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WO1998032019A1 - Dispositif servant a detecter une substance a analyser et procede d'analyse - Google Patents

Dispositif servant a detecter une substance a analyser et procede d'analyse Download PDF

Info

Publication number
WO1998032019A1
WO1998032019A1 PCT/EP1998/000156 EP9800156W WO9832019A1 WO 1998032019 A1 WO1998032019 A1 WO 1998032019A1 EP 9800156 W EP9800156 W EP 9800156W WO 9832019 A1 WO9832019 A1 WO 9832019A1
Authority
WO
WIPO (PCT)
Prior art keywords
sample liquid
reagent
detection zone
absorber element
flow
Prior art date
Application number
PCT/EP1998/000156
Other languages
English (en)
Inventor
Hermanus Johannes Maria Kreuwel
Wilhelmus Maria Carpay
Original Assignee
Akzo Nobel N.V.
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 Akzo Nobel N.V. filed Critical Akzo Nobel N.V.
Priority to AU62089/98A priority Critical patent/AU6208998A/en
Publication of WO1998032019A1 publication Critical patent/WO1998032019A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54386—Analytical elements
    • G01N33/54387—Immunochromatographic test strips
    • G01N33/54388—Immunochromatographic test strips based on lateral flow

Definitions

  • the present invention relates to a device for the autonomous, specific detection of an analyte, said device comprising a means through which a sample liquid can be transported, said means comprising a proximal end to receive the sample liquid, a detection zone having an upstream end and a downstream end, and a distal end, said detection zone at the downstream distal end being operatively connected to an absorber element capable of absorbing the sample liquid and maintaining a flow of sample liquid through the means.
  • a device according to the preamble is disclosed in
  • the means through which the sample liquid can be transported is a porous carrier, for example an oblong rectangular nitrocellulose strip.
  • a section of the porous strip comprises an immobilized reagent and acts as the detec- tion zone.
  • Sample can be applied, indirectly via a proximal absorber element or directly, to the proximal end of the strip.
  • the sample liquid is transported by the capillary action of the porous strip towards the distal end of the strip.
  • a mobile reagent is supplied between the proximal end and the detection zone.
  • the porous strip comprises a further section extending from the detection zone towards the distal end of the porous strip and this section functions as an integrated absorber element, capable of washing at least parts of the excess mobile reagent and aspecifically-bound reagent from the detection zone.
  • Said device is autonomous in the sense that, after application of the sample, no further operations are required for the detection reaction to occur and to obtain a reading.
  • a par- ticular drawback is the fact that the porous carrier imposes limitations, for instance with respect to the flow of sample liquid through the means.
  • the object of the present invention is to improve on the device according to the preamble.
  • the device according to the invention is characterized in that the absorber element is capable of increasing the flow of sample liquid through the means, and in particular through the detection zone, after a predetermined reaction time, by absorption of sample liquid.
  • the device according to the present invention allows for a controlled flow rate of sample liquid through the means, said flow rate being adapted to the stage of the assay performed.
  • the device according to the present invention may provide a quick wash step after the reaction of analyte and reagent, resulting in a faster assay and a reduced background.
  • Control over the flow rate allows the transport function of the means to be separated from other functions, such as the suitability of the means as a substrate for immobilizing the reagent in the detection zone.
  • the present invention gives the expert a greater degree of freedom when developing assays.
  • the means through which the sample liquid is to be transported is a conduit .
  • a conduit as the means through which the sample liquid is to be transported reduces loss of mobile reagent due to adsorption or physical entrapment and in addition reduces the loss of analyte due to aspecific binding of the analyte to the means. Furthermore, a conduit has a very low flow resistance for the sample liquid, allowing the absorber element to achieve a wider range of sample liquid flow rates.
  • a very interesting embodiment is characterized in that the conduit is capable of passing sample liquid pushed from the proximal end towards the distal end at least up to the detection zone, and preferably up to the absorber element.
  • the absorber element is capable of at least a twofold increase of the flow of sample liquid through the means, and preferably of at least a fivefold increase of flow.
  • twofold (or fivefold) increase is intended to mean an increase of a sample flow rate through the means to a sample flow rate which is twice, or five times as high.
  • the proximal end of the means is capable of receiving a sample taker comprising the sample liquid.
  • the invention also relates to a method of detecting an analyte in a sample liquid by
  • the method is characterized in that after the predetermined reaction time the flow of sample liquid through the detection zone is increased by an absorber element capable of increasing the flow of sample liquid through the detection zone as the absorber element.
  • an absorber element capable of increasing the flow of sample liquid through the detection zone as the absorber element.
  • the means comprises a conduit, and sample liquid is pushed through the conduit until the sample liquid is in contact with an absorbing zone, after which the device autonomously maintains a flow for a predetermined time to allow a reaction to occur, after which the flow is increased to wash the detection zone.
  • the sample taker may be used to push the sample liquid to the detection zone, and more preferably the sample taker is used to push the sample liquid to the absorber element as the absorbing zone.
  • this zone determines the flow rate of sample liquid for a comparatively short time. If the sample liquid is pushed to the absorber element, this absorber element fully controls the flow rate of sample liquid. If, for instance, it is desired to remove proteins interfering with the assay or detection from the sample liquid, it is possible to use a hydrophobic section, for example a macroporous pad, to absorb the proteins. In devices according to the state of the art, the presence of a hydrophobic section would result in a stop of capillary flow.
  • FIG. 1 shows a schematic cross-section of a device according to the invention
  • the device for the specific detection of an analyte shown m Fig. 1 comprises a single conduit 1 having a proxi- mal end 2 and a distal end 3.
  • the conduit 1 is provided with a porous pad 4.
  • This pad 4 comprises an immobilised reagent in a detection zone 5.
  • a mobile reagent 6 is provided m a reagent zone between the proximal end 2 and the pad 4.
  • a sample liquid comprising the analyte, if any, can be applied to the proximal end 2.
  • an absorber element 7 Downstream of the detection zone 5 an absorber element 7 is provided. According to the invention, this absorber element 7 is arranged to increase the flow rate of the sample liquid through and along the conduit 1, and more m particular through the detection zone 5. This may be achieved in one of several ways.
  • the absorber element 7 may comprise a section 8 with increased geometrical dimensions, as is shown m Fig. 1.
  • section 8 may also have a more hydrophillic character, for example due to the presence or lack of a coat- mg.
  • the capillary structure may be modified.
  • Another possibility is the presence of flow-enhancing reagent.
  • the flow rate may also be controlled using viscosity as the parameter. For example, a substance increasing the viscosity of the sample liquid may be added to the sample liquid upstream from section 8, for example between the detection zone 5 and section 8, said substance being diluted or degraded m section 8.
  • the mobile reagent 6 is dissolved or dispersed m the sample liquid. Depending on the type of assay, the mobile reagent 6 may react with the analyte, as is the case for an lmmunological sandwich assay. There the mobile reagent 6 is usually a labelled antibody or lmmunologically active fragment thereof capable of specifically binding the analyte.
  • the label may be any of those known m the art, and is preferably a particle, such as a carbon, gold or latex particle.
  • the detection zone 5 will comprise antibodies capable of binding the bound analyte.
  • the absorber element 7 After a predetermined reaction time the absorber element 7 increases the speed with which the sample liquid flows through the conduit 1 and m particular the detection zone 5. Thus any surplus of mobile reagent is quickly and effectively removed.
  • the conduit 1 may have the capability to transport liquid by capillary action over a part or its full length, be it by the conduit 1 itself or any porous material in the conduit 1, the conduit 1 according to the invention allows for the increased transport of sample liquid as generated by the absorber element 7, preferably by a factor of at least 2 and more preferably by a factor of at least 5.
  • the conduit may be over at least part of its length incapable of supporting autonomous capillary transport of sample liquid. This may be the case if a hydrophobic zone is provided to remove certain components from the sample liquid.
  • sample liquid is forced through the conduit 1, for example using a sample taker 9.
  • a basic sample taker 9 comprises a handle 10 and an absorber element 11.
  • the sample taker 9 and the proximal end 2 may be designed such that the proximal end 2 is capable of receiving the sample taker 9 such that a predetermined amount of sample liquid is pushed into the conduit 1.
  • the sample liquid must be pushed beyond any zone incapable of supporting capillary transport, and preferably up to the detection zone 5 and more preferably up to the absorber element 7. After that, the device operates autonomously.
  • the volume of sample liquid squeezed out of the sample taker 9 suffices to fill the conduit 1 up to the point where capillary action takes over.
  • the capillary action generated by the absorber element 7 should be enough to draw sample liquid from the absorber element 11.
  • the absorber element 7 is capable of maintaining a flow for a predeter- mined reaction time and subsequently an increased flow for a predetermined wash time.
  • the mobile reagent 6 remains substantially in the reagent zone until the sample liquid reaches the detection zone 5, and more preferably until the sample liquid reaches the absorber element 7.
  • the device and more in particular the absorber element 7, can control the reaction conditions.
  • the mobile reagent 6 may be a slowly solubilizing or dispersing compound or may be comprised in a matrix allowing for the suitably slow release. If the reagent remains substantially in the reagent zone, this may result in a more sensitive competition assay. Analyte in the sample liquid pushed up to the detection zone 5, and in particular to the absorber element 7, has a chance to occupy binding sites in the reaction zone 5 before the mobile reagent has.
  • the device according to the invention may be used to detect any kind of analyte, for example antigens using antibodies or specific DNA or RNA sequences using complementary sequences . It goes without saying that the device may contain several detection zones for different analytes.

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  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

Dispositif servant à détecter de façon autonome une substance à analyser et dans lequel le spécimen de liquide est transporté à travers un conduit. Ce conduit comprend une zone de détection reliée à un élément absorbant. Ce dernier est capable, par absorption du spécimen de liquide, d'augmenter l'écoulement dudit spécimen à travers la zone de détection après une durée prédéterminée de réaction.
PCT/EP1998/000156 1997-01-14 1998-01-12 Dispositif servant a detecter une substance a analyser et procede d'analyse WO1998032019A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU62089/98A AU6208998A (en) 1997-01-14 1998-01-12 Device for detecting an analyte and an analytical method

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP97200094.7 1997-01-14
EP97200094 1997-01-14

Publications (1)

Publication Number Publication Date
WO1998032019A1 true WO1998032019A1 (fr) 1998-07-23

Family

ID=8227928

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/000156 WO1998032019A1 (fr) 1997-01-14 1998-01-12 Dispositif servant a detecter une substance a analyser et procede d'analyse

Country Status (2)

Country Link
AU (1) AU6208998A (fr)
WO (1) WO1998032019A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007065695A1 (fr) 2005-12-08 2007-06-14 Coris Bioconcept Dispositif de test pour des diagnostics rapides
WO2009153503A2 (fr) * 2008-06-20 2009-12-23 Applistick Dispositif et procede de test pour la detection d'une substance

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0306336A2 (fr) * 1987-09-04 1989-03-08 Syntex (U.S.A.) Inc. Dispositif d'essai à multiples orifices
EP0319294A2 (fr) * 1987-12-03 1989-06-07 Quidel Corporation Examen de membrane utilisant l'application concentrée d'un échantillon
EP0480497A1 (fr) * 1990-10-08 1992-04-15 Akzo Nobel N.V. Appareil pour l'exécution d'un dosage à la main unique et rapide
WO1994022011A1 (fr) * 1993-03-17 1994-09-29 Akzo Nobel N.V. Appareil de detection d'une substance a reactivite specifique
WO1995034815A1 (fr) * 1994-06-13 1995-12-21 Gks Technologies Dispositif de diagnostic rapide de toute molecule glyquee et procede de mise en ×uvre
WO1996022532A1 (fr) * 1995-01-20 1996-07-25 Pharmacia Ab Procede d'immunodosage et reactif associe, utilisant des particules bioaffines marquees au carbone suspensibles
EP0724909A1 (fr) * 1994-11-28 1996-08-07 Akzo Nobel N.V. Dispositif collecteur d'échantillons

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0306336A2 (fr) * 1987-09-04 1989-03-08 Syntex (U.S.A.) Inc. Dispositif d'essai à multiples orifices
EP0319294A2 (fr) * 1987-12-03 1989-06-07 Quidel Corporation Examen de membrane utilisant l'application concentrée d'un échantillon
EP0480497A1 (fr) * 1990-10-08 1992-04-15 Akzo Nobel N.V. Appareil pour l'exécution d'un dosage à la main unique et rapide
WO1994022011A1 (fr) * 1993-03-17 1994-09-29 Akzo Nobel N.V. Appareil de detection d'une substance a reactivite specifique
WO1995034815A1 (fr) * 1994-06-13 1995-12-21 Gks Technologies Dispositif de diagnostic rapide de toute molecule glyquee et procede de mise en ×uvre
EP0724909A1 (fr) * 1994-11-28 1996-08-07 Akzo Nobel N.V. Dispositif collecteur d'échantillons
WO1996022532A1 (fr) * 1995-01-20 1996-07-25 Pharmacia Ab Procede d'immunodosage et reactif associe, utilisant des particules bioaffines marquees au carbone suspensibles

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007065695A1 (fr) 2005-12-08 2007-06-14 Coris Bioconcept Dispositif de test pour des diagnostics rapides
US8389209B2 (en) 2005-12-08 2013-03-05 Coris Bioconcept Test device for rapid diagnostics
WO2009153503A2 (fr) * 2008-06-20 2009-12-23 Applistick Dispositif et procede de test pour la detection d'une substance
FR2932890A1 (fr) * 2008-06-20 2009-12-25 Applistick Dispositif et procede de test pour la detection d'une substance.
WO2009153503A3 (fr) * 2008-06-20 2010-04-01 Applistick Dispositif et procede de test pour la detection d'une substance

Also Published As

Publication number Publication date
AU6208998A (en) 1998-08-07

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