Self-mixing interferometry for absorption or color detection and applications in lateral flow tests

Abstract

It is proposed to use self-mixing interferometry for determining absorption. A monitoring device for use in a lateral flow test for analyzing the presence or amount of an analyte (1) in a liquid (L) comprises a housing comprising a carrier holder for holding a carrier (10) for transporting the liquid (L); at least a first light source (41) being a resonator cavity light source having a cavity (C); and an evaluation unit (50) operably connected to the at least first light source (41) for detecting a measurement signal. The first light source (41) is constructed and arranged to illuminate a test range in a test area (13) of the carrier (10) held in the carrier holder with light; and to couple a portion of the light returned from the test range (13) back into the cavity (C) of the first light source (41).

Description

[0001] This invention relates to the field of sensing, and more particularly to optical sensing. More specifically, it relates to methods for detecting or determining changes in absorption or color. The invention also relates to applications of sensing, namely chemical analysis based on optical properties, particularly light absorption properties, and more specifically on the optical and absorption properties of binding ligands to the analyte, respectively. For example, sensing can be applied to transverse flow testing. This invention relates to methods and apparatus according to the opening claim.

[0002] Self-mixing interferometry (SMI) is a known technique. It is described and its current applications in Thomas Taimre et al.'s "Laser feedback interferometry: a tutorial on the self-mixing effect for coherent sensing" (Advances in Optics and Photonics 7, 570–631, 2015). To date, SMI has been applied to sensing magnitudes related to path length differences, such as displacement, distance, velocity, flow rate, and refractive index.

[0003] SMI (Simulated Motion Interferometry) is a technique in which a beam of light from a resonant cavity source is reflected from an object back into the cavity of the source. The reflected light interacts with, and particularly interferes with, the light inside the source; more specifically, it interacts with, and particularly interferes with, the light inside the cavity, causing changes in the optical and electrical properties of the source. By analyzing this information, information about the object can be obtained. SMI is also known as feedback interferometry, inductively modulated interferometry, or backscattered modulation interferometry.

[0004] The resonant cavity light source is, for example, a laser or a resonant cavity light-emitting diode (RC-LED).

[0005] Furthermore, methods for detecting analytes in samples are known, where detection is accomplished by detecting changes in the color intensity of a marker bound to the analyte. For example, in a transverse flow test (LFT), particularly a transverse flow immunochromatographic assay, the presence of the analyte (target substance) in a liquid sample is visually detected as follows: the liquid sample is applied to a carrier, for example, to a strip, more specifically to a sample pad of the carrier, and extends along the carrier through a pad called a conjugate pad, which provides a marker bound to the analyte. The liquid then flows further to a test area where the analyte binder is immobilized to the carrier such that at least a portion of the analyte remains there instead of continuing through the carrier. Upon binding to the analyte binder, the marker bound to the analyte displays a specific color (a first color). Detection of this color signifies a positive test result: the liquid contains the analyte. For control purposes, such as for verification, the carrier can have a control area where the marker binder is immobilized to the carrier such that the marker remains there instead of continuing through the carrier, for example, so that it may eventually be absorbed by a porous material. When the marker binds to the marker adhesive, the marker also displays a specific color (second color). The first and second colors can be the same or different.

[0006] When the analyte is present in the liquid, the test area will display a first color after the liquid has had sufficient time to reach it. The intensity of this color indicates the concentration of the analyte in the liquid sample. When the liquid sample has had sufficient time to reach the control area, it will also display a specific color, the second color—this is especially important when the liquid sample does not contain any analyte, i.e., to ensure the test proceeds correctly and that the test area does not display the first color.

[0007] The inventors recognized that SMI can also be used to detect or determine absorption, and therefore also to detect and determine color intensity and / or changes in color intensity. Furthermore, they recognized that applying SMI to chemistry or biology, particularly LFT, could enable new sensing or testing devices.

[0008] One possible objective of this invention is to create a new method for sensing absorption.

[0009] One possible objective of this invention is to create a new method for detecting color and / or color changes.

[0010] Another possible objective of the present invention is to provide a novel method for detecting substances, particularly optically detected substances.

[0011] Another possible object of the present invention is to provide a new method for detecting substances, particularly optically, in an automated manner.

[0012] Another possible object of the present invention is to provide a method for the automated detection of substances, which is particularly cost-effective.

[0013] Another possible object of the present invention is to provide a method for detecting substances with particularly high sensitivity.

[0014] Another possible object of the present invention is to provide a method for detecting substances in a particularly rapid manner.

[0015] Another possible object of the present invention is to provide a method for detecting substances with particularly good reproducibility.

[0016] Another possible object of the present invention is to provide a device for detecting particularly small substances.

[0017] Another possible object of the present invention is to provide a device for detecting substances in a particularly energy-efficient manner.

[0018] Another possible object of the present invention is to provide an apparatus for simultaneously detecting multiple substances, particularly said substances being located in small points close to each other.

[0019] Another possible objective of the present invention is to provide a new method for sensing absorption in an automated manner.

[0020] Another possible object of the present invention is to provide a method for sensing absorption in an automated manner, which is particularly cost-effective.

[0021] Another possible object of the present invention is to provide a method for sensing absorption with particularly high sensitivity.

[0022] Another possible object of the present invention is to provide a method for sensing absorption in a particularly rapid manner.

[0023] Another possible object of the present invention is to provide a method for sensing absorption with particularly good reproducibility.

[0024] Another possible object of the present invention is to provide a device for sensing particularly small absorptions.

[0025] Another possible object of the present invention is to provide a device for sensing absorption in a particularly energy-efficient manner.

[0026] Another possible object of the present invention is to provide a device for simultaneously sensing absorption in multiple small points that are close to each other.

[0027] Other objectives and various advantages will become apparent from the following description and examples.

[0028] In some embodiments of the apparatus and / or methods described in this disclosure, at least one of these objectives can be achieved in part.

[0029] As will become clear, the invention has various aspects.

[0030] In a first, more general aspect, the present invention relates to applying SMI to absorption sensing and / or color sensing.

[0031] In a second, more specific aspect, the present invention relates to applying SMI to LFT.

[0032] The second aspect relates to specific embodiments of the first aspect. Therefore, any feature or embodiment described with respect to the first aspect can be applied to any embodiment of the second aspect. However, features or embodiments described with respect to the second aspect can also be logically applied to the first aspect as much as possible.

[0033] The first aspect specifically includes using SMI to detect or determine absorption. In particular, it allows for the determination of absorption (or absorption intensity). Based on appropriate measurements, absorption can be determined from SMI data. Furthermore, because the measurement work can be reduced, detecting changes in absorption becomes easier.

[0034] For example, this application could be to use SMI to detect or determine changes in absorption, more specifically, to determine changes in absorption during lateral flow testing.

[0035] This use can include irradiating a material with light emitted from a light source, causing the light to interact with the material, and coupling a portion of the light that has already interacted with the material back to the light source.

[0036] For example, this use can include detecting or determining absorption at a specific wavelength, wherein the light emitted from the light source includes that specific wavelength.

[0037] It is possible to define and determine the absorption of a substance, and light has wavelengths within the absorption band of the substance.

[0038] The first aspect can also include using SMI (Surface Intensity Measurement) to detect color intensity. Based on appropriate measurements, color intensity can be determined from SMI data. Furthermore, since the measurement work can be reduced, detecting changes in color intensity becomes easier.

[0039] Generally, there is a relationship between color intensity and absorption: the higher the color intensity, for example, due to the higher concentration of the colorant, the greater the absorption (within the absorption band of the substance). Therefore, the methods for detecting color intensity disclosed herein can also be applied to the detection of absorption, and vice versa.

[0040] Furthermore, color intensity can be detected by detecting absorption, and more specifically, absorption at color-related wavelengths, particularly at wavelengths complementary to the color.

[0041] Similarly, the second aspect can specifically include using SMI to detect absorption (or color intensity) in a transverse flow test (LFT), and more specifically, to detect changes in absorption (or color intensity) during the transverse flow test. Specifically, absorption and color intensity can be the absorption and color intensity of the test area of ​​the carrier of the LFT device, respectively. Alternatively or additionally, absorption and color intensity can be the absorption and color intensity of the control area of ​​the LFT device, respectively. Another alternative or additional possibility is that absorption and color intensity are the absorption and color intensity of a reference area of ​​the LFT device, respectively. The reference area will be described separately below.

[0042] In LFT, the concentration of the color carrier in the test area increases over time, causing the color intensity and corresponding absorption in the test area to increase over time. This can be detected using SMI, which uses light with wavelengths that are absorbed by the substance.

[0043] At this point, we will clarify the possible implications of using SMI. It can more specifically represent the use of a resonant cavity light source, where light emitted from the source interacts with an object (e.g., with matter), and a portion of the light that has interacted with the object is coupled back into the cavity of the light source. This causes changes in the optical and electrical properties of the light source, which can be monitored by monitoring the corresponding measurement signals. The light coupled back into the cavity can include, for example, light reflected by the matter. In examples, it can also include light that passes through the matter, particularly light that passes through the matter twice, as further explained below for embodiments where the device includes a mirror.

[0044] The measurement signal depends on the object (or substance), and more specifically, on the object's color and / or its absorption properties. The measurement signal can be correlated with the signal or amplitude of the interference between light generated in the cavity of the light source and light coupled back into the cavity. The measurement signal, or more specifically, the amplitude or intensity of the measurement signal, can indicate the absorption (and color) of the object (or substance). More specifically, it can indicate the amount of absorption occurring from the light emitted from the light source used to illuminate the object (or substance), particularly through the interaction between the light and the object (or substance).

[0045] To understand an object, at least two measurement signals can be monitored. These measurement signals are the same as those known in the field of SMI; see, for example, the article by Thomas Taimre et al. mentioned above. Light emitted from the light source can be monitored, and more specifically, the intensity of the light emitted from the light source can be monitored. This can be achieved, for example, by a photodetector. For example, stray light or a portion of the light coupled out of a beam emitted from the light source, for example, by a beam splitter, can be monitored. However, this requires a photodetector.

[0046] A simpler method is to monitor the power supply signal to the light source. The light source can be powered by a power supply signal, such as a power supply voltage or a power supply current. The power supply signal is applied to the power supply terminal of the light source, making it possible to measure a measurement signal, for example, at the power supply terminal. Therefore, the measurement signal can be, for example, the voltage or current present at the power supply terminal of the light source, or it can be the impedance of the light source.

[0047] Unlike existing SMI measurements, which involve counting and evaluating the number of minimum and / or maximum values ​​(derived from interference), this paper proposes to monitor the intensity (optical) and amplitude (electrical) and / or phase (electrical) associated with (and affected by interference) the light source; where, for example, impedance (electrical) can be monitored.

[0048] In particular, it is possible to perform time averaging on the measured signal to remove rapid changes that are irrelevant to the monitored area and object or substance. For example, vibrations can be averaged in this way. For example, the measured signal can be time-averaged over a duration of 1 to 20 seconds.

[0049] Furthermore, the waviness of the carrier (in the irradiated area, e.g., in the test area) and the irregularity or inhomogeneity of the carrier can affect the measurement, thereby reducing the quality of the measurement results. This problem can be mitigated by irradiating a relatively large area of ​​the carrier, in other words, by spatial averaging. Moreover, specific embodiments particularly well-suited for this purpose are described below, for example, in which a lens is used to generate parallel light for irradiating an object (or substance). For example, the beam emitted from the light source can be broadened in this way.

[0050] The physical source of the measurement signal can be understood at least partially as follows (in this case, assuming the light source is a laser): the coupled-back light alters the laser threshold condition, which in turn changes the carrier density N = N(Φ), specifying the interference phase. The result is a change in the power supply signal, more specifically a change in the power supply voltage applied to the laser, from which the measurement signal can be obtained since V = V(N(Φ)). Another result is a change in the emitted light power P, since P = P(N(Φ)), from which the measurement signal can be obtained, for example, from the light intensity measurement via a photodiode.

[0051] Examples of resonant cavity light sources are lasers and RC-LEDs. To generate interference in a light source, particularly within its cavity, it is advantageous to ensure that the light from the source has a significant coherence length. From this perspective, lasers, which typically have very large coherence lengths, are more likely to provide stronger measurement signals than RC-LEDs, which typically have only very small coherence lengths. However, both can be used as light sources.

[0052] In particular, a resonant cavity light source that can be considered is one with a coherence length longer than the length of the cavity of the light source.

[0053] In order to adjust the ratio of the intensity of light coupled from the light source to the brightness of light coupled into the light source, the transmittance of the end mirror of the light source can be appropriately adjusted or selected.

[0054] In particular, vertical-cavity surface-emitting lasers (VCSELs) and edge-emitting lasers (EELs) are especially suitable light sources. They can be very small.

[0055] Regarding the wavelength of the light emitted from the light source, it is preferably a wavelength within the absorption band of the substance or color under study. For example, if the substance (or object) under study has an absorption band in the visible part of the spectrum (e.g., in the blue range, such as approximately 470 nm), then the light from the light source should also have a wavelength close to 470 nm. This allows for the acquisition of a higher intensity measurement signal.

[0056] The method according to the first aspect can be a method for detecting or determining absorption within a test range, wherein the method includes

[0057] —Illuminate the test area with light emitted from a resonant cavity light source;

[0058] —The optical coupling returned from the test range will be returned to the cavity;

[0059] —This results in changes in the light produced in the light source, especially due to the interference between the coupled-back light and the light produced in the light source;

[0060] —Monitor the measurement signals of the light source related to this change.

[0061] As is typical in SMI, light interacts with an object (or substance) present within the test range, and a portion of the light that has interacted with the object (or substance) is coupled back into the cavity of the light source, more specifically, into the cavity of the light source. The light coupled back into the cavity can include light reflected from the object (or substance). The absorption of the object (or substance) can be determined. The absorption can be correlated with or indicate the concentration of the substance within the test range.

[0062] Similarly, another method according to the first aspect can be a method for detecting or determining color intensity in a test range, wherein the method is otherwise identical to the method described for detecting or determining absorption in a test range.

[0063] Considering both the color-carrying object and the substance, another method according to the first aspect can be a method for detecting the presence or amount of a substance within a test range. Furthermore, this method can particularly include the same method steps as the described method for detecting or determining absorption within a test range.

[0064] By monitoring and measuring the signals, the absorption and / or color intensity and / or presence or quantity of substances within the test range can be determined.

[0065] The device according to the first aspect can be a device for detecting or determining absorption within a test range. It can also (see above) be a device for detecting or determining color intensity within a test range, and a device for detecting the presence or amount of a substance within a test range. In all three cases, the device includes...

[0066] —A resonant cavity light source for illuminating the test area, wherein the light source, in particular its external coupling mirror, is adapted to couple light returning from the test area back into the cavity of the light source;

[0067] —Evaluation unit for monitoring measurement signals of the light source, which are related to changes in the generation of light in the light source, which arise from the interference between the coupled-back light and the light generated in the light source.

[0068] Referring to the above, the evaluation unit can monitor the intensity or amplitude of the measured signal, which is related to the amount or concentration of the substance within the test range due to the amount of substance absorbed.

[0069] Now we turn back to the second aspect. The monitoring device according to the second aspect can be a monitoring device used in transverse flow tests, specifically wherein, in a transverse flow test, the presence or amount of an analyte in the liquid is detected. This device can include:

[0070] —A housing, the housing including a carrier holder for holding a carrier, particularly for holding a carrier for conveying liquid;

[0071] —At least the first light source is a resonant cavity light source with a cavity;

[0072] —An evaluation unit, operatively connected to at least a first light source, for detecting a measurement signal and optionally also for evaluating the measurement signal;

[0073] The first light source is constructed and configured to...

[0074] —The test area within the test region of the carrier held in the carrier holder is illuminated with light; and

[0075] —A portion of the light returning from the test range will be coupled back into the cavity of the first light source.

[0076] The light returning from the test range is particularly capable of including light reflected back from the test range.

[0077] The measurement signal can be a signal that depends on the interference between the coupled light that occurs in the cavity and the light generated in the light source and respectively existing in the cavity.

[0078] The measurement signal can be a signal that depends on the coupled-back light.

[0079] The amount of light coupled back into the cavity of the first light source depends on the amount of substance (analyte) within the test range.

[0080] In some embodiments, the evaluation unit includes an optical detector for detecting the intensity of light emitted by the light source. Specifically, a measurement signal can be obtained from the optical detector. For example, the detected intensity can be evaluated by the evaluation unit and correlated with the amount of analyte present in the liquid.

[0081] In some embodiments, the evaluation unit includes an electrical detector for detecting a power supply signal to the light source, particularly wherein the measurement signal originates from the electrical detector. For example, the detected power supply signal can be evaluated by the evaluation unit and can be correlated with the amount of analyte in the liquid.

[0082] For example, a constant voltage can be supplied to the first light source, and the current can be used as a measurement signal. Alternatively, in another example, a constant current can be supplied to the first light source, and the voltage can be used as a measurement signal. Or, in yet another example, the impedance of the first light source can be determined based on the current and voltage of the power supply signal, and can be used as a measurement signal.

[0083] At least the first light source can be housed within the housing, and in particular, it can be fixed to a portion of the housing.

[0084] In some embodiments, the housing includes a compartment in which at least a first light source is disposed. In particular, the compartment can be designed to prevent light from outside the housing from reaching the test range of the carrier when the carrier is held in the carrier holder.

[0085] In some embodiments, the monitoring device further includes a mirror disposed within the housing (particularly fixed to a portion of the housing). The mirror can be set and aligned to reflect light emitted from the first light source, which has passed through a carrier held in a carrier holder, back onto the carrier so that it passes through the carrier again. A portion of the light can then be coupled back into the cavity of the light source.

[0086] In this way, light can pass through the carrier (more specifically, the test area) twice, thereby increasing absorption. This improves sensitivity even at low analyte concentrations.

[0087] Of course, in order to utilize this effect, a carrier that is at least partially transparent to the light emitted from the first light source should be used.

[0088] For example, the mirror can be configured such that when the carrier is held in the carrier holder, the carrier is positioned between the mirror and the first light source. The mirror, more specifically its reflective surface, can face the carrier.

[0089] In some embodiments, the mirror is a plane mirror.

[0090] In some embodiments, the mirror is a curved mirror, such as a convex mirror. This helps to focus light back into the cavity.

[0091] In some embodiments, the monitoring device further includes at least a first lens disposed within the housing. It can be fixed to a portion of the housing and / or to a first light source. This provides improved stability. The first lens can be positioned in the optical path of light emitted from the first light source toward a carrier held in the carrier holder, i.e., between the first light source and the carrier held in the carrier holder.

[0092] For example, the first lens can be configured such that when the carrier is held in the carrier holder, the first lens is positioned between the carrier and the first light source.

[0093] In some embodiments, the first lens is constructed and configured to generate a parallel beam of light based on light emitted from a first light source. For example, the first light source is capable of emitting light through a first end mirror (first end reflector or external coupling mirror) of the cavity, and the lens can be a convex lens disposed at a distance from the first end mirror corresponding to the focal length of the first lens.

[0094] In some embodiments, the first lens is constructed and configured to generate a beam of light based on light emitted from a first light source, the beam having a cross-sectional area exceeding that of the beam emitted from the first light source when it strikes the first lens.

[0095] In some embodiments, the first lens is constructed and configured to generate a beam of light based on light emitted from a first light source, the beam cross-sectional area of ​​which is smaller than the beam cross-sectional area of ​​the light emitted from the first light source when it strikes the first lens.

[0096] In some embodiments, the first lens is constructed and configured to focus light emitted from the first light source.

[0097] Specifically, the first lens can be constructed and configured to focus light emitted from the first light source onto the test area.

[0098] This allows for increased light intensity over the test area. This method can operate within a very small test range, for example, enabling the investigation of a large number of analytes within a relatively small test area (and small test zone).

[0099] In some embodiments, the monitoring device further includes a printed circuit board held by a housing, on which at least a first light source is mounted. Specifically, when the carrier is held in a carrier holder, the printed circuit board is capable of being aligned parallel to the carrier. More specifically, when the carrier is held in a carrier holder, the printed circuit board is capable of being aligned parallel to a surface of the carrier, wherein the surface faces the printed circuit board.

[0100] At least a portion or all of the printed circuit board can be disposed inside the housing. In some embodiments, a portion of the printed circuit board extends outside the housing.

[0101] The monitoring device may include an interface, such as an interface between the monitoring device and an external device, such as an interface to an external processing unit or mobile computing device (e.g., a smartphone). The interface may be an electrical interface, such as a digital interface. The interface may be a wired interface. In other embodiments, the interface is a wireless interface.

[0102] For example, monitoring devices can be connected to readers via an interface.

[0103] This interface can improve the level of automation.

[0104] For example, the monitoring device can be connected to an external device for one or more of the following purposes.

[0105] —Provide a power signal to the light source, such as power supply voltage;

[0106] —Provides power signals, such as power voltage, to all components mounted on the printed circuit board;

[0107] —Detect and / or evaluate the measurement signal.

[0108] In some embodiments, the portion of a printed circuit board extending outside the housing can provide the interface. This allows for a particularly compact device.

[0109] For example, monitoring equipment can be used to transmit measurement signals and / or evaluation results via an interface, such as the results of a lateral flow test.

[0110] In this regard, it should be mentioned that the assessment unit does not necessarily need to be included in the monitoring equipment. And it can, but does not need to, be connected to or housed within the housing.

[0111] For example, with the help of an interface, the monitoring device can be operatively connected to an external device in which an evaluation unit is implemented or in which the evaluation of the measurement signal is performed.

[0112] In some embodiments, the monitoring device further includes a second light source, particularly wherein the second light source is configured and arranged to...

[0113] —The control range within the control area of ​​the carrier held in the carrier holder is illuminated; and

[0114] —A portion of the light returning from the control range will be coupled back into the cavity of the second light source.

[0115] It can also be configured to operatively connect a second light source to the evaluation unit for detecting a measurement signal, which should be referred to as a control measurement signal.

[0116] Alternatively, a first light source can be used for this purpose. For example, the control range and the test range can be alternately illuminated by the first light source (e.g., in a time-multiplexed manner). And / or the light returning from the test range and the light returning from the control range can be alternately coupled back into the cavity of the first light source (e.g., in a time-multiplexed manner). This can be achieved in a direct manner, for example, using light guides and switchable beam splitters.

[0117] The functions of the control area are described elsewhere in this application.

[0118] In some embodiments, the monitoring device further includes a third light source, particularly wherein the third light source is configured and arranged to...

[0119] —Illuminate the reference range within the reference region of the carrier held in the carrier holder with light; and

[0120] —A portion of the light returning from the reference range will be coupled back into the cavity of the third light source.

[0121] This can be used for further calibration.

[0122] It can also be configured to operatively connect a third light source to the evaluation unit for detecting a measurement signal, which should be referred to as a reference measurement signal.

[0123] Optionally, a first light source (or a second light source) can also be used for this purpose. For example, the reference range and the test range can be alternately illuminated by means of a first light source, or the reference range and the control range can be alternately illuminated by means of a second light source (e.g., in a time-multiplexed manner). And / or it is possible to alternately—couple light returning from the test range and light returning from the reference range back to the cavity of the first light source, respectively; or

[0124] —The light returning from the control range and the light returning from the reference range are coupled back into the cavity of the second light source, respectively;

[0125] For example, in a time-multiplexed manner. This can be achieved directly, for example, using optical guides and switchable beam splitters.

[0126] Similarly, the first light source can be used in a similar way to achieve the functions of the first light source, the second light source, and the third light source.

[0127] In other words:

[0128] In some embodiments, the second light source is the same as the first light source.

[0129] In some embodiments, the third light source is the same as the second light source.

[0130] In some embodiments, the second and third light sources are the same as the first light source.

[0131] The reference area will be explained below.

[0132] Similar to the first lens described in this paper with respect to the first light source, the second and / or third lenses can be combined with the second and third light sources respectively to provide similar features.

[0133] In some embodiments, the monitoring device further includes an additional first light source. This additional first light source can be specifically configured and positioned to...

[0134] —The test area in another test region of the carrier held in the carrier holder is illuminated with light; and

[0135] —A portion of the light returning from another test range will be coupled back into the cavity of another first light source.

[0136] This enables, for example, the detection of two different analytes in a single test involving a single carrier, as will be explained further below. Similarly, it is possible to provide one or more additional first light sources for testing additional analytes.

[0137] Similarly, it is also possible to provide one or more additional second light sources.

[0138] Similarly, it is also possible to provide one or more additional third light sources.

[0139] Because of the small size of the available light sources and the ability to limit the illumination of the carrier by each light source to a small point ("small lateral range"), different analytes on the same carrier can be tested using the same lateral flow testing equipment (parallel testing) even without excessively expanding the width of the carrier. In particular, VCSELs, EELs, and RC-LEDs are suitable for this purpose.

[0140] The transverse flow testing apparatus according to the second aspect can include monitoring equipment as described herein and a carrier held in a carrier holder. The carrier can specifically include...

[0141] —A sample pad, used to apply the liquid;

[0142] —A binding pad, which provides a marker for labeling an analyte by binding to it;

[0143] —Test area, in which an analyte binder for specific binding to the analyte is immobilized to a carrier;

[0144] —Control region, in which a marker binder for specific binding to the marker is immobilized to the carrier;

[0145] The carrier can be configured to allow liquid to be transported, particularly by capillary forces, from the sample pad to the conjugate pad, then to the test area, and then to the control area.

[0146] In some embodiments of the transverse flow testing equipment, the carrier also includes

[0147] —A reference region that is not bound to a carrier, and in particular, is free of analyte and label binders.

[0148] A reference region is extremely useful for calibration purposes. When a liquid wets a carrier, the carrier's optical properties (e.g., reflectivity) may change, which can and often leads to changes in the measurement signal. Illuminating the reference region and coupling the light back into a cavity, such as a third light source, allows the acquisition of a reference measurement signal, which provides useful information for interpreting the measurement signal (from the test range). For example, the measurement signal can be evaluated based on the reference measurement signal. In simple cases, for example, for evaluation, the difference between the measurement signal and the reference measurement signal can be determined.

[0149] In some embodiments, a reference region (relative to the direction of liquid flow) is located between the sample pad and the conjunctival pad. The reference region can be downstream of the sample pad and upstream of the conjunctival pad.

[0150] In some embodiments, a reference region (relative to the flow direction of the liquid) is located between the conjugate pad and the test region. The reference region can be downstream of the conjugate pad and upstream of the test region.

[0151] In some embodiments, the material properties of the carrier are nominally the same in the test area and the reference area.

[0152] In some embodiments, the material properties of the carrier are nominally the same in the control region and the reference region.

[0153] In some embodiments, the material properties of the carrier are nominally the same in the control region, reference region, and test region.

[0154] These embodiments can help improve the comparability of reference measurement signals with measurement signals and / or control measurement signals, thereby achieving more accurate and / or reliable results.

[0155] In some embodiments, the carrier is a strip.

[0156] In some embodiments, the carrier can be strip-shaped.

[0157] In some embodiments, the carrier is operable to deliver liquid. In particular, each pad and area is capable of delivering liquid.

[0158] In some embodiments, the carrier is a carrier of semiconductor material, particularly where the semiconductor material is microstructured, for example, etched.

[0159] In some embodiments, the carrier is a glass material, particularly where the glass material is microstructured, for example, etched.

[0160] In some embodiments, the carrier is a polymer carrier, particularly wherein the polymer is microstructured.

[0161] In some embodiments, the carrier is a carrier of fibrous material, particularly a paper carrier.

[0162] In some embodiments, the carrier includes a mirror. The mirror may include, in particular, a reflective coating. For example, when the carrier is held in a carrier holder, the carrier has a first side facing a first light source and / or a printed circuit board and a second side opposite to the first side, and the mirror is present on the second side.

[0163] This could be an alternative to the described embodiment, where the mirror is a component of the detection device. It can achieve the same purpose.

[0164] In some embodiments, the liquid is a bodily fluid, particularly human body fluid. For example, the liquid could be urine or blood.

[0165] In some embodiments, particularly for parallel testing, a transverse flow testing device is a transverse flow testing device used to detect the presence or amount of an analyte and other analytes in a liquid.

[0166] —The binding pad can provide additional markers for labeling additional analytes by binding to them;

[0167] —The test area may include a test area in which an analyte binder for specific binding to an analyte is immobilized to a carrier, and may also include a separate test area in which a separate analyte binder for specific binding to a separate analyte is immobilized to a carrier.

[0168] —The control area may include a control area in which a marker binder for binding to a marker is fixed to a carrier, and may include a further control area in which a further marker binder for binding to a further marker is fixed to a carrier.

[0169] Furthermore, the test range is located within the test area; and the lateral flow test device includes a second light source, which is a resonant cavity light source and has a cavity. It can be the same as or different from the first light source, and can be constructed and configured to...

[0170] —Illuminate the control area within the control zone with light; and

[0171] —A portion of the light returning from the control range will be coupled back into the cavity of the second light source.

[0172] The transverse flow testing equipment may also include an additional first light source and an additional second light source, both of which are resonant cavity light sources and each has a cavity. The additional second light source may be the same as or different from the additional first light source. The additional first light source is constructed and configured to...

[0173] —Illuminate the test area in another test zone with light; and

[0174] —A portion of the light returning from another test range will be coupled back into the cavity of another first light source.

[0175] The additional second light source is constructed and configured to...

[0176] —Illuminate another control area within another control zone with light; and

[0177] —A portion of the light returning from another control range will be coupled back into the cavity of another second light source.

[0178] It is possible to configure a second light source, another first light source, and another second second light source to be operatively connected to the evaluation unit. This allows for the determination of measurement signals from all light sources, and optionally, for evaluation by the evaluation unit. Therefore, the presence or amount of two substances (analytes) can be detected.

[0179] It is obvious to extend this directly to two or more different analytes, such as a 3x3 matrix for the test range (and optionally, the control range).

[0180] It is possible to configure each light source (the first light source, and for now, the second light source, the third light source, another first light source, and another second light source) to emit light through the first end mirror (external coupling mirror) of its corresponding cavity.

[0181] In some embodiments, the distance between the corresponding end mirror and the carrier (more specifically, the surface of the carrier facing the corresponding end mirror) is 0.05 mm to 10 mm, more specifically 0.1 mm to 5 mm.

[0182] In some embodiments, each of the ranges (test range and control range to date, reference range, additional test range, additional control range) has a diameter of 0.2 mm. 2 Up to 8mm 2 The area, especially 0.5mm 2 Up to 4mm 2 The area.

[0183] The method according to the second aspect can be a method for detecting the presence or amount of an analyte in a liquid by means of a transverse flow test. This method can include:

[0184] — Illuminate the test area of ​​the carrier with light from a first light source, which is a resonant cavity light source with a cavity;

[0185] —A portion of the light returning from the test range will be coupled back into the cavity of the first light source;

[0186] —The measurement signal is detected by means of an evaluation unit that is operatively connected to the first light source.

[0187] In some embodiments, the carrier includes

[0188] —Sample pad;

[0189] —A binding pad, which provides a marker for labeling an analyte by binding to it;

[0190] —Test area, in which an analyte binder for specific binding to the analyte is immobilized to a carrier;

[0191] —A control region in which a marker binder for specific binding to the marker is immobilized to a carrier; and

[0192] The method includes

[0193] —Enables the carrier to transport liquid from the sample pad to the control area, especially by capillary force;

[0194] —Apply the liquid to the sample pad;

[0195] —To allow the marker to bind to the analyte at the conjugation pad;

[0196] —This allows the analyte binder to bind to the analyte at the test pad;

[0197] —This allows the marker binder to bind to the marker at the control area.

[0198] In some embodiments, the conjugate pad is located downstream of the sample pad relative to the direction of liquid flow, the test area is located downstream of the conjugate pad, and the control area is located downstream of the test area.

[0199] In some embodiments, the method further includes

[0200] —The control area within the control region of the carrier is illuminated by light from a second light source, wherein the first light source is a resonant cavity light source with a cavity; and

[0201] —A portion of the light returning from the control range will be coupled back into the cavity of the second light source;

[0202] The second light source is operatively connected to the evaluation unit for detecting control measurement signals by means of the evaluation unit.

[0203] In some embodiments, the carrier includes a reference region to which no binder is attached, and the method further includes...

[0204] —Illuminate a reference region within the reference area of ​​the carrier with light from a third light source, wherein the first light source is a resonant cavity light source having a cavity; and

[0205] —A portion of the light returning from the reference range will be coupled back into the cavity of the third light source;

[0206] The third light source is operatively connected to the evaluation unit for detecting a reference measurement signal by means of the evaluation unit.

[0207] This method can specifically include:

[0208] —The evaluation unit evaluates the measurement signal based on the reference measurement signal.

[0209] The combined evaluation of the measurement signal and the reference measurement signal can improve the results because, as mentioned above, it is possible to monitor and account for changes in reflectivity caused by the liquid.

[0210] Note that these methods can be performed while the test area is still wetted by the liquid. They can also be performed while the liquid is still flowing (being transported by a carrier). However, the methods can also be performed after the liquid has left the test area (e.g., through evaporation). In this case, the reference measurement signal can be used as a reference for the measurement signal. For example, the evaluation unit can jointly evaluate the reference measurement signal and the measurement signal, for example, to determine absorption.

[0211] Furthermore, it should be noted that providing a control area is generally an option. Therefore, the described method and apparatus can also be implemented without a control area, and of course, without features and components related to, for example, a second light source.

[0212] The present invention, particularly its second aspect, can be applied to the detection of biomolecules, such as viruses. In this case, for example, the marker can be a biodiagnostic colorimetric marker, such as an antibody bound to colored particles or molecules (e.g., latex spheres or gold nanoparticles); and the analyte binder can be an antibody (immobilized onto a carrier in the test area), and the marker binder can be another antibody (immobilized onto a carrier in the test area).

[0213] It should be noted that, in both aspects of the invention, and therefore for the methods and apparatus described herein, irradiation can be implemented in a pulsed manner. Furthermore, it is then possible to configure the detection of a measurement signal simultaneously with irradiation, for example, in a pulsed manner concurrent with irradiation.

[0214] It should be noted that in both aspects of the invention, and therefore for the methods and apparatus described herein, the sample (liquid; substance) can be stationary (meaning it does not move, remains stationary) during irradiation. If the sample flows during irradiation, the direction of irradiation can be perpendicular to the direction of sample flow.

[0215] Furthermore, for the methods and apparatus described herein, if the sample is flowing, the flow direction of the sample (liquid; substance) can be parallel to the test range.

[0216] The SMI technique is known to be used in a refractometer from the paper “Compact and self-aligned fluid refractometer based on the Doppler-induced self-mixing effect” (Applied Optics Vol. 59, No. 10 / 1 April 2020) by Vibhor Kumar Bhardwaj and Surita Maini. In contrast, the apparatus and method described herein do not include a refractometer or refractive measurement. Furthermore, while in the aforementioned paper, the Doppler shift is determined, and the fluid under study must flow at a non-zero velocity that should be constant (during the measurement), and the direction of illumination of the sample in Doppler-based measurements should be approximately parallel to the flow direction of the sample, for the apparatus and method described herein, one or more of the following are applicable:

[0217] -They do not include the determination of the Doppler shift;

[0218] - Samples may or may not flow;

[0219] - The sample can flow at an indefinite rate;

[0220] - The flow rate of the sample may change (significantly) during the measurement;

[0221] - The sample can flow in a direction that is substantially perpendicular to the direction of illumination on the sample.

[0222] The apparatus and methods described herein do not include determining (or do not include the sensing means for determining) the frequency shift (e.g., Doppler shift / flow velocity-induced shift) of light coupled back into the light source cavity.

[0223] The measurement signal detected by the device or method described herein is substantially independent of the flow rate that the sample may have.

[0224] As will be readily understood, the features of the method mentioned herein can also be similarly applied to the described device or application. Similarly, the features of the device mentioned herein can also be similarly applied to the described method or application. And similarly, the features of the application mentioned herein can also be similarly applied to the described method or device. The achievable effects correspond to each other.

[0225] Further embodiments and advantages are derived from the following description and drawings, as well as from the dependent claims.

[0226] The invention will now be described in more detail with reference to examples and accompanying drawings. In the drawings, the same reference numerals denote the same or similar elements. The figures show:

[0227] Figure 1 A side view of an LFT device used for detecting SMI is shown very schematically;

[0228] Figure 2 A top view of a portion of the carrier is shown in a very schematic manner;

[0229] Figure 3 A side view of the LFT device used for detecting SMI is shown very schematically.

[0230] The described embodiments are intended as examples or to illustrate the invention, and should not be construed as limiting the invention.

[0231] Figure 1 A schematic side view of an LFT device implementing SMI for detection is shown. This figure emphasizes LFT aspects and related methods, therefore... Figure 1 Some details, such as the device housing, are not shown.

[0232] The carrier 10 in the insertion device includes a sample pad 11, a conjugate pad 12, a test area 13, and an optional control area 14. It also includes two reference areas 15a and 15b, which are typically optional, and in some cases a single reference area may be sufficient.

[0233] Liquid L, representing the sample, is applied to sample pad 11. From there, liquid L is transported by carrier 10, for example, by capillary force, along the transport direction indicated by the thick dashed arrow in the figure. Liquid L is capable of (and indeed is in the case shown) containing analyte 1, such as a virus.

[0234] On the binding pad 12, a marker 2 capable of binding to analyte 1 is present. Upon reaching the test area, particles formed in this manner bind to the analyte binding member 31, which is fixed to the carrier 10 in the test area 13. Therefore, the particle concentration can increase over time. Particles bound to the analyte binding member 31 exhibit a specific color, such that the color intensity increases with time and the concentration of bound particles in the test area 13. This can be detected by detecting absorption (particularly at the wavelength of the absorption band of the bound particles).

[0235] The marker 2 that is not bound to analyte 1 is further conveyed to control region 14 and is able to bind to the marker binding member 32 of carrier 10 fixed in control region 14. The marker 2 bound to marker binding member 32 exhibits a specific color such that the intensity of the color can increase with time and the concentration of these bound particles in control region 14.

[0236] SMI is used to detect the presence and / or concentration of each bound particle. Absorption can be detected due to color, where the absorption depends on the presence and / or concentration of the corresponding bound particle.

[0237] Therefore, the device includes one or more light sources; in the example shown, four light sources 41, 42, 43a, and 43b are illustrated. These are all resonant cavity light sources comprising a cavity C. Each cavity C has two end mirrors, one of which is an external coupling mirror from which the corresponding light source emits light. The light generated in the light source circulates within the cavity, resonating within it. The hollow arrows in the figure symbolize light.

[0238] Light emitted from the respective light sources illuminates corresponding areas of the carrier 10 in regions 13, 14, 15a, and 15b, respectively. Figure 1 These ranges are indicated by short, thick lines.

[0239] A portion of the light is reflected back into cavity C of the corresponding light source. However, some light is absorbed, particularly by the corresponding binding particles in test region 13 and control region 14.

[0240] The light re-entering cavity C can affect the light generation in the light source, particularly due to interference with the light present in the cavity, i.e., interference with the light generated in the light source. Therefore, a significant coherence length of the light can be advantageous. For example, lasers such as VCSELs and EELs can be used. However, RC-LEDs can also be used.

[0241] This effect on light can be detected, for example, by monitoring the power signal applied to the corresponding light source. Figure 1 As shown, each light source is operatively connected to evaluation unit 50, which can be included in the device or can be a separate unit. For example, a power supply signal is provided and monitored by evaluation unit 50. In one example, the current drawn by the light source at a constant power supply voltage can be a measurement signal relating to the effect on the light produced in the light source and thus on the absorption.

[0242] Reference measurement signals from reference regions 15a, 15b (or one of them) can be used for calibration purposes, such as monitoring the wetting effect of liquid L on carrier 10. This can lead to more accurate and / or more reliable results.

[0243] However, when the liquid has left the carrier (or at least the corresponding regions 13, 14, 15a, 15b), the reference measurement signals from the reference regions 15a, 15b (or from one of them) can be used for calibration purposes, i.e., to compare the absorption at regions (15a; 15b) where the color particles are not bound to the carrier 10 with the absorption at regions (13; 14) where the color particles are bound to the carrier 10 (at least in the presence of analyte 1 and / or label 2).

[0244] Optional mirror 19a, such as Figure 1 As shown, for example, the mirror could be a reflective coating on one side of the carrier 10. This can increase absorption because light, after being emitted from the light source, can pass through the carrier for the first time, then be reflected by the mirror 19a, and can pass through the carrier a second time before it can re-enter the cavity C.

[0245] This method and apparatus can also be used to detect two or more analytes simultaneously. Figure 2 A top view schematic diagram of the portion of carrier 10 prepared for the detection of two analytes is shown.

[0246] Test region 13 includes two test areas 23a and 23b, in which different analyte binders are immobilized to the carrier 10, each analyte binder being specific to its corresponding analyte. Similarly, control region 14 also includes two control areas 24a and 24b, in which different component binders are immobilized to the carrier 10, each component binder being specific to its corresponding label.

[0247] Each zone can be provided with a separate light source to illuminate the corresponding ranges 33a, 33b, 34a and 34b respectively.

[0248] like Figure 2 As shown, it would be sufficient to use only one light source to illuminate only one reference range 23 (e.g., in reference region 15a). However, since the wavelengths used to probe different test regions 23a and 23b can be different, it is necessary to use two light sources to illuminate two reference ranges ( Figure 2 (not shown in the image) to achieve better evaluation and / or calibration can be advantageous.

[0249] Because a very small light source can be used here, a relatively large number of different analytes can be detected, while only using the relatively small surface area of ​​the carrier 10, thus achieving a small carrier and a small device.

[0250] Figure 3 A schematic side view of an LFT device implementing SMI for detection is shown. Most details have been incorporated. Figure 1 A description has been provided. Therefore, please refer to the above text for this part.

[0251] The device includes a housing 60 and a sample inlet 61. The housing 60 includes several baffles. Figure 3 (Thick lines or shaded lines in the image) are used to block ambient light from entering the housing, especially away from the range (test range, control range, reference range). The sample inlet can also be used as such a baffle.

[0252] The carrier 10 is held by the carrier holder. Figure 3 (represented by large angles in the text).

[0253] Alternatively, for the aforementioned purpose, mirror 19b is disposed in housing 60.

[0254] For each light source, lenses 71, 72, and 73a are provided in the optical path between the corresponding light source and the carrier 10. This allows the light beam exiting the corresponding light source to be, for example, broadened and / or parallelized. The lenses can optionally be attached to the corresponding light source.

[0255] The device also includes a printed circuit board 80 on which the light source is mounted. The device may also include an interface 85, which may be implemented at or through the printed circuit board 80. As shown, the interface 85 may be included in a portion of the printed circuit board 80 that extends outside the housing 60. This interface provides enhanced interconnectivity.

[0256] As shown, the evaluation unit 50 may optionally be included in the device, for example, within the housing 60, or on the printed circuit board 80. The functionality of the evaluation unit may also be at least partially implemented in an external device, for example, connected to the device via interface 85.

[0257] In addition, the applicant has explicitly disclosed the following examples:

[0258] Example 1. A monitoring device for detecting the presence or amount of an analyte in a liquid during a transverse flow test, the device comprising:

[0259] —A housing, the housing including a carrier holder for holding a carrier for conveying liquid;

[0260] —At least the first light source is a resonant cavity light source with a cavity;

[0261] —An evaluation unit, which is operatively connected to at least a first light source to detect a measurement signal;

[0262] The first light source is constructed and configured to...

[0263] —Illuminating a test area within the test region of the carrier held in the carrier holder with light, particularly wherein the irradiation is performed perpendicular to the test area; and

[0264] —A portion of the light returning from the test range will be coupled back into the cavity of the first light source.

[0265] Example 2. The monitoring device according to Example 1, wherein the evaluation unit includes an optical detector for detecting the intensity of light emitted by the light source, and in particular, wherein the measurement signal originates from the optical detector.

[0266] Example 3. The monitoring device according to Example 1, wherein the evaluation unit includes an electrical detector for detecting the power supply signal supplied to the light source, and in particular, wherein the measurement signal originates from the electrical detector.

[0267] Example 4. The monitoring device according to any one of Examples 1 to 3 further includes a mirror disposed in the housing, particularly a mirror fixed to a part of the housing, the mirror being configured and aligned to reflect light emitted from the first light source that has passed through the carrier held in the carrier holder back to the carrier, so as to pass through the carrier again.

[0268] Example 5. The monitoring device according to any one of Examples 1 to 4 further includes at least a first lens disposed in the housing, particularly fixed to a portion of the housing, and more particularly fixed to the first light source. The first lens is disposed in the optical path of light emitted from the first light source toward a carrier held in the carrier holder, between the first light source and the carrier held in the carrier holder.

[0269] Example 6. According to the monitoring device of Example 5, a first lens is constructed and configured to generate a parallel beam of light based on light emitted from a first light source, specifically wherein the first light source emits light through a first end mirror of the cavity, and the lens is a convex lens disposed at a distance from the first end mirror corresponding to the focal length of the first lens.

[0270] Example 7. The monitoring device according to any one of Examples 1 to 6 further includes a printed circuit board held by a housing, on which at least a first light source is mounted, and in particular, wherein the printed circuit board is aligned parallel to the carrier when the carrier is held in a carrier holder.

[0271] Example 8. The monitoring device according to any one of Examples 1 to 7 further includes a second light source, particularly wherein the second light source is constructed and configured to...

[0272] —The control range within the control area of ​​the carrier held in the carrier holder is illuminated; and

[0273] —A portion of the light returning from the control range will be coupled back into the cavity of the second light source.

[0274] Example 9. The monitoring device according to any one of Examples 1 to 8 further includes a third light source, particularly wherein the third light source is constructed and configured to...

[0275] —Illuminate the reference range within the reference region of the carrier held in the carrier holder with light; and

[0276] —A portion of the light returning from the reference range will be coupled back into the cavity of the third light source.

[0277] Example 10. A transverse flow testing device for detecting the presence or amount of an analyte in a liquid, comprising a monitoring device according to any one of Examples 1 to 9 and a carrier held in a carrier holder, the carrier comprising

[0278] —A sample pad, used to apply the liquid;

[0279] —A binding pad, which provides a marker for labeling an analyte by binding to it;

[0280] —Test area, in which an analyte binder for specific binding to the analyte is immobilized to a carrier;

[0281] —Control region, in which a marker binder for specific binding to the marker is immobilized to the carrier;

[0282] The carrier is configured to allow liquid to be transported, particularly by capillary force, from the sample pad to the conjugate pad, then to the test area, and then to the control area; and

[0283] In particular, the direction of illumination along the test area is perpendicular to the direction of liquid transport (flow direction) within the test area.

[0284] Example 11. The transverse flow testing apparatus according to Example 10, further comprising:

[0285] —A reference region that is not bound to a carrier, and in particular, is free of analyte and label binders.

[0286] Example 12. In the transverse flow testing apparatus according to Example 10 or 11, the carrier further includes a mirror, particularly wherein the mirror is a reflective coating.

[0287] Example 13. A transverse flow testing apparatus according to Examples 10 to 12, wherein the transverse flow testing apparatus is used to detect the presence or amount of an analyte and other analytes in a liquid.

[0288] —The binding pad provides an additional marker for marking another analyte by binding to it;

[0289] —The test area includes a test area in which an analyte binder for specific binding to an analyte is immobilized to a carrier, and includes a further test area in which a further analyte binder for specific binding to another analyte is immobilized to a carrier.

[0290] —The control area includes a control region in which a marker binder for binding to a marker is fixed to a carrier, and includes a further control region in which a further marker binder for binding to a further marker is fixed to a carrier.

[0291] The test range is located within the test area; and

[0292] The transverse flow testing device includes a second light source, which may be the same as or different from the first light source, and the first light source is constructed and configured to...

[0293] —Illuminate the control area within the control zone with light;

[0294] —A portion of the light returning from the control range will be coupled back into the cavity of the second light source;

[0295] The transverse flow testing device includes a first light source and a second light source, both of which are resonant cavity light sources and each has a cavity. The second light source may be the same as or different from the first light source. The first light source is constructed and configured to...

[0296] —Illuminate the test area in another test zone with light; and

[0297] —A portion of the light returning from another test range will be coupled back into the cavity of another first light source; and in which

[0298] The additional second light source is constructed and configured to...

[0299] —Illuminate another control area within another control zone with light; and

[0300] —A portion of the light returning from another control range will be coupled back into the cavity of another second light source.

[0301] Example 14. A method for detecting the presence or amount of an analyte in a liquid by means of a transverse flow test, the method comprising:

[0302] —The test area within the test region of the carrier is illuminated with light from a first light source, which is a resonant cavity light source having a cavity, and specifically, the illumination is performed perpendicular to the test area; and

[0303] —A portion of the light returning from the test range will be coupled back into the cavity of the first light source;

[0304] —The measurement signal is detected by means of an evaluation unit that is operatively connected to the first light source.

[0305] Example 15. According to the method of Example 14, the carrier includes...

[0306] —Sample pad;

[0307] —A binding pad, which provides a marker for labeling an analyte by binding to it;

[0308] —Test area, in which an analyte binder for specific binding to the analyte is immobilized to a carrier;

[0309] —Control region, in which a marker binder for specific binding to the marker is immobilized to the carrier;

[0310] The method includes:

[0311] —Enables the carrier to transport liquid from the sample pad to the control area, especially by capillary force;

[0312] —Apply the liquid to the sample pad;

[0313] —To allow the marker to bind to the analyte at the conjugation pad;

[0314] —This allows the analyte binder to bind to the analyte at the test area;

[0315] —To bind the marker binder to the marker at the control area; and

[0316] In particular, the method can include

[0317] —The light irradiation test area is carried out along the irradiation direction perpendicular to the liquid transport direction (flow direction) within the test area.

[0318] Example 16. The method according to Example 15 further includes...

[0319] —Illuminate the control area within the control region with light from a second light source, the second light source being a resonant cavity light source having a cavity, specifically wherein the illumination of the control area with the light is performed along an illuminating direction perpendicular to the transport direction (flow direction) of the liquid within the control area; and

[0320] —A portion of the light returning from the control range will be coupled back into the cavity of the second light source;

[0321] The second light source is operatively connected to the evaluation unit for detecting control measurement signals by means of the evaluation unit.

[0322] Example 17. The method according to Examples 14 to 16, wherein the carrier includes a reference region of binder not fixed to the carrier, the method further includes...

[0323] —Illuminate a reference area within the reference region with light from a third light source, the third light source being a resonant cavity light source having a cavity, specifically wherein the illumination of the reference area with the light is performed along an illumination direction perpendicular to the transport direction (flow direction) of the liquid in the reference area; and

[0324] —A portion of the light returning from the reference range will be coupled back into the cavity of the third light source;

[0325] The third light source is operatively connected to the evaluation unit for detecting a reference measurement signal by means of the evaluation unit, and in particular, the method includes...

[0326] —The evaluation unit evaluates the measurement signal based on the reference measurement signal.

[0327] Example 18. A method for detecting the presence or amount of a substance within a test range, the method comprising:

[0328] —The test area is illuminated with light emitted from a resonant cavity light source having a cavity, and in particular, the illumination is performed perpendicular to the test area;

[0329] —The optical coupling returned from the test range will be returned to the cavity;

[0330] —This results in changes in the light produced in the light source, especially due to the interference between the coupled-back light and the light produced in the light source;

[0331] —Monitor the measurement signals of the light source related to this change.

[0332] Example 19. The method according to Example 18 includes allowing a substance (if present in the test range) to absorb a portion of the light illuminating the test range.

[0333] Example 20. The method according to Example 18 or 19, wherein the light emitted from the resonant cavity light source includes wavelengths contained in the absorption band of the material.

[0334] Example 21. A method for detecting or determining absorption within a test range, the method comprising:

[0335] —The test area is illuminated with light emitted from a resonant cavity light source having a cavity, and in particular, the illumination is performed perpendicular to the test area;

[0336] —The optical coupling returned from the test range will be returned to the cavity;

[0337] —This results in changes in the light produced in the light source, especially due to the interference between the coupled-back light and the light produced in the light source;

[0338] —Monitor the measurement signals of the light source related to this change.

[0339] Example 22. An apparatus for detecting the presence or amount of a substance within a test range, comprising:

[0340] —A resonant cavity light source for illuminating the test range, wherein the light source, particularly the external coupling mirror of the light source, is adapted to couple light returning from the test range back into the cavity of the light source;

[0341] —An evaluation unit that monitors measurement signals from a light source that are related to changes in the light produced in the light source, which arise from interference between the coupled-back light and the light produced in the light source.

[0342] Example 23. According to the device of Example 22, the evaluation unit is operable to monitor at least one of the following:

[0343] —The power signal supplied to the light source;

[0344] —The intensity of light emitted from a light source.

[0345] Example 24. An apparatus for detecting or determining absorption within a test range, comprising:

[0346] —A resonant cavity light source for illuminating the test range, wherein the light source, particularly the external coupling mirror of the light source, is adapted to couple light returning from the test range back into the cavity of the light source;

[0347] —An evaluation unit that monitors a measurement signal from a light source that is related to changes in the light produced in the light source, which arise from interference between the coupled-back light and the light produced in the light source;

[0348] In particular, the device is configured such that the irradiation is perpendicular to the test range.

[0349] Example 25. In transverse flow testing, self-mixing interferometry is used to determine absorption, specifically, to detect changes in absorption, and more specifically, to determine changes in absorption.

[0350] Example 26. The use according to Example 25 includes irradiating a material with light emitted from a light source, causing the light to interact with the material, and coupling a portion of the light that has interacted with the material back into the light source; particularly wherein, when the material flows along a flow direction, the irradiation is performed along an irradiation direction aligned perpendicular to the flow direction.

[0351] Example 27. The use according to Example 26, wherein absorption at a specific wavelength is determined, and wherein the light emitted from the light source includes that specific wavelength.

[0352] Example 28. The use according to Example 26 or 27, wherein the absorption of the substance is determined, and the light has a wavelength within the absorption band of the substance.

[0353] Example 29. The use according to one of Examples 25 to 28, wherein the use is to employ self-mixing interferometry in a transverse flow test to determine absorption, and more specifically to determine changes in absorption.

[0354] Example 30. According to the use described in any one of Examples 25 to 29, wherein the self-mixing interferometry is used to detect one or more of the following

[0355] —Absorption of substances in the test area of ​​the LFT device;

[0356] —Absorption of substances in the control area of ​​the LFT device;

[0357] —Absorption of substances in the reference region of the LFT device;

[0358] Example 31. In transverse flow testing, self-mixing interferometry is used to detect color intensity, particularly changes in color intensity, and more specifically, changes in color intensity.

Claims

1. A monitoring device for detecting the presence or amount of an analyte in a liquid during a transverse flow test, the device comprising: — A housing, the housing including a carrier holder for holding a carrier for conveying liquid; — At least the first light source is a resonant cavity light source with a cavity; — An evaluation unit operatively connected to the at least first light source to detect a measurement signal; The first light source is constructed and configured to... — Illuminate the test area of ​​the carrier held in the carrier holder with light; and — A portion of the light returning from the test range is coupled back into the cavity of the first light source.

2. The monitoring device according to claim 1, wherein, The evaluation unit includes an optical detector for detecting the intensity of light emitted by the light source.

3. The monitoring device according to claim 1, wherein, The evaluation unit includes an electrical detector for detecting the power signal supplied to the light source.

4. The monitoring device according to any one of claims 1 to 3 further includes a mirror disposed in the housing, the mirror being configured and aligned to reflect light emitted from the first light source that has passed through the carrier held in the carrier holder back to the carrier so as to pass through the carrier again.

5. The monitoring device according to any one of claims 1 to 3 further includes at least a first lens disposed in the housing, the first lens being arranged in the optical path of light emitted from the first light source toward the carrier held in the carrier holder, between the first light source and the carrier held in the carrier holder.

6. The monitoring device according to claim 5, wherein, The first lens is constructed and configured to generate a parallel beam of light based on light emitted from the first light source.

7. The monitoring device according to any one of claims 1 to 3 further includes a printed circuit board held by a housing, at least the first light source being mounted on the printed circuit board.

8. The monitoring device according to any one of claims 1 to 3 further includes a second light source.

9. The monitoring device according to any one of claims 1 to 3 further includes a third light source.

10. The monitoring device according to claim 2, wherein, The measurement signal originates from the optical detector.

11. The monitoring device according to claim 3, wherein, The measurement signal originates from an electrical detector.

12. The monitoring device according to claim 4, wherein, The mirror is fixed to a portion of the housing.

13. The monitoring device according to claim 5, wherein, The first lens is fixed to a portion of the housing.

14. The monitoring device according to claim 5, wherein, The first lens is fixed to the first light source.

15. The monitoring device according to claim 6, wherein, The first light source emits light through the first end mirror of the cavity, and the lens is a convex lens, which is disposed at a distance from the first end mirror corresponding to the focal length of the first lens.

16. The monitoring device according to claim 7, wherein, When the carrier is held in the carrier holder, the printed circuit board is aligned parallel to the carrier.

17. The monitoring device according to claim 8, wherein, The second light source is constructed and set to — The control range within the control area of ​​the carrier held in the carrier holder is illuminated; and — A portion of the light returning from the control range is coupled back into the cavity of the second light source.

18. The monitoring device according to claim 9, wherein, The third light source is constructed and configured to... — Illuminate the reference range within the reference area of ​​the carrier held in the carrier holder with light; and — A portion of the light returning from the reference range will be coupled back into the cavity of the third light source.

19. A transverse flow testing apparatus for detecting the presence or amount of an analyte in a liquid, comprising a monitoring device according to any one of claims 1 to 18 and a carrier held in a carrier holder, the carrier comprising — Sample pad, used to apply liquid; — A binding pad that provides a marker for labeling an analyte by binding to it; — A test area in which an analyte binder for specific binding to the analyte is immobilized to the carrier; — A control region in which a marker binder for specific binding to the marker is immobilized to the carrier; The carrier is configured such that liquid is transported from the sample pad to the conjugate pad, then to the test area, and then to the control area.

20. The transverse flow testing device according to claim 19, wherein the carrier further comprises... — Reference region, which is not bound to the carrier.

21. The transverse flow testing apparatus according to claim 19 or 20, wherein the carrier further comprises a mirror.

22. The transverse flow testing apparatus according to claim 19 or 20, wherein the transverse flow testing apparatus is a transverse flow testing apparatus for detecting the presence or amount of an analyte and other analytes in a liquid. — The binding pad provides an additional marker for marking the additional analyte by binding to it; — The test area includes a test area in which an analyte binder for specific binding to an analyte is immobilized to a carrier, and includes a further test area in which a further analyte binder for specific binding to another analyte is immobilized to a carrier. — The control area includes a control area in which a marker binder for binding to a marker is fixed to a carrier, and includes a further control area in which a further marker binder for binding to a further marker is fixed to a carrier; The test range is located within the test area; and The transverse flow testing device includes a second light source, which may be the same as or different from the first light source, and the second light source is constructed and configured to... — Illuminate the control area within the control zone with light; — A portion of the light returning from the control range will be coupled back into the cavity of the second light source; The transverse flow testing device includes a first light source and a second light source, both of which are resonant cavity light sources and each has a cavity. The second light source may be the same as or different from the first light source. The second light source is constructed and configured to... — Illuminate another test area within another test zone with light; and — A portion of the light returning from another test range is coupled back into the cavity of another first light source; and in which The additional second light source is constructed and configured to... — Illuminate another control area within another control zone with light; and — A portion of the light returning from another control range is coupled back into the cavity of another second light source.

23. The transverse flow testing device according to claim 19, wherein, The carrier is configured to allow liquid to be transported by capillary force from the sample pad to the conjugate pad, then to the test area, and then to the control area.

24. The transverse flow testing device according to claim 20, wherein, The reference region contains no analyte binders or marker binders.

25. The transverse flow testing device according to claim 21, wherein, The mirror has a reflective coating.

26. A method for detecting the presence or amount of an analyte in a liquid by means of a transverse flow test, the method comprising: — Illuminate the test area of ​​the carrier with light from a first light source, which is a resonant cavity light source with a cavity; and — A portion of the light returning from the test range will be coupled back into the cavity of the first light source; — The measurement signal is detected by means of an evaluation unit operatively connected to the first light source.

27. The method of claim 26, wherein the carrier comprises — Sample pad; — A binding pad that provides a marker for labeling an analyte by binding to it; — Test area, in which an analyte binder for specific binding to the analyte is immobilized to a carrier; — A control region in which a marker binder for specific binding to a marker is immobilized to a carrier; The method includes: — Enables the carrier to deliver liquid from the sample pad to the control area; — Apply the liquid to the sample pad; — To allow the marker to bind to the analyte at the conjugation pad; — To enable the analyte binder to bind to the analyte at the test area; — To enable the marker binder to bind to the marker at the control area.

28. The method of claim 27, wherein the method comprises: The carrier uses capillary force to transport liquid from the sample pad to the control area.

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