wherein the solid immersion lens (33) comprises a hemispherical SIL or a Weierstrass SIL.

15. The test assay according to one of claims 12 to 14, wherein the optics (32) attached to the carrier (41) are configured to mechanically lock into an optical module to be connected to the test assay.

16. An assay reader device, comprising: an optical module according to one of claims 1 to 11, a printed or flexible circuit board, a test assay (40) comprising target regions (42) , permanently attached or removeably attached to the sample plane (11) and aligned with the target regions (42) to the optical module.

17. The reader device according to claim 15, wherein the test assay comprises a test assay (40) according to one of claims 12 to 15. 18. The reader device according to claim 16 or 17, further comprising means for sample flow from an opening (35) to the test assay (40) .