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WO2022128997A1 - Dispositif de test immunochromatographique - Google Patents

Dispositif de test immunochromatographique Download PDF

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Publication number
WO2022128997A1
WO2022128997A1 PCT/EP2021/085617 EP2021085617W WO2022128997A1 WO 2022128997 A1 WO2022128997 A1 WO 2022128997A1 EP 2021085617 W EP2021085617 W EP 2021085617W WO 2022128997 A1 WO2022128997 A1 WO 2022128997A1
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WIPO (PCT)
Prior art keywords
flow
electrode
test
test device
lateral flow
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Ceased
Application number
PCT/EP2021/085617
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English (en)
Inventor
Erik Jan Lous
Chong CHEAH BONG
Filip Frederix
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Ams International AG
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Ams International AG
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Publication date
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Publication of WO2022128997A1 publication Critical patent/WO2022128997A1/fr
Anticipated expiration legal-status Critical
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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84—Systems specially adapted for particular applications
    • G01N21/8483—Investigating reagent band
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/7769—Measurement method of reaction-produced change in sensor
    • G01N2021/7773—Reflection
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/7769—Measurement method of reaction-produced change in sensor
    • G01N2021/7786—Fluorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence

Definitions

  • the disclosure relates to a lateral flow test device such as may be useful in biological applications, for example, in the areas of medical, environmental and veterinary diagnostics.
  • Diagnostic tests are commonly used for identifying diseases.
  • a diagnostic test may be carried out in a central laboratory, whereby a sample, for example blood, is taken from a patient and sent to the central laboratory where the sample is analysed.
  • a different setting for processing samples is at the point where care for the patient is delivered, which is referred to as point-of-care (POC) tests.
  • POC tests allow for a faster diagnosis.
  • different technology platforms can be used.
  • a first class of POC tests are high end, microfluidic-based POC tests. These POC tests are mainly used in a professional environment such as hospitals or emergency rooms.
  • a different technology platform is provided by lateral flow test technology. Lateral flow tests tend to be used in the consumer area, such as for pregnancy tests, but are also used across the whole diagnostic field as they are easy to produce and very cost-effective.
  • a lateral flow assay includes a series of capillary beds, such as pieces of porous paper, nitrocellulose membranes, microstructured polymer, or sintered polymer for transporting fluid across a series of pads by capillary forces.
  • a sample pad acts as a sponge and is arranged to receive a sample fluid, and further holds an excess of the sample fluid. After the sample pad is saturated with sample fluid, the sample fluid migrates to a conjugate pad in which the manufacturer has stored the so-called conjugate.
  • the conjugate is a dried format of bio-active particles in a salt-sugar matrix intended to create a chemical reaction between the target molecule (e.g., an antigen) and its chemical partner (e.g. antibody or receptor).
  • the sample fluid dissolves the salt-sugar matrix, it also mobilizes the bio-active particles and in one combined transport action the sample and conjugate mix with each other while flowing through the capillary beds.
  • the analyte binds to the bio-active particles while migrating further through the third capillary bed.
  • This material has one or more areas, which are called stripes, where a third type of molecule has been immobilized by the manufacturer, in most cases an antibody or receptor addressed against another part of the antigen.
  • a control stripe/line that captures the conjugate and thereby shows that reaction conditions and technology work
  • a second stripe the test stripe/line
  • the test stripe/line that contains a specific capture molecule and only captures those particles onto which an analyte or antigen molecule has been immobilized.
  • Some test results rely on the presence of fluorescent particles, which may not be visible to the user but can instead be detected by optical detectors when the stripes are illuminated.
  • the fluid After passing the different reaction zones, the fluid enters the final porous material, which is a wick that acts as a waste container.
  • the stripes may be replaced with a series of dots on a test strip (e.g. in a matrix of 3x3 or 4x4 or 5x5 dots), with each dot potentially providing a different test.
  • lateral flow tests as such are well known and have four key elements: the antibody, the antigen, the conjugate and the complex.
  • the antibody is also referred to as a receptor, chemical partner, or capture molecule.
  • the antigen is also referred to as an analyte, target molecule, antigen molecule, target analyte or biomarkers.
  • the sample typically contains the analyte, although that is not always the case.
  • the conjugate is also referred to as (analyte) tags, tagging particles, chemical partner, (sample) conjugate mix, bioactive particles or conjugate receptors.
  • conjugates are fluorescent particles, red particles or dyes.
  • the complex is the combination of the antigen and conjugate.
  • the complex is also referred to as a tagged analyte, or particles onto which the analyte molecule has been immobilised.
  • users of lateral flow tests wait for a reaction to be completed and then measure the outcome. However, this does not allow for dynamic measurements or any analysis of how a test is progressing.
  • sample progress along test strip is only detected and concluded from evolution of the test signal itself (i.e. due to the optical signal measured in the test window). However, this can result in initial response data and/or important kinetic data being missed (i.e. not observed).
  • this disclosure proposes to overcome the above problems by including a sensor to act as a switch to detect the start of fluid transport along the test strip.
  • this arrangement allows for dynamic measurements and data analysis.
  • the speed of sample flow along the test strip can be determined, which in turn can provide information on the viscosity and thereby nature or species in the sample (e.g. urine, blood, saliva, amount of enzymes etc.).
  • Activity and transport kinetics can also be determined, for example, based on a speed of reaction (e.g. measured from when the fluid reaches the test region as opposed to when an optical change is observed).
  • knowledge that a test has begun and/or is in progress can be useful for a user and can enable information to be gathered on how well tests are performing in practice.
  • detection of the start of fluid movement can be useful in saving energy (e.g. battery power), for example, by only powering on the optical detector and/or other functions like data analysis or data transfer, in time to start observing a reaction in the test region, when the fluid is actually expected to reach the test region.
  • a lateral flow test device comprising: an optical detector configured to receive light from a test region of an assay test strip and to generate an electrical output based on the received light; an electrical signal processor for analysing the electrical output; and a flow sensor configured to detect flow from a sample provided on the assay test strip prior to the flow reaching the test region.
  • embodiments of this disclosure provide an additional sensor arranged to detect the ‘real’ start of the test (e.g. when the test paper is wetted and the fluid flow begins).
  • this can be advantageous for dynamic lateral flow tests (e.g. where multiple measurements are taken over time) by allowing kinetic data to be gathered to provide additional information on the test activity and progress.
  • static lateral flow tests e.g. where a measurement is only taken at a single point in time
  • disposable lateral flow tests may be provided which may be switched on, for example, by removing a plastic insulating strip from a battery contact, and, in normal circumstances, it may take some time for a sample to be deposited on a test strip and the actual test to begin.
  • the optical detector would be powered on, draining battery power by sensing light signals from the test region long before a sample actually reaches the test region.
  • the flow sensor may be configured to provide a signal indicating that a sample has actually been deposited (e.g. the test paper is moist and flow has begun) and therefore the optical detector can be switched on only when it is likely that the sample will reach the test region, thereby saving battery power.
  • the flow sensor may be configured to relay a message to the electrical signal processor in response to flow detection.
  • the message may signify that sample flow has begun (i.e. a test is in progress).
  • the message may comprise an instruction to begin a timer or counter. This information can be used together with information from the optical detector to determine a speed of flow of the sample and/or a speed of reaction.
  • the message may comprise an instruction to begin analysing the electrical output from the optical detector.
  • the analysis may be instructed immediately or after a pre- determined period (e.g. to allow for the flow to reach the test region and/or to allow for a reaction to take place).
  • the message may comprise an instruction to wake or power on the optical detector and/or another component.
  • the device may be in a power-saving mode prior to detection of the start of fluid flow.
  • the message may comprise an instruction to notify a user that a test is in progress and/or relay information about a quality of a test.
  • a user may be provided with further instructions for carrying out the test and/or obtaining the results of the test (i.e. when to read a test output).
  • the electrical signal processor may be configured to perform kinetic analysis of the electrical output.
  • the kinetic analysis may comprise dynamic measurement of the output from the optical detector (based on measurement in the test region), with respect to early fluid flow detection by the flow sensor. For example, a speed of fluid flow and/or a speed of reaction may be determined based on a time of detection by the flow sensor and a time of detection by the optical detector. In some embodiments, the kinetic analysis may be used to determine fluid characteristics (e.g. viscosity or a type of fluid - blood, urine, saliva etc.).
  • the flow sensor may comprise a droplet detector, for example, at or near an entry aperture of the device.
  • the flow sensor may comprise a capacitive sensor configured to sense a change in capacitance due to sample flow.
  • the capacitive sensor may comprise a first electrode and a second electrode, wherein the first electrode and the second electrode are arranged to be in a spaced relationship in a plane parallel and in proximity to a first side of the assay test strip, when the assay test strip is inserted into the device.
  • the first electrode and the second electrode may be generally aligned with a direction of sample flow. However, it will be understood that the first electrode and the second electrode may be arranged at an angle (e.g. diagonally) across the direction of sample flow or they may be arranged transversely to the direction of sample flow.
  • the first electrode and the second electrode may be arranged to be in a spaced relationship such that the first electrode is adjacent a first side of the assay test strip and the second electrode is adjacent a second side of the assay test strip, when the assay test strip is inserted into the device.
  • the first electrode and the second electrode may be in a plane orthogonal to a direction of sample flow along the assay test strip.
  • the first electrode and the second electrode may be spaced along a direction of sample flow.
  • the first electrode and the second electrode may be arranged at an angle (e.g. diagonally) across the direction of sample flow.
  • the first and second electrodes may be arranged to be in non-contact proximity with the assay test strip (i.e. test paper) when inserted into the device.
  • an insulator may be provided between each of the first and second electrodes and the assay test strip (i.e. test paper).
  • the first and second electrodes may be arranged to monitor dielectric permittivity, which will change when the test paper goes from dry to wet (e.g. when a fluid such as a water-based sample is deposited on the assay test strip).
  • water has a high dielectric constant of approximately 80, which will result in a notable change in the dielectric permittivity sensed by the capacitive sensor.
  • the capacitive sensor may comprise at least a third electrode, wherein the third electrode is arranged to be in a spaced relationship with the first and second electrodes in the plane parallel and in proximity to the first side of the assay test strip, when the assay test strip is inserted into the device.
  • the first electrode, the second electrode and the third electrode may be arranged such that one of the first electrode, the second electrode and the third electrode is arranged to form a capacitive coupling with each remaining electrode (i.e. there may be one common electrode in a two capacitor series).
  • the flow sensor may comprise a resistive sensor configured to sense a change in resistance due to sample flow.
  • the resistive sensor may comprise a first electrode and a second electrode, wherein the first electrode and the second electrode are arranged to be in a spaced relationship such that the first electrode is adjacent a first side of the assay test strip and the second electrode is adjacent a second side of the assay test strip, when the assay test strip is inserted into the device.
  • the first electrode and the second electrode may be in a plane orthogonal to a direction of sample flow along the assay test strip. In some embodiments, the first electrode and the second electrode may be spaced along a direction of sample flow.
  • the first electrode and the second electrode may be arranged at an angle (e.g. diagonally) across the direction of sample flow.
  • the first electrode and the second electrode are arranged to be in a spaced relationship in a plane parallel and in proximity to a first side of the assay test strip, when the assay test strip is inserted into the device.
  • the first electrode and the second electrode may be generally aligned with a direction of sample flow.
  • the first electrode and the second electrode may be arranged at an angle (e.g. diagonally) across the direction of sample flow or they may be arranged transversely to the direction of sample flow.
  • the first and second electrodes may be arranged to be in contact with the assay test strip (i.e. test paper) when inserted into the device.
  • the first and second electrodes may be arranged to monitor current flow through the assay test strip and to detect when resistance is reduced (conductance increased) due to the presence of moisture from a sample flow through the assay test strip. It will be noted that the current flow through the assay test strip will be small such that it not interfere with the sample flow and/or any chemical reactions in the sample flow and/or any carrier materials on or in the test paper.
  • any number of electrodes can be provided.
  • the electrodes may be provided on the same side of the assay test strip or they may be provided on opposite sides of the assay test strip or any combination of these options is possible.
  • the main difference is that, for the resistive sensor the electrodes are arranged to be in contact with the assay test strip (i.e. test paper) when inserted into the device and for the capacitive sensor the electrodes are arranged not to be in direct contact with the assay test strip (i.e. test paper) when inserted into the device.
  • the flow sensor may comprise an optical sensor configured to sense a change in an optical property due to sample flow.
  • the optical sensor may be in addition to the optical detector arranged to receive light from the test region or an optical path may be provided such that a single optical detector may be configured to detect light from either or both of the test region and a start region.
  • the optical property may be reflectance, transmission, chemiluminescence or fluorescence, which may change when a sample is present.
  • the optical detector and/or optical sensor may be configured to detect light generated in the assay test strip (e.g. due to fluorescence of a target molecule) or to detect light reflected from or transmitted through the assay test strip.
  • the device may comprise one or more illuminators for generating light to be reflected from or transmitted through the assay test strip such that a change in reflectance or transmission may be observed by the optical detector and/or optical sensor based on a condition of the assay test strip (e.g. based on a presence of a sample flow or analyte).
  • the optical detector may be configured to receive light from a control region of an assay test strip and to generate a control electrical output based on the received light for analysis by the electrical signal processor.
  • Two or more flow sensors may be provided along a flow path of the assay test strip to allow for detection of flow at two or more regions of the flow path.
  • the electrical signal processor may be configured to receive input from each flow sensor and to determine a speed of flow based on a time of the detection of flow at each of the two or more regions.
  • a double set of flow sensors allows for an initial speed determination of the sample before it reaches the test region.
  • the lateral flow test device may be configured as a point-of-care device. In some embodiments, the lateral flow test device may be a disposable device.
  • the lateral flow test device may be configured to detect one or more of: coronavirus; coronavirus antibodies. Many other applications are also possible within the areas of biological, medical, environmental and veterinary diagnostics.
  • a method of operating a lateral flow test device comprising: detecting, using a flow sensor, flow from a sample provided on an assay test strip prior to the flow reaching a test region of the assay test strip; receiving light, at an optical detector, from the test region; generating, at the optical detector, an electrical output based on the received light; and analysing the electrical output at an electrical signal processor.
  • the method may comprise the flow sensor relaying a message to the electrical signal processor in response to flow detection.
  • the message may signify that sample flow has begun (i.e. a test is in progress).
  • the message may comprise an instruction to begin a timer or counter.
  • the method may comprise beginning a timer or counter in response to flow detection.
  • the method may comprise the electrical signal processor measuring a time from an initial flow detection by the flow sensor to one or more of: a start of detection of light, a predefined change in detection of light, a threshold value of detection of light, a peak value of detection of light or an end of detection of light, by the optical detector 102.
  • the method may comprise determining kinetic information such as a speed of flow of the sample or a speed of reaction.
  • the method may comprise analysing the electrical output from the optical detector in response to flow detection.
  • the analysis may be commenced immediately following flow detection or after a pre-determined period (e.g. to allow for the flow to reach the test region and/or to allow for a reaction to take place).
  • the method may comprise waking or powering on the optical detector in response to flow detection.
  • the device may be in a power-saving mode prior to detection of the start of fluid flow.
  • the method may comprise notifying a user that a test is in progress.
  • the method may comprise providing a user with further instructions for carrying out the test and/or obtaining the results of the test (i.e. when to read a test output).
  • the method may comprise performing kinetic analysis of the electrical output. This may comprise, for example, measuring a change in received light over a test period.
  • the kinetic analysis may comprise dynamic measurement of the output from the optical detector (based on measurement in the test region and/or control region), with respect to early fluid flow detection by the flow sensor. For example, a speed of fluid flow and/or a speed of reaction may be determined based on a time of detection by the flow sensor and a time of detection by the optical detector.
  • the kinetic analysis may be used to determine fluid characteristics (e.g. viscosity or a type of fluid - blood, urine, saliva etc.). This improves the quality of the analysis.
  • the method may comprise receiving input from two or more flow sensors and determining a speed of flow based on a time of the detection of flow by at least two of the two or more flow sensors.
  • Lateral flow test devices advantageously are more user-friendly because the device is able to detect when a test is being carried out (e.g. when a sample has been deposited) and so the device can offer analysis and/or guidance to a user during the measurement process, which increases the quality of the test. Furthermore, kinetic information can in some cases be used to determine whether an expected sample has been deposited or not (e.g. blood vs. urine) as a difference in viscosity may be deduced and this information can be used to ensure that accurate and reliable results are provided.
  • kinetic information can in some cases be used to determine whether an expected sample has been deposited or not (e.g. blood vs. urine) as a difference in viscosity may be deduced and this information can be used to ensure that accurate and reliable results are provided.
  • Figure 1 shows a lateral flow test device including a sensor in accordance with the present disclosure
  • Figure 2 shows a lateral flow test device including a sensor in accordance with the present disclosure
  • Figure 3 shows a lateral flow test device including an optical sensor in accordance with the present disclosure
  • Figure 4 shows a lateral flow test device including two sensors in accordance with the present disclosure
  • Figure 5 shows a lateral flow test device including two sensors, with a middle electrode in common, in accordance with the present disclosure
  • Figure 6 shows a lateral flow test device including two separate sensors in accordance with the present disclosure
  • Figure 7 shows a method of operating a lateral flow test device in accordance with the present disclosure.
  • Figure 8 shows a graph illustrating optical measurements from a test region over time.
  • the disclosure provides a lateral flow test device including a sensor configured to detect the start of fluid transport along a test strip.
  • Figure 1 shows a first lateral flow test device 100 including a first flow sensor 106 in the form of a resistive sensor in accordance with the present disclosure.
  • the first lateral flow test device 100 comprises an optical detector 102, and illumination sources (not shown), configured to receive light (which may be reflected or from fluorescence of the test material) from a test region 112 of an assay test strip 110 and to generate an electrical output based on the received light.
  • the optical detector 102 is also configured to receive light from a control region 114 of the assay test strip 110 and to generate an electrical output based on the light received from the control region 114.
  • the inclusion of a control region 114 is optional, but generally used to indicate that the fluid has been transported correctly over the assay test strip 110 (e.g. paper).
  • light from the test region 112 and control region 114 is arranged to pass through a respective window or gap in a baffle substrate 116 defining an optical path to the optical detector 102. This ensures that only light from a respective one of the test region 112 and control region 114 is received in a respective region (which may be different or the same) of the optical detector 102.
  • the baffle substrate 116 may take a different form or may not be required.
  • the optical detector 102 may take the form of any known optical detector.
  • the optical detector 102 may be provided in an optical module such as that described in patent application no. GB2004488.9, which is incorporated herein by reference.
  • the optical module may include a first light source (not shown) for illuminating the test region 112 of the assay and a second light source (not show) for illuminating the control region 114 of the assay.
  • no light sources may be required.
  • the electrical output from the optical detector 102 is input to an electrical signal processor 104 for analysis.
  • the electrical signal processor 104 may take the form of any known electrical signal processor.
  • the electrical signal processor 104 may be configured to measure the light detected by the optical detector 102 and to correlate said measurement with an expected measurement dependent on an amount of analyte present in the test region 112 at least.
  • the electrical signal processor 104 and the optical detector 102 may be integrated in one application specific integrated circuit (ASIC).
  • the optical detector 102 may contain spectral analysing capabilities, where multiple diodes are provided with different optical filters passing different optical wavelengths of light to the diodes.
  • the first flow sensor 106 is in the form of a resistive sensor configured to detect flow from a sample 118 provided on the assay test strip 110 prior to the flow reaching the test region 112.
  • the first flow sensor 106 is configured to sense a change in resistance due to sample fluid flow.
  • the first flow sensor 106 comprises a first electrode 108a and a second electrode 108b.
  • the first electrode 108a and the second electrode 108b are arranged to be in a spaced relationship in a plane orthogonal to a direction of sample flow along the assay test strip 110 such that the first electrode 108a is adjacent a first side of the assay test strip 110 and the second electrode 108b is adjacent a second side of the assay test strip 110, when the assay test strip 110 is inserted into the device 100.
  • the first and second electrodes 108a, 108b are arranged to be in contact with the assay test strip 110 (i.e. test paper) when inserted into the device 100.
  • the first and second electrodes 108a, 108b are arranged to monitor current flow through the assay test strip 110 and to detect when resistance is reduced (conductance increased) due to the presence of moisture from the sample flow along the assay test strip 110.
  • the first flow sensor 106 can be used in a capacitive (as opposed to resistive) mode.
  • both electrodes 108a, 108b would not be in direct contact with the assay test strip 110 (i.e. test paper), but they would be in close proximity to assay test strip 110 (i.e. test paper), for example, with an insulator therebetween.
  • the wetting of the test paper by the sample 118 would be observed as a change in the dielectric constant of the test paper between the electrodes 108a, 108b and hence detected as a change in capacity value of the two electrodes 108a, 108b.
  • the first flow sensor 106 is provided between the test region 112 and a region where the sample 118 is deposited on the assay test strip 110. Ideally the first flow sensor 106 is provided closer to the region where the sample 118 is deposited than the test region 112.
  • the assay test strip 110 is provided in the first lateral flow test device 100 and a sample 118 is deposited.
  • the sample 118 may be, for example, blood, urine, saliva or any other liquid-based material on which the test is to be performed (e.g. derivatives of blood, urine, saliva or pre-treated liquids). Due to capillary action, the sample 118 will travel along the assay test strip 110 towards the test region 112 and control region 114.
  • the fluid front of the sample 118 enters a region monitored by the first flow sensor 106 (e.g. the region between the first and second electrodes 108a, 108b) the resistivity (or capacitance) between the electrodes is altered due to the presence of the fluid and the sample flow is detected.
  • the first flow sensor 106 is coupled to the electrical signal processor 104 such that the detected change in resistivity (or capacitance) is communicated via a wired (or wireless) connection to the electrical signal processor 104.
  • the electrical signal processor 104 knows that a test is in progress and may communicate this to a user via a display (not shown).
  • the device may then offer guidance to a user during the measurement process (e.g. to inform them that the result is being processed and/or when a result will be communicated).
  • the optical response e.g. amount or spectrum of light
  • kinetic information (e.g. such as the speed of flow along the assay test strip 110) may be calculated and may be used to determine whether an expected sample has been deposited or not (e.g. blood vs. urine). This may be possible because a difference in viscosity may result in a different speed of flow and this information can be used to ensure that accurate and reliable results are provided, based on the sample deposited.
  • a speed of fluid flow and/or a speed of reaction may be determined based on a time of detection by the flow sensor 106 and a time of detection by the optical detector 102, since the distance between the two regions on the assay test strip 110 will be known.
  • disposable lateral flow tests may be provided which may be switched on, for example, by removing a plastic insulating strip from a battery contact, and, in normal circumstances, it may take some time for the sample 118 to be deposited on the assay test strip 110 and the actual test to begin.
  • the flow sensor 106 may be configured to provide a signal indicating that the sample 118 has actually been deposited (e.g. the test paper of the assay test strip 110 is moist and flow has begun) and therefore the optical detector 102 and/or any other parts/components of the device 100 can be switched on only when it is likely that the sample 118 will reach the test region 112, thereby saving battery power.
  • FIG. 2 shows a second lateral flow test device 200 including a second flow sensor 206 in the form of a single-sided sensor configured to sense a change in capacitance or resistance due to sample flow, in accordance with the present disclosure.
  • the second lateral flow test device 200 is similar to that described above for the first lateral flow test device 100 and so like reference numerals have been included.
  • the only difference between the first lateral flow test device 100 and the second lateral flow test device 200 is the configuration of the second flow sensor 206.
  • the second flow sensor 206 comprises a first electrode 208a and a second electrode 208b.
  • the first electrode 208a and the second electrode 208b are arranged to be in a spaced relationship in a plane parallel and in proximity to a first side of the assay test strip 110, when the assay test strip 110 is inserted into the device 200.
  • the first and second electrodes 208a, 208b are arranged to be in non-contact proximity with the assay test strip 110 (i.e. test paper) when inserted into the device 200, for example, with an insulator such as air or plastic in-between.
  • the first and second electrodes 208a, 208b are arranged to monitor dielectric permittivity, which will change when the test paper goes from dry to wet (e.g. when a fluid such as a water-based sample 118 is deposited on the assay test strip 110).
  • water has a high dielectric constant of approximately 80, which will result in a notable change in the dielectric permittivity sensed by the second flow sensor 206.
  • the second flow sensor 206 may be configured for operation as a resistive sensor and, in which case, the electrodes 208a, 208b will be in direct contact with the assay test strip 110 (e.g. test paper).
  • the assay test strip 110 e.g. test paper
  • the second flow sensor 206 is coupled to the electrical signal processor 104 such that the detected change in capacitance (or resistance) is communicated via a wired (or wireless) connection to the electrical signal processor 104.
  • Figure 3 shows a third lateral flow test device 300 including a third flow sensor 306 in the form of an optical sensor in accordance with the present disclosure.
  • the third lateral flow test device 300 is similar to that described above for the first lateral flow test device 100 and so like reference numerals have been included.
  • the only difference between the first lateral flow test device 100 and the third lateral flow test device .300 is the configuration of the third flow sensor 306 which is an optical sensor configured to sense a change in an optical property due to sample flow.
  • the optical sensor of the third flow sensor 306 is in addition to the optical detector 102 arranged to receive light from the test region 112 and control region 114.
  • an optical path may be provided such that a single optical detector 102 may be configured to detect light from either or both of the test region 112 and a start region (e.g. near where the sample 118 is deposited).
  • the optical property in the present embodiment is transmission as measured through the assay test strip 110.
  • the third flow sensor 306 comprises an optical emitter 302 provided on a first side of the assay test strip 110 and an optical detector 304 provided on a second side of the assay test strip 110.
  • the optical emitter 302 is configured to emit light through the assay test strip 110 (which may be provided with a suitably positioned optical window there-though) such that light transmitted through the assay test strip 110 is detected by the optical detector 304.
  • the third flow sensor 306 will detect a change in optical transmission, which will indicate the start of fluid flow along the assay test strip 110.
  • the third flow sensor 306 is coupled to the electrical signal processor 104 such that a detected change in transmission is communicated via a wired (or wireless) connection to the electrical signal processor 104.
  • the third flow sensor 306 may be configured to measure reflectance or fluorescence or chemi-luminescence from the assay test strip 110 to determine when a sample fluid is present (e.g. by locating an emitter and detector on a same side of the assay test strip 110).
  • Figure 4 shows a fourth lateral flow test device 400 including two flow sensors 106, 406 in accordance with the present disclosure.
  • the first of the two flow sensors is a sensor identical to the first flow sensor 106 described above in relation to Figure 1 .
  • the second of the two flow sensors is an additional flow sensor 406, which is configured to detect flow from a sample 118 provided on the assay test strip 110 after it has passed through a region monitored by the first flow sensor 106 and prior to the flow reaching the test region 112.
  • the additional flow sensor 406 is configured to sense a change in resistance (or capacitance) due to sample flow in a similar manner that of the first flow sensor 106.
  • the additional flow sensor 406 comprises a first electrode 408a and a second electrode 408b.
  • the first electrode 408a and the second electrode 408b are arranged to be in a spaced relationship in a plane orthogonal to a direction of sample flow along the assay test strip 110 such that the first electrode 408a is adjacent a first side of the assay test strip 110 and the second electrode 408b is adjacent a second side of the assay test strip 110, when the assay test strip 110 is inserted into the device 100.
  • the first and second electrodes 408a, 408b are arranged to be in contact with the assay test strip 110 (i.e. test paper) when inserted into the device 100.
  • the first and second electrodes 408a, 408b are arranged to monitor current flow through the assay test strip 110 and to detect when resistance is reduced (conductance increased) due to the presence of moisture from the sample flow along the assay test strip 110.
  • the electrodes 108a, 108b, 408a, 408b will not be in direct contact with the assay test strip 110 (e.g. test paper). Instead, a thin insulator may be provided.
  • the insulator may be, for example, air and/or plastic.
  • the additional flow sensor 406 is coupled to the electrical signal processor 104 such that the detected change in resistance (or capacitance) is communicated via a wired (or wireless) connection to the electrical signal processor 104.
  • the electrical signal processor 104 may be configured to determine a speed of flow based on a time of the detection of flow at each of the two regions monitored by the two flow sensors 106, 406.
  • a double set of flow sensors 106, 406 allows for an initial speed determination of the sample before it reaches the test region 118.
  • further analysis of the test may be carried in the same ways as described above.
  • embodiments where multiple electrodes or flow sensors are provided are advantageous in that the flow speed of the sample fluid can be determined at the start of the assay test strip 110 and this can enable a prediction of when the sample fluid will arrive at the test region and/or control region. This allows for a more complete and quantitative analysis of the test results and cleaner dynamic measurements with clearer timing information.
  • FIG. 5 shows a fifth lateral flow test device 500 including a double flow sensor 506 forming two sensors, with a middle electrode in common, in accordance with the present disclosure.
  • the double flow sensor 506 is similar to that described above in Figure 2 and so like reference numerals will be used.
  • the double flow sensor 506 comprises a first electrode 208a, a second electrode 208b and a third electrode 208c.
  • the third electrode 208c is arranged to be in a spaced relationship with the first and second electrodes 208a, 208b in the plane parallel and in proximity to the first side of the assay test strip 110, when the assay test strip 110 is inserted into the device 500.
  • the first electrode 208a and the second electrode 208b form a first coupling 502 and the second electrode 208b and the third electrode 208c form a second coupling 504.
  • the second electrode 208b is a common common electrode in a two sensor series.
  • the electrodes 208a, 208b, 508c will not be in direct contact with the assay test strip 110 (e.g. test paper). Instead, a thin insulator may be provided.
  • the insulator may be, for example, air and/or plastic.
  • the double flow sensor 506 may be configured for operation as two resistive sensors and, in which case, the electrodes 208a, 208b, 508c will be in direct contact with the assay test strip 110 (e.g. test paper).
  • the assay test strip 110 e.g. test paper
  • the first coupling 502 effectively serves to detect a change in capacitance (or resistance) in a first region of the assay test strip 110 and the second coupling 504 effectively serves to detect a change in capacitance (or resistance) in a second region of the assay test strip 110.
  • the double flow sensor 506 functions in a similar manner to the two flow sensors 106, 406 of Figure 4 in allowing for detection of flow at two regions of the flow path, prior to the fluid flow reaching the test region 112.
  • the double flow sensor 506 is coupled to the electrical signal processor 104 such that the detected change in capacitance (or resistance) for each of the first and second couplings 502, 504 is communicated via a wired (or wireless) connection to the electrical signal processor 104.
  • the electrical signal processor 104 may be configured to determine a speed of flow based on a time of the detection of flow at each of the two regions monitored by the first and second couplings 502, 504. As above, further analysis of the test may be carried in the same ways as described above.
  • the first coupling 502 is a resistive path effectively serving to detect a change in resistance in a first region of the assay test strip 110 and the second coupling 504 is a resistive path effectively serving to detect a change in resistance in a second region of the assay test strip 110.
  • the double flow sensor 506 functions in a similar manner to the two flow sensors 106, 406 of Figure 4 in allowing for detection of flow at two regions of the flow path, prior to the fluid flow reaching the test region 112.
  • Figure 6 shows a lateral flow test device 600 including two separate sensors 206, 606 in accordance with the present disclosure.
  • the first of the two separate sensors is a sensor identical to the second flow sensor 206 described above in relation to Figure 2.
  • the second of the two separate sensors is an additional flow sensor 606, which is configured to detect flow from a sample 118 provided on the assay test strip 110 after it has passed through a region monitored by the second flow sensor 206 and prior to the flow reaching the test region 112.
  • the additional flow sensor 606 may be configured to sense a change in capacitance or resistance due to sample flow in a similar manner to that of the second flow sensor 206.
  • the additional flow sensor 606 comprises a third electrode 608a and a fourth electrode 608b.
  • the first electrode 608a and the second electrode 608b are arranged to be in a spaced relationship in a plane parallel and in proximity to a first side of the assay test strip 110, when the assay test strip 110 is inserted into the device 600.
  • the second flow sensor 206 forms a first coupling 602 and the additional flow sensor 606 forms a second coupling 604.
  • the electrodes 208a, 208b, 608a, 608b will not be in direct contact with the assay test strip 110 (e.g. test paper). Instead, a thin insulator may be provided.
  • the insulator may be, for example, air and/or plastic.
  • the two separate sensors 206, 606 may be configured for operation as resistive sensors and, in which case, the electrodes 208a, 208b, 608a, 608b will be in direct contact with the assay test strip 110 (e.g. test paper).
  • the assay test strip 110 e.g. test paper
  • capacitive flow sensors and resistive flow sensors may be mixed on one assay test strip.
  • the first coupling 602 effectively serves to detect a change in capacitance (or resistance) in a first region of the assay test strip 110 and the second coupling 604 effectively serves to detect a change in capacitance (or resistance) in a second region of the assay test strip 110.
  • the two separate sensors 206, 606 function in a similar manner to the two flow sensors 106, 406 of Figure 4 in allowing for detection of flow at two regions of the flow path, prior to the fluid flow reaching the test region 112.
  • the two separate sensors 206, 606 are coupled to the electrical signal processor 104 such that the detected change in capacitance (or resistance) for each of the first and second couplings 602, 604 is communicated via a wired (or wireless) connection to the electrical signal processor 104.
  • the electrical signal processor 104 may be configured to determine a speed of flow based on a time of the detection of flow at each of the two regions monitored by the first and second couplings 602, 604. As above, further analysis of the test may be carried in the same ways as described above.
  • the electrodes may comprise narrow metal or conductive polymer strips deposited on the assay test strip 110 (e.g. test paper), which are arranged for electrical connection to corresponding electrodes in the device.
  • the assay test strip 110 e.g. test paper
  • the optical detector 102 may be configured to detect light generated in the assay test strip 110 (e.g. due to fluorescence of a target molecule) or to detect emitted light after it has been reflected from or transmitted through the assay test strip 110.
  • the device may comprise one or more illuminators for generating light to be reflected from or transmitted through the assay test strip 110 such that a change in reflectance or transmission may be observed by the optical detector 102 based on a condition of the assay test strip 110 (e.g. based on a presence of a sample flow or analyte) in the test region 112.
  • the optical detector 102 may be further configured to receive light from the control region 114 of the assay test strip 110 and to generate a control electrical output based on the received light for analysis by the electrical signal processor 104.
  • Figure 7 shows a method 700 of operating a lateral flow test device in accordance with the present disclosure.
  • the method 700 comprises a first step 702 of detecting, using a flow sensor 106, flow from a sample 118 provided on an assay test strip 110 prior to the flow reaching a test region 112 of the assay test strip 110.
  • a second step 704 comprises receiving light, at an optical detector 102, from the test region 112 and a third step 706 comprises generating, at the optical detector 102, an electrical output based on the received light.
  • a fourth step 708 comprises analysing the electrical output at an electrical signal processor 104. The electrical output may be analysed in any of the ways described above.
  • the lateral flow test device may be configured as a disposable item, which may be in storage for a long period, before being bought or provided to a user.
  • the user wishes to use the device for a test they begin by either inserting a battery into the device or by removing a plastic insulating strip to activate the battery powered electronics of the device.
  • the electronic circuitry in the device begins to monitor the flow sensor for any change indicative of the assay test strip changing from dry to wet (e.g. by monitoring the capacitive/resistive/optical properties of the flow sensor as described above).
  • the user deposits the sample fluid as a droplet on the assay test strip and the flow sensor detects the droplet induced wetting of the assay test strip (e.g. paper).
  • the flow sensor notifies the electrical signal processor that fluid has been detected and the device is primed for optical detection from the test region (i.e. test line) such that measurements can be taken and recorded to monitor the dynamic response as the fluid reaches the test region. Subsequently, the same process happens at the control region (i.e. control line).
  • the electrical signal processor is able to analyse the dynamic response from signals detected by the optical detector from the start of fluid flow detection by the flow sensor until a pre-determined time after the fluid has reached the test region and/or control region. The analysis may then be presented to the user, for example, via communication to a mobile phone application or any other display method.
  • Figure 8 shows a graph 800 illustrating example optical measurements from the test region 112 over time.
  • the graph 800 shows a first optical response 802 with an initial peak and long tail of reducing signal intensity and a second optical response 804 having a delayed start when compared with the first optical response 802 and a slower, gradual increase in signal intensity up to a plateau.
  • a static measurement taken at time A would indicate a higher signal intensity for the first optical response 802 and a lower signal intensity for the second optical response 804.
  • a static measurement taken at time B would indicate a higher signal intensity for the second optical response 804 and a lower signal intensity for the first optical response 802.
  • the output from a given test may be highly dependent on the time when a static measurement is taken during the test.
  • results may be directly comparable across different tests as they will always be taken at the same point in time with respect to the optical response curve (i.e. at time A).
  • the lateral flow test devices described in this disclosure may be configured as point-of- care devices, which may optionally be disposable and which may be configured to detect one or more of: coronavirus; coronavirus antibodies; or many other things.
  • Embodiments of the present disclosure can be employed in many different applications, in particular, in the areas of biological, medical, environmental and veterinary diagnostics.

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Abstract

L'invention concerne un dispositif de test immunochromatographique comprenant un détecteur optique configuré pour recevoir de la lumière d'une région de test d'une bandelette réactive et pour générer une sortie électrique basée sur la lumière reçue. Un processeur de signaux électriques est prévu pour analyser la sortie électrique et un capteur de flux est configuré pour détecter le flux d'un échantillon fourni sur la bandelette réactive au moins avant que le flux n'atteigne la région de test. L'invention concerne également un procédé de fonctionnement d'un dispositif de test immunochromatographique.
PCT/EP2021/085617 2020-12-15 2021-12-14 Dispositif de test immunochromatographique Ceased WO2022128997A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB2019775.2A GB202019775D0 (en) 2020-12-15 2020-12-15 Lateral Flow Test Device
GB2019775.2 2020-12-15

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WO2022128997A1 true WO2022128997A1 (fr) 2022-06-23

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5837546A (en) * 1993-08-24 1998-11-17 Metrika, Inc. Electronic assay device and method
GB2402473A (en) * 2003-06-04 2004-12-08 Inverness Medical Switzerland Analyte assay reading device involving sample flow rate measurement
EP1992951A2 (fr) * 1998-11-23 2008-11-19 Praxsys Biosystems, LLC. Procédé et appareil pour effectuer une analyse biologique à écoulement latéral
US20160252441A1 (en) * 2007-06-20 2016-09-01 Cozart Bioscience Limited Monitoring an immunoassay
US20160303558A1 (en) * 2013-12-04 2016-10-20 Spd Swiss Precision Diagnostics Gmbh Assay device
US20180059105A1 (en) * 2006-03-29 2018-03-01 Inverness Medical Switzerland Gmbh Assay Device and Method
US20200217799A1 (en) * 2010-08-26 2020-07-09 Charm Sciences, Inc. Assay analysis

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5837546A (en) * 1993-08-24 1998-11-17 Metrika, Inc. Electronic assay device and method
EP1992951A2 (fr) * 1998-11-23 2008-11-19 Praxsys Biosystems, LLC. Procédé et appareil pour effectuer une analyse biologique à écoulement latéral
GB2402473A (en) * 2003-06-04 2004-12-08 Inverness Medical Switzerland Analyte assay reading device involving sample flow rate measurement
US20180059105A1 (en) * 2006-03-29 2018-03-01 Inverness Medical Switzerland Gmbh Assay Device and Method
US20160252441A1 (en) * 2007-06-20 2016-09-01 Cozart Bioscience Limited Monitoring an immunoassay
US20200217799A1 (en) * 2010-08-26 2020-07-09 Charm Sciences, Inc. Assay analysis
US20160303558A1 (en) * 2013-12-04 2016-10-20 Spd Swiss Precision Diagnostics Gmbh Assay device

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