EP1091808B1 - Device for determining an analyte in a liquid sample - Google Patents

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 characterized 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

The present invention relates to a device for determination of an analyte present in a sample liquid.

"Analyte" means any entity, chemical, biochemical, or biological, that we want to determine, that is to say, identify or detect, and / or quantify, and / or measure.

As a preferential, and non-exclusive, the present invention will be introduced, defined, and described by reference to the determination of a biological entity, especially a hormone, for example the hormone hcG to detect the pregnancy status of a woman.

"Liquid sample" means any sample in which the analyte sought is in solution or suspension, as directly applied or treated by the device of determination of which it will be question below. This liquid sample can itself have been obtained from a sample or other sample containing the analyte, for example a fluid body, by physical treatment, and / or chemical, and / or organic. This means in particular that the middle of Dissolution or dispersion belonging to the sample liquid is not necessarily aqueous.

According to Figures 8 and 9 of EP-A-0291 194, there has been described a device for determining a analyte, especially for the determination of the hormone hcG, as defined below.

a) un support de préhension, ayant la forme d'un boítier, 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 boítier, et ayant une zone de collection d'un échantillon liquide ; ce boítier 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 batonnet rigide, monté et solidaire du support de préhension, de manière à établir en permanence dans le boítier 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.

Such a device comprises:

a) a gripping support, having 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 a zone collection of a liquid sample; this housing comprises, opposite the capturing member, a window registered 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 zone accessible to an external observation, by means of the aforementioned window registered with said downstream zone;

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, said first reagent being disposed in the free state, in an upstream zone of the first capillary diffusion means;
• and a second reagent attached, i.e. immobilized, in the downstream zone of the first capillary diffusion means, for the direct or indirect capture of the first reagent;

d) said second capillary diffusion means, in the form of a rigid batten, mounted and integral with the gripping support, so as to establish permanently in the housing capillary flow continuity, from the collection area of the second capillary diffusion means, towards the upstream zone of the first capillary diffusion means, and then of the latter towards the downstream zone of the first capillary diffusion means,

e) and a removable cap, for protecting the projecting portion of the second capillary diffusion means, and more precisely of its collection zone.

The operation of the device previously described is deduced from the previous description.

The user removes the cap, then puts the liquid sample, for example a stream of urine, in direct contact with the collection area of the second means of capillary diffusion. The liquid sample migrates first, in the reference direction, to the zone upstream of the first capillary diffusion means, in which, on the one hand, causes 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 aforementioned conjugate arrives via capillary drive in the downstream zone, in which the second reagent captures, and therefore immobilizes and concentrate, directly or indirectly, the first reagent, and hence the conjugate. Through the window of housing, the existence and / or the captured quantity of the conjugate can be read, and / or measured, directly or indirectly, for example to the naked eye in the case of a particulate marker, or by any means of detection and / or appropriate measure.

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 boítier 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 boítier 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 boítier, comprenant une zone aval accessible à une observation externe, et d'autre part un deuxième moyen de diffusion capillaire, compris pour partie dans le boítier, et comprenant une zone extrême de collection de l'échantillon liquide, saillant à l'extérieur du boítier ; le boítier 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 boítier est masquée par le support de préhension, en dehors du support de préhension, à une position rétractée, dans laquelle, la zone de collection précitée est comprise et incorporée entièrement dans le support de préhension, et dans laquelle la fenêtre du boítier 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 FIGS. 1 to 6, the document WO-A-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 both ends, having on one face and at one end a window; this housing serves as a slide to the liquid sample collection member which will be discussed below.

b) a movable member in the manner of a slider, movably mounted relative to the gripping support; this movable member consists of an elongated housing, obtained by definitively assembling two complementary parts or shells, and incorporates, in continuity of capillary flow, firstly a first capillary diffusion means, entirely comprised in the housing, comprising a zone downstream accessible to an external observation, and secondly a second capillary diffusion means, partly comprised in the housing, and comprising an end zone for collecting the liquid sample, projecting outside the housing; the housing further comprises, opposite to 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 collection zone of the liquid sample of the movable member is likely to be brought into contact with the latter, and in which the window of the housing is masked by the gripping support, outside the gripping support, to a retracted position, in which, the aforesaid collection zone is included and incorporated entirely in the gripping support, and in which the window housing is registered with that of the gripping support, which makes the downstream zone of the first capillary diffusion means, accessible to an observation.

• 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.

The operation of the device described above is deduced from its structure:

• 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 previously described, have in on the one hand, the provision of the two means of capillary diffusion, on one and the same element, know the grip support in the first case, and the movable organ in the second case, and on the other hand a structural continuity of capillary flow, this is at say permanent, the liquid sample of the second means of capillary diffusion to the first means of capillary diffusion.

The present invention relates to a device for removing any additional means of removable protection of the collection area of the liquid sample, while isolating the latter from the outside of the device, as the latter is not used, ie used or armed for taking a liquid sample, and then reading the result concerning the analyte.
Compared to WO 97/26083, a device according to the present invention is distinguished in that the transfer zone of the second capillary diffusion means is removably arranged with respect to an upstream zone of the first capillary diffusion means, so that, in the projecting position of the capturing member, said transfer zone is not in continuity of capillary flow with said upstream zone, and in the retracted position of said capturing member, said transfer zone and said zone upstream are in continuity of capillary flow, while a set of reagents predetermined for the detection and / or quantification of the analyte comprises at least, on the one hand a first reagent comprising a marker, visible and / or measurable, deposited in the free state, or on the first capillary diffusion means, upstream of said downstream zone, or on the second capillary diffusion means, and secondly a second reagent fixed in the zone e downstream of the first capillary diffusion means, for the direct or indirect capture of the first reagent.

Therefore, compared to EP-A-0291 194 and WO-A-97 26083, the device according to the invention is distinguished by the dissociation of the two means of capillary diffusion, and by the possibility of isolating temporarily these two means with respect to the flow capillary of the liquid sample.

And moreover, compared to the document WO-A-97 26083, the device according to the invention is distinguished, besides the set of predetermined reagents chosen for the detection and / or quantification of the analyte, by the fact that the first means of capillary diffusion remains side of the gripping support, and as a result the capture organ is essentially assigned to the sampling of the liquid sample.

The invention brings the following advantages.

The possibility of isolating, with respect to the flow liquid both capillary diffusion means, allows to separate and sequence the actual sample, and the or the reactions required for detection and / or quantification of the analyte, namely to perform said sampling before the reaction (s).

This is important to avoid starting the or required reactions before allowing a collection of a maximum or optimum amount of the liquid sample to be analyzed.

The displacement of the second diffusion means capillary, away from and away from the first means of capillary diffusion, allows for a length or a given size of the device, to have a more large collection length of the liquid sample, in the projecting or protruding position of said device.

A device according to the invention can be used with any set of predetermined reagents, depending of the desired analyte in the liquid sample, of a and the operating protocol adopted for the determination on the other hand.

Reagent means any entity, chemical, biochemical, or biological likely to bind with the analyte and / or another reagent.

By "bind", or "link", is meant any link strong, for example covalent, or weak, for example type antigen / antibody or avidin / streptavidin.

Preferentially, but not exclusively, the reagents considered according to the invention are entities ligand or anti-ligand type, and this by relative to the analyte or other reagent, of type organic. In this category are stored the reagents such as antibodies, antigens, haptens, avidin / streptavidin, but also peptides, proteins, and polynucleotides.

By way of example, the first and second reagents are respectively two monoclonal antibodies specific, identical or different, directed against the analyte.

"Marker" means any physical entity, chemical, biochemical, or biological, allowing directly or indirectly the determination of the first reagent, particularly when bound, directly or indirectly indirectly, to the analyte. Such a marker, known per se, can be for example an enzyme, or particles metal, for example gold particles, obtained by example from colloidal gold.

According to the invention, the first reagent is deposited on the second means of capillary diffusion, in particular downstream of the organ collection area of capture, or the first reagent is deposited on the first means of capillary diffusion, in particular downstream of the upstream zone of the said first means, but upstream of the downstream zone accessible to an observation external.

• 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 ;
• selon un format compétition, le premier réactif ou le second réactif est prédéterminé à l'identique ou de manière similaire à l'analyte, pour se lier avec l'autre réactif, en compétition avec l'analyte.

In a manner known per se, the set of reagents predetermined according to the analyte and the determination protocol can be implemented according to various formats:

• 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;
• in a competition format, the first reagent or the second reagent is predetermined identically or in a manner similar to the analyte, to bind with the other reagent, in competition with the analyte.

And again, in the case of an analyte constituted by a biological entity comprising two ligands, likely to link with the first reagent and a third reagent, the latter is deposited at the free state, on a porous support, in this case the second means of capillary diffusion or the first means capillary scattering at a functionally upstream of the downstream zone of the first diffusion means. And the second reagent is predetermined for capturing the third reagent.

To control that the necessary reaction (s) the determination of the analyte took place, another predetermined reagent for binding directly or indirectly with the first reagent, is fixed in a adjacent area but downstream of the downstream zone of the first means of diffusion, this adjacent zone being also accessible to an external observation.

By way of example, the first reagent comprises a particulate marker, for example gold particles, visible and / or directly measurable, when concentrated in the downstream zone of the first diffusion means.

• 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 ;
• 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 l'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 ;
• 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.

The present invention is now described with reference to the accompanying drawing, in which:

• Figure 1 shows in perspective, partially broken away, in the projecting position of the capture member, a device according to a first embodiment of the invention;
• FIG. 2 represents the device represented in FIG. 1, in longitudinal and vertical section, in the retracted position of the capturing member;
• FIG. 3 represents a perspective view, in the projecting position of the capture member, of a device according to a second embodiment of the invention;
• FIG. 4 represents an exploded perspective view of the device represented in FIG. 3, in the retracted position of the capturing member;
• Figure 5 shows a longitudinal and horizontal sectional view of the device shown in Figure 4, in the retracted position of the capture member;
• Figure 6 shows a cross-sectional view at the member 42b for holding the rod 41 in position, the device shown in Figures 4 and 5;
• FIG. 7 represents 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 by FIGS. 1 and 2 in particular.

• un support de préhension 1 ayant la forme d'un boítier, comprenant, à une extrémité distale une ouverture 1c 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 1d registrée avec au moins une zone aval 2a du premier moyen 2 de diffusion capillaire, décrit ci-après ;
• 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 :
  • 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 ;
  • 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 1d du boítier 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.

According to FIGS. 1 and 2, a device according to the invention comprises:

• a gripping support 1 having the shape of a housing, comprising, at a distal end, an opening 1c for the passage of the capturing member 4 described hereinafter towards the projecting position, and opposite this end a window 1d registered with at least one downstream zone 2a of the first capillary diffusion means 2, described hereinafter;
• the first of the two capillary diffusion means, in the form of a multi-layer strip, secured to the gripping support 1, and comprising the downstream zone 2a accessible to an external observation; this first means is more particularly shown in exploded view in FIG. 2, and will be described hereinafter 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 placed in the free state on the first diffusion means 2, in particular downstream of the upstream zone 2b, which will be discussed below;
  • 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 to bind with the first reagent 31, fixed in an area 2c, adjacent but downstream of the aforementioned downstream zone 2a of the first diffusion means 2, this adjacent zone being also accessible to an external observation, for example with the same window 1d of the housing 1;
• a capture member 4 of the liquid sample, mounted on the support 1 removably, or vice versa; this member 4 comprises a second means 41 of capillary diffusion, in the same direction and the same direction 60 as those determined by the first means 2 of capillary diffusion; this second means 41 extends from the collection zone 41a of the sample, to a transfer zone 41b of the latter; this capturing member 4 is movable and displaceable in translation, with respect to the gripping support 1, between two extreme positions, namely one protruding (see FIG. 1) with respect to said gripping support, in which the collection zone 41a is capable of being brought into contact with the liquid sample, outside the gripping support, and in which the transfer zone (41b) is not in continuity of capillary flow with, and therefore isolated from the upstream zone (2b) of the first capillary diffusion means (2) and the other retracted region (see FIG. 2), in which the collection zone 41a is included in the said gripping support, and in which the transfer zone (41b) of the second capillary diffusion means (41) is removably, ie temporarily, in continuity of capillary flow with the upstream zone (2b) of the first capillary diffusion means (2); this explains that the capturing member 4 and the gripping support 1 are elongate in the direction of translation.

• 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 capillary flow continuity with the transfer zone 41b of the second capillary diffusion means 41, in the retracted position of the organ 4, and to be isolated with respect to the same capillary flow, with respect to the same transfer zone 41b, in the protruding position of the capture member 4.
• and the first reagent 31 is deposited in the free state on the first diffusion means 2, as previously described, in an area 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 directly on the second capillary diffusion means 41.

To actuate the displacement of the organ capture 4, as shown in Figure 2, the support of 1 comprises a longitudinal slide 5, of which the shape is adapted to the movement path of said member 4, and the latter comprises a control member 6 manual crossing this slide. The race of the organ 6 in the slide 5 determines the two extreme positions of the capture member 4, and as shown in FIG. has a length greater than the recovery length of the transfer zone 41b of the second diffusion means 41 capillary, and the upstream zone (2b) of the first means of capillary diffusion, in the retracted position of device.

As shown more particularly by the FIG. 7, the first means 2 of capillary diffusion is obtained by assembling different sections or pieces, themselves fixed on a band 28 made of plastic transparent, and in permanent continuity of flow capillary when assembled to each other.

• 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 ;
• 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 ;
• 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 1d du boítier 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.

According to FIG. 7, and in the direction and direction 60 of the capillary flow, in addition to the transparent band 28, the first capillary diffusion means 2 comprises:

• a first section 21 of relatively large porosity, for example cellulose, with a pore size of between 2 microns and 50 microns, 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 22 constituted for example by fiberglass, having a pore size of between 2 μm and 500 μm, on which the first reagent 31 is deposited in the free state;
• a section 24 of relatively low porosity, for example consisting of nitrocellulose, with a porosity of between 1 .mu.m and 30 .mu.m, comprising, and the downstream zone 2a in which the second reagent 32 is fixed, and the adjacent zone in which is fixed other reagent 33, these two zones being accessible to external observation by the registered window 1d of the housing 1;
• a section 27, constituted for example by 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 capillary diffusion means 2, beyond the downstream zones 2a ; this collection section is thus secured to 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.

The device according to Figures 3 to 5 has the same general structure as defined above. The same numerical references identify parts or components having the same function as that described by reference to Figures 1 and 2. Only the differences following will be described below.

The capture member 4 comprises a carriage 42 of supporting the second means 41 of capillary diffusion, included in the housing 1 or gripping support. This last and the carriage 42 comprise guide means moving said carriage, more particularly visible in Figure 6, consisting of two slides 45 and 46 belonging to the housing 1, the superior and the other bottom, and aligned, and in two ribs 43 and 44 corresponding to the carriage 42, sliding in the slides 45 and 46 respectively.

The second diffusion means 41 is in the form of a relatively rigid rod, and the carriage 42 comprises a rear stop 42a with respect to the direction of travel said carriage, and a member 42b for holding the rod 41, having the shape of a ring.

The housing 1 also includes a means 47 for actuating the carriage 42, with manual control 48. More specifically, the actuating means 47 comprises a band 49 semi-rigid, shaped hairpin, one of which branch 49a has on its outer face a member 48 the other limb has one end linked to the carriage 42. In correspondence, the housing 1 comprises a path 50 for guiding and pulling the strip, also shaped hairpin, and secondly a 1f window adapted to the passage of the organ of 48, the length of which is adapted to the race of displacement of the capture organ 4. as shown the comparison between figures 4 and 5, this race a much longer length than the recovery length of the transfer zone 41b of the second means of capillary diffusion 41, and the upstream zone 2b of the first capillary diffusion means 2, in the position retracted device.

Therefore, by pushing organ 48 gripping towards the proximal end of the housing 1, as shown in FIG. 3, the band 49 circulates in the guide path 50 and pushes the carriage 42 towards the protruding position of the capture member 2. In sense reverse, the carriage 42 is moved to the position retracted from the capture member 4.

As also shown in Figures 4 and 5, the first means 2 of capillary diffusion is tight and kept inside the housing between ribs on arranged parallel to the flow direction 60 capillary.

• 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 boítier 1 est une entité fermée, à l'exception de la fenêtre 1d ; 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 1c ; 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 1c (cf. figure 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 l'analyte est mis en contact avec la zone de collection 41a ;
• avec la même main, le même organe de captation est ramené dans la position rétractée, avec fermeture de l'ouverture 1c, comme décrit précédemment
• 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 1d, 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.

The operation of a device according to the invention is deduced from the preceding description:

• initially, that is to say before use, the capture member 4 is in the retracted position (see Fig.2 and 4), so that the housing 1 is a closed entity, with the exception from window 1d; in the case of Figure 1, it is a flap 61 integral with the proximal end of the sensor member 4, which closes the opening 1c; and in the case of Figures 4 and 5, it is the end of the band 49 semi-rigid, opposite the carriage 42, which closes the opening 1c (see Figure 5);
• by the control member 6 or 48, the user brings the sensor member 4 into the projecting position, in which a flow or liquid sample containing the analyte is brought into contact with the collection zone 41a;
• with the same hand, the same capture member is returned to the retracted position, with closure of the opening 1c, as previously described
• it is only in this latter position, without further intervention by 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 the upstream to the the downstream; the reactions generated by the reagents described above are carried out; the result is accessible to an external observation through the window 1d, for example with the naked eye;
• then the disposable determination device can be discarded in the retracted position of Figures 2 and 4.

In accordance with Figure 5, in relation to the meaning of the observation by the window 1d, it will be observed that the zone 41b transfer of the second means 41 broadcast capillary comes below the upstream zone 2b of the first medium 2 capillary diffusion, in the position retracted organ 4 capture, and this to promote the capillary flow at the junction between the two means 2 and 41 of capillary diffusion, in the position retracted from the capture member 4.

Claims (11)

1. Device for determination of an analyte in a liquid sample, comprising:

   a) a support (1) to be gripped;

   b) a first means (2) for capillary diffusion in a reference direction (60), secured to the support (1) to the gripped, comprising a downstream zone (2a) which is accessible to external observation;

   c) a predetermined reagent (32) for detecting and/or quantifying the analyte, fixed in the downstream zone (2a) of the first capillary diffusion means;

   d) a second capillary diffusion means (41) with, on the one hand, a zone (41a) for collecting the said sample and, on the other hand, a transfer zone (41b) opposite the said collection zone (41a);

   e) a component (4) for taking up the liquid sample, to which the second capillary diffusion means (41) is secured, mounted so that it can move with respect to the said support to be gripped, between two extreme positions, namely:

   one which protrudes from the said support to be gripped, in which the collecting zone (41a) of the second capillary diffusion means (41) can be brought into contact with the liquid sample outside of the support to be gripped,

   and the other which is retracted, in which the collection zone (41a) of the second capillary diffusion means (41) is contained in the support to be gripped,

   characterized in that the transfer zone (41b) of the second capillary diffusion means (41) is arranged removably, with respect to an upstream zone (2b) of the first capillary diffusion means (2), so that when the take-up member (4) is in the protruding position), the said transfer zone (41b) is not in capillary flow continuity with the said upstream zone (2b), and when the said take-up member (4) is in the retracted position, the said transfer zone (41b) and the said upstream zone (2b) are in capillary flow continuity, whereas a predetermined set of reagents for detecting and/or quantifying the analyte comprises, at least, on the one hand, a reagent (31) comprising a visible and/or measurable marker, deposited in the free state either on the first capillary diffusion means (2), upstream of the downstream zone (2a), or on the second capillary diffusion means (41) and, on the other hand, the reagent fixed in the downstream zone (2a) of the first capillary diffusion means for the direct or indirect take-up of the reagent comprising the marker.
2. Device according to Claim 1, characterized in that the reagent (31) comprising the marker is deposited on the second diffusion means (41), in particular downstream of the collection zone (41a).
3. Device according to Claim 1, characterized in that the reagent (31) comprising the marker is deposited on the first diffusion means (2), in particular downstream of the said upstream zone (2b).
4. Device according to Claim 1, characterized in that the support (1) to be gripped is in the form of a kit which, at one end, comprises an opening (1c) for the take-up component (4) to pass through into the protruding position, and on the opposite side from the said end, a window (1d) registered with at least the downstream zone (2a) of the first capillary diffusion means (2).
5. Device according to Claim 1, characterized in that the support (1) to be gripped includes a slideway (5) whose shape is adapted to the path along which the take-up component (4) moves, and the said take-up component includes a manual control component (6) passing through the said slideway.
6. Device according to Claim 1, characterized in that the take-up component (4) can be moved and be translated relative to the support (1) to be gripped, and the said component and the said support are elongated in the translation direction.
7. Device according to Claim 1, characterized in that the first capillary diffusion means (2) includes two separate sections, in permanent capillary flow continuity, namely a first section (21) of relatively high porosity, designed to come removably into capillary flow continuity with the transfer zone (41b) of the second capillary diffusion means (41), and a second section (24) of relatively low porosity, including the said downstream zone (2a).
8. Device according to Claim 4, characterized in that the take-up component (4) comprises a carriage (42) for supporting the second capillary diffusion means (41), the kit and the carriage includes means (43 to 46) for guiding the said carriage as it moves, and the kit incorporates a means (47) for actuating the said carriage, with manual control (48).
9. Device according to Claim 8, characterized in that the second diffusion means (41) is in the form of a stick, and the carriage includes a rear stop (42a) relative to the direction of movement, and a component (42b) for holding the said stick in position.
10. Device according to Claim 8, characterized in that the actuation means (47) comprises a hairpin-shaped semirigid band (49), one branch (49a) of which has a component (48) to be gripped on its outer face, and the other branch (49b) of which has an end joined to the carriage (42), and in that the kit (1) comprises, on the one hand, a path (50) which is intended for pulling the band and is also shaped as a hairpin, and on the other hand a window (1d) which is designed for the passage of the component (48) to be gripped, and whose length is adapted to the displacement travel of the take-up component (4).
11. Device according to Claim 4, characterized in that the first capillary diffusion means (2) is clamped and held inside the kit, between ribs (1c) extending parallel to the direction of the capillary flow.

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