EP1261850A1 - Automaton for processing, signal acquisition and biochip analysis - Google Patents

Automaton for processing, signal acquisition and biochip analysis

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Publication number
EP1261850A1
EP1261850A1 EP01913977A EP01913977A EP1261850A1 EP 1261850 A1 EP1261850 A1 EP 1261850A1 EP 01913977 A EP01913977 A EP 01913977A EP 01913977 A EP01913977 A EP 01913977A EP 1261850 A1 EP1261850 A1 EP 1261850A1
Authority
EP
European Patent Office
Prior art keywords
reactor
biochip
support
guide
volume
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.)
Withdrawn
Application number
EP01913977A
Other languages
German (de)
French (fr)
Inventor
Michel Gazeau
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.)
Genomic SA
Original Assignee
Genomic SA
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Filing date
Publication date
Application filed by Genomic SA filed Critical Genomic SA
Publication of EP1261850A1 publication Critical patent/EP1261850A1/en
Withdrawn legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • G01N1/312—Apparatus therefor for samples mounted on planar substrates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00158—Elements containing microarrays, i.e. "biochip"

Definitions

  • Biochips allow a very large number of molecules to be analyzed in parallel. They are mainly nucleic acids and proteins.
  • the basic principle is the recognition and pairing of two molecules, which have affinities.
  • One of the collections of molecules is fixed, in the form of mini or microdeposits, on a solid support, fabric, glass slide, silicon chip ...
  • the other molecule which is labeled, generally in solution, is brought into contact with the samples deposited on the solid support. After an incubation time, the excess of labeled molecule is eliminated and the support is washed thoroughly. It is then a question of detecting and quantifying the signal emitted by the molecules retained on the deposits. In some cases, the retained molecule can be "dropped" from the deposits and a new molecule can be tested with the same solid support.
  • biochips Generally, to treat biochips, put the deposits in contact with different reagents and then wash them thoroughly. The temperature of the reagents and biochips must be adjusted. The markers are most often fluorescent, but other labeling techniques can be used.
  • the labeled molecule is a rare and / or expensive element.
  • the volume required should be minimized.
  • the other reagents, and in particular the detergents, are inexpensive and the reduction in the volumes used is much less.
  • the invention relates to an automaton capable of carrying out, without human intervention, the processing of biochips and the acquisition of signals for their analysis. In addition to saving reagents, the automated system can process a large number of biochips. Its simplicity makes it relatively inexpensive equipment.
  • the heart of the device is a battery of reactors which are described below.
  • the device cover has different elements:
  • a number of regularly spaced fixed nozzles equal to the number of reactors and located so as to dispense liquid therein. These nozzles are connected by calibrated catheters to the cover of an airtight enclosure which comprises a number of tubes containing the labeled molecules.
  • This enclosure can be put under a given pressure for a given time, thanks to a gas cylinder, for example, which has the effect of driving back by the catheters to the reactors the same volume of the liquids contained in the tubes.
  • This enclosure can be cooled by any method to ensure good conservation of the labeled molecules.
  • a number of nozzles fixed on the cover between the previous ones connected to pressure or vacuum bottles, or to pumps, allows the common reagents to be distributed in large volumes (a few milliliters) to each reactor. Some of these nozzles can spray liquids for cleaning and decontaminating the device.
  • a mechanical translation device makes it possible to move apart, then to return to its initial position, a sliding piece supporting biochips of each reactor or in other cases the reactors, themselves, successively.
  • the temperature inside the enclosure containing the reactors is regulated.
  • the movable strip has a thermostat element, for heating and / or cooling the biochip.
  • These heating or cooling elements are constituted by a PELTIER effect element.
  • They can also be produced by conduits for the circulation of heat transfer fluids, making it possible to adjust the temperature cycles between 97 ° C and 50 ° C, with cyclic temperature changes.
  • Thermoregulation can also be achieved by a two-phase capillary pumping loop. If necessary, the humidity of the air in the enclosure can be checked.
  • Figures 1, 2 and 3 respectively illustrate a front view, a side view and a top view of the reactor; • Figure 4 illustrates a top view of the centrifuge; • Figures 5 and 6 respectively illustrate a side view and a front view of the carrier device with centripetal valve;
  • Figures 7, 8 and 9 respectively illustrate a side view, a front view and a top view of the carrier device with centrifugal drainage
  • Figures 10 and 11 respectively illustrate a side view and a front view of the capillary support device.
  • the invention relates to a reactor (1), illustrated in FIGS. 1 to 3, for biological analysis by biochips (2) characterized in that the biochip (2) is movable relative to a surface which faces it between a first position in which the biochip (2) is close to a surface to define a first volume of small container, and a second position in which the biochip is moved away from said surface to define a dynamically variable volume.
  • the reactors (1) are aligned and inclined so that the biochips (2) can directly receive the dispensed reagents.
  • the body (3) of the reactor has a guide on one of its two large faces. It can also on one of the perpendicular faces include an orifice closed by a plug from the inside, held in abutment by a spring. This orifice is connected to a pipe which allows a liquid under pressure to be injected into the reactor
  • a sliding piece (4) supporting biochips which when it is provided with the biochip and fully engaged in its guide, closes one of the two large faces of the reactor.
  • the biochip support can be moved one or two millimeters in its guide, without affecting the tightness of the reactor, to improve the contact of deposits with reagents. It can be moved away from its original position to the outside by six or seven millimeters to open the reactor and allow the flow of its contents. Finally, it can be moved away from its original position by a few centimeters to leave the enclosure and place itself in the field of the signal acquisition system. It is the mechanical translation device mentioned above which actuates the biochip supports or in other cases the reactors.
  • An agitator (5) composed of a strip (6) which can either rest on the lower part of the biochip (2) forming a solid angle which retains a small volume of liquid, or from this position come to apply on the biochip "spreading" on its surface and without air bubble the volume of liquid retained, or enter completely into the body of the reactor to allow the sliding of the biochip support.
  • the continuous passage between these three positions causes the washing liquid to be projected onto the active surface of the biochip.
  • reactors can be designed, such as for example the three versions of carrier devices (10) presented in FIGS. 5 and 6, 7 to 9 and 10 and 11. They are simpler and less expensive to produce, but do not not allow you to approach the active surface of the biochip very closely for signal acquisition. In this case, the entire reactor is pushed outside the enclosure of the centrifuge.
  • the biochip consists of a glass slide, like microscope slide, on which a hydrophobic paint frame of two to three millimeters in width and regular thickness has been deposited. One side of this frame is interrupted to allow the passage of liquids down the biochip.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

The invention concerns a reactor for biological analysis with biochips characterised in that the biochip is mobile relative to a surface facing it between a first position wherein the biochip is close to a surface to define a first low capacity volume, and a second position wherein the biochip is spaced apart from said surface to define a dynamically variable volume.

Description

AUTOMATE POUR TRAITEMENT, ACQUISITION DE SIGNAL ET ANALYSE DE BIOPUCES AUTOMATON FOR PROCESSING, SIGNAL ACQUISITION AND ANALYSIS OF BIOCHIPS
Les biopuces permettent d'analyser en parallèle un très grand nombre de molécules. Il s'agit essentiellement d'acides nucléiques et de protéines.Biochips allow a very large number of molecules to be analyzed in parallel. They are mainly nucleic acids and proteins.
Le principe de base est la reconnaissance et 1 ' appariement de deux molécules, qui présentent des affinités . L'une des collections de molécules est fixée, sous forme de mini ou microdépôts, sur un support solide, tissu, lame de verre, puce de silicium ...The basic principle is the recognition and pairing of two molecules, which have affinities. One of the collections of molecules is fixed, in the form of mini or microdeposits, on a solid support, fabric, glass slide, silicon chip ...
L'autre molécule, qui est marquée, en général en solution, est mise en contact avec les échantillons déposés sur le support solide. Après un temps d'incubation, l'excès de molécule marquée est éliminé et le support est soigneusement lavé. Il s'agit alors de détecter et quantifier le signal émis par les molécules retenues sur les dépôts. Dans certains cas, la molécule retenue peut être «décrochée» des dépôts et une nouvelle molécule peut être testée avec le même support solide.The other molecule, which is labeled, generally in solution, is brought into contact with the samples deposited on the solid support. After an incubation time, the excess of labeled molecule is eliminated and the support is washed thoroughly. It is then a question of detecting and quantifying the signal emitted by the molecules retained on the deposits. In some cases, the retained molecule can be "dropped" from the deposits and a new molecule can be tested with the same solid support.
D'une façon générale, pour traiter les biopuces, il faut mettre les dépôts en contact avec différents réactifs puis les laver soigneusement. Il faut adapter la température des réactifs et des biopuces. Les marqueurs sont le plus souvent fluorescents, mais d'autres techniques de marquage peuvent être utilisées.Generally, to treat biochips, put the deposits in contact with different reagents and then wash them thoroughly. The temperature of the reagents and biochips must be adjusted. The markers are most often fluorescent, but other labeling techniques can be used.
La molécule marquée est un élément rare et/ou coûteux. Il convient de minimiser le volume nécessaire. Les autres réactifs, et en particulier les produits de lavage, sont peu onéreux et la réduction des volumes utilisés est beaucoup moins importante. L'invention concerne un automate capable de réaliser sans intervention humaine le traitement des biopuces et l'acquisition des signaux en vue de leur analyse. Outre des économies de réactifs, l'automate permet de traiter un grand nombre de biopuces. Sa simplicité en fait un équipement relativement peu coûteux.The labeled molecule is a rare and / or expensive element. The volume required should be minimized. The other reagents, and in particular the detergents, are inexpensive and the reduction in the volumes used is much less. The invention relates to an automaton capable of carrying out, without human intervention, the processing of biochips and the acquisition of signals for their analysis. In addition to saving reagents, the automated system can process a large number of biochips. Its simplicity makes it relatively inexpensive equipment.
Le cœur de l'appareil est une batterie de réacteurs qui sont décrits plus loin.The heart of the device is a battery of reactors which are described below.
Le couvercle de l'appareil comporte différents éléments :The device cover has different elements:
• Un nombre de buses fixes régulièrement espacées, égales au nombre de réacteurs et situées de façon à dispenser du liquide dans ces derniers . Ces buses sont reliées par des cathéters calibrés au couvercle d'une enceinte hermétique qui comporte un nombre de tubes contenant les molécules marquées . Cette enceinte peut être mise sous une pression donnée pendant un temps donné, grâce à une bombonne de gaz, par exemple, ce qui a pour effet de refouler par les cathéters vers les réacteurs un même volume des liquides contenus dans les tubes . Cette enceinte peut être refroidie par un procédé quelconque pour assurer une bonne conservation des molécules marquées .• A number of regularly spaced fixed nozzles, equal to the number of reactors and located so as to dispense liquid therein. These nozzles are connected by calibrated catheters to the cover of an airtight enclosure which comprises a number of tubes containing the labeled molecules. This enclosure can be put under a given pressure for a given time, thanks to a gas cylinder, for example, which has the effect of driving back by the catheters to the reactors the same volume of the liquids contained in the tubes. This enclosure can be cooled by any method to ensure good conservation of the labeled molecules.
• Un nombre de buses fixées sur le couvercle entre les précédentes reliées à des flacons sous pression, ou en dépression, ou à des pompes, permet de distribuer dans chaque réacteur les réactifs communs, en grand volume (quelques millilitres) . Certaines de ces buses peuvent projeter des liquides pour le nettoyage et la décontamination de l'appareil.• A number of nozzles fixed on the cover between the previous ones connected to pressure or vacuum bottles, or to pumps, allows the common reagents to be distributed in large volumes (a few milliliters) to each reactor. Some of these nozzles can spray liquids for cleaning and decontaminating the device.
• Un dispositif mécanique de translation permet d'écarter, puis de ramener à sa position initiale une pièce coulissante support de biopuces de chaque réacteur ou dans d'autres cas les réacteurs, eux-mêmes, successivement.• A mechanical translation device makes it possible to move apart, then to return to its initial position, a sliding piece supporting biochips of each reactor or in other cases the reactors, themselves, successively.
La température à 1 ' intérieur de 1 ' enceinte contenant les réacteurs est régulée. A cet effet, la lamelle mobile comporte un élément de thermostatage , pour le chauffage et/ou le refroidissement de la biopuce.The temperature inside the enclosure containing the reactors is regulated. For this purpose, the movable strip has a thermostat element, for heating and / or cooling the biochip.
Ces éléments de chauffage ou de refroidissement sont constitués par un élément à effet PELTIER.These heating or cooling elements are constituted by a PELTIER effect element.
Ils peuvent aussi être réalisé par des conduits pour la circulation de fluides caloporteurs , permettant d'ajuster les cycles de température entre 97°C et 50°C, avec des changements de température cyclique.They can also be produced by conduits for the circulation of heat transfer fluids, making it possible to adjust the temperature cycles between 97 ° C and 50 ° C, with cyclic temperature changes.
La thermorégulation peut aussi être réalisée par une boucle biphasique à pompage capillaire. Le cas échéant, l'hygrométrie de l'air dans l'enceinte peut être contrôlée.Thermoregulation can also be achieved by a two-phase capillary pumping loop. If necessary, the humidity of the air in the enclosure can be checked.
On comprendra mieux l'invention à l'aide de la description, faite ci-après à titre purement explicatif, d'un mode de réalisation de l'invention, en référence aux figures annexées :The invention will be better understood with the aid of the description, given below for purely explanatory purposes, of an embodiment of the invention, with reference to the appended figures:
• les figures 1, 2 et 3 illustrent respectivement une vue de face, une vue de côté et une vue de dessus du réacteur ; • la figure 4 illustre une vue de dessus de la centrifugeuse ; • les figures 5 et 6 illustrent respectivement une vue de côté et une vue de face du dispositif porteur à valve centripète ;• Figures 1, 2 and 3 respectively illustrate a front view, a side view and a top view of the reactor; • Figure 4 illustrates a top view of the centrifuge; • Figures 5 and 6 respectively illustrate a side view and a front view of the carrier device with centripetal valve;
• les figures 7, 8 et 9 illustrent respectivement une vue de côté, une vue de face et une vue de dessus du dispositif porteur à drainage centrifuge ;• Figures 7, 8 and 9 respectively illustrate a side view, a front view and a top view of the carrier device with centrifugal drainage;
• les figures 10 et 11 illustrent respectivement une vue de côté et une vue de face du dispositif porteur capillaire. L'invention concerne un réacteur (1), illustré figures 1 à 3, pour analyse biologique par des biopuces (2) caractérisé en ce que la biopuce (2) est mobile par rapport à une surface qui lui fait face entre une première position dans laquelle la biopuce (2) est proche d'une surface pour définir un premier volume de faible contenant, et une deuxième position dans laquelle la biopuce est écartée de ladite surface pour définir un volume variable dynamiquement.• Figures 10 and 11 respectively illustrate a side view and a front view of the capillary support device. The invention relates to a reactor (1), illustrated in FIGS. 1 to 3, for biological analysis by biochips (2) characterized in that the biochip (2) is movable relative to a surface which faces it between a first position in which the biochip (2) is close to a surface to define a first volume of small container, and a second position in which the biochip is moved away from said surface to define a dynamically variable volume.
Les réacteurs (1) sont alignés et inclinés de telle sorte que les biopuces (2) puissent recevoir directement les réactifs dispensés.The reactors (1) are aligned and inclined so that the biochips (2) can directly receive the dispensed reagents.
Ils sont constitués de trois éléments : Le corps (3) du réacteur. Il comporte sur l'une de ses deux grandes faces un guidage. Il peut aussi sur l'une des faces perpendiculaires comporter un orifice obturé par un bouchon de l'intérieur, maintenu en appui par un ressort. Cet orifice est relié à une tuyauterie qui permet d'injecter un liquide sous pression dans le réacteurThey consist of three elements: The body (3) of the reactor. It has a guide on one of its two large faces. It can also on one of the perpendicular faces include an orifice closed by a plug from the inside, held in abutment by a spring. This orifice is connected to a pipe which allows a liquid under pressure to be injected into the reactor
Une pièce coulissante (4) support de biopuces qui lorsqu'elle est munie de la biopuce et engagée à fond dans son guidage, obture l'une des deux grandes faces du réacteur. Le support de biopuces peut être déplacé d'un ou deux millimètres dans son guidage, sans nuire à l'étanchéité du réacteur, pour améliorer le contact des dépôts avec les réactifs. Il peut être éloigné de sa position d'origine vers l'extérieur de six ou sept millimètres pour ouvrir le réacteur et permettre l'écoulement de son contenu. Il peut enfin être éloigné de sa position d'origine de quelques centimètres pour sortir de l'enceinte et se placer dans le champ du système d'acquisition du signal. C'est le dispositif mécanique de translation évoqué plus haut qui actionne les support de biopuces ou dans d'autres cas les réacteurs. Un agitateur (5) composé d'une lamelle (6) qui peut soit prendre appui sur la partie inférieure de la biopuce (2) formant un angle solide qui retient un faible volume de liquide, soit à partir de cette position venir s'appliquer sur la biopuce «étalant» sur sa surface et sans bulle d'air le volume de liquide retenu, soit entrer complètement dans le corps du réacteur pour permettre le coulissement du support de biopuces.A sliding piece (4) supporting biochips which when it is provided with the biochip and fully engaged in its guide, closes one of the two large faces of the reactor. The biochip support can be moved one or two millimeters in its guide, without affecting the tightness of the reactor, to improve the contact of deposits with reagents. It can be moved away from its original position to the outside by six or seven millimeters to open the reactor and allow the flow of its contents. Finally, it can be moved away from its original position by a few centimeters to leave the enclosure and place itself in the field of the signal acquisition system. It is the mechanical translation device mentioned above which actuates the biochip supports or in other cases the reactors. An agitator (5) composed of a strip (6) which can either rest on the lower part of the biochip (2) forming a solid angle which retains a small volume of liquid, or from this position come to apply on the biochip "spreading" on its surface and without air bubble the volume of liquid retained, or enter completely into the body of the reactor to allow the sliding of the biochip support.
Le passage continu entre ces trois positions provoque la projection du liquide de lavage sur la surface active de la biopuce.The continuous passage between these three positions causes the washing liquid to be projected onto the active surface of the biochip.
D'autres types de réacteurs peuvent être conçus, comme par exemple les trois versions de dispositifs porteurs (10) présentés dans les figures 5 et 6, 7 à 9 et 10 et 11. Ils sont plus simples et moins coûteux à réaliser, mais ne permettent pas d'approcher la surface active de la bio puce de très près pour l'acquisition du signal. Dans ce cas, c'est le réacteur tout entier qui est poussé à l'extérieur de l'enceinte de la centrifugeuse.Other types of reactors can be designed, such as for example the three versions of carrier devices (10) presented in FIGS. 5 and 6, 7 to 9 and 10 and 11. They are simpler and less expensive to produce, but do not not allow you to approach the active surface of the biochip very closely for signal acquisition. In this case, the entire reactor is pushed outside the enclosure of the centrifuge.
La biopuce est constituée d'une lamelle de verre, type lamelle de microscope, sur laquelle un cadre de peinture hydrophobe de deux à trois millimètres de largeur et d'épaisseur régulière a été déposé. L'un des côtés de ce cadre est interrompu pour permettre le passage des liquides vers le bas de la biopuce. The biochip consists of a glass slide, like microscope slide, on which a hydrophobic paint frame of two to three millimeters in width and regular thickness has been deposited. One side of this frame is interrupted to allow the passage of liquids down the biochip.

Claims

REVENDICATIONS
1 - Réacteur (1) pour analyse biologique par des biopuces (2) caractérisé en ce que la biopuce est mobile par rapport à une surface qui lui fait face entre une première position dans laquelle la biopuce est proche d'une surface pour définir un premier volume de faible contenant, et une deuxième position dans laquelle la biopuce est écartée de ladite surface pour définir un volume variable dynamiquement.1 - Reactor (1) for biological analysis by biochips (2) characterized in that the biochip is movable relative to a surface which faces it between a first position in which the biochip is close to a surface to define a first small container volume, and a second position in which the biochip is moved away from said surface to define a dynamically variable volume.
2 - Réacteur (1) selon la revendication 1 caractérisé en ce que la biopuce est supportée par une pièce coulissante (4) support de biopuces qui lorsqu'elle est munie de la biopuce et engagée à fond dans son guidage, obture l'une des deux grandes faces du réacteur (1).2 - Reactor (1) according to claim 1 characterized in that the biochip is supported by a sliding part (4) biochip support which when it is provided with the biochip and fully engaged in its guide, closes one of the two large faces of the reactor (1).
3 - Réacteur (1) selon la revendication 1 caractérisé en ce qu'il est constitué par un corps (3) présentant une fente d'introduction d'une pièce coulissante, et un agitateur.3 - Reactor (1) according to claim 1 characterized in that it is constituted by a body (3) having a slot for introducing a sliding part, and an agitator.
4 - Réacteur (1) selon la revendication 3 caractérisé en ce que le corps (3) comporte sur l'une de ses deux grandes faces un guidage pour la pièce coulissante.4 - Reactor (1) according to claim 3 characterized in that the body (3) has on one of its two large faces a guide for the sliding part.
5 - Réacteur (1) selon la revendication 3 caractérisé en ce que le corps (3) présente sur l'une des faces perpendiculaires un orifice obturé par un bouchon de l'intérieur, maintenu en appui par un ressort. 6 - Réacteur (1) selon la revendication 5 caractérisé en ce que ledit orifice est relié à une tuyauterie qui permet d'injecter un liquide sous pression dans le réacteur.5 - Reactor (1) according to claim 3 characterized in that the body (3) has on one of the perpendicular faces an orifice closed by a plug from the inside, supported by a spring. 6 - Reactor (1) according to claim 5 characterized in that said orifice is connected to a pipe which allows to inject a pressurized liquid into the reactor.
7 - Réacteur (1) selon la revendication 3 caractérisé en ce que la pièce coulissante (4) support de biopuces obture, lorsqu'elle est munie de la biopuce et engagée à fond dans son guidage, l'une des deux grandes faces du réacteur.7 - Reactor (1) according to claim 3 characterized in that the sliding part (4) biochip support closes, when provided with the biochip and fully engaged in its guide, one of the two large faces of the reactor .
8 - Réacteur (1) selon la revendication 3 caractérisé en ce que le support de biopuces peut être déplacé d'un ou deux millimètres dans son guidage, pour améliorer le contact des dépôts avec les réactifs.8 - Reactor (1) according to claim 3 characterized in that the biochip support can be moved by one or two millimeters in its guide, to improve the contact of the deposits with the reagents.
9 - Réacteur (1) selon la revendication 3 caractérisé en ce que le support de biopuces peut être éloigné de sa position d'origine vers l'extérieur de six ou sept millimètres pour ouvrir le réacteur et permettre l'écoulement de son contenu.9 - Reactor (1) according to claim 3 characterized in that the biochip support can be moved away from its original position towards the outside by six or seven millimeters to open the reactor and allow the flow of its contents.
9 - Réacteur (1) selon la revendication 3 caractérisé en ce que le support de biopuces peut être éloigné de sa position d'origine de quelques centimètres pour sortir de l'enceinte et se placer dans le champ du système d'acquisition du signal.9 - Reactor (1) according to claim 3 characterized in that the biochip support can be moved away from its original position by a few centimeters to leave the enclosure and be placed in the field of the signal acquisition system.
10 - Réacteur (1) selon la revendication 3 caractérisé en ce que l'agitateur (5) est composé d'une lamelle (6) qui peut soit prendre appui sur la partie inférieure de la biopuce (2) formant un angle solide qui retient un faible volume de liquide, soit à partir de cette position venir s'appliquer sur la biopuce «étalant» sur sa surface et sans bulle d'air le volume de liquide retenu, soit entrer complètement dans le corps du réacteur pour permettre le coulissement du support de biopuces. 10 - Reactor (1) according to claim 3 characterized in that the agitator (5) is composed of a strip (6) which can either be supported on the lower part of the biochip (2) forming a solid angle which retains a small volume of liquid, either from this position come to apply on the biochip "spreading" on its surface and without air bubble the volume of liquid retained, or enter completely into the reactor body to allow sliding biochip support.
EP01913977A 2000-03-09 2001-03-09 Automaton for processing, signal acquisition and biochip analysis Withdrawn EP1261850A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0003139A FR2806166B1 (en) 2000-03-09 2000-03-09 AUTOMATON FOR PROCESSING, SIGNAL ACQUISITION AND ANALYSIS OF BIOCHIPS
FR0003139 2000-03-09
PCT/FR2001/000717 WO2001067065A1 (en) 2000-03-09 2001-03-09 Automaton for processing, signal acquisition and biochip analysis

Publications (1)

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EP1261850A1 true EP1261850A1 (en) 2002-12-04

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EP01913977A Withdrawn EP1261850A1 (en) 2000-03-09 2001-03-09 Automaton for processing, signal acquisition and biochip analysis

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US (1) US20030059930A1 (en)
EP (1) EP1261850A1 (en)
AU (1) AU3937301A (en)
FR (1) FR2806166B1 (en)
WO (1) WO2001067065A1 (en)

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WO2003106999A1 (en) * 2002-06-01 2003-12-24 Chengdu Kuachang Science & Technology Co., Ltd Biochip with maximization of the reactor number
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US20040157336A1 (en) * 2002-11-14 2004-08-12 Affymetrix, Inc. Automated fluid control system and process
US20060246576A1 (en) * 2005-04-06 2006-11-02 Affymetrix, Inc. Fluidic system and method for processing biological microarrays in personal instrumentation

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Also Published As

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FR2806166A1 (en) 2001-09-14
WO2001067065A1 (en) 2001-09-13
AU3937301A (en) 2001-09-17
US20030059930A1 (en) 2003-03-27
FR2806166B1 (en) 2002-11-15

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