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WO2024033027A1 - Système de lecture pour test imunochromatographique et procédé correspondant - Google Patents

Système de lecture pour test imunochromatographique et procédé correspondant Download PDF

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Publication number
WO2024033027A1
WO2024033027A1 PCT/EP2023/069860 EP2023069860W WO2024033027A1 WO 2024033027 A1 WO2024033027 A1 WO 2024033027A1 EP 2023069860 W EP2023069860 W EP 2023069860W WO 2024033027 A1 WO2024033027 A1 WO 2024033027A1
Authority
WO
WIPO (PCT)
Prior art keywords
strip assay
light
light source
control line
reader system
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2023/069860
Other languages
English (en)
Inventor
Boon Chong CHEAH
Axel Schubert
Alec Reader
Giuliano Manzi
Sandesh CHITTOORI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ams Osram AG
Original Assignee
Ams Osram AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ams Osram AG filed Critical Ams Osram AG
Publication of WO2024033027A1 publication Critical patent/WO2024033027A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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

Definitions

  • the invention relates to a reader system for reading out a test line or a control line of a strip assay of a lateral flow test .
  • the invention also relates to a corresponding method .
  • a fluid sample In a lateral flow test ( LET ) a fluid sample , called analyte , is applied to a sample pad of an elongate strip assay . Driven by capillary forces , the sample spreads laterally towards an absorbent pad, thereby crossing several biologically or chemically active regions .
  • the underlying chemical reactions can be used to detect the presence of a target substance (e . g . , an antigen) in the analyte , which is usually indicated by colouring of a test line embedded into the strip assay . Similarly, colouring of a control line indicates validity of the test .
  • LFTs are predominantly in-vitro bio-diagnostics devices with applications in medical , veterinary, environmental or food safety .
  • Prominent uses relate , for example , to the detection of C0VID19 , HIV, or glucose (diabetes ) .
  • test line or control line of a LET may be inspected visually .
  • an automated, obj ective , and quantitative assessment or readout is required .
  • the light source is as source of a dominant background noise which decreases the signal to noise ratio ( SNR) .
  • SNR signal to noise ratio
  • the fluorescent dyes are excited by a light source for a short pulse , and the decay of the emission light from the dyes is immediately measured back by the sensor .
  • most of the fluorescent dyes have a short li fetime , around 1 ns to 100 ns . Only a few fluorescent dyes , such as lanthanides have li fetimes within ps to ms .
  • An obj ective underlying the present invention is to provide a reader system for reading out a test line or a control line of a strip assay of a lateral flow test .
  • the reader system shall work with a large variety of simple light sources and simple spectral sensors and shall provide readouts with a high signal-to-noise ratio . Furthermore , a corresponding method shall be provided .
  • the device-related obj ective is met by a reader system for reading out a test line or a control line of a strip assay of a lateral flow test , comprising • a support on which the strip assay rests in a nominal position during readout ,
  • a spectral sensor located above the strip assay when the strip assay is in the nominal position, for sensing light emerging from the test line or the control line , wherein the light source is located to a side of the strip assay when the strip assay is in the nominal position, such that light emitted by the light source predominantly impinges or impacts on a side edge of the strip assay and couples essentially co-planarly into the strip assay .
  • the light enters the strip assay from the side . This prevents light from the light source from reaching the sensor directly, since the gradient of the light emission is oriented perpendicular to the surface normal of the sensor . This configuration will therefore yield high signal-to-noise ratios .
  • the spectral sensor is configured to sense fluorescent light emerging from a dye in the test line or the control light after excitation by the light of the light source .
  • the light source will not need to be pulsed since the signal- to-noise ratio is optimi zed, and time-gated measurement is not required .
  • the light source is placed such that only a small fraction of the light from the light source (preferably ⁇ 10% ) can reach the sensor . More preferably, the light source is placed such that light from the light source does not directly reach the spectral sensor . Furthermore , the light source is preferably placed such that only a small portion of the light from the light source (preferably ⁇ 10% ) can reach the spectral sensor by a single reflection at an outer surface of the strip assay . More preferably, the light source is placed such that no light from the light source does reach the spectral sensor by a single reflection at an outer surface of the strip assay .
  • the light source preferably is a directed light source and preferably arranged such that the light of the light source is directed parallel to the test line or the control line .
  • the light source is a LED or an OLED .
  • Spectral multiplexing may be applied for a preferred embodiment , wherein a plurality of spectral sensors , preferably with di f ferent spectral ranges , is assigned to the test line or the control line .
  • said plurality of spectral sensors preferably senses light ef fected by a single light source . This also allows for LFTs designed for multianalyte tests . Di f ferent segments or areas of a test or control line or area may then be read out simultaneously .
  • the present invention provides a method for reading out a test line or a control line of a strip assay of a lateral flow test , wherein light from a light source is directed onto a side edge of the strip assay and coupled co-planarly into the strip assay in a region comprising the test line or the control line , and wherein light emerging from or passing through the test line or the control line is sensed by a spectral sensor above the strip assay .
  • the present invention allows for a low-cost reader system for a strip assay of a LET with low demands on the light source and the sensor .
  • simple DC light sources may be suf ficient . Consequently, there is no need for time gated sensors with complicated timing speci fications .
  • In fluorescent mode all fluorescent dyes can be used, there is no restriction to long fluorescence li fetimes . Hence , a large variety of di f ferent LFTs can be sensed .
  • Spectral multiplexing and multi-analyte configurations may be reali zed in a simple manner .
  • the whole reader system can be built with a small form factor .
  • Fig . 1 shows a partially cut perspective view of a lateral flow test with a strip assay .
  • Fig . 2 shows in a purely schematic manner a cross section through a reader system for reading out a test line or a control line of such a strip assay, wherein the section plane runs through the according test line or control line .
  • Fig . 3 shows a partially cut perspective view of said reader system .
  • FIG. 1 shows in a schematic manner a perspective view of a partially cut lateral flow test ( LFT ) 2 .
  • LFT 2 comprises an assay also known as a lateral flow device , lateral flow immunochromatographic assay, or rapid test , which is a simple device intended to detect the presence of a target substance in a liquid sample without the need for speciali zed and costly equipment .
  • LFTs 2 are widely used in medical diagnostics in the home , at the point of care , and in the laboratory .
  • the LFT 2 comprises an elongated strip assay 4 which in a view from above may have a generally rectangular shape with a longitudinal direction x and a transverse direction y .
  • the height of the strip assay 4 in direction z is relatively small in comparison to the lateral dimensions , i . e . , to the dimensions in longitudinal direction and transverse direction .
  • the strip assay 4 typically comprises a sample pad 10 , a conj ugate pad 12 , a membrane or reaction matrix 14 with a test line 16 and a control line 18 , and an absorbent pad 20 , arranged in this order along longitudinal direction x .
  • the individual components or regions may overlap each other and are applied to a common backing card 22 for fixation .
  • the backing card 22 forms a lower side of the strip assay 4 , while the other components mentioned above form an upper side .
  • the strip assay 4 may be at least partially enclosed by a housing 24 which provides protection for the strip assay 4 against physical damage and environmental influences . Access to certain regions on the upper side of the strip assay 4 is provided by means of openings or windows in the housing 24 .
  • a sample port 26 providing physical access to the sample pad 10
  • a readout port 28 facilitating at least visual or optical access to the test line 16 and the control line 18 .
  • the housing 24 typically comprises a lower part and an upper part , being engaged with a snap lock or the like . Both parts can be separated from each other to remove or exchange the strip assay 4 .
  • analyte As is well-known in the art , a sample fluid called analyte is applied through the sample port 26 on the sample pad 10 .
  • the sample pad 10 acts as a sponge and holds an excess of sample fluid .
  • the analyte flows along longitudinal x- direction to the absorbent pad 20 , thereby passing the other regions of the upper side of the strip assay 4 .
  • the conj ugate pad 12 Once the analyte passes the conj ugate pad 12 , there occurs a reaction between the analyte and some reactive constituents embedded into the conj ugate pad 12 .
  • the thus-modi fied analyte then migrates to the reaction matrix 14, usually leading to further reactions in the test line 16 and/or the control line 18.
  • test line 16 and/or the control line 18 may be visually or optically inspected.
  • the test line 16 and the control line 18 are typically aligned along transverse direction (in y- direction) and extend over some portion of the width of the strip assay 4.
  • the analyte reaches the absorbent pad 20 or wicking pad which wicks the liquid from the reaction matrix 14, thereby ensuring flow from the sample pad 10 through the conjugate pad 12 and the membrane or reaction matrix 14.
  • the LFT 2 is intended to detect the presence of a target substance in a liquid sample.
  • the target substance is often a biological antigen
  • many lateral flow tests 2 are known as rapid antigen tests.
  • the conjugate pad 12 may be a pad in which the manufacturer has stored freeze dried bio-active particles called conjugates in a salt-sugar matrix.
  • the conjugate pad 12 contains all the reagents required for an optimized chemical reaction between the target molecule (e.g., an antigen) and its chemical partner (e.g., antibody) that has been immobilized on the particle's surface. This marks target particles as they pass through the pad and continue across to the test and control lines 16, 18.
  • the test line 16 shows a signal, often a (change of) colour.
  • the control line 18 contains affinity ligands which show whether the sample has flowed through and the biomolecules in the conjugate pad 12 are active. After passing these reaction zones, the fluid enters the final porous material, the wick or absorbent pad 20, that acts as a waste container.
  • the test line 16 and/or the control line 18 may change their colour (e.g., hue and/or saturation) , depending on the outcome of the underlying chemical direction.
  • colourimetry an optical measuring process known as colorimetry may be used. This may involve illuminating the test line 16 and/or the control line 18 from above with a dedicated light source and measuring spectral properties of the reflected light with a spectral sensor or detector arranged above the respective portion of the reaction matrix 14 .
  • test line 16 and/or the control line 18 may comprise a fluorescent dye which is to be activated or altered by the underlying chemical reaction .
  • a measurement of fluorescent light emitted by the dye upon excitation is employed . This may involve illuminating the test line 16 and/or the control line 18 from above with a dedicated light source and measuring spectral properties of the emitted fluorescent light with a spectral sensor or detector arranged above the respective portion of the reaction matrix 14 .
  • the fluorescent light has a di f ferent wavelength than the incident stimulating or exciting light , which has to be considered for the measurement .
  • the measurement has to adapt to the comparatively short li fe span of the fluorescent light centres in the dye and therefore the pulsed nature of the fluorescent light .
  • the described reflective mode of the measurement has drawbacks in that the light used for illuminating the test line 16 and/or the control line 18 is reflected back into the spectral sensor .
  • the illuminating light source causes a dominant background noise which increases the signal-to- noise ratio ( SNR) .
  • SNR signal-to- noise ratio
  • This is particularly annoying for the fluorescence measurement scenario in which the fluorescent dye has a low luminosity anyway .
  • time-gated fluorescence may to some extent solve this problem but usually leads to complex illumination and sensor designs and also imposes constraints on possible light sources and fluorescent dyes to be used in the strip assay 4 .
  • the invention provides a di f ferent kind of solution which is schematically illustrated in Fig . 2 and Fig . 3 .
  • a LFT readout device or reader system 30 comprises a support 32 or seat onto which a strip assay 4 of the kind described above is to be placed during measurement .
  • the strip assay 4 is preferably removed and isolated from the housing 24 .
  • the support 32 comprises a flat bearing area on which the backing card 22 of the strip assay 4 lies flat such that the functional elements of the strip assay 4 like the sample pad 10 , the conj ugate pad 12 , the reaction matrix 14 , and the absorbent pad 20 point upwards . Lateral and/or longitudinal stops may ensure that the strip assay 4 rests in a predetermined position during measurement .
  • the strip assay 4 may be removed or disposed from the reader system 30 , giving way for the next strip assay 4 to be assessed or read out .
  • a light source 36 preferably a directed light source , is placed lateral ( sideways ) to the support 32 of the strip assay 4 and thus lateral to the strip assay 4 when it rests in its intended measurement position .
  • the arrangement is such that light emitted by the light source 36 couples essentially co-planarly ( from the side , parallel to the plane of the strip assay 4 ) into the backing card 22 and/or reaction matrix 14 of the strip assay 4 to illuminate either the test line 16 or the control line 18 ( or both) . Therefore , the light source 36 is placed preferably at the same x-position as the test line 16 or the control line 18 and at roughly the same height z as the strip assay 4 .
  • the light source 36 has a light emission area 38 facing the adj acent side area or side edge 40 of the strip assay 4 .
  • the light source 36 emits a light beam or light cone predominantly in y-direction towards and into the strip assay 4 via its side edge 40 . Utili zing the materials of the backing card 22 and/or the reaction matrix 14 , the light can enter them and travels through the material .
  • This fluorescent light is sensed by an optical sensor, in particular a spectral senor 42 , placed above the strip assay 4 , preferably at the same x-position as the light source 36 and at a suitable y-position corresponding to a fluorescent light emitting region of the reaction matrix 14 . Therefore , essentially only or mainly fluorescent light enters the spectral sensor 42 .
  • the light source 36 can be almost any light-emitting diode ( LED) or other light source 36 with a suitable frequency range .
  • the spectral sensor 42 may in principle be any optical sensor which is sensitive to incident light of a certain frequency range which is compatible with the measurement principle . This may be light in the visual range , but neighbouring ranges like infrared (IR) and ultraviolet (UV) may be included as well . In a simple case the spectral sensor 42 may be a photodiode. Optional upstream colour filters may be present for adjusting the sensed frequency range.
  • the associated measurement and evaluation routines or algorithms may be implemented in hardware, in software, or in a combination of both.
  • the readout or control electronics may be integrated into a single sensor device or may be placed off-site, with suitable cable-based or wireless line connections to the actual sensor probe .
  • fluorescent dyes in particular single or multiple dyes, in the reaction matrix 14 can be used.
  • the choice it not limited to such dyes with long fluorescence lifetimes, leading to great freedom of design in different application areas of LFTs, such as testing for C0VID19, HIV, glucose, or pregnancy.
  • test line 16 and the control line 18 are to be sensed within a singer reader system 30, then there expediently is a first light source 36 with an associated spectral sensor 42 at the x-position of the test line 16, and there is a second light source 36' with an associated spectral sensor 42' at the x-position of the control line 18.
  • first light source 36 with an associated spectral sensor 42 at the x-position of the test line 16
  • second light source 36' with an associated spectral sensor 42' at the x-position of the control line 18.
  • this can be generalized to further test or control or similar lines.
  • the light source 36 preferably is arranged in a small lateral distance or gap (in y-direction) to the strip assay 4 in the range of millimetres or less. It may even be in contact with the strip assay 4 when the latter is in the intended measurement position. Hence, a direct coupling of the source light into the strip assay 4 without noteworthy attenuation and without much stray light reaching the spectral sensor 42 directly is achieved.
  • a focussing optical element like a lens arranged between the light source 36 and the strip assay 4 to ef fectively direct the light into the strip assay 4 .
  • the spectral sensor 42 is preferably arranged in a small distance ( in z-direction) or with a small gap above the strip assay 4 in the range of millimetres or less , such that incoming light from the reaction matrix 14 is attenuated as little as possible while ambient light or direct light from the light source 36 does not reach the spectral sensor 42 .
  • spectral sensors 42 there may be several spectral sensors 42 associated with and illuminated by a single light source 36 .
  • the spectral sensors 42 of such a row may be designed to operate in di f ferent spectral ranges , therefore allowing for multispectral analysis and/or spectral multiplexing .
  • test or control " line” can be divided into line segments , the segments possibly being designed to support di f ferent chemical reactions .
  • the system described above with all its variations can also be used for the colorimetry case .
  • light from the light source 36 is coupled into the strip assay 4 from the side , leading to an " internal illumination" of the test line 16 or the control line 18 .
  • the light is at least partially internally deflected or scattered in upward direction to reach the spectral sensor 42 placed above the strip assay 4 . Again, direct impact of the source light or of outer-surface reflected source light onto the spectral sensor 42 is avoided . This will again yield high signal-to-noise ratios .
  • the measurement will in principle also work for a strip assay 4 enclosed by a housing 10 , provided that the housing 10 comprises a suitable opening or window at the side edge 40 facing the light source 36 to allow for coupling of incident source light .
  • the light source 36 and the spectral sensor 42 may be fixed to suitable elements or supports of a housing or a frame of the reader system 30 .
  • the whole system might in principle be aligned or rotated in arbitrary manner in space , provided that the strip assay 4 is suitably fixed or kept in the intended position during measurement .
  • test line 16 and the control line 18 preferably have indeed a " line" shape
  • the terminology used here is intended to also cover the slightly more general case of a test area or a control area of any suitable shape . That is , the terms “test line” or “control line” are generally to be understood in a broad sense .
  • aspects of the present invention can be implemented in any convenient way including by way of suitable hardware and/or software .
  • a device arranged to implement the invention may be created using appropriate hardware components .
  • a programmable device may be programmed to implement at least some of the algorithms or method steps of some of the embodiments of the disclosure .
  • the invention therefore also provides suitable computer programs for implementing aspects of the invention . Such computer programs can be carried on suitable carrier media including tangible carrier media ( e . g . , hard disks , CD ROMs and so on) and intangible carrier media such as communications signals .

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

L'invention concerne un système de lecture (30) pour lire une ligne de test (16) ou une ligne de contrôle (18) d'une bandelette réactive (4) d'un test immunochromatographique (2). Le système de lecture (30) doit fonctionner avec une grande variété de sources lumineuses et de capteurs spectraux simples et doit fournir des lectures avec un rapport signal/bruit élevé. Selon l'invention, le système de lecture (30) comprend un support (32) sur lequel la bandelette réactive (4) repose dans une position nominale pendant la lecture, une source de lumière (36) pour éclairer la bandelette réactive (4) dans une zone comprenant la ligne de test (16) et/ou la ligne de contrôle (18), un capteur spectral (42) situé au-dessus de la bandelette réactive (4) lorsque cette dernière se trouve dans la position nominale, pour détecter la lumière émergeant de la ligne de test (16) ou de la ligne de contrôle (18), la source de lumière (36) étant située sur le côté de la bandelette réactive (4) lorsque cette dernière se trouve dans la position nominale, de sorte que la lumière émise par la source de lumière (36) frappe principalement un bord latéral (40) de la bandelette réactive (4) et se couple de préférence de manière coplanaire dans la bandelette réactive (4)
PCT/EP2023/069860 2022-08-11 2023-07-18 Système de lecture pour test imunochromatographique et procédé correspondant Ceased WO2024033027A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102022208395.4 2022-08-11
DE102022208395 2022-08-11

Publications (1)

Publication Number Publication Date
WO2024033027A1 true WO2024033027A1 (fr) 2024-02-15

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PCT/EP2023/069860 Ceased WO2024033027A1 (fr) 2022-08-11 2023-07-18 Système de lecture pour test imunochromatographique et procédé correspondant

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060289787A1 (en) * 2005-06-17 2006-12-28 Amic Ab Optical assay system
EP3004847A1 (fr) * 2013-06-03 2016-04-13 Ventana Medical Systems, Inc. Système d'imagerie par fluorescence pour détection de tissu
US20160313254A1 (en) * 2004-04-01 2016-10-27 Alverix, Inc. Lateral flow assay systems and methods
US20220175319A1 (en) * 2019-04-01 2022-06-09 Given Imaging Ltd In vivo immunoassay system

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160313254A1 (en) * 2004-04-01 2016-10-27 Alverix, Inc. Lateral flow assay systems and methods
US20060289787A1 (en) * 2005-06-17 2006-12-28 Amic Ab Optical assay system
EP3004847A1 (fr) * 2013-06-03 2016-04-13 Ventana Medical Systems, Inc. Système d'imagerie par fluorescence pour détection de tissu
US20220175319A1 (en) * 2019-04-01 2022-06-09 Given Imaging Ltd In vivo immunoassay system

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