WO2004099525A2 - Reaction module for biological analysis - Google Patents

Reaction module for biological analysis Download PDF

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Publication number
WO2004099525A2
WO2004099525A2 PCT/FR2004/050181 FR2004050181W WO2004099525A2 WO 2004099525 A2 WO2004099525 A2 WO 2004099525A2 FR 2004050181 W FR2004050181 W FR 2004050181W WO 2004099525 A2 WO2004099525 A2 WO 2004099525A2
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WO
WIPO (PCT)
Prior art keywords
biological
reaction
hquide
reagent
injection
Prior art date
Application number
PCT/FR2004/050181
Other languages
French (fr)
Other versions
WO2004099525A3 (en
Inventor
Bruno Colin
Frédéric PAULHET
Original Assignee
Biomerieux
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 Biomerieux filed Critical Biomerieux
Priority to EP04742862A priority Critical patent/EP1620724A2/en
Priority to US10/553,440 priority patent/US20070172886A1/en
Publication of WO2004099525A2 publication Critical patent/WO2004099525A2/en
Publication of WO2004099525A3 publication Critical patent/WO2004099525A3/en

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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
    • G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5023—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0825—Test strips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates

Definitions

  • the present invention relates to automated devices for performing immunological tests.
  • the invention particularly relates to a means of controlling these tests.
  • Medical biology plays a major role in public health, whether in terms of the diagnosis of the disease, the care of the patient and his treatment. Efes automated instruments intended for medical analyzes and quality control of products in the food industry, cosmetics ... are therefore commonly used in the laboratory.
  • There are many automated diagnostic devices on the market which allow, in particular, by immunological assays, such as an ELISA test, the detection of pathogenic agents responsible for many diseases.
  • These immunoassay analyzers generally implement successive steps of automated injection / aspiration of the biological sample which it is desired to analyze and of reagents for the detection of one or more given pathogens.
  • the first step may consist in coating on the walls of a solid support recognition antibodies, specific for a target antigen of a given pathogenic agent, which it is desired to demonstrate in a sample. patient's biology.
  • the second step then consists in bringing the biological sample of the patient into contact with said recognition antibodies. If the patient's sample contains the target antigen, a complex forms between the target antigen and the recognition antibody. The target antigens attached to the recognition antibodies are then brought into contact with labeled detection antibodies, which makes it possible to reveal the presence of the recognition antibody - target antigen - detection antibody sandwich.
  • Such tests are well known to those skilled in the art.
  • VIDAS® device which is a multi-parameter automated device for immunoassays. This device is composed of an analytical module which automatically takes care of all the stages of the analysis until the complete edition of the results.
  • the principle of the VIDAS® test is based on the use of a cone and a reaction bar:
  • the cone is the solid phase of the reaction, and includes the recognition antibodies coated on its wall. It is for single use and acts as a sampling needle. During the test, it is subjected to injection / aspiration steps in order to bring the multiple test reagents into contact successively.
  • the reaction strip contains all the reagents ready for use, distributed in the various wells of the strip, and in particular the detection antibodies.
  • a well also allows the deposit of the sample that one wishes to analyze.
  • the cone sucks and delivers the reagent contained in the various wells of the strip several times until the final stage of the analysis.
  • the last well of the bar is the reading tank where the final intensity of the reaction is measured in fluorescence.
  • these automated devices require a proper functioning check which must be carried out regularly, in order to avoid any risk of false positives, ie to indicate to the patient that he is sick when he is not is not, but also false negatives, that is to say to the patient that he is not sick when he is.
  • false negatives can be observed in particular when the injection of the different reagents has not taken place, or when the volume of reagent is not the right volume.
  • this control can be done by weighing the unit reaction bars, before and after the test, but this induces a cumbersome protocol for the user.
  • the control can also be carried out by pressure sensors, placed within the automaton, in order to detect whether the sample, or the reagent has indeed been injected. This however increases the cost of manufacturing the machines.
  • the present invention proposes to solve all the drawbacks of the state of the art by improving the current control systems of automatic dosing machines. by presenting a very simple and rapid control system, allowing a visual interpretation of the results, at low cost, without requiring a total calibration of the automatic biological assay. Before going further, a few definitions are given in order to facilitate understanding of the description of the invention.
  • reaction module is meant any device capable of being inserted into a biological assay atomate for carrying out a biological reaction.
  • this reaction module can be a reaction bar comprising several reaction wells as used in Vidas® machines, but can also be a 96-well microplate, or any other container used by a person skilled in the art to perform immunological tests.
  • biological fluid any Hquide in which it is desired to demonstrate the presence of a given antigen (or of an antibody).
  • This liquid can thus be a clinical sample of blood, urine, saliva, plasma ...
  • This Hquide can also be a food sample of water, drinks, in which one wishes to determine the presence of an organism ( bacteria, parasites, viruses ).
  • biological Hquide is a clinical sample of blood, urine or plasma.
  • reagent any chemical solution necessary for the development of an immunological test. Such a solution may include in particular recognition antibodies, detection antibodies, but also washing solutions ...
  • biological reaction is meant any reaction capable of demonstrating the presence of an antigen (or an antibody ) given.
  • this biological reaction is an antigen-antibody recognition reaction.
  • control means is meant a means making it possible to highlight the presence of false negatives or false positives in a test.
  • This control means can be in particular absorbent paper, comprising a dehydrated dye capable of diffusing and creating a colorimetric signal when it is in the presence of a biological liquid and / or a reagent. This means of control can allow quantitative control of the volume necessary biological fluid and / or reagent during the immunological test, and / or a qualitative control.
  • the present invention relates to a reaction module comprising at least one reaction well for biological analysis comprising the injection of biological fluid and / or of reagent allowing a determined biological reaction and at least one means of controlling the quantity of biological fluid and / or injected reagent, characterized in that the control means is a caHbred colorimetric strip.
  • the module comprises a graduated scale along the strip for a visual determination of the volume.
  • This caHbred colorimetric strip thus allows quantitative control of the biological analysis, by checking the volume injected with biological fluid and / or reagent during each step of the biological analysis.
  • the invention also relates to a module as defined above, characterized in that the control means is a colorimetric patch.
  • the colorimetric pellet allows quantitative control of the biological analysis, by verifying the injection of biological Hquide and or reagent during each step of the biological analysis.
  • FIG. 1 represents a first embodiment of the invention.
  • FIG. 1a represents a side view of a reaction module, which is a reaction bar (1) comprising a control means (2) according to the invention.
  • This control means is a strip of absorbent paper, comprising a charred volumetric drop (4).
  • the injection of biological Hquide and / or of reagent takes place through an orifice (3), and the Hquide diffuses along the volumetric scale.
  • the charred volumetric flow (4) is integrated into the bar so that the user is not in direct contact with the biological fluid and / or the reagent which is absorbed by the control means (2). This is important especially when the biological Hquide is likely to be contaminated.
  • This strip includes 8 reaction wells (5).
  • FIG. 1b represents a top view of a reaction bar (1) comprising the control means as defined above.
  • FIG. 2 shows in a more detailed manner the control means (2) presented in FIG. 1.
  • a first absorbent layer (7) is deposited on the bar (1).
  • This first layer comprises a dried dye.
  • a second layer (8) of absorbent paper but not comprising dye is placed above.
  • This first and second layer make it possible to obtain a simple and inexpensive means of control: when a Hquide is in contact with the second layer (8), it diffuses through to the first layer (7) by rehydrating the dye. which in turn diffuses within the second layer (8).
  • the second layer (8) is colored, this means for the user that an injection of Hquide has taken place.
  • a last layer which is a protective means (9) such as a plastic film makes it possible to isolate the control means (2).
  • FIG. 3 represents different successive steps carried out during an immunological test.
  • FIG. 3a represents the first step of an immunological test such as a Vidas® test in which a reaction cone (10) sucks in the first well of the bar a determined volume of biological fluid.
  • This reaction cone (10) comprises, on its wall, recognition antibodies, which form, with the target antigens of the biological fluid, an antigen - antibody complex.
  • FIG. 3b represents the second step of the test which consists in aspirating and discharging a reagent, such as in particular a washing liquid contained in a second well, in order to remove the target antigens which would have been badly fixed on the recognition antibodies.
  • the cone (10) automatically passes from the first well of the bar to the second well.
  • a control step is carried out in order to determine whether the aspiration / injection steps have been carried out correctly.
  • the automaton withdraws by the cone (10) a determined volume of Hquide (which can be a biological Hquide, a reagent, or a simple aqueous solution) in the last well of the reaction bar, and deposits this volume on the means of control (2).
  • Hquide then diffuses within the second layer as shown in Figure 2 until reaching the first layer comprising a dye.
  • FIG. 4 shows another control means according to the invention.
  • the control means is then a colorimetric tablet, allowing a quantitative control of the aspiration / injection stages carried out during the test.
  • reaction bar 1. reaction bar 2. control means
  • first absorbent layer comprising a dye

Abstract

The invention relates to a reaction module for biological analysis comprising the injection of a biological liquid and/or reagent enabling a specific biological reaction comprising at least one means for controlling the amount of biological liquid and/or reagent thus injected.

Description

Module de réaction pour l'analyse biologique Reaction module for biological analysis
La présente invention concerne les appareils automatisés pour réaliser des tests immunologiques. L'invention concerne particulièrement un moyen de contrôle de ces tests. La biologie médicale joue un rôle majeur dans la santé publique, que ce soit au niveau du diagnostic de la maladie, de la prise en charge du patient et de son traitement. Efes instruments automatisés destinés aux analyses médicales et au contrôle de la qualité des produits des industries agro- alimentaires, cosmétiques... sont à ce titre, utilisés couramment en laboratoire. II existe sur le marché de nombreux appareils de diagnostic automatisés qui permettent notamment, par des dosages immunologiques, comme un test ELISA, la mise en évidence d'agents pathogènes, responsables de nombreuses maladies. Ces automates d'analyse immunologique mettent généralement en œuvre des étapes successives d'injection / aspiration automatisées de l'échantillon biologique que l'on souhaite analyser et de réactifs pour la détection d'un ou de plusieurs agents pathogènes donnés. Ces automates permettent notamment le développement rapide et pour un grand nombre d'échantillon d'un test sandwich de type ELISA (Enzyme Linked ImmunoSorbent Assay). Ainsi, à titre indicatif, la première étape peut consister à coater sur les parois d'un support solide des anticorps de reconnaissance, spécifiques d'un antigène cible d'un agent pathogène donné, que l'on souhaite mettre en évidence dans un échantillon biologique d'un patient. La deuxième étape consiste ensuite à mettre en contact l'échantillon biologique du patient avec lesdits anticorps de reconnaissance. Si Péchantillon du patient contient l'antigène cible, il se forme un complexe entre l'antigène cible et l'anticorps de reconnaissance. Les antigènes cibles fixés sur les anticorps de reconnaissance sont alors mis en contact avec des anticorps de détection, marqués, qui permet de révéler la présence du sandwich anticorps de reconnaissance - antigène cible - anticorps de détection. De tels tests sont bien connus de l'homme du métier.The present invention relates to automated devices for performing immunological tests. The invention particularly relates to a means of controlling these tests. Medical biology plays a major role in public health, whether in terms of the diagnosis of the disease, the care of the patient and his treatment. Efes automated instruments intended for medical analyzes and quality control of products in the food industry, cosmetics ... are therefore commonly used in the laboratory. There are many automated diagnostic devices on the market which allow, in particular, by immunological assays, such as an ELISA test, the detection of pathogenic agents responsible for many diseases. These immunoassay analyzers generally implement successive steps of automated injection / aspiration of the biological sample which it is desired to analyze and of reagents for the detection of one or more given pathogens. These machines allow in particular the rapid development and for a large number of samples of an ELISA (Enzyme Linked ImmunoSorbent Assay) sandwich test. Thus, by way of indication, the first step may consist in coating on the walls of a solid support recognition antibodies, specific for a target antigen of a given pathogenic agent, which it is desired to demonstrate in a sample. patient's biology. The second step then consists in bringing the biological sample of the patient into contact with said recognition antibodies. If the patient's sample contains the target antigen, a complex forms between the target antigen and the recognition antibody. The target antigens attached to the recognition antibodies are then brought into contact with labeled detection antibodies, which makes it possible to reveal the presence of the recognition antibody - target antigen - detection antibody sandwich. Such tests are well known to those skilled in the art.
Comme exemple d'appareils automatisés pour des dosages immunologiques, on peut citer notamment, l'appareil VIDAS® qui est un automate multiparamétrique pour les immunoanalyses. Cet appareil est composé d'un module analytique qui prend en charge automatiquement toutes les étapes de l'analyse jusqu'à l'édition complète des résultats. Le principe du test VIDAS® est basé sur l'utilisation d'un cône et d'une barrette de réaction :As an example of automated devices for immunoassays, mention may be made in particular of the VIDAS® device which is a multi-parameter automated device for immunoassays. This device is composed of an analytical module which automatically takes care of all the stages of the analysis until the complete edition of the results. The principle of the VIDAS® test is based on the use of a cone and a reaction bar:
• le cône est la phase solide de la réaction, et comprend les anticorps de reconnaissance coatés sur sa paroi. Il est à usage unique et fait office d'aiguille de prélèvement. Il est soumis durant le test à des étapes d'injection / aspiration afin de mettre successivement en contact les multiples réactifs du test.• the cone is the solid phase of the reaction, and includes the recognition antibodies coated on its wall. It is for single use and acts as a sampling needle. During the test, it is subjected to injection / aspiration steps in order to bring the multiple test reagents into contact successively.
• la barrette de réaction contient tous les réactifs prêts à l'emploi, repartis dans les différents puits de la barrette, et notamment les anticorps de détection. Un puit permet également le dépôt de l'échantillon que l'on souhaite analyser. A chaque étape de l'immunoanalyse, le cône aspire et refoule plusieurs fois le réactif contenus dans les différents puits de la barrette jusqu'à l'étape finale de l'analyse. Le dernier puit de la barrette est la cuve de lecture où l'intensité finale de la réaction est mesurée en fluorescence.• the reaction strip contains all the reagents ready for use, distributed in the various wells of the strip, and in particular the detection antibodies. A well also allows the deposit of the sample that one wishes to analyze. At each stage of the immunoanalysis, the cone sucks and delivers the reagent contained in the various wells of the strip several times until the final stage of the analysis. The last well of the bar is the reading tank where the final intensity of the reaction is measured in fluorescence.
D'une manière générale, ces appareils automatisés nécessitent un contrôle de bon fonctionnement qui doit être régulièrement effectué, afin d'éviter tout risque de faux positifs, c'est à dire indiquer au patient qu'il est malade alors qu'il ne l'est pas, mais aussi de faux négatifs, c'est à dire indiquer au patient qu'il n'est pas malade alors qu'il l'est. De tels faux négatifs peuvent être observés notamment lorsque l'injection des différents réactifs n'a pas heu, ou que le volume de réactif n'est pas le bon volume. Outre une maintenance effectuée régulièrement, qui permet d'éviter de tels faux négatifs, ce contrôle peut se faire par la pesée des barrettes de réaction unitaires, avant et après le test, mais cela induit un protocole lourd pour Putilisateur. Le contrôle peut être également réalisé par des capteurs de pression, disposés au sein de l'automate, afin de détecter si l'échantillon, ou le réactif a bien été injecté. Ceci augmente toutefois le coût de fabrication des automates. La présente invention se propose de résoudre l'ensemble des inconvénients de l'état de la technique en améliorant les systèmes de contrôle actuels des automates de dosage biologique et en présentant un système de contrôle très simple et rapide, permettant une interprétation visuelle des résultats, de faible coût, sans nécessiter un étalonnage total de l'automate de dosage biologique. Avant d'aller plus avant, il est donné quelques définitions afin de faciliter la compréhension de l'exposé de l'invention.In general, these automated devices require a proper functioning check which must be carried out regularly, in order to avoid any risk of false positives, ie to indicate to the patient that he is sick when he is not is not, but also false negatives, that is to say to the patient that he is not sick when he is. Such false negatives can be observed in particular when the injection of the different reagents has not taken place, or when the volume of reagent is not the right volume. In addition to regular maintenance, which makes it possible to avoid such false negatives, this control can be done by weighing the unit reaction bars, before and after the test, but this induces a cumbersome protocol for the user. The control can also be carried out by pressure sensors, placed within the automaton, in order to detect whether the sample, or the reagent has indeed been injected. This however increases the cost of manufacturing the machines. The present invention proposes to solve all the drawbacks of the state of the art by improving the current control systems of automatic dosing machines. by presenting a very simple and rapid control system, allowing a visual interpretation of the results, at low cost, without requiring a total calibration of the automatic biological assay. Before going further, a few definitions are given in order to facilitate understanding of the description of the invention.
Par module de réaction, on entend tout dispositif apte à être inséré dans un atomate de dosage biologique pour la réalisation d'une réaction biologique. A titre indicatif, ce module de réaction peut être une barrette de réaction comprenant plusieurs puits de réaction telle qu'utilisée dans les automates Vidas®, mais peut être également une microplaque de 96 puits, ou tout autre contenant utilisé par l'homme du métier pour réaliser des tests immunologiques.By reaction module is meant any device capable of being inserted into a biological assay atomate for carrying out a biological reaction. As an indication, this reaction module can be a reaction bar comprising several reaction wells as used in Vidas® machines, but can also be a 96-well microplate, or any other container used by a person skilled in the art to perform immunological tests.
Par liquide biologique, on entend tout Hquide dans lequel on souhaite mettre en évidence la présence d'un antigène (ou d'un anticorps) donné. Ce liquide peut être ainsi un échantillon clinique de sang, d'urine, de salive, de plasma... Ce Hquide peut être également un échantillon alimentaire d'eau, de boissons, dans lequel on souhaite déterminer la présence d'un organisme (bactéries, parasites, virus...).By biological fluid is meant any Hquide in which it is desired to demonstrate the presence of a given antigen (or of an antibody). This liquid can thus be a clinical sample of blood, urine, saliva, plasma ... This Hquide can also be a food sample of water, drinks, in which one wishes to determine the presence of an organism ( bacteria, parasites, viruses ...).
PréférentieUement, le Hquide biologique est un échantillon clinique de sang, d'urine ou de plasma. Par réactif, on entend toute solution chimique nécessaire au développement d'un test immunologique. Une teUe solution peut comprendre notamment les anticorps de reconnaissance, les anticorps de détection, mais aussi les solutions de lavage ... Par réaction biologique, on entend toute réaction susceptible de mettre en évidence la présence d'un antigène (ou d'un anticorps) donné. Préférentiellement, cette réaction biologique est une réaction de reconnaissance antigène - anticorps. Par moyen de contrôle, on entend un moyen permettant de mettre en évidence la présence de faux négatifs ou de faux positifs dans un test. Ce moyen de contrôle peut être notamment en papier absorbant, comprenant un colorant déshydraté susceptible de diffuser et de créer un signal colorimétrique lorsqu'il est en présence d'un liquide biologique et/ou d'un réactif. Ce moyen de contrôle peut permettre un contrôle quantitatif du volume nécessaire de Hquide biologique et/ou de réactif lors du test immunologique, et/ou un contrôle qualitatif.Preferably, biological Hquide is a clinical sample of blood, urine or plasma. By reagent is meant any chemical solution necessary for the development of an immunological test. Such a solution may include in particular recognition antibodies, detection antibodies, but also washing solutions ... By biological reaction is meant any reaction capable of demonstrating the presence of an antigen (or an antibody ) given. Preferably, this biological reaction is an antigen-antibody recognition reaction. By control means is meant a means making it possible to highlight the presence of false negatives or false positives in a test. This control means can be in particular absorbent paper, comprising a dehydrated dye capable of diffusing and creating a colorimetric signal when it is in the presence of a biological liquid and / or a reagent. This means of control can allow quantitative control of the volume necessary biological fluid and / or reagent during the immunological test, and / or a qualitative control.
A cet effet, la présente invention concerne un module de réaction comprenant au moins un puit de réaction pour l'analyse biologique comprenant l'injection de Hquide biologique et/ou de réactif permettant une réaction biologique déterminée et au moins un moyen de contrôle de la quantité de Hquide biologique et/ou de réactif injecté caractérisée en ce que le moyen de contrôle est une bandelette colorimetrique caHbrée.To this end, the present invention relates to a reaction module comprising at least one reaction well for biological analysis comprising the injection of biological fluid and / or of reagent allowing a determined biological reaction and at least one means of controlling the quantity of biological fluid and / or injected reagent, characterized in that the control means is a caHbred colorimetric strip.
Selon un mode préféré de réaHsation de l'invention, le module comprend une écheUe graduée le long de la bandelette pour une détermination visueUe du volume. Cette bandelette colorimetrique caHbrée permet ainsi un contrôle quantitatif de l'analyse biologique, par la vérification du volume injectée de Hquide biologique et/ou de réactif lors de chaque étape de l'analyse biologique.According to a preferred embodiment of the invention, the module comprises a graduated scale along the strip for a visual determination of the volume. This caHbred colorimetric strip thus allows quantitative control of the biological analysis, by checking the volume injected with biological fluid and / or reagent during each step of the biological analysis.
L'invention concerne également un module tel que défini précédemment caractérisée en ce que le moyen de contrôle est une pastille colorimetrique. Dans ce cas, la pastille colorimetrique permet un contrôle quaUtatif de l'analyse biologique, par la vérification de l'injection de Hquide biologique et ou de réactif lors de chaque étape de l'analyse biologique.The invention also relates to a module as defined above, characterized in that the control means is a colorimetric patch. In this case, the colorimetric pellet allows quantitative control of the biological analysis, by verifying the injection of biological Hquide and or reagent during each step of the biological analysis.
Les figures ci-jointes sont données à titre d'exemple expHcatif et n'ont aucun caractère limitatif. Elles peπnettront de mieux comprendre l'invention.The attached figures are given by way of an illustrative example and are in no way limiting. They will understand better the invention.
La figure 1 représente un premier mode de réaHsation de l'invention. La figure la représente une vue de coté d'un module de réaction, qui est une barrette de réaction (1) comprenant un moyen de contrôle (2) selon l'invention. Ce moyen de contrôle est une bandelette en papier absorbant, comprenant une écheUe volumétrique caHbrée (4). L'injection de Hquide biologique el/ou de réactif s'effectue par un orifice (3), et le Hquide diffuse le long de l'échelle volumétrique. PréférentieUement, l'écheUe volumétrique caHbrée (4) est intégré dans la barrette afin que l'utilisateur ne soit pas en contact direct avec le Hquide biologique et/ou le réactif qui est absorbé par le moyen de contrôle (2). Ceci est important notamment lorsque le Hquide biologique est susceptible d'être contaminé. Cette barrette comprend 8 puits (5) de réaction. La figure lb représente une vue de dessus d'une barrette de réaction (1) comprenant le moyen de contrôle tel que défini ci dessus.FIG. 1 represents a first embodiment of the invention. FIG. 1a represents a side view of a reaction module, which is a reaction bar (1) comprising a control means (2) according to the invention. This control means is a strip of absorbent paper, comprising a charred volumetric drop (4). The injection of biological Hquide and / or of reagent takes place through an orifice (3), and the Hquide diffuses along the volumetric scale. Preferably, the charred volumetric flow (4) is integrated into the bar so that the user is not in direct contact with the biological fluid and / or the reagent which is absorbed by the control means (2). This is important especially when the biological Hquide is likely to be contaminated. This strip includes 8 reaction wells (5). FIG. 1b represents a top view of a reaction bar (1) comprising the control means as defined above.
La figure 2 représente d'une manière plus détaiïlée le moyen de contrôle (2) présenté dans la figure 1. On distingue alors successivement différentes couches qui se superpose sur la barrette de réaction (1) comprenant les puits (5). Une première couche absorbante (7) est déposé sur la barrette (1). Cette première couche comprend un colorant séché. Au dessus est placé une deuxième couche (8) en papier absorbant mais ne comprenant pas de colorant. Cette première et deuxième couche permettent d'obtenir un moyen de contrôle simple et peu coûteux : lorsqu'un Hquide est en contact avec la deuxième couche (8), il difruse à travers jusqu'à la première couche (7) en rehydratant le colorant qui diffuse à son tour au sein de la deuxième couche (8). Lorsque la deuxième couche (8) est coloré, cela signifie pour l'utiHsateur qu'une injection de Hquide a eu Heu. Enfin une dernière couche qui est un moyen de protection (9) tel qu'un film en matière plastique permet d'isoler le moyen de contrôle (2). On distingue alors un orifice (3) pour le dépôt de liquide, et une fenêtre de lecture (6).FIG. 2 shows in a more detailed manner the control means (2) presented in FIG. 1. A distinction is then made between different layers which overlap on the reaction bar (1) comprising the wells (5). A first absorbent layer (7) is deposited on the bar (1). This first layer comprises a dried dye. Above is placed a second layer (8) of absorbent paper but not comprising dye. This first and second layer make it possible to obtain a simple and inexpensive means of control: when a Hquide is in contact with the second layer (8), it diffuses through to the first layer (7) by rehydrating the dye. which in turn diffuses within the second layer (8). When the second layer (8) is colored, this means for the user that an injection of Hquide has taken place. Finally a last layer which is a protective means (9) such as a plastic film makes it possible to isolate the control means (2). There is then an orifice (3) for depositing liquid, and a reading window (6).
La figure 3 représente différentes étapes successives réafisées lors d'un test immunologique. La figure 3a représente la première étape d'un test immunologique tel qu'un test Vidas® dans laqueUe un cône de réaction (10) aspire dans le premier puit de la barette un volume déterminé de liquide biologique. Ce cône de réaction (10) comprend sur sa paroi des anticorps de reconnaissance, qui forme avec les antigènes cibles du Hquide biologique un complexe antigène - anticorps. La figure 3b représente la deuxième étape du test qui consiste à aspirer et refouler un réactif, tel que notamment un liquide de lavage contenu dans un deuxième puit, afin de supprimer les antigènes cibles qui se seraient mal fixés sur les anticorps de reconnaissance. Pour cela, le cône (10) passe automatiquement du premier puit de la barrette jusqu'au deuxième puit. L'ensemble du test se poursuit par des étapes successives d'aspiration / injection par le cône en contact avec les différents réactifs des différents puits. Ces étapes sont bien connues de l'homme du métier. A la fin du test, et tel que représentée figure 3c, une étape de contrôle est réaHsée afin de déterminer si les étapes d'aspiration / injection ont été réalisées correctement. Pour cela, l'automate prélève par le cône (10) un volume déterminé de Hquide (qui peut être un Hquide biologique, un réactif, ou une simple solution aqueuse) dans le dernier puit de la barrette de réaction, et dépose ce volume sur le moyen de contrôle (2). Le Hquide diffuse alors au sein de la deuxième couche tel que présenté dans la figure 2 jusqu'à atteindre la première couche comprenant un colorant. Ce colorant réhydraté diffuse alors jusqu'à atteindre la surface de la deuxième couche de colorant. Lorsque l'injection de Hquide a Heu, l'utilisateur peut visualiser alors aisément la coloration qui diffuse le long de l'écheUe volumétrique caHbré, la diffusion étant proportionnelle au volume injecté. Cela permet ainsi un contrôle quantitatif aisé du test réaHsé précédemment. La figure 4 présente un autre moyen de contrôle selon l'invention. Le moyen de contrôle est alors une pastille colorimetrique, permettant un contrôle quaHtatif des étapes d'aspiration / injection effectués lors du test. FIG. 3 represents different successive steps carried out during an immunological test. FIG. 3a represents the first step of an immunological test such as a Vidas® test in which a reaction cone (10) sucks in the first well of the bar a determined volume of biological fluid. This reaction cone (10) comprises, on its wall, recognition antibodies, which form, with the target antigens of the biological fluid, an antigen - antibody complex. FIG. 3b represents the second step of the test which consists in aspirating and discharging a reagent, such as in particular a washing liquid contained in a second well, in order to remove the target antigens which would have been badly fixed on the recognition antibodies. For this, the cone (10) automatically passes from the first well of the bar to the second well. The whole test is continued by successive steps of aspiration / injection by the cone in contact with the different reagents of the different wells. These steps are well known to those skilled in the art. At the end of the test, and as shown in FIG. 3c, a control step is carried out in order to determine whether the aspiration / injection steps have been carried out correctly. For it, the automaton withdraws by the cone (10) a determined volume of Hquide (which can be a biological Hquide, a reagent, or a simple aqueous solution) in the last well of the reaction bar, and deposits this volume on the means of control (2). The Hquide then diffuses within the second layer as shown in Figure 2 until reaching the first layer comprising a dye. This rehydrated dye then diffuses until it reaches the surface of the second layer of dye. When the injection of Hquide a Heu, the user can then easily visualize the coloration which diffuses along the charred volumetric scale, the diffusion being proportional to the volume injected. This allows easy quantitative control of the test carried out previously. FIG. 4 shows another control means according to the invention. The control means is then a colorimetric tablet, allowing a quantitative control of the aspiration / injection stages carried out during the test.
REFERENCESREFERENCES
1. barrette de réaction 2. moyen de contrôle1. reaction bar 2. control means
3. orifice pour le dépôt de Hquide3. port for the deposit of Hquide
4. écheUe volumétrique graduée4. graduated volumetric scale
5. puits de réaction5. reaction well
6. fenêtre de lecture 7. première couche absorbante comprenant un colorant6. reading window 7. first absorbent layer comprising a dye
8. deuxième couche absorbante8. second absorbent layer
9. moyen de protection9. means of protection
10. cône de réaction 10. reaction cone

Claims

REVENDICATIONS
1. Module de léaction pour l'analyse biologique comprenant au moins un puit de réaction pour l'injection de Hquide biologique et/ou de réactif permettant une réaction biologique déterminée et comprenant au moins un moyen de contrôle de la quantité de Hquide biologique et/ou de réactif injecté caractérisée en ce que le moyen de contrôle est une bandelette colorimetrique caHbrée.1. Reaction module for biological analysis comprising at least one reaction well for the injection of biological Hquide and / or of reagent allowing a determined biological reaction and comprising at least one means of controlling the quantity of biological Hquide and / or injected reagent characterized in that the control means is a caHbred colorimetric strip.
2. Module selon la revendication 2 caractérisé en ce qu'il comprend une écheUe graduée le long de la bandelette pour une détermination visueUe du volume.2. Module according to claim 2 characterized in that it comprises a graduated drop along the strip for a visual determination of the volume.
3. Module de réaction pour l'analyse biologique comprenant au moins un puit de réaction pour l'injection de Hquide biologique et/ou de réactif permettant une réaction biologique déterminée et comprenant au moins un moyen de contrôle de la quantité de Hquide biologique et/ou de réactif injecté caractérisée en ce que le moyen de contrôle est une pastille colorimetrique. 3. Reaction module for biological analysis comprising at least one reaction well for the injection of biological Hquide and / or of reagent allowing a determined biological reaction and comprising at least one means of controlling the quantity of biological Hquide and / or of injected reagent characterized in that the control means is a colorimetric tablet.
PCT/FR2004/050181 2003-05-07 2004-05-06 Reaction module for biological analysis WO2004099525A2 (en)

Priority Applications (2)

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EP04742862A EP1620724A2 (en) 2003-05-07 2004-05-06 Reaction module for biological analysis
US10/553,440 US20070172886A1 (en) 2003-05-07 2004-05-06 Reaction module for biological analysis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0305544A FR2854695B1 (en) 2003-05-07 2003-05-07 REACTION MODULE FOR BIOLOGICAL ANALYSIS
FRFR0305544 2003-05-07

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WO2004099525A2 true WO2004099525A2 (en) 2004-11-18
WO2004099525A3 WO2004099525A3 (en) 2005-01-20

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US20020045195A1 (en) * 2000-10-13 2002-04-18 Hubscher Thomas T. Method for the visual detection of specific antibodies in human serum by the use of lateral flow assays

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EP1620724A2 (en) 2006-02-01
WO2004099525A3 (en) 2005-01-20
FR2854695B1 (en) 2006-01-21
FR2854695A1 (en) 2004-11-12

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