EP1091808A1 - Device for determining an analyte in a liquid sample - Google Patents

Device for determining an analyte in a liquid sample

Info

Publication number
EP1091808A1
EP1091808A1 EP99925064A EP99925064A EP1091808A1 EP 1091808 A1 EP1091808 A1 EP 1091808A1 EP 99925064 A EP99925064 A EP 99925064A EP 99925064 A EP99925064 A EP 99925064A EP 1091808 A1 EP1091808 A1 EP 1091808A1
Authority
EP
European Patent Office
Prior art keywords
capillary
diffusion means
zone
capillary diffusion
reagent
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.)
Granted
Application number
EP99925064A
Other languages
German (de)
French (fr)
Other versions
EP1091808B1 (en
Inventor
Milovan Stankov
Raphael Donati
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.)
VEDA LAB
Original Assignee
VEDA LAB
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Filing date
Publication date
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Application filed by VEDA LAB filed Critical VEDA LAB
Publication of EP1091808A1 publication Critical patent/EP1091808A1/en
Application granted granted Critical
Publication of EP1091808B1 publication Critical patent/EP1091808B1/en
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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5023Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0825Test strips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406Moving fluids with specific forces or mechanical means specific forces capillary forces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0633Valves, specific forms thereof with moving parts
    • B01L2400/065Valves, specific forms thereof with moving parts sliding valves
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/806Fertility tests

Definitions

  • the present invention relates to a device for determining an analyte present in a liquid sample.
  • analyte means any entity, chemical, biochemical, or biological, which one wants to determine, that is to say identify or detect, and / or quantify, and / or measure.
  • the present invention will be introduced, defined and described with reference to the determination of a biological entity, in particular a hormone, for example the hormone hcG making it possible to detect the state of pregnancy d 'a woman.
  • a biological entity in particular a hormone, for example the hormone hcG making it possible to detect the state of pregnancy d 'a woman.
  • liquid sample any sample in which the analyte sought is in solution or suspension, as it is directly applied or treated by the determination device which will be discussed below.
  • This liquid sample may itself have been obtained from a sample or other sample containing the analyte, for example a body fluid, by physical, and / or chemical, and / or biological treatment. This means in particular that the dissolution or dispersion medium belonging to the liquid sample is not necessarily aqueous.
  • a device for determining an analyte comprises: a) a gripping support, in the form of a housing, comprising at one end an opening for the passage of the second capillary diffusion means which will be discussed below, projecting outside the housing , and having an area for collecting a liquid sample; this box comprises, opposite the sensing member, a registered window with at least the downstream zone of the first capillary diffusion means which will be discussed below; b) said first capillary diffusion means, in a direction and a reference direction, integral and fixed in the gripping support, comprising a downstream area accessible to external observation, thanks to the aforementioned window recorded with said downstream area; c) a set of predetermined reagents for the detection and / or quantification of the analyte, comprising: a first reagent comprising a marker,
  • the user removes the cap, then puts the liquid sample, for example a stream of urine, in direct contact with the collection zone of the second capillary diffusion means.
  • Liquid sample migrates first, in the reference direction, towards the upstream zone of the first capillary diffusion means, in which, on the one hand it entrains the first reagent, and on the other hand the analyte binds to the latter, to form a conjugate.
  • the abovementioned conjugate arrives by capillary entrainment in the downstream zone, in which the second reagent captures, and therefore immobilizes and concentrates, directly or indirectly, the first reagent, and therefore the conjugate.
  • the existence and / or the amount captured of the conjugate can be read, and / or measured, directly or indirectly, for example with the naked eye in the case of a particulate marker, or by any means appropriate detection and / or measurement.
  • document OA-97 26 083 describes a device for determining an analyte in a liquid sample, comprising: a) a gripping support, in the form of an elongated and flat case, open at its two ends, comprising on one face and at a first end a window; this housing serves as a slide for the liquid sample collection member which will be discussed below.
  • this movable member consists of an elongated housing, obtained by definitive assembly of two complementary parts or shells, and incorporates, in continuity of capillary flow, on the one hand a first capillary diffusion means, entirely included in the housing, comprising a zone downstream accessible to external observation, and secondly a second capillary diffusion means, partly included in the housing, and comprising an end zone for collecting the liquid sample, protruding outside the housing; the casing also comprises, opposite a part allowing its manipulation, a window registered with the downstream zone of the first capillary diffusion means; the movable member is movable relative to the gripping support, from a starting position in which the zone for collecting the liquid sample from the movable member is capable of being brought into contact with the latter, and in which the window of the housing is masked by the gripping support, outside the gripping support, in a definitive retracted position, in which the
  • the previously exposed device requires a removable means of protection of the collection area of the second capillary diffusion means, in the starting position of the movable member, in which the collection area protrudes outside the grip support.
  • additional means provided, on one side on the movable member or housing, for example notches, and on the other side on the gripping support, for example tongues engaging in abutment in the aforementioned notches , the retracted position is final, as said above.
  • the means of protection of the collection area is removed, to obtain the device ready for use, with its protruding collection area, - after collection of the liquid sample, the movable member is brought into the retracted position, -
  • the result of the reaction on the first capillary diffusion means is observable through the two registered windows of the movable member and the gripping support respectively.
  • the two devices described above have in common, on the one hand, the arrangement of the two capillary diffusion means, on a single element, namely the gripping support in the first case, and the movable member in the second case. , and on the other hand a structural continuity of capillary flow, that is to say permanent, from the liquid sample from the second capillary diffusion means to the first capillary diffusion means.
  • a removable protection means must be provided for the collection area of the second capillary diffusion means in its starting position, that is to say protruding for the collection of the liquid sample.
  • the subject of the present invention is a device as defined above making it possible to remove the additional means of removable protection of the zone for collecting the liquid sample, while isolating the latter from the outside of the device, as long as the latter is not used, that is to say implemented or armed for the taking of a liquid sample, then the reading of the result concerning the analyte.
  • the device comprises a member for collecting the liquid sample, of which the second capillary diffusion means is integral, excluding the first capillary diffusion means .
  • This pick-up member is mounted so as to be movable relative to the gripping support, for example in translation, between two extreme positions, namely: - one projecting with respect to the gripping support, in which on the one hand the area of collection of the liquid sample, belonging to the second capillary diffusion means, is capable of being brought into contact with the latter, outside the gripping support, and on the other hand an opposite transfer zone from the second capillary diffusion means to the collection zone is not in continuity of capillary flow, and therefore isolated with respect to the upstream zone of the first capillary diffusion means.
  • the transfer zone of the second capillary diffusion means is, in a removable or temporary manner, in continuity of capillary flow, with the upstream zone of the first capillary diffusion means, and on the other hand the collection zone of the second capillary diffusion means is included in the gripping support.
  • the device according to the invention is characterized by the dissociation of the two capillary diffusion means, and by the possibility of temporarily isolating these two means from screw of the capillary flow of the liquid sample.
  • the device according to the invention is characterized, in addition to the set of predetermined reagents chosen for the detection and / or quantification of the analyte, by the fact that the first capillary diffusion means remains on the side of the gripping support, and that consequently the collection member is mainly assigned to the collection of the liquid sample.
  • the two capillary diffusion means makes it possible to separate and sequence the sample itself, and the reaction or reactions required for the detection and / or quantification of the analyte, namely carrying out said sampling before the reaction (s).
  • the displacement of the second capillary diffusion means, away from and at a distance from the first capillary diffusion means makes it possible, for a given length or size of the device, to have a greater length of collection of the liquid sample, in the projecting or projecting position of said device.
  • a device according to the invention can be used with any set of predetermined reagents, depending on the analyte sought in the liquid sample, on the one hand, and the operating protocol used for the determination on the other hand.
  • reagent any chemical, biochemical, or biological entity capable of binding with the analyte and / or another reagent.
  • link is meant any strong bond, for example covalent, or weak, for example of the antigen / antibody or avidin / streptavidin type.
  • the reagents considered according to the invention are biological entities, of the ligand or anti-ligand type, and this with respect to the analyte or another reagent, of the biological type.
  • reagents such as antibodies, antigens, haptens, avidin / streptavidin, but also peptides, proteins, and polynucleotides are classified.
  • the first and second reagents are respectively two specific, identical or different monoclonal antibodies, directed against the analyte.
  • marker is meant any physical, chemical, biochemical or biological entity allowing directly or indirectly the determination of the first reagent, in particular when it is linked, directly or indirectly, to the analyte.
  • a marker known per se, can be for example an enzyme, or also metallic particles, for example gold particles, obtained for example from colloidal gold.
  • the first reagent is deposited on the second capillary diffusion means, in particular downstream of the collection zone of the capture member, or else the first reagent is deposited on the first capillary diffusion means, particularly downstream of the upstream area of said first means, but upstream of the downstream area accessible to external observation.
  • the first and second reagents are then predetermined to bind respectively and specifically with the analyte, for example on two epitopic sites, identical or different from the analyte, when it consists of a biological molecule;
  • the first reagent or the second reagent is predetermined 1 identical or similarly to the analyte, to bind with the other reagent, in competition with the analyte.
  • an analyte constituted by a biological entity comprising two ligands, capable of binding respectively with the first reagent and a third reagent the latter is deposited in the free state, on a porous support, in l the second means of capillary diffusion or the first means capillary diffusion, at a location functionally upstream of the downstream zone of the first diffusion means.
  • the second reagent is predetermined for the capture of the third reagent.
  • another predetermined reagent to bind directly or indirectly with the first reagent is fixed in an adjacent area but downstream of the downstream area of the first means of diffusion, this adjacent area also being accessible to external observation.
  • the first reagent comprises a particulate marker, for example gold particles, visible and / or measurable directly, when it is concentrated in the downstream region of the first diffusion means.
  • a particulate marker for example gold particles, visible and / or measurable directly, when it is concentrated in the downstream region of the first diffusion means.
  • FIG. 2 shows the device shown in Figure 1, in longitudinal and vertical section, in the retracted position of the capture member;
  • - Figure 3 shows a perspective view, in the projecting position of the sensing member, a device according to a second embodiment of one invention;
  • Figure 4 shows an exploded perspective view of the device shown in Figure 3, in the retracted position of the pickup member;
  • a device according to the invention comprises:
  • a gripping support 1 having the shape of a housing, comprising, at a distal end an opening for the passage of the capture member 4 described below towards the projecting position, and opposite this end a window ld registered with at least one downstream zone 2a of the first capillary diffusion means 2, described below;
  • the first of the two capillary diffusion means having the form of a multi-layer strip, integral with the gripping support 1, and comprising the downstream zone 2a accessible to external observation; this first means is more particularly shown in exploded view in Figure 2, and will be described below in detail;
  • a set of predetermined reagents for the detection and / or quantification of the analyte comprising at least:
  • a first reagent 31 comprising a visible and / or measurable marker, this first reagent being disposed in the free state on the first diffusion means 2, in particular downstream of the upstream zone 2b, which will be discussed below ;
  • FIG. 1) relative to said gripping support, in which the collection zone 41a is capable of being brought into contact with the liquid sample, outside of the gripping support, and in which the transfer zone (41b) is not in capillary flow continuity with, and therefore isolated from the upstream zone (2b) of the first capillary diffusion means (2), and the other retracted (cf. FIG. 2), in which the collection zone 41a is included in said gripping support, and in which the transfer zone (41b) of the second capillary diffusion means (41) is removably, that is to say temporary, in continuity of capillary flow with the upstream zone (2b) of the first capillary diffusion means (2); which explains why the capture member 4 and the gripping support 1 are elongated in the direction of translation.
  • the upstream zone 2b of the first capillary diffusion means 2 is arranged to come, removably or temporarily, in continuity of capillary flow with the transfer zone 41b of the second capillary diffusion means 41, in the retracted position of the in order to be isolated with respect to the same capillary flow, with respect to the same transfer zone 41b, in the projecting position of the capture member 4.
  • the first reagent 31 is deposited on the free state on the first diffusion means 2, as described above, in a zone 2a downstream of the upstream zone 2b; but of course, the first reagent can be deposited directly in the upstream zone 2b of the first capillary diffusion means 2, or even directly on the second capillary diffusion means 41.
  • the gripping support 1 comprises a longitudinal slide 5, the shape of which is adapted to the path of movement of said member 4, and the latter comprises a member 6 of manual control crossing this slide.
  • the stroke of the member 6 in the slide 5 determines the two extreme positions of the capture member 4, and as shown in Figure 2, has a length greater than the length of overlap of the transfer zone 41b of the second means 41 of capillary diffusion, and of the upstream zone (2b) of the first capillary diffusion means, in the retracted position of the device. As shown more particularly in FIG.
  • the first capillary diffusion means 2 is obtained by assembling different sections or pieces, themselves fixed on a strip 28 of transparent plastic material, and in permanent continuity of capillary flow once assembled each other.
  • the first capillary diffusion means 2 comprises: - a first section 21 of relatively large porosity, for example in cellulose, with a pore size of between 2 ⁇ m and 50 ⁇ m, arranged to come into capillary flow continuity with the transfer zone 41b of the second capillary diffusion means 41; it is this section which constitutes the upstream zone 2b of the first diffusion means 2;
  • a section 24 of relatively low porosity for example made of nitrocellulose, with a porosity of between 1 ⁇ m and 30 ⁇ m, comprising, and the downstream zone 2a in which the second reagent 32 is fixed, and the adjacent zone in which is fixed the other reagent 33, these two zones being accessible to external observation through the registered window ld of the housing 1;
  • the capture member 4 comprises a carriage 42 for supporting the second capillary diffusion means 41, included in the housing 1 or gripping support.
  • the latter and the carriage 42 comprise means for guiding the displacement of said carriage, more particularly visible in FIG. 6, consisting of two slides 45 and 46 belonging to the housing 1, one upper and the other lower, and aligned, and in two corresponding ribs 43 and 44 belonging to the carriage 42, sliding in the slides 45 and 46 respectively.
  • the second diffusion means 41 has the form of a relatively rigid rod, and the carriage 42 comprises a rear stop 42a relative to the direction of movement of said carriage, and a member 42b for holding the rod 41 in position, having the form of 'a ring.
  • the housing 1 also incorporates a means 47 for actuating the carriage 42, with manual control 48.
  • the actuation means 47 comprises a semi-rigid strip 49, shaped as a pin, of which a branch 49a has on its face outside a gripping member 48, the other branch of which has one end linked to the carriage 42.
  • the housing 1 comprises a path 50 for guiding and pulling the strip, also in the form of a pin, and on the other hand a window lf adapted to the passage of the gripping member 48, the length of which is adapted to the travel of displacement of the capture member 4.
  • this stroke has a much greater length to the overlap length of the transfer zone 41b of the second capillary diffusion means 41, and of the upstream zone 2b of the first capillary diffusion means 2, in the retracted position of the device. Consequently, by pushing the gripping member 48 towards the proximal end of the housing 1, as shown in FIG. 3, the strip 49 circulates in the guide path 50 and pushes the carriage 42 towards the projecting position of the member 2. In the opposite direction, the carriage 42 is moved to the retracted position of the capture member 4.
  • the first capillary diffusion means 2 is clamped and held inside the housing between ribs 1a arranged parallel to the direction 60 of the capillary flow.
  • the collecting member 4 is in the retracted position (cf. FIGS. 2 and 4 ), so that the box 1 is a closed entity, with the exception of the window ld; in the case of Figure 1, it is a flap 61, integral with the proximal end of the capture member 4, which closes the opening; and in the case of FIGS. 4 and 5, it is the end of the semi-rigid strip 49, opposite the carriage 42, which closes the opening on (cf. FIG. 5);
  • the user brings the capture member 4 in the projecting position, in which a flow or liquid sample containing the analyte is brought into contact with the collection zone 41a;

Abstract

The invention concerns a device for determining an analyte in a liquid sample, comprising: a) a gripping support (1); b) first capillary diffusing means (2) integral with the gripping support (1) comprising a downstream zone (2a) accessible to external observation; c) a set of predetermined reagents for detecting and/or quantifying the analyte; d) a member for collecting (4) the liquid sample mounted on the support (1). The invention is characterised in that the member for collecting (4) the liquid sample is mounted mobile or fixed on the support; second capillary diffusion means (41) extends from a zone collecting (41a) said sample, to a zone transferring (41b) the latter; and an upstream zone (2b) of said first capillary diffusion means (2) is arranged to be urged temporarily to constitute continuous capillary flow with the second diffusion means (41) transferring zone (41b), when the collecting member (4) is in the retracted position.

Description

DISPOSITIF DE DETERMINATION D'UN ANALYTE DANS UN ECHANTILLON LIQUIDE DEVICE FOR DETERMINING AN ANALYTE IN A LIQUID SAMPLE
La présente invention concerne un dispositif de détermination d'un analyte présent dans un échantillon liquide.The present invention relates to a device for determining an analyte present in a liquid sample.
Par "analyte", on entend toute entité, chimique, biochimique, ou biologique, que l'on veut déterminer, c'est-à-dire identifier ou détecter, et/ou quantifier, et/ou mesurer.By "analyte" means any entity, chemical, biochemical, or biological, which one wants to determine, that is to say identify or detect, and / or quantify, and / or measure.
A titre préférentiel, et de manière non exclusive, la présente invention sera introduite, définie, et décrite par référence à la détermination d'une entité biologique, notamment une hormone, par exemple l'hormone hcG permettant de détecter l'état de grossesse d'une femme.Preferably, and not exclusively, the present invention will be introduced, defined and described with reference to the determination of a biological entity, in particular a hormone, for example the hormone hcG making it possible to detect the state of pregnancy d 'a woman.
Par "échantillon liquide", on entend tout échantillon dans lequel l' analyte recherché est en solution ou suspension, tel qu'il est directement appliqué ou traité par le dispositif de détermination dont il sera question ci-après. Cet échantillon liquide peut lui-même avoir été obtenu à partir d'un prélèvement ou autre échantillon contenant 1 'analyte, par exemple un fluide corporel, par traitement physique, et/ou chimique, et/ou biologique. Ceci signifie en particulier que le milieu de dissolution ou dispersion appartenant à l'échantillon liquide n'est pas nécessairement aqueux.By "liquid sample" is meant any sample in which the analyte sought is in solution or suspension, as it is directly applied or treated by the determination device which will be discussed below. This liquid sample may itself have been obtained from a sample or other sample containing the analyte, for example a body fluid, by physical, and / or chemical, and / or biological treatment. This means in particular that the dissolution or dispersion medium belonging to the liquid sample is not necessarily aqueous.
Conformément aux Figures 8 et 9 du document EP-A- 0291 194, on a décrit un dispositif de détermination d'un analyte, en particulier pour la détermination de l'hormone hcG, répondant à la définition générale suivante. Un tel dispositif comprend : a) un support de préhension, ayant la forme d'un boîtier, comprenant à une extrémité une ouverture pour le passage du deuxième moyen de diffusion capillaire dont il sera question ci-après, saillant à l'extérieur du boîtier, et ayant une zone de collection d'un échantillon liquide ; ce boîtier comporte, à l'opposé de l'organe de captation, une fenêtre registrée avec au moins la zone aval du premier moyen de diffusion capillaire dont il sera question ci-après ; b) ledit premier moyen de diffusion capillaire, dans une direction et un sens de référence, solidaire et fixé dans le support de préhension, comprenant une zone aval accessible à une observation externe, grâce à la fenêtre précitée registrée avec ladite zone aval ; c) un ensemble de réactifs prédéterminés pour la détection et/ou quantification de l' analyte, comprenant : un premier réactif comprenant un marqueur, visible et/ou mesurable, ce premier réactif étant disposé à l'état libre, dans une zone amont du premier moyen de diffusion capillaire ; et un second réactif fixé, c'est-à-dire immobilisé, dans la zone aval du premier moyen de diffusion capillaire, pour la capture directe ou indirecte du premier réactif ; d) ledit deuxième moyen de diffusion capillaire, ayant la forme d'un bâtonnet rigide, monté et solidaire du support de préhension, de manière à établir en permanence dans le boîtier une continuité d'écoulement capillaire, à partir de la zone de collection du deuxième moyen de diffusion capillaire, vers la zone amont du premier moyen de diffusion capillaire, puis de cette dernière vers la zone aval du premier moyen de diffusion capillaire, e) et un capuchon amovible, de protection de la partie saillante du deuxième moyen de diffusion capillaire, et plus précisément de sa zone de collection.In accordance with FIGS. 8 and 9 of document EP-A-0291 194, a device for determining an analyte has been described, in particular for the determination of the hormone hcG, corresponding to the following general definition. Such a device comprises: a) a gripping support, in the form of a housing, comprising at one end an opening for the passage of the second capillary diffusion means which will be discussed below, projecting outside the housing , and having an area for collecting a liquid sample; this box comprises, opposite the sensing member, a registered window with at least the downstream zone of the first capillary diffusion means which will be discussed below; b) said first capillary diffusion means, in a direction and a reference direction, integral and fixed in the gripping support, comprising a downstream area accessible to external observation, thanks to the aforementioned window recorded with said downstream area; c) a set of predetermined reagents for the detection and / or quantification of the analyte, comprising: a first reagent comprising a marker, visible and / or measurable, this first reagent being disposed in the free state, in an upstream region of the first means of capillary diffusion; and a second fixed reagent, that is to say immobilized, in the downstream region of the first capillary diffusion means, for the direct or indirect capture of the first reagent; d) said second capillary diffusion means, having the shape of a rigid rod, mounted and integral with the gripping support, so as to permanently establish in the housing a capillary flow continuity, from the collection zone of the second capillary diffusion means, towards the upstream zone of the first capillary diffusion means, then from the latter towards the downstream zone of the first capillary diffusion means, e) and a removable cap, for protecting the projecting part of the second diffusion means capillary, and more precisely its collection area.
Le fonctionnement du dispositif précédemment décrit se déduit de la description précédente.The operation of the device described above is deduced from the previous description.
L'utilisateur retire le capuchon, puis met l'échantillon liquide, par exemple un flot d'urine, en contact direct avec la zone de collection du deuxième moyen de diffusion capillaire. L'échantillon liquide migre d'abord, dans la direction de référence, vers la zone amont du premier moyen de diffusion capillaire, dans laquelle, d'une part il entraîne le premier réactif, et d'autre part l' analyte se lie à ce dernier, pour former un conjugué. Puis, toujours par migration capillaire de l'échantillon liquide, le conjugué précité parvient par entraînement capillaire dans la zone aval, dans laquelle le second réactif capture, et donc immobilise et concentre, directement ou indirectement, le premier réactif, et partant le conjugué. Par la fenêtre du boîtier, l'existence et/ou la quantité capturée du conjugué peut être lue, et/ou mesurée, directement ou indirectement, par exemple à l'oeil nu dans le cas d'un marqueur particulaire, ou par tous moyens de détection et/ou mesure appropriés.The user removes the cap, then puts the liquid sample, for example a stream of urine, in direct contact with the collection zone of the second capillary diffusion means. Liquid sample migrates first, in the reference direction, towards the upstream zone of the first capillary diffusion means, in which, on the one hand it entrains the first reagent, and on the other hand the analyte binds to the latter, to form a conjugate. Then, still by capillary migration of the liquid sample, the abovementioned conjugate arrives by capillary entrainment in the downstream zone, in which the second reagent captures, and therefore immobilizes and concentrates, directly or indirectly, the first reagent, and therefore the conjugate. Through the window of the housing, the existence and / or the amount captured of the conjugate can be read, and / or measured, directly or indirectly, for example with the naked eye in the case of a particulate marker, or by any means appropriate detection and / or measurement.
Sans que l'ensemble de réactifs mis en oeuvre ou les réactifs soient précisés, par référence à ses figures 1 à 6, le document O-A-97 26 083 décrit un dispositif de détermination d'un analyte dans un échantillon liquide, comprenant : a) un support de préhension, ayant la forme d'un étui allongé et plat, ouvert à ses deux extrémités, comportant sur une face et à une première extrémité une fenêtre ; ce boîtier sert de coulisse à l'organe de captation de l'échantillon liquide dont il sera question ci-après. b) un organe mobile à la manière d'un coulisseau, monté de manière déplaçable par rapport au support de préhension ; cet organe mobile consiste en un boîtier allongé, obtenu par assemblage définitif de deux parties ou coques complémentaires, et incorpore, en continuité d'écoulement capillaire, d'une part un premier moyen de diffusion capillaire, entièrement compris dans le boîtier, comprenant une zone aval accessible à une observation externe, et d'autre part un deuxième moyen de diffusion capillaire, compris pour partie dans le boîtier, et comprenant une zone extrême de collection de l'échantillon liquide, saillant à l'extérieur du boîtier ; le boîtier comporte par ailleurs, à l'opposé d'une partie permettant sa manipulation, une fenêtre registrée avec la zone aval du premier moyen de diffusion capillaire ; l'organe mobile est déplaçable par rapport au support de préhension, à partir d'une position de départ dans laquelle la zone de collection de l'échantillon liquide de l'organe mobile est susceptible d'être mise au contact de ce dernier, et dans laquelle la fenêtre du boîtier est masquée par le support de préhension, en dehors du support de préhension, à une position rétractée définitive, dans laquelle, la zone de collection précitée est comprise et incorporée entièrement dans le support de préhension, et dans laquelle la fenêtre du boîtier est registrée avec celle du support de préhension, ce qui rend la zone aval du premier moyen de diffusion capillaire, accessible à une observation.Without the set of reagents used or the reagents being specified, with reference to its figures 1 to 6, document OA-97 26 083 describes a device for determining an analyte in a liquid sample, comprising: a) a gripping support, in the form of an elongated and flat case, open at its two ends, comprising on one face and at a first end a window; this housing serves as a slide for the liquid sample collection member which will be discussed below. b) a movable member in the manner of a slide, mounted so as to be movable relative to the gripping support; this movable member consists of an elongated housing, obtained by definitive assembly of two complementary parts or shells, and incorporates, in continuity of capillary flow, on the one hand a first capillary diffusion means, entirely included in the housing, comprising a zone downstream accessible to external observation, and secondly a second capillary diffusion means, partly included in the housing, and comprising an end zone for collecting the liquid sample, protruding outside the housing; the casing also comprises, opposite a part allowing its manipulation, a window registered with the downstream zone of the first capillary diffusion means; the movable member is movable relative to the gripping support, from a starting position in which the zone for collecting the liquid sample from the movable member is capable of being brought into contact with the latter, and in which the window of the housing is masked by the gripping support, outside the gripping support, in a definitive retracted position, in which the aforementioned collection zone is understood and entirely incorporated in the gripping support, and in which the window of the housing is registered with that of the gripping support, which makes the downstream area of the first capillary diffusion means, accessible to observation.
Quoique cela ne soit pas expressément décrit dans le document OA-97 26083, le dispositif précédemment exposé requiert un moyen amovible de protection de la zone de collection du deuxième moyen de diffusion capillaire, dans la position de départ de l'organe mobile, dans laquelle la zone de collection saille à l'extérieur du support de préhension. En effet, compte tenu de moyens complémentaires prévus, d'un côté sur l'organe mobile ou boîtier, par exemple encoches, et de l'autre côté sur le support de préhension, par exemple languettes s ' engageant en butée dans les encoches précitées, la position rétractée est définitive, comme dit plus haut. Le fonctionnement du dispositif précédemment décrit se déduit de sa structure :Although this is not expressly described in document OA-97 26083, the previously exposed device requires a removable means of protection of the collection area of the second capillary diffusion means, in the starting position of the movable member, in which the collection area protrudes outside the grip support. Indeed, taking into account additional means provided, on one side on the movable member or housing, for example notches, and on the other side on the gripping support, for example tongues engaging in abutment in the aforementioned notches , the retracted position is final, as said above. The operation of the device described above is deduced from its structure:
- le moyen de protection de la zone de collection est retiré, pour obtenir le dispositif prêt à l'emploi, avec sa zone de collection saillante, - après collection de l'échantillon liquide, l'organe mobile est amené dans la position rétractée, - le résultat de la réaction sur le premier moyen de diffusion capillaire, est observable au travers des deux fenêtres registrées de l'organe mobile et du support de préhension respectivement. Les deux dispositifs précédemment décrits, ont en commun, d'une part la disposition des deux moyens de diffusion capillaire, sur un seul et même élément, à savoir le support de préhension dans le premier cas, et l'organe mobile dans le second cas, et d'autre part une continuité structurelle d'écoulement capillaire, c'est à dire permanente, de l'échantillon liquide du deuxième moyen de diffusion capillaire vers le premier moyen de diffusion capillaire.- the means of protection of the collection area is removed, to obtain the device ready for use, with its protruding collection area, - after collection of the liquid sample, the movable member is brought into the retracted position, - The result of the reaction on the first capillary diffusion means, is observable through the two registered windows of the movable member and the gripping support respectively. The two devices described above have in common, on the one hand, the arrangement of the two capillary diffusion means, on a single element, namely the gripping support in the first case, and the movable member in the second case. , and on the other hand a structural continuity of capillary flow, that is to say permanent, from the liquid sample from the second capillary diffusion means to the first capillary diffusion means.
Dans les deux cas, il faut prévoir un moyen de protection amovible de la zone de collection du deuxième moyen de diffusion capillaire dans sa position de départ, c'est à dire saillante pour le prélèvement de l'échantillon liquide.In both cases, a removable protection means must be provided for the collection area of the second capillary diffusion means in its starting position, that is to say protruding for the collection of the liquid sample.
La présente invention a pour objet un dispositif tel que précédemment défini permettant de supprimer le moyen supplémentaire de protection amovible de la zone de collection de l'échantillon liquide, tout en isolant cette dernière par rapport à l'extérieur du dispositif, tant que ce dernier n'est pas utilisé, c'est à dire mis en oeuvre ou armé pour le prélèvement d'un échantillon liquide, puis la lecture du résultat concernant l' analyte.The subject of the present invention is a device as defined above making it possible to remove the additional means of removable protection of the zone for collecting the liquid sample, while isolating the latter from the outside of the device, as long as the latter is not used, that is to say implemented or armed for the taking of a liquid sample, then the reading of the result concerning the analyte.
Conformément à 1 ' invention et par rapport au document EP-A-0291 194, le dispositif comprend un organe de captation de l'échantillon liquide, duquel est solidaire le deuxième moyen de diffusion capillaire, à l'exclusion du premier moyen de diffusion capillaire. Cet organe de captation est monté de manière déplaçable par rapport au support de préhension, par exemple en translation, entre deux positions extrêmes, à savoir : - l'une saillante par rapport au support de préhension, dans laquelle d'une part la zone de collection de l'échantillon liquide, appartenant au deuxième moyen de diffusion capillaire, est susceptible d'être mise en contact de ce dernier, en dehors du support de préhension, et d'autre part une zone de transfert du deuxième moyen de diffusion capillaire, opposée à la zone de collection n'est pas en continuité d'écoulement capillaire, et donc isolée vis à vis de la zone amont du premier moyen de diffusion capillaire.In accordance with the invention and with respect to document EP-A-0291 194, the device comprises a member for collecting the liquid sample, of which the second capillary diffusion means is integral, excluding the first capillary diffusion means . This pick-up member is mounted so as to be movable relative to the gripping support, for example in translation, between two extreme positions, namely: - one projecting with respect to the gripping support, in which on the one hand the area of collection of the liquid sample, belonging to the second capillary diffusion means, is capable of being brought into contact with the latter, outside the gripping support, and on the other hand an opposite transfer zone from the second capillary diffusion means to the collection zone is not in continuity of capillary flow, and therefore isolated with respect to the upstream zone of the first capillary diffusion means.
- et l'autre rétractée par rapport au support de préhension, dans laquelle, d'une part la zone de transfert du deuxième moyen de diffusion capillaire est, de manière amovible ou temporaire, en continuité d'écoulement capillaire, avec la zone amont du premier moyen de diffusion capillaire, et d'autre part la zone de collection du deuxième moyen de diffusion capillaire est comprise dans le support de préhension.- and the other retracted with respect to the gripping support, in which, on the one hand, the transfer zone of the second capillary diffusion means is, in a removable or temporary manner, in continuity of capillary flow, with the upstream zone of the first capillary diffusion means, and on the other hand the collection zone of the second capillary diffusion means is included in the gripping support.
Par conséquent, par rapport aux documents EP-A- 0291 194 et O-A-97 26083, le dispositif selon l'invention se caractérise par la dissociation des deux moyens de diffusion capillaire, et par la possibilité d'isoler temporairement ces deux moyens vis à vis de 1 ' écoulement capillaire de l'échantillon liquide.Consequently, compared to documents EP-A-0291 194 and OA-97 26083, the device according to the invention is characterized by the dissociation of the two capillary diffusion means, and by the possibility of temporarily isolating these two means from screw of the capillary flow of the liquid sample.
Et de plus, par rapport au document WO-A-97 26083, le dispositif selon l'invention se caractérise, outre l'ensemble de réactifs prédéterminés choisis pour la détection et/ou quantification de 1 'analyte, par le fait que le premier moyen de diffusion capillaire demeure du côté du support de préhension, et qu'en conséquence l'organe de captation est affecté pour l'essentiel au prélèvement de l'échantillon liquide.And in addition, compared to document WO-A-97 26083, the device according to the invention is characterized, in addition to the set of predetermined reagents chosen for the detection and / or quantification of the analyte, by the fact that the first capillary diffusion means remains on the side of the gripping support, and that consequently the collection member is mainly assigned to the collection of the liquid sample.
La solution selon 1 ' invention apporte en outre des avantages déterminants .The solution according to the invention also provides decisive advantages.
La possibilité d'isoler, vis à vis de l'écoulement liquide les deux moyens de diffusion capillaire, permet de séparer et séquencer le prélèvement proprement dit, et la ou les réactions requises pour la détection et/ou quantification de l' analyte, à savoir d'effectuer ledit prélèvement avant la ou les réactions.The possibility of isolating, with respect to the liquid flow, the two capillary diffusion means, makes it possible to separate and sequence the sample itself, and the reaction or reactions required for the detection and / or quantification of the analyte, namely carrying out said sampling before the reaction (s).
Ceci est important pour éviter le démarrage de la ou des réactions requises avant d'avoir permis un prélèvement d'une quantité maximum ou optimum de l'échantillon liquide à analyser.This is important to avoid starting the required reaction (s) before allowing a maximum or optimum amount of the liquid sample to be analyzed to be taken.
Le déplacement du deuxième moyen de diffusion capillaire, à l'écart et à distance du premier moyen de diffusion capillaire, permet pour une longueur ou un encombrement donné du dispositif, de disposer d'une plus grande longueur de collection de l'échantillon liquide, dans la position saillante ou en saillie dudit dispositif.The displacement of the second capillary diffusion means, away from and at a distance from the first capillary diffusion means, makes it possible, for a given length or size of the device, to have a greater length of collection of the liquid sample, in the projecting or projecting position of said device.
Un dispositif selon l'invention peut être utilisé avec tout ensemble de réactifs prédéterminés, en fonction de l' analyte recherché dans l'échantillon liquide, d'une part, et du protocole opératoire retenu pour la détermination d'autre part.A device according to the invention can be used with any set of predetermined reagents, depending on the analyte sought in the liquid sample, on the one hand, and the operating protocol used for the determination on the other hand.
Par réactif, on entend toute entité, chimique, biochimique, ou biologique susceptible de se lier avec 1' analyte et/ou un autre réactif.By reagent is meant any chemical, biochemical, or biological entity capable of binding with the analyte and / or another reagent.
Par "lier", ou "liaison", on entend toute liaison forte, par exemple covalente, ou faible, par exemple du type antigène/anticorps ou avidine/streptavidine. Préférentiellement, mais de manière non exclusive, les réactifs considérés selon l'invention sont des entités biologiques, du type ligand ou anti-ligand, et ceci par rapport à l' analyte ou un autre réactif, de type biologique. Dans cette catégorie, sont rangés les réactifs tels que anticorps, antigènes, haptènes, avidine/streptavidine, mais aussi les peptides, protéines, et polynucléotides.By "link", or "bond", is meant any strong bond, for example covalent, or weak, for example of the antigen / antibody or avidin / streptavidin type. Preferably, but not exclusively, the reagents considered according to the invention are biological entities, of the ligand or anti-ligand type, and this with respect to the analyte or another reagent, of the biological type. In this category, reagents such as antibodies, antigens, haptens, avidin / streptavidin, but also peptides, proteins, and polynucleotides are classified.
A titre d'exemple, les premier et second réactifs sont respectivement deux anticorps monoclonaux spécifiques, identiques ou différents, dirigés contre 1 • analyte . Par "marqueur", on entend toute entité physique, chimique, biochimique, ou biologique, permettant directement ou indirectement la détermination du premier réactif, en particulier lorsqu'il est lié, directement ou indirectement, à l' analyte. Un tel marqueur, connu en soi, peut être par exemple une enzyme, ou encore des particules métalliques, par exemple des particules d'or, obtenues par exemple à partir d'or colloïdal.By way of example, the first and second reagents are respectively two specific, identical or different monoclonal antibodies, directed against the analyte. By "marker" is meant any physical, chemical, biochemical or biological entity allowing directly or indirectly the determination of the first reagent, in particular when it is linked, directly or indirectly, to the analyte. Such a marker, known per se, can be for example an enzyme, or also metallic particles, for example gold particles, obtained for example from colloidal gold.
Selon l'invention, le premier réactif est déposé sur le second moyen de diffusion capillaire, en particulier en aval de la zone de collection de l'organe de captation, ou encore le premier réactif est déposé sur le premier moyen de diffusion capillaire, en particulier en aval de la zone amont dudit premier moyen, mais en amont de la zone aval accessible à une observation externe.According to the invention, the first reagent is deposited on the second capillary diffusion means, in particular downstream of the collection zone of the capture member, or else the first reagent is deposited on the first capillary diffusion means, particularly downstream of the upstream area of said first means, but upstream of the downstream area accessible to external observation.
De manière connue en soi, l'ensemble des réactifs prédéterminés en fonction de l' analyte et du protocole de détermination, peut être mis en oeuvre selon différents formats :In a manner known per se, all of the reagents predetermined as a function of the analyte and of the determination protocol, can be implemented according to different formats:
- selon un format sandwich, les premier et second réactifs sont alors prédéterminés pour se lier respectivement et spécifiquement avec l' analyte, par exemple sur deux sites épitopiques, identiques ou différents de l' analyte, lorsqu'il consiste en une molécule biologique ;- in a sandwich format, the first and second reagents are then predetermined to bind respectively and specifically with the analyte, for example on two epitopic sites, identical or different from the analyte, when it consists of a biological molecule;
- selon un format compétition, le premier réactif ou le second réactif est prédéterminé à 1 ' identique ou de manière similaire à l' analyte, pour se lier avec l'autre réactif, en compétition avec l' analyte.- According to a competition format, the first reagent or the second reagent is predetermined 1 identical or similarly to the analyte, to bind with the other reagent, in competition with the analyte.
Et encore, dans le cas d'un analyte constitué par une entité biologique comprenant deux ligands, susceptibles de se lier respectivement avec le premier réactif et un troisième réactif, ce dernier est déposé à l'état libre, sur un support poreux, en l'occurrence le second moyen de diffusion capillaire ou le premier moyen de diffusion capillaire, à un endroit fonctionnellement en amont de la zone aval du premier moyen de diffusion. Et le deuxième réactif est prédéterminé pour la capture du troisième réactif. Pour contrôler que la ou les réactions nécessaires à la détermination de l' analyte ont bien eu lieu, un autre réactif prédéterminé pour se lier directement ou indirectement avec le premier réactif, est fixé dans une zone adjacente mais en aval de la zone aval du premier moyen de diffusion, cette zone adjacente étant également accessible à une observation externe.And again, in the case of an analyte constituted by a biological entity comprising two ligands, capable of binding respectively with the first reagent and a third reagent, the latter is deposited in the free state, on a porous support, in l the second means of capillary diffusion or the first means capillary diffusion, at a location functionally upstream of the downstream zone of the first diffusion means. And the second reagent is predetermined for the capture of the third reagent. To check that the reaction (s) necessary for the determination of the analyte have indeed taken place, another predetermined reagent to bind directly or indirectly with the first reagent, is fixed in an adjacent area but downstream of the downstream area of the first means of diffusion, this adjacent area also being accessible to external observation.
A titre d'exemple, le premier réactif comprend un marqueur particulaire, par exemple des particules d'or, visibles et/ou mesurables directement, lorsqu'il est concentré dans la zone aval du premier moyen de diffusion. La présente invention est maintenant décrite par référence au dessin annexé, dans lequel : la figure 1 représente en perspective, avec arrachement partiel, dans la position saillante de l'organe de captation, un dispositif selon un premier mode d'exécution de l'invention ;For example, the first reagent comprises a particulate marker, for example gold particles, visible and / or measurable directly, when it is concentrated in the downstream region of the first diffusion means. The present invention is now described with reference to the accompanying drawing, in which: FIG. 1 shows in perspective, with partial cutaway, in the projecting position of the capture member, a device according to a first embodiment of the invention ;
- la figure 2 représente le dispositif représenté à la figure 1, en coupe longitudinale et verticale, dans la position rétractée de l'organe de captation ; - la figure 3 représente une vue en perspective, dans la position saillante de l'organe de captation, un dispositif selon un deuxième mode d'exécution de 1 ' invention ; la figure 4 représente une vue éclatée en perspective du dispositif représenté à la figure 3, dans la position rétractée de l'organe de captation ;- Figure 2 shows the device shown in Figure 1, in longitudinal and vertical section, in the retracted position of the capture member; - Figure 3 shows a perspective view, in the projecting position of the sensing member, a device according to a second embodiment of one invention; Figure 4 shows an exploded perspective view of the device shown in Figure 3, in the retracted position of the pickup member;
- la figure 5 représente une vue en coupe longitudinale et horizontale du dispositif représenté à la figure 4, dans la position rétractée de l'organe de captation ; la figure 6 représente une vue en coupe transversale au niveau de l'organe 42b de maintien en position du bâtonnet 41, du dispositif représenté aux figures 4 et 5 ; - la figure 7 représente une vue éclatée du premier moyen de diffusion capillaire, identique pour les deux modes d'exécution de l'invention, et mis en oeuvre dans la même position, comme montré par les figures 1 et 2 en particulier. Conformément aux figures 1 et 2, un dispositif selon 1 ' invention comprend :- Figure 5 shows a longitudinal and horizontal sectional view of the device shown in Figure 4, in the retracted position of the capture member; 6 shows a cross-sectional view at the level of the member 42b for holding in position the rod 41, of the device shown in Figures 4 and 5; - Figure 7 shows an exploded view of the first capillary diffusion means, identical for the two embodiments of the invention, and implemented in the same position, as shown in Figures 1 and 2 in particular. In accordance with FIGS. 1 and 2, a device according to the invention comprises:
- un support de préhension 1 ayant la forme d'un boîtier, comprenant, à une extrémité distale une ouverture le pour le passage de l'organe de captation 4 décrit ci-après vers la position saillante, et à l'opposé de cette extrémité une fenêtre ld registrée avec au moins une zone aval 2a du premier moyen 2 de diffusion capillaire, décrit ci-après ;- A gripping support 1 having the shape of a housing, comprising, at a distal end an opening for the passage of the capture member 4 described below towards the projecting position, and opposite this end a window ld registered with at least one downstream zone 2a of the first capillary diffusion means 2, described below;
- le premier des deux moyens de diffusion capillaire, ayant la forme d'une bandelette multi-couche, solidaire du support de préhension 1, et comprenant la zone aval 2a accessible à une observation externe ; ce premier moyen est plus particulièrement représenté en vue éclatée à la figure 2, et sera décrit ci-après en détail ; - un ensemble de réactifs prédéterminés pour la détection et/ou quantification de l' analyte, comprenant au moins :- The first of the two capillary diffusion means, having the form of a multi-layer strip, integral with the gripping support 1, and comprising the downstream zone 2a accessible to external observation; this first means is more particularly shown in exploded view in Figure 2, and will be described below in detail; - a set of predetermined reagents for the detection and / or quantification of the analyte, comprising at least:
* un premier réactif 31, comprenant un marqueur visible et/ou mesurable, ce premier réactif étant disposé à l'état libre sur le premier moyen de diffusion 2, en particulier en aval de la zone amont 2b, dont il sera question ci-après ;* a first reagent 31, comprising a visible and / or measurable marker, this first reagent being disposed in the free state on the first diffusion means 2, in particular downstream of the upstream zone 2b, which will be discussed below ;
* et un second réactif 32 fixé dans la zone aval 2a du premier moyen de diffusion 2, pour la capture directe ou indirecte du premier réactif ; * un autre réactif 33, prédéterminé pour se lier avec le premier réactif 31, fixé dans une zone 2c, adjacente, mais en aval de la zone aval 2a précitée du premier moyen 2 de diffusion, cette zone adjacente étant également accessible à une observation externe, par exemple avec la même fenêtre ld du boîtier 1 ; un organe de captation 4 de l'échantillon liquide, monté sur le support 1 de manière amovible, ou inversement ; cet organe 4 comporte un deuxième moyen 41 de diffusion capillaire, dans la même direction et le même sens 60 que ceux déterminés par le premier moyen 2 de diffusion capillaire ; ce deuxième moyen 41 s'étend de la zone de collection 41a de l'échantillon, à une zone de transfert 41b de ce dernier ; cet organe de captation 4 est mobile et déplaçable en translation, par rapport au support de préhension 1, entre deux positions extrêmes, à savoir l'une saillante (cf. figure 1) par rapport audit support de préhension, dans laquelle la zone de collection 41a est susceptible d'être mise en contact avec l'échantillon liquide, en dehors du support de préhension, et dans laquelle la zone de transfert (41b) n'est pas en continuité d'écoulement capillaire avec, et donc isolée par rapport à la zone amont (2b) du premier moyen (2) de diffusion capillaire, et l'autre rétractée (cf. figure 2), dans laquelle la zone de collection 41a est comprise dans ledit support de préhension, et dans laquelle la zone de transfert (41b) du deuxième moyen (41) de diffusion capillaire est, de manière amovible, c'est à dire temporaire, en continuité d'écoulement capillaire avec la zone amont (2b) du premier moyen (2) de diffusion capillaire ; ce qui explique que l'organe de captation 4 et le support de préhension 1 sont allongés selon la direction de translation.* and a second reagent 32 fixed in the downstream zone 2a of the first diffusion means 2, for the direct or indirect capture of the first reagent; * another reagent 33, predetermined for binding with the first reagent 31, fixed in an adjacent area 2c, but downstream of the aforementioned downstream area 2a of the first means 2 of diffusion, this adjacent area also being accessible to external observation , for example with the same window ld of the housing 1; a member 4 for collecting the liquid sample, mounted on the support 1 in a removable manner, or vice versa; this member 4 comprises a second means 41 for capillary diffusion, in the same direction and the same direction 60 as those determined by the first means 2 for capillary diffusion; this second means 41 extends from the collection zone 41a of the sample, to a transfer zone 41b of the latter; this capture member 4 is movable and displaceable in translation, relative to the gripping support 1, between two extreme positions, namely the projecting one (cf. FIG. 1) relative to said gripping support, in which the collection zone 41a is capable of being brought into contact with the liquid sample, outside of the gripping support, and in which the transfer zone (41b) is not in capillary flow continuity with, and therefore isolated from the upstream zone (2b) of the first capillary diffusion means (2), and the other retracted (cf. FIG. 2), in which the collection zone 41a is included in said gripping support, and in which the transfer zone (41b) of the second capillary diffusion means (41) is removably, that is to say temporary, in continuity of capillary flow with the upstream zone (2b) of the first capillary diffusion means (2); which explains why the capture member 4 and the gripping support 1 are elongated in the direction of translation.
En correspondance avec la structure générale décrite précédemment : - la zone amont 2b du premier moyen 2 de diffusion capillaire est agencée pour venir, de manière amovible ou temporaire, en continuité d'écoulement capillaire avec la zone de transfert 41b du second moyen 41 de diffusion capillaire, dans la position rétractée de l'organe de captation 4, et pour être isolée vis à vis du même écoulement capillaire, par rapport à la même zone de transfert 41b, dans la position saillante de l'organe de captation 4. - et le premier réactif 31 est déposé à l'état libre sur le premier moyen de diffusion 2, comme décrit précédemment, dans une zone 2a en aval de la zone amont 2b ; mais bien entendu, le premier réactif peut être déposé directement dans la zone amont 2b du premier moyen 2 de diffusion capillaire, ou encore directement sur le deuxième moyen 41 de diffusion capillaire.In correspondence with the general structure described above: the upstream zone 2b of the first capillary diffusion means 2 is arranged to come, removably or temporarily, in continuity of capillary flow with the transfer zone 41b of the second capillary diffusion means 41, in the retracted position of the in order to be isolated with respect to the same capillary flow, with respect to the same transfer zone 41b, in the projecting position of the capture member 4. - and the first reagent 31 is deposited on the free state on the first diffusion means 2, as described above, in a zone 2a downstream of the upstream zone 2b; but of course, the first reagent can be deposited directly in the upstream zone 2b of the first capillary diffusion means 2, or even directly on the second capillary diffusion means 41.
Pour actionner le déplacement de l'organe de captation 4, comme montré à la figure 2, le support de préhension 1 comporte une glissière longitudinale 5, dont la forme est adaptée à la trajectoire de déplacement dudit organe 4 , et ce dernier comporte un organe 6 de commande manuelle traversant cette glissière. La course de l'organe 6 dans la glissière 5 détermine le deux positions extrêmes de l'organe de captation 4, et comme montré à la figure 2, a une longueur supérieure à la longueur de recouvrement de la zone de transfert 41b du deuxième moyen 41 de diffusion capillaire, et de la zone amont (2b) du premier moyen de diffusion capillaire, dans la position rétractée du dispositif. Comme montré plus particulièrement par la figure 7, le premier moyen 2 de diffusion capillaire est obtenu par assemblage de différentes sections ou morceaux, eux-mêmes fixés sur une bande 28 en matière plastique transparente, et en continuité permanente d'écoulement capillaire une fois assemblés les uns aux autres. Conformément à la figure 7, et dans le sens et la direction 60 de l'écoulement capillaire, en plus de la bande 28 transparente, le premier moyen de diffusion capillaire 2 comporte : - une première section 21 de porosité relativement importante, par exemple en cellulose, avec une taille de pores comprise entre 2 μm et 50 μm, agencée pour venir en continuité d'écoulement capillaire avec la zone de transfert 41b du second moyen 41 de diffusion capillaire ; c'est cette section qui constitue la zone amont 2b du premier moyen 2 de diffusion ;To actuate the movement of the capture member 4, as shown in FIG. 2, the gripping support 1 comprises a longitudinal slide 5, the shape of which is adapted to the path of movement of said member 4, and the latter comprises a member 6 of manual control crossing this slide. The stroke of the member 6 in the slide 5 determines the two extreme positions of the capture member 4, and as shown in Figure 2, has a length greater than the length of overlap of the transfer zone 41b of the second means 41 of capillary diffusion, and of the upstream zone (2b) of the first capillary diffusion means, in the retracted position of the device. As shown more particularly in FIG. 7, the first capillary diffusion means 2 is obtained by assembling different sections or pieces, themselves fixed on a strip 28 of transparent plastic material, and in permanent continuity of capillary flow once assembled each other. In accordance with FIG. 7, and in the direction and direction 60 of the capillary flow, in addition to the transparent strip 28, the first capillary diffusion means 2 comprises: - a first section 21 of relatively large porosity, for example in cellulose, with a pore size of between 2 μm and 50 μm, arranged to come into capillary flow continuity with the transfer zone 41b of the second capillary diffusion means 41; it is this section which constitutes the upstream zone 2b of the first diffusion means 2;
- une section 22 constituée par exemple en fibre de verre, ayant une taille de pores comprise entre 2 μm et 500 μm, sur laquelle est déposé à l'état libre le premier réactif 31 ;- A section 22 made for example of glass fiber, having a pore size of between 2 μm and 500 μm, on which the first reagent 31 is deposited in the free state;
- une section 24 de porosité relativement faible, par exemple constituée en nitrocellulose, avec une porosité comprise entre 1 μm et 30 μm, comportant, et la zone aval 2a dans laquelle est fixé le second réactif 32, et la zone adjacente dans laquelle est fixé l'autre réactif 33, ces deux zones étant accessibles à une observation externe par la fenêtre registrée ld du boîtier 1 ; une section 27, constituée par exemple en cellulose, ayant une porosité comprise entre 2 μm et 50 μm, pour le recueil par absorption de l'ensemble des liquides ayant circulé sur le premier moyen 2 de diffusion capillaire, au-delà des zones aval 2a ; cette section de recueil est donc solidaire du support préhension 1, et disposée en aval et en continuité d'écoulement capillaire avec la zone aval 2a du premier moyen de diffusion capillaire 1.a section 24 of relatively low porosity, for example made of nitrocellulose, with a porosity of between 1 μm and 30 μm, comprising, and the downstream zone 2a in which the second reagent 32 is fixed, and the adjacent zone in which is fixed the other reagent 33, these two zones being accessible to external observation through the registered window ld of the housing 1; a section 27, made for example of cellulose, having a porosity of between 2 μm and 50 μm, for the collection by absorption of all the liquids having circulated on the first means 2 of capillary diffusion, beyond the downstream areas 2a ; this collection section is therefore integral with the gripping support 1, and disposed downstream and in continuity of capillary flow with the downstream zone 2a of the first capillary diffusion means 1.
Le dispositif conforme aux figures 3 à 5 a la même structure générale que celle définie précédemment. Les mêmes références numériques identifient des pièces ou composants ayant la même fonction que celle décrite par référence aux figures 1 et 2. Seules les différences suivantes seront décrites ci-après.The device according to Figures 3 to 5 has the same general structure as that defined above. The same reference numbers identify parts or components having the same function as that described by reference to Figures 1 and 2. Only the following differences will be described below.
L'organe de captation 4 comprend un chariot 42 de support du second moyen 41 de diffusion capillaire, compris dans le boîtier 1 ou support de préhension. Ce dernier et le chariot 42 comportent des moyens de guidage en déplacement dudit chariot, plus particulièrement visibles sur la figure 6, consistant en deux glissières 45 et 46 appartenant au boîtier 1, l'une supérieure et l'autre inférieure, et alignées, et en deux nervures correspondantes 43 et 44 appartenant au chariot 42, coulissant dans les glissières 45 et 46 respectivement.The capture member 4 comprises a carriage 42 for supporting the second capillary diffusion means 41, included in the housing 1 or gripping support. The latter and the carriage 42 comprise means for guiding the displacement of said carriage, more particularly visible in FIG. 6, consisting of two slides 45 and 46 belonging to the housing 1, one upper and the other lower, and aligned, and in two corresponding ribs 43 and 44 belonging to the carriage 42, sliding in the slides 45 and 46 respectively.
Le second moyen de diffusion 41 a la forme d'un bâtonnet relativement rigide, et le chariot 42 comporte une butée arrière 42a par rapport au sens de déplacement dudit chariot, et un organe 42b de maintien en position du bâtonnet 41, ayant la forme d'un anneau.The second diffusion means 41 has the form of a relatively rigid rod, and the carriage 42 comprises a rear stop 42a relative to the direction of movement of said carriage, and a member 42b for holding the rod 41 in position, having the form of 'a ring.
Le boîtier 1 intègre également un moyen 47 d' actionnement du chariot 42, avec une commande manuelle 48. Plus précisément, le moyen d ' actionnement 47 comprend une bande 49 semi-rigide, conformée en épingle, dont une branche 49a comporte sur sa face extérieure un organe 48 de préhension, et dont l'autre branche a une extrémité liée au chariot 42. En correspondance, le boîtier 1 comprend un chemin 50 de guidage et tirage de la bande, également conformé en épingle, et d'autre part une fenêtre lf adaptée au passage de 1 ' organe de préhension 48, dont la longueur est adaptée à la course de déplacement de l'organe de captation 4. Comme le montre bien le rapprochement des figures 4 et 5, cette course a une longueur bien supérieure à la longueur de recouvrement de la zone de transfert 41 b du deuxième moyen de diffusion capillaire 41, et de la zone amont 2b du premier moyen de diffusion capillaire 2, dans la position rétractée du dispositif. Par conséquent, en repoussant l'organe 48 de préhension vers l'extrémité proximale du boîtier l, comme montré à la figure 3, la bande 49 circule dans le chemin 50 de guidage et repousse le chariot 42 vers la position saillante de l'organe de captation 2. En sens inverse, le chariot 42 est déplacé vers la position rétractée de l'organe de captation 4.The housing 1 also incorporates a means 47 for actuating the carriage 42, with manual control 48. More specifically, the actuation means 47 comprises a semi-rigid strip 49, shaped as a pin, of which a branch 49a has on its face outside a gripping member 48, the other branch of which has one end linked to the carriage 42. In correspondence, the housing 1 comprises a path 50 for guiding and pulling the strip, also in the form of a pin, and on the other hand a window lf adapted to the passage of the gripping member 48, the length of which is adapted to the travel of displacement of the capture member 4. As the comparison of FIGS. 4 and 5 clearly shows, this stroke has a much greater length to the overlap length of the transfer zone 41b of the second capillary diffusion means 41, and of the upstream zone 2b of the first capillary diffusion means 2, in the retracted position of the device. Consequently, by pushing the gripping member 48 towards the proximal end of the housing 1, as shown in FIG. 3, the strip 49 circulates in the guide path 50 and pushes the carriage 42 towards the projecting position of the member 2. In the opposite direction, the carriage 42 is moved to the retracted position of the capture member 4.
Comme le montrent également les figures 4 et 5 , le premier moyen 2 de diffusion capillaire est serré et maintenu à 1 ' intérieur du boîtier entre des nervures le disposées parallèlement à la direction 60 du flux capillaire.As also shown in FIGS. 4 and 5, the first capillary diffusion means 2 is clamped and held inside the housing between ribs 1a arranged parallel to the direction 60 of the capillary flow.
Le fonctionnement d'un dispositif selon l'invention se déduit de la description précédente : - au départ, c'est-à-dire avant utilisation, l'organe 4 de captation est dans la position rétractée (cf. Fig.2 et 4), de telle sorte que le boîtier 1 est une entité fermée, à l'exception de la fenêtre ld ; dans le cas de la figure 1, c'est un volet 61, solidaire de l'extrémité proximale de l'organe de captation 4, qui ferme l'ouverture le ; et dans le cas des figures 4 et 5, c'est l'extrémité de la bande 49 semi-rigide, opposée au chariot 42, qui obture l'ouverture le (cf. figure 5) ;The operation of a device according to the invention is deduced from the preceding description: - at the start, that is to say before use, the collecting member 4 is in the retracted position (cf. FIGS. 2 and 4 ), so that the box 1 is a closed entity, with the exception of the window ld; in the case of Figure 1, it is a flap 61, integral with the proximal end of the capture member 4, which closes the opening; and in the case of FIGS. 4 and 5, it is the end of the semi-rigid strip 49, opposite the carriage 42, which closes the opening on (cf. FIG. 5);
- par l'organe de commande 6 ou 48, l'utilisateur amène l'organe de captation 4 dans la position saillante, dans laquelle un flux ou échantillon liquide contenant 1' analyte est mis en contact avec la zone de collection 41a ;- By the control member 6 or 48, the user brings the capture member 4 in the projecting position, in which a flow or liquid sample containing the analyte is brought into contact with the collection zone 41a;
- avec la même main, le même organe de captation est ramené dans la position rétractée, avec fermeture de l'ouverture le, comme décrit précédemment- with the same hand, the same sensing member is brought back to the retracted position, with closing of the opening on, as described above
- c'est uniquement dans cette dernière position, sans autre intervention de l'utilisateur, que l'échantillon liquide migre successivement du deuxième moyen de diffusion capillaire 41, vers le premier moyen de diffusion capillaire 42, et sur ce dernier de l'amont vers l'aval ; les réactions générées par les réactifs précédemment décrits s'effectuent ; le résultat est accessible à une observation externe par la fenêtre ld, par exemple à l'oeil nu ; - puis le dispositif de détermination, à usage unique, peut être jeté, dans la position rétractée des Figures 2 et 4.- It is only in this latter position, without any other intervention from the user, that the liquid sample migrates successively from the second capillary diffusion means 41, to the first capillary diffusion means 42, and on the latter from upstream. towards downstream; the reactions generated by the reagents previously described are carried out; the result is accessible to an external observation through the window ld, for example with the naked eye; - then the disposable determination device can be discarded in the retracted position of Figures 2 and 4.
Conformément à la figure 5, par rapport au sens de l'observation par la fenêtre ld, on observera que la zone de transfert 41b du deuxième moyen 41 de diffusion capillaire vient au-dessous de la zone amont 2b du premier moyen 2 de diffusion capillaire, dans la position rétractée de l'organe 4 de captation, et ce pour favoriser l'écoulement capillaire à la jonction entre les deux moyens 2 et 41 de diffusion capillaire, dans la position rétractée de l'organe de captation 4. In accordance with FIG. 5, with respect to the direction of observation through the window ld, it will be observed that the transfer zone 41b of the second capillary diffusion means 41 comes below the upstream zone 2b of the first capillary diffusion means 2 , in the retracted position of the capture member 4, and this to promote capillary flow at the junction between the two capillary diffusion means 2 and 41, in the retracted position of the capture member 4.

Claims

REVENDICATIONS
1) Dispositif de détermination d'un analyte dans un échantillon liquide, comprenant : a) un support de préhension (1) ; b) un premier moyen de diffusion (2) capillaire dans une direction de référence (60), solidaire du support de préhension (1) , comprenant une zone aval (2a) accessible à une observation externe ; c) un ensemble de réactifs prédéterminés pour la détection et/ou quantification de l' analyte, comprenant au moins :1) Device for determining an analyte in a liquid sample, comprising: a) a gripping support (1); b) a first capillary diffusion means (2) in a reference direction (60), integral with the gripping support (1), comprising a downstream zone (2a) accessible to external observation; c) a set of predetermined reagents for the detection and / or quantification of the analyte, comprising at least:
- un premier réactif (31) comprenant un marqueur, visible et/ou mesurable, ledit premier réactif étant disposé à l'état libre sur un support poreux, fonctionnellement en amont de la zone aval (2a) du premier moyen de diffusion ;- a first reagent (31) comprising a marker, visible and / or measurable, said first reagent being disposed in the free state on a porous support, functionally upstream of the downstream zone (2a) of the first diffusion means;
- et un second réactif (32) fixé dans la zone aval (2a) du premier moyen de diffusion capillaire, pour la capture directe ou indirecte du premier réactif ; d) un deuxième moyen (41) de diffusion capillaire, avec une zone de collection (41a) dudit échantillon, ledit premier réactif (31) étant déposé à l'état libre, ou sur le premier moyen de diffusion capillaire (2) , ou sur le second moyen (41) de diffusion capillaire. caractérisé en ce que :- And a second reagent (32) fixed in the downstream area (2a) of the first capillary diffusion means, for the direct or indirect capture of the first reagent; d) a second capillary diffusion means (41), with a collection zone (41a) of said sample, said first reagent (31) being deposited in the free state, or on the first capillary diffusion means (2), or on the second capillary diffusion means (41). characterized in that:
- le dispositif comprend un organe de captation (4) de l'échantillon liquide, duquel est solidaire le deuxième moyen de diffusion capillaire (41) , monté de manière déplaçable par rapport au support de préhension, entre deux positions extrêmes, à savoir :the device comprises a member for capturing (4) the liquid sample, of which the second capillary diffusion means (41) is integral, mounted so as to be displaceable relative to the gripping support, between two extreme positions, namely:
- l'une saillante (Fig. 1 et 3 ) par rapport audit support de préhension, dans laquelle, d'une part la zone de collection (41a) de l'échantillon liquide du deuxième moyen (41) de diffusion capillaire est susceptible d'être mise au contact de ce dernier, en dehors de préhension, et d'autre part une zone de transfert (41b) du deuxième moyen (41) de diffusion capillaire, opposée à ladite zone de collection (41a), n'est pas en continuité d'écoulement capillaire avec la zone amont (2b) du premier moyen (2) de diffusion capillaire.- one projecting (Fig. 1 and 3) relative to said gripping support, in which, on the one hand the collection area (41a) of the liquid sample from the second capillary diffusion means (41) is capable of '' be put in contact with the latter, outside of gripping, and on the other hand a transfer zone (41b) of the second capillary diffusion means (41), opposite to said collection zone (41a), is not in continuity of capillary flow with the upstream zone (2b) of the first means (2) of capillary diffusion.
- et l'autre retractée (Fig 2 et 5), dans laquelle d'une part, la zone de transfert (41b) du deuxième moyen (41) de diffusion capillaire est, de manière amovible, en continuité d'écoulement capillaire avec la zone amont (2b) du premier moyen (2) de diffusion capillaire, et d'autre part la zone de collection (41b) du deuxième moyen (41) de diffusion capillaire est comprise dans le support de préhension (1)- And the other retracted (Fig 2 and 5), in which on the one hand, the transfer zone (41b) of the second capillary diffusion means (41) is, in a removable manner, in continuity of capillary flow with the upstream zone (2b) of the first capillary diffusion means (2), and on the other hand the collection zone (41b) of the second capillary diffusion means (41) is included in the gripping support (1)
2) Dispositif selon la revendication 1, caractérisé en ce que le premier réactif (31) est déposé sur le second moyen de diffusion (41) , en particulier en aval de la zone de collection (41a) .2) Device according to claim 1, characterized in that the first reagent (31) is deposited on the second diffusion means (41), in particular downstream of the collection zone (41a).
3) Dispositif selon la revendication 1, caractérisé en ce que le premier réactif (31) est déposé sur le premier moyen de diffusion (2) , en particulier en aval de ladite zone amont (2b) .3) Device according to claim 1, characterized in that the first reagent (31) is deposited on the first diffusion means (2), in particular downstream of said upstream area (2b).
4) Dispositif selon la revendication 1, caractérisé en ce que le support de préhension (1) a la forme d'un boîtier comprenant, à une extrémité une ouverture (le) pour le passage de l'organe de captation (4) vers la position saillante, et à l'opposé de ladite extrémité une fenêtre registrée (ld) avec au moins la zone aval (2a) du premier moyen (2) de diffusion capillaire. 5) Dispositif selon la revendication 1, caractérisé en ce que le support de préhension (1) comporte une glissière (5) dont la forme est adaptée à la trajectoire de déplacement de l'organe de captation (4), et ledit organe de captation comporte un organe (6) de commande manuelle, traversant ladite glissière. 6) Dispositif selon la revendication 1, caractérisé en ce que l'organe de captation (4) est mobile et déplaçable en translation par rapport au support de préhension (1) , et ledit organe et ledit support étant allongés selon la direction de translation.4) Device according to claim 1, characterized in that the gripping support (1) has the form of a housing comprising, at one end an opening (le) for the passage of the capture member (4) to the projecting position, and opposite said end a registered window (ld) with at least the downstream zone (2a) of the first capillary diffusion means (2). 5) Device according to claim 1, characterized in that the gripping support (1) comprises a slide (5) whose shape is adapted to the path of movement of the capture member (4), and said capture member comprises a member (6) for manual control, passing through said slide. 6) Device according to claim 1, characterized in that the capture member (4) is movable and displaceable in translation relative to the gripping support (1), and said member and said support being elongated in the direction of translation.
7) Dispositif selon la revendication 1, caractérisé en ce que le premier moyen (2) de diffusion capillaire comporte deux sections distinctes, en continuité permanente d'écoulement capillaire, à savoir une première section (21) de porosité relativement importante, agencée pour venir, de manière amovible, en continuité d'écoulement capillaire avec la zone de transfert (41b) du second moyen (41) de diffusion capillaire, et une deuxième section (24) de porosité relativement faible, comportant ladite zone aval (2a) .7) Device according to claim 1, characterized in that the first means (2) of capillary diffusion comprises two distinct sections, in permanent continuity of capillary flow, namely a first section (21) of relatively large porosity, arranged to come , removably, in capillary flow continuity with the transfer zone (41b) of the second capillary diffusion means (41), and a second section (24) of relatively low porosity, comprising said downstream zone (2a).
8) Dispositif selon la revendication 4, caractérisé en ce l'organe de captation (4) comprend un chariot (42) de support du second moyen (41) de diffusion capillaire, le boîtier et le chariot comportent des moyens (43 à 46) de guidage en déplacement dudit chariot, et le boîtier intègre un moyen (47) d ' actionnement dudit chariot, avec commande manuelle (48) .8) Device according to claim 4, characterized in that the capture member (4) comprises a carriage (42) for supporting the second means (41) for capillary diffusion, the housing and the carriage comprise means (43 to 46) for guiding the movement of said carriage, and the housing includes a means (47) for actuating said carriage, with manual control (48).
9) Dispositif selon la revendication 8, caractérisé en ce que le second moyen de diffusion (41) a la forme d'un bâtonnet, et le chariot comporte une butée arrière (42a) par rapport au sens de déplacement, et un organe (42b) de maintien en position dudit bâtonnet.9) Device according to claim 8, characterized in that the second diffusion means (41) has the shape of a stick, and the carriage comprises a rear stop (42a) relative to the direction of movement, and a member (42b ) maintaining said rod in position.
10) Dispositif selon la revendication 8, caractérisé en ce que le moyen d ' actionnement (47) comprend une bande (49) semi-rigide, conformée en épingle, dont une branche (49a) comporte sur sa face extérieure un organe (48) de préhension, et dont l'autre branche (49b) a une extrémité liée au chariot (42) , et en ce que le boîtier (1) comprend, d'une part un chemin (50) de tirage de la bande, également conformé en épingle, et d'autre part une fenêtre (ld) adaptée au passage de l'organe (48) de préhension, dont la longueur est adaptée à la course de déplacement de l'organe de captation (4).10) Device according to claim 8, characterized in that the actuating means (47) comprises a strip (49) semi-rigid, shaped as a hairpin, of which a branch (49a) has on its outer face a member (48) gripping, and whose other branch (49b) has one end connected to the carriage (42), and in that the housing (1) comprises, on the one hand a path (50) for pulling the strip, also shaped hairpin, and on the other hand a window (ld) adapted to the passage of the member (48) gripping device, the length of which is adapted to the travel of movement of the pick-up member (4).
11) Dispositif selon la revendication 4, caractérisé en ce que le premier moyen (2) de diffusion capillaire est serré et maintenu à l'intérieur du boîtier, entre des nervures (le) s ' étendant parallèlement à la direction du flux capillaire. 11) Device according to claim 4, characterized in that the first means (2) of capillary diffusion is clamped and held inside the housing, between ribs (the) extending parallel to the direction of capillary flow.
EP99925064A 1998-06-30 1999-06-10 Device for determining an analyte in a liquid sample Expired - Lifetime EP1091808B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9808480 1998-06-30
FR9808480A FR2780317B1 (en) 1998-06-30 1998-06-30 DEVICE FOR DETERMINING AN ANALYTE IN A LIQUID SAMPLE
PCT/FR1999/001380 WO2000000288A1 (en) 1998-06-30 1999-06-10 Device for determining an analyte in a liquid sample

Publications (2)

Publication Number Publication Date
EP1091808A1 true EP1091808A1 (en) 2001-04-18
EP1091808B1 EP1091808B1 (en) 2003-07-09

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EP99925064A Expired - Lifetime EP1091808B1 (en) 1998-06-30 1999-06-10 Device for determining an analyte in a liquid sample

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US (1) US7459125B1 (en)
EP (1) EP1091808B1 (en)
JP (1) JP4505138B2 (en)
CN (1) CN1185050C (en)
AT (1) ATE244602T1 (en)
AU (1) AU4148399A (en)
CA (1) CA2335458A1 (en)
DE (1) DE69909484T2 (en)
ES (1) ES2204132T3 (en)
FR (1) FR2780317B1 (en)
HU (1) HUP0102735A3 (en)
IL (1) IL140165A (en)
PL (1) PL194051B1 (en)
RS (1) RS49670B (en)
RU (1) RU2205693C2 (en)
WO (1) WO2000000288A1 (en)

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WO2013140089A1 (en) 2012-03-19 2013-09-26 Milovan Stankov Device for determining at least one analyte capable of being contained in a liquid sample

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FR2890173B1 (en) 2005-08-23 2008-02-22 Vedalab Sa DEVICE FOR DETERMINING AN ANALYTE IN A LIQUID SAMPLE BY A SANDWICH TEST AND A COMPETITION TEST
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JP5175395B2 (en) * 2008-07-17 2013-04-03 ザ プロクター アンド ギャンブル カンパニー Method of using a flow cell apparatus to visualize additive deposition on a substrate
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US9140700B2 (en) 2012-03-19 2015-09-22 Milovan Stankov Device for determining at least one analyte capable of being contained in a liquid sample

Also Published As

Publication number Publication date
JP2002519650A (en) 2002-07-02
HUP0102735A2 (en) 2001-11-28
WO2000000288A1 (en) 2000-01-06
IL140165A (en) 2004-05-12
DE69909484D1 (en) 2003-08-14
US7459125B1 (en) 2008-12-02
PL194051B1 (en) 2007-04-30
RU2205693C2 (en) 2003-06-10
JP4505138B2 (en) 2010-07-21
FR2780317A1 (en) 1999-12-31
YU83300A (en) 2003-04-30
AU4148399A (en) 2000-01-17
DE69909484T2 (en) 2004-04-15
HUP0102735A3 (en) 2005-11-28
EP1091808B1 (en) 2003-07-09
PL345160A1 (en) 2001-12-03
ATE244602T1 (en) 2003-07-15
ES2204132T3 (en) 2004-04-16
CN1308562A (en) 2001-08-15
CA2335458A1 (en) 2000-01-06
IL140165A0 (en) 2002-02-10
RS49670B (en) 2007-09-21
FR2780317B1 (en) 2000-08-11
CN1185050C (en) 2005-01-19

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