EP1476755A1 - Composite material for a biological or biochemical analysis microfluidic system - Google Patents

Composite material for a biological or biochemical analysis microfluidic system

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Publication number
EP1476755A1
EP1476755A1 EP03717419A EP03717419A EP1476755A1 EP 1476755 A1 EP1476755 A1 EP 1476755A1 EP 03717419 A EP03717419 A EP 03717419A EP 03717419 A EP03717419 A EP 03717419A EP 1476755 A1 EP1476755 A1 EP 1476755A1
Authority
EP
European Patent Office
Prior art keywords
composite material
support
functionalizable
inert
elements
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.)
Ceased
Application number
EP03717419A
Other languages
German (de)
French (fr)
Inventor
Philippe Combette
Frédéric Revol-Cavalier
Frédérique Mittler
Bernard Beneyton
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.)
Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Original Assignee
Commissariat a lEnergie Atomique CEA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Commissariat a lEnergie Atomique CEA filed Critical Commissariat a lEnergie Atomique CEA
Publication of EP1476755A1 publication Critical patent/EP1476755A1/en
Ceased legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/545—Synthetic resin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
    • G01N33/552—Glass or silica
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic

Definitions

  • the present invention relates to a component for microsystem for biological or biochemical analysis, this component using a composite material. It also relates to a method for producing such a component.
  • a microsystem for biological or biochemical analysis is produced from a support or substrate chosen so that a surface (which may consist of several zones) of this support or substrate provides one or more functions. It can be a chemical functionality or an electrical functionality.
  • the supports are made of glass or silica, which allows the attachment of biological or biochemical elements by a well controlled coupling chemistry, for example by silanization.
  • Fluid circulation microsystems generally use electrokinetic pumps, such as electro-osmosis, to circulate fluids in micro-channels and micro-reservoirs made in the supports. These pumping modes impose the existence of electrically active surfaces. It is the use of high electric fields, combined with the presence of electrically active surfaces, which allows fluid flow.
  • electrokinetic pumps such as electro-osmosis
  • Glass or silicon supports are therefore very suitable for obtaining chemical and electrical functionalities.
  • inert materials such as polymers, plastics, glues
  • the chemistry for attaching biological or biochemical elements to these inert materials depends on their chemical formulation and remains difficult to implement.
  • Materials such as molded plastics for making micro-channels, polymers or photosensitive resins for making microstructures would be very widely used since it would be possible to easily attach biological or biochemical elements to them. Indeed, these materials are low cost and can be used in large series.
  • electrokinetic flows are problematic in materials such as conventional polymers and require the use of heavy techniques such as plasma activation in order to generate surfaces. electrically charged. However, it has been shown that this does not permanently activate the treated surface. The system therefore evolves over time.
  • the present invention provides a solution to the problems set out above. It allows the use of chemically inert materials (polymers, resins, plastics, adhesives, etc.) to make supports for components for microsystems of biological or biochemical analysis, these inert materials being used in combination with a material functionalizable to allow the attachment of biological or biochemical elements.
  • the biological or biochemical elements can then be grafted by conventional techniques, for example by a silanization technique.
  • the biologically or biochemically functionalizable material is incorporated directly into the inert material (plastic, glue) to obtain a composite material.
  • the inert material plastic, glue
  • Several solutions can be envisaged to obtain this composite material.
  • One solution is to make a mixture of two liquid phases which, after several technological steps, are frozen in the form of a composite material.
  • One of the phases (for example synthetic silica) makes it possible to ensure functionalization by a bonding chemistry identical to that carried out on a glass substrate (for example silanization).
  • Another solution consists in mixing, either directly with a plastic constituting the inert material, or with a photosensitive polymer or not, elements (preferably beads) made of silica, glass, metal or functionalizable polymer.
  • elements preferably beads
  • the beads ensure the attachment of biological or biochemical elements and also have the advantage of increasing the attachment surface for biological or biochemical elements.
  • the composite material obtained makes it possible to produce components structured by methods used in microtechnology. Functionalization also takes place either on the phase dispersed in the photosensitive material, or on elements included in this material.
  • the deposited material can also be a material providing electrical functionality to the component, which allows the circulation of fluids by electrokinetic pumping.
  • the subject of the invention is therefore a component for a biological or biochemical analysis microsystem formed from a support and having at least one surface area chemically functionalized, to allow the formation of a chemistry for the attachment of elements.
  • biological or biochemical, and / or electrically to allow the formation of electric charges therein
  • the support comprises at least one part made of composite material, the composite material being a mixture of at least one inert material and at least one chemically and / or electrically functionalizable material for providing said functionalized surface area.
  • the inert material of the composite material is a material chosen from a polymer, a plastic, a resin and an adhesive.
  • the polymer can be a polyimide, a poly (dimethylsiloxane) or a photosensitive resin of the epoxy type.
  • Said part can form the support in its entirety.
  • the support may comprise a substrate supporting said part.
  • the substrate can be made of a material chosen from glass, silica, silicon, a polymer and a metal.
  • the functionalizable material is chosen from silica, synthesized silica, silicon nitride, a metal and a functionalizable polymer.
  • the composite material can be a mixture comprising a phase of inert material and a phase of functionalizable material.
  • the functionalizable material can be in the form of beads.
  • Said surface area can support chemical functions capable of ensuring the attachment of biological elements or other chemical functions to said surface area.
  • Said surface area can support chemical functions capable of ensuring the presence of electrical charges on said surface area.
  • the subject of the invention is also a method of producing a component for a microsystem for biological or biochemical analysis from a support, the support having to present at least one surface area chemically functionalized to allow the formation of a chemistry for attaching biological or biochemical elements, and / or electrically, to allow the formation of electrical charges therein, characterized in that it comprises the production of a support comprising at least one part made of composite material, the composite material being a mixture of at least one inert material and at least one chemically and / or electrically functionalizable material to provide said functionalized surface area.
  • the composite material can be obtained by mixing in liquid phases the inert material and the functionalizable material, the mixture then being solidified to provide said part in composite material.
  • the composite material can be obtained by dispersing elements of functionalizable material in the inert material in the liquid phase, the mixture then being solidified to provide said part in composite material.
  • said elements made of functionalizable material are in the form of balls.
  • the inert liquid phase material in which said elements are dispersed can be poured onto a support with imprint (s) before being solidified.
  • the impression support (s) can be removed after the mixture has solidified.
  • the inert liquid phase material in which said elements are dispersed can be deposited on a support before being solidified. If the inert material is a photosensitive material, said part made of composite material can be, after solidification, structured by photo-lithography. If the deposit is made on a surface of the support having at least one imprint, the composite material can be, after solidification, removed from the imprint. If the inert material is a photosensitive material, the removal of the composite material from the imprint can be done by photo-lithography.
  • the support having a face with at least one imprint
  • elements of functionalizable material are deposited at the bottom of the imprint, then the inert material in liquid phase is poured onto said face of the support, then the inert material is solidified to provide the composite material at the bottom of the imprint, the support being finally removed.
  • said elements made of functionalizable material are in the form of balls. Whatever the mode of implementation, solidification can be obtained by heat treatment.
  • FIGS. 1A and 1B are sectional views illustrating the production of a first component for a biological or biochemical analysis microsystem according to the invention
  • FIGS. 2A and 2B are sectional views illustrating the production of a second component for a biological or biochemical analysis microsystem according to the invention
  • FIG. 3A and 3B are sectional views illustrating the production of a third component for a biological or biochemical analysis microsystem according to the invention
  • FIG. 4A to 4C are sectional views illustrating the production of a fourth component for microsystem for biological or biochemical analysis according to the invention.
  • FIGS. 1A and 1B illustrate the production of a component for a biological or biochemical analysis microsystem using an imprint support.
  • FIG. 1A shows a support 10, for example made of silicon, the upper face of which has been machined or engraved to form an imprint consisting of a depression 11 extended by trenches 12.
  • liquid composite material e.g. poly (dimethylsiloxane)
  • microbeads for example silica beads 1 ⁇ m in diameter
  • the medium and its content are. then placed in an oven maintained at 60 ° C for 4 hours.
  • the component 16 obtained is shown in FIG. 1B. It comprises a base 14 complementary to the depression 11 and walls 15 perpendicular to the base and complementary to the trenches 12. Two consecutive walls define a channel. The component obtained is ready to undergo chemical and / or electrical protocols allowing it to be functionalized.
  • FIGS. 2A and 2B illustrate the production of a component for a microsystem for biological or biochemical analysis from a photosensitive composite material.
  • Polymer or photosensitive resin patterns can be produced on flat substrates, which avoids the use of complex engraving machines. For example, the production of studs or channels in a glass or silicon slide is replaced by a simple photo-1ithography.
  • the deep etching of the glass is delicate. It cannot be produced by plasma because of the blocking of the etching by the ionic and metallic impurities contained in the glass.
  • the glass is therefore etched by isotropic chemistry, which prevents the production of fine patterns with low steps.
  • the invention allows to realize such structures using a photosensitive composite material.
  • FIG. 2A shows a silicon support 20 with a diameter of 100 mm, the upper face of which is covered with a layer of composite material 21.
  • the composite material consists of a photosensitive polyimide sold under the name "Probimide 7510" in which microbeads are dispersed, for example silica beads 1 ⁇ m in diameter.
  • the mixture is deposited with the spinner on the support 20 at a speed of 3000 revolutions / minute then annealed at 110 ° C. on a hot plate.
  • the composite material is exposed by ultraviolet rays through a mask and then developed in order to obtain the desired component, for example that shown in FIG. 2B where trenches 22 are visible in the composite material 21.
  • the composite material is annealed at 150 ° C on a hot plate, then at 300 ° C in a heat treatment oven.
  • FIGS. 3A and 3B illustrate the production of a component for a biological or biochemical analysis microsystem for which the composite material is located in a channel.
  • FIG. 3A shows a polymer support 30, one face of which has an imprint 31 produced by a conventional technique such as stamping, molding or laser ablation.
  • a layer 32 of composite material is deposited on the face having an imprint by covering the walls of the imprint.
  • the composite material consists of a photosensitive polyimide sold under the name "Probimide 7510" in which microbeads are dispersed, for example silica beads of 1 ⁇ m in diameter.
  • the composite material is deposited by soaking and then annealed at 110 ° C on a heating plate.
  • FIGS. 4A to 4C illustrate the production of a component for a biological or biochemical analysis microsystem where the composite material is obtained by depositing inert material on a bed of beads.
  • FIG. 4A shows a support 40, for example a silicon support 100 mm in diameter, the upper face of which has been machined or engraved to form an imprint consisting of a series of parallel trenches 41. Trenches 41 are deposited at the bottom 42 silica beads 100 ⁇ m in diameter.
  • an inert material 43 for example a poly (dimethylsiloxane)
  • the inert material fills the trenches 41 and mixes with the balls 42 at the bottom of the trenches.
  • the whole is placed in an oven at 60 ° C for 4 hours. After evacuation of the solvents contained in the polymer, the mold is removed.
  • the component shown in Figure 4C consisting of a base 44 and walls 45, the top 46 of the walls being of composite material. The component is ready to undergo chemical protocols allowing it to be functionalized.
  • a silanization treatment makes it possible to fix chemical functions on the surface of these materials which will subsequently ensure the attachment of biological elements or chemical functions.
  • silanes can be used. Each has its own fixing protocol on the surface of the material to be functionalized. The choice of silane to use depends on the chemical function that you want to use either directly or for the subsequent carrying out of a chemical reaction or the fixation of a biological element. Among the most commonly used silanes, mention may be made of aminopropyltriethoxysilane, aminopropyldimethylethoxysilane, epoxy silane, 2- (hydroxyethyl) -3- aminopropyltriethoxysilane.
  • silanization protocol used for aminopropyltriethoxysilane is as follows: treatment of the surface concerned with an oxygen plasma (Nextral 310) at 150 watts for 30 seconds to create silanol functions on the surface;
  • Oligonucleotides synthesized with an aldehyde function can be fixed directly or via a glutaraldehyde if the oligonucleotides are synthesized with an NH 2 function.
  • This silanization technique makes it possible to fix oligonucleotides, proteins or any biological or chemical element compatible with the functions present on the silane attached to the functionalized material (amino functions, aldehyde acid, activated ester, etc.).
  • the material to be functionalized is a layer of gold, the fixing of thiols or of disulfurized compounds on the surface of this metallic layer.
  • different thiols make it possible to obtain on the surface of the layer to functionalize the chemical functions necessary for the desired chemical reactions.
  • electrical charges can be obtained on the surface of synthetic silica, silicon, silicon nitride and silicon oxide by grafting an aminopropyltriethoxysilane onto the layer to be functionalized according to the protocol presented above.
  • a treatment in an acid medium (for example 0.2M HCl) makes it possible to protect the amino group of the silane and to obtain electrical charges on the surface of the functionalized material.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
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  • Physics & Mathematics (AREA)
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  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention concerns a component for a biological or biochemical analysis microfluidic system made from a support and having at least a chemically functionalized surface zone, to enable therein formation of a chemical function for adhesion of biological or biochemical elements, and/or electrically functionalized, to enable therein formation of electric loads. The support comprises at least a part (21) made of composite material, the composite material being a mixture of at least an inert material and at least a material capable of being chemically and/or electrically functionalized to provide said functionalized surface zone.

Description

MATERIAU COMPOSITE POUR MICROSYSTEME D ' ANALYSE BIOLOGIQUE OU BIOCHIMIQUECOMPOSITE MATERIAL FOR BIOLOGICAL OR BIOCHEMICAL ANALYSIS MICROSYSTEM
DESCRIPTIONDESCRIPTION
5 DOMAINE TECHNIQUE5 TECHNICAL AREA
La présente invention concerne un composant pour microsystème d'analyse biologique ou biochimique, ce composant utilisant un matériau composite. Elle concerne également un procédé de réalisation d'un tel 0 composant.The present invention relates to a component for microsystem for biological or biochemical analysis, this component using a composite material. It also relates to a method for producing such a component.
ETAT DE LA TECHNIQUE ANTERIEURESTATE OF THE PRIOR ART
Un microsystème pour 1 ' analyse biologique ou biochimique est réalisé à partir d'un support ou substrat choisi pour qu'une surface (qui peut être 5 constituée de plusieurs zones) de ce support ou substrat apporte une ou plusieurs fonctions. Il peut s'agir d'une fonctionnalité chimique ou d'une fonctionnalité électrique.A microsystem for biological or biochemical analysis is produced from a support or substrate chosen so that a surface (which may consist of several zones) of this support or substrate provides one or more functions. It can be a chemical functionality or an electrical functionality.
La fonctionnalité chimique intervient 0 lorsque des éléments biologiques ou biochimiques doivent être accrochés au support. Généralement, les supports sont en verre ou en silice, ce qui permet l'accrochage des éléments biologiques ou biochimiques par une chimie de couplage bien maîtrisée, par exemple 5 par silanisation.The chemical functionality intervenes 0 when biological or biochemical elements must be attached to the support. Generally, the supports are made of glass or silica, which allows the attachment of biological or biochemical elements by a well controlled coupling chemistry, for example by silanization.
La fonctionnalité électrique intervient pour la circulation de fluides dans des micro-canaux ou des micro-réservoirs. Les microsystèmes à circulation de fluides utilisent généralement des pompages 0 électrocinétiques, tels que 1 ' électro-osmose, pour faire circuler des fluides dans des micro-canaux et micro-réservoirs réalisés dans les supports. Ces modes de pompage imposent l'existence de surfaces électriquement actives. C'est l'utilisation de champs électriques élevés, combinés à la présence de surfaces électriquement actives, qui permet un écoulement fluidique. Les supports connus, en verre ou en silice, conviennent bien à ces modes de pompage.The electrical functionality intervenes for the circulation of fluids in micro-channels or micro-tanks. Fluid circulation microsystems generally use electrokinetic pumps, such as electro-osmosis, to circulate fluids in micro-channels and micro-reservoirs made in the supports. These pumping modes impose the existence of electrically active surfaces. It is the use of high electric fields, combined with the presence of electrically active surfaces, which allows fluid flow. The known supports, made of glass or silica, are well suited to these pumping modes.
Les supports en verre ou en silicium conviennent donc bien à l'obtention des fonctionnalités chimique et électrique.Glass or silicon supports are therefore very suitable for obtaining chemical and electrical functionalities.
Il est de plus en plus fait référence à l'utilisation de matériaux inertes tels que les polymères, les plastiques, les colles, dans la réalisation de ces microsystèmes. Cependant, la chimie d'accrochage des éléments biologiques ou biochimiques sur ces matériaux inertes dépend de leur formulation chimique et reste délicat à mettre en œuvre. Des matériaux tels que les plastiques moulés pour réaliser des micro-canaux, des polymères ou des résines photosensibles pour réaliser des microstructures seraient très largement utilisées dès lors qu'il serait possible d'y accrocher facilement des éléments biologiques ou biochimiques. En effet, ces matériaux sont de faible coût et sont utilisables en grande série .There is more and more reference to the use of inert materials such as polymers, plastics, glues, in the production of these microsystems. However, the chemistry for attaching biological or biochemical elements to these inert materials depends on their chemical formulation and remains difficult to implement. Materials such as molded plastics for making micro-channels, polymers or photosensitive resins for making microstructures would be very widely used since it would be possible to easily attach biological or biochemical elements to them. Indeed, these materials are low cost and can be used in large series.
Par ailleurs, les écoulements électrocinëtiques sont problématiques dans des matériaux tels que les polymères classiques et nécessitent l'emploi de techniques lourdes telles que l'activation par plasma afin de générer des surfaces électriquement chargées. Cependant, il a été montré que ceci ne permet pas d'activer définitivement la surface traitée. Le système évolue donc dans le temps.In addition, electrokinetic flows are problematic in materials such as conventional polymers and require the use of heavy techniques such as plasma activation in order to generate surfaces. electrically charged. However, it has been shown that this does not permanently activate the treated surface. The system therefore evolves over time.
EXPOSÉ DE L'INVENTION La présente invention apporte une solution aux problèmes exposés ci-dessus. Elle permet l'utilisation de matériaux chimiquement inertes (les polymères, les résines, les plastiques, les colles, etc.) pour réaliser des supports de composants pour microsystèmes d'analyse biologique ou biochimique, ces matériaux inertes étant utilisés en combinaison avec un matériau fonctionnalisable afin de permettre l'accrochage d'éléments biologiques ou biochimiques. Les éléments biologiques ou biochimiques peuvent ensuite être greffés par des techniques classiques, par exemple par une technique de silanisation.PRESENTATION OF THE INVENTION The present invention provides a solution to the problems set out above. It allows the use of chemically inert materials (polymers, resins, plastics, adhesives, etc.) to make supports for components for microsystems of biological or biochemical analysis, these inert materials being used in combination with a material functionalizable to allow the attachment of biological or biochemical elements. The biological or biochemical elements can then be grafted by conventional techniques, for example by a silanization technique.
Le matériau fonctionnalisable biolo- giquement ou biochimiquement est incorporé directement au matériau inerte (plastique, colle) pour obtenir un matériau composite. Plusieurs solutions peuvent être envisagées pour obtenir ce matériau composite.The biologically or biochemically functionalizable material is incorporated directly into the inert material (plastic, glue) to obtain a composite material. Several solutions can be envisaged to obtain this composite material.
Une solution consiste à réaliser un mélange de deux phases liquides qui, après plusieurs étapes technologiques, sont figées sous la forme d'un matériau composite. L'une des phases (par exemple de la silice synthétique) permet d'assurer la fonctionnalisation par une chimie d'accrochage identique à celle réalisée sur un substrat en verre (par exemple la silanisation) .One solution is to make a mixture of two liquid phases which, after several technological steps, are frozen in the form of a composite material. One of the phases (for example synthetic silica) makes it possible to ensure functionalization by a bonding chemistry identical to that carried out on a glass substrate (for example silanization).
Une autre solution consiste à mélanger, soit directement à un plastique constituant le matériau inerte, soit à un polymère photosensible ou non, des éléments (de préférence des billes) en silice, en verre, en métal ou en polymère fonctionnalisable. Les billes assurent la fixation des éléments biologiques ou biochimiques et ont également l'avantage d'augmenter la surface d'accrochage pour les éléments biologiques ou biochimiques .Another solution consists in mixing, either directly with a plastic constituting the inert material, or with a photosensitive polymer or not, elements (preferably beads) made of silica, glass, metal or functionalizable polymer. The beads ensure the attachment of biological or biochemical elements and also have the advantage of increasing the attachment surface for biological or biochemical elements.
Si un matériau photosensible est utilisé comme matériau inerte, le matériau composite obtenu permet de réaliser des composants structurés par des méthodes utilisées en microtechnologie. La fonctionnalisation a encore lieu soit sur la phase dispersée dans le matériau photosensible, soit sur deséléments inclus dans ce matériau.If a photosensitive material is used as an inert material, the composite material obtained makes it possible to produce components structured by methods used in microtechnology. Functionalization also takes place either on the phase dispersed in the photosensitive material, or on elements included in this material.
Le matériau déposé peut aussi être un matériau procurant une fonctionnalité électrique au composant, ce qui autorise la circulation de fluides par pompage électrocinétique.The deposited material can also be a material providing electrical functionality to the component, which allows the circulation of fluids by electrokinetic pumping.
L'invention a donc pour objet un composant pour microsystème d'analyse biologique ou biochimique formé à partir d'un support et possédant au moins une zone de surface fonctionnalisée chimiquement, pour y permettre la formation d'une chimie d'accrochage d'éléments biologiques ou biochimiques, et/ou électriquement, pour y permettre la formation de charges électriques, caractérisé en ce que le support comprend au moins une partie réalisée en matériau composite, le matériau composite étant un mélange d'au moins un matériau inerte et d'au moins un matériau fonctionnalisable chimiquement et/ou électriquement pour fournir ladite zone de surface fonctionnalisée. De préférence, le matériau inerte du matériau composite est un matériau choisi parmi un polymère, un plastique, une résine et une colle. Le polymère peut être un polyimide, un poly (diméthylsiloxane) ou une résine photosensible de type époxy.The subject of the invention is therefore a component for a biological or biochemical analysis microsystem formed from a support and having at least one surface area chemically functionalized, to allow the formation of a chemistry for the attachment of elements. biological or biochemical, and / or electrically, to allow the formation of electric charges therein, characterized in that the support comprises at least one part made of composite material, the composite material being a mixture of at least one inert material and at least one chemically and / or electrically functionalizable material for providing said functionalized surface area. Preferably, the inert material of the composite material is a material chosen from a polymer, a plastic, a resin and an adhesive. The polymer can be a polyimide, a poly (dimethylsiloxane) or a photosensitive resin of the epoxy type.
Ladite partie peut former le support dans sa totalité.Said part can form the support in its entirety.
Le support peut comprendre un substrat supportant ladite partie. Le substrat peut être en un matériau choisi parmi le verre, la silice, le silicium, un polymère et un métal .The support may comprise a substrate supporting said part. The substrate can be made of a material chosen from glass, silica, silicon, a polymer and a metal.
Ladite partie peut être structurée. Avantageusement, le matériau fonctionnalisable est choisi parmi la silice, la silice synthétisée, le nitrure de silicium, un métal et un polymère fonctionnalisable.Said part can be structured. Advantageously, the functionalizable material is chosen from silica, synthesized silica, silicon nitride, a metal and a functionalizable polymer.
Le matériau composite peut être un mélange comprenant une phase de matériau inerte et une phase de matériau fonctionnalisable.The composite material can be a mixture comprising a phase of inert material and a phase of functionalizable material.
Il peut aussi être constitué d'éléments d'un matériau fonctionnalisable dispersés dans le matériau inerte. Le matériau fonctionnalisable peut se présenter sous la forme de billes. Ladite zone de surface peut supporter des fonctions chimiques aptes à assurer la fixation d'éléments biologiques ou d'autres fonctions chimiques sur ladite zone de surface.It can also consist of elements of a functionalizable material dispersed in the inert material. The functionalizable material can be in the form of beads. Said surface area can support chemical functions capable of ensuring the attachment of biological elements or other chemical functions to said surface area.
Ladite zone de surface peut supporter des fonctions chimiques aptes à assurer la présence de charges électriques sur ladite zone de surface. L'invention a aussi pour objet un procédé de réalisation d'un composant pour microsystème d'analyse biologique ou biochimique à partir d'un support, le support devant présenter au moins une zone de surface fonctionnalisée chimiquement pour y permettre la formation d'une chimie d'accrochage d'éléments biologiques ou biochimiques, et/ou électriquement, pour y permettre la formation de charges électriques, caractérisé en ce qu'il comprend la réalisation d'un support comprenant au moins une partie en matériau composite, le matériau composite étant un mélange d'au moins un matériau inerte et d'au moins un matériau fonctionnalisable chimiquement et/ou électriquement pour fournir ladite zone de surface fonctionnalisée.Said surface area can support chemical functions capable of ensuring the presence of electrical charges on said surface area. The subject of the invention is also a method of producing a component for a microsystem for biological or biochemical analysis from a support, the support having to present at least one surface area chemically functionalized to allow the formation of a chemistry for attaching biological or biochemical elements, and / or electrically, to allow the formation of electrical charges therein, characterized in that it comprises the production of a support comprising at least one part made of composite material, the composite material being a mixture of at least one inert material and at least one chemically and / or electrically functionalizable material to provide said functionalized surface area.
Selon une première variante de mise en œuvre, le matériau composite peut être obtenu par mélange en phases liquides du matériau inerte et du matériau fonctionnalisable, le mélange étant ensuite solidifié pour fournir ladite partie en matériau composite.According to a first implementation variant, the composite material can be obtained by mixing in liquid phases the inert material and the functionalizable material, the mixture then being solidified to provide said part in composite material.
Selon une deuxième variante de mise en œuvre, le matériau composite peut être obtenu par dispersion d'éléments en matériau fonctionnalisable dans le matériau inerte en phase liquide, le mélange étant ensuite solidifié pour fournir ladite partie en matériau composite. De préférence, lesdits éléments en matériau fonctionnalisable sont sous forme de billes.According to a second implementation variant, the composite material can be obtained by dispersing elements of functionalizable material in the inert material in the liquid phase, the mixture then being solidified to provide said part in composite material. Preferably, said elements made of functionalizable material are in the form of balls.
Le matériau inerte en phase liquide dans lequel sont dispersés lesdits éléments peut être coulé sur un support à empreinte (s) avant d'être solidifié. Le support à empreinte (s) peut être retiré après solidification du mélange.The inert liquid phase material in which said elements are dispersed can be poured onto a support with imprint (s) before being solidified. The impression support (s) can be removed after the mixture has solidified.
Le matériau inerte en phase liquide dans lequel sont dispersés lesdits éléments peut être déposé sur un support avant d'être solidifié. Si le matériau inerte est un matériau photosensible, ladite partie en matériau composite peut être, après solidification, structurée par photo-lithographie. Si le dépôt se fait sur une surface du support présentant au moins une empreinte, le matériau composite peut être, après solidification, éliminé hors de l'empreinte. Si le matériau inerte est un matériau photosensible, l'élimination du matériau composite hors de l'empreinte peut se faire par photo-lithographie. Selon une troisième variante de mise en œuvre, le support présentant une face avec au moins une empreinte, des éléments en matériau fonctionnalisable sont déposés au fond de l'empreinte, puis le matériau inerte en phase liquide est coulé sur ladite face du support, ensuite le matériau inerte est solidifié pour fournir le matériau composite au fond de l'empreinte, le support étant enfin retiré. Avantageusement, lesdits éléments en matériau fonctionnalisable sont sous forme de billes. Quel que soit le mode de mise en œuvre, la solidification peut être obtenue par un traitement thermique .The inert liquid phase material in which said elements are dispersed can be deposited on a support before being solidified. If the inert material is a photosensitive material, said part made of composite material can be, after solidification, structured by photo-lithography. If the deposit is made on a surface of the support having at least one imprint, the composite material can be, after solidification, removed from the imprint. If the inert material is a photosensitive material, the removal of the composite material from the imprint can be done by photo-lithography. According to a third implementation variant, the support having a face with at least one imprint, elements of functionalizable material are deposited at the bottom of the imprint, then the inert material in liquid phase is poured onto said face of the support, then the inert material is solidified to provide the composite material at the bottom of the imprint, the support being finally removed. Advantageously, said elements made of functionalizable material are in the form of balls. Whatever the mode of implementation, solidification can be obtained by heat treatment.
BRÈVE DESCRIPTION DES DESSINSBRIEF DESCRIPTION OF THE DRAWINGS
L'invention sera mieux comprise et d'autres avantages et particularités apparaîtront à la lecture de la description qui va suivre, donnée à titre d'exemple non limitatif, accompagnée des dessins annexés parmi lesquels :The invention will be better understood and other advantages and features will appear on reading the description which follows, given by way of non-limiting example, accompanied by the appended drawings in which:
- les figures 1A et 1B sont des vues en coupe illustrant la réalisation d'un premier composant pour microsystème d'analyse biologique ou biochimique selon 1 ' invention,FIGS. 1A and 1B are sectional views illustrating the production of a first component for a biological or biochemical analysis microsystem according to the invention,
- les figures 2A et 2B sont des vues en coupe illustrant la réalisation d'un deuxième composant pour microsystème d'analyse biologique ou biochimique selon l'invention,FIGS. 2A and 2B are sectional views illustrating the production of a second component for a biological or biochemical analysis microsystem according to the invention,
- les figures 3A et 3B sont des vues en coupe illustrant la réalisation d'un troisième composant pour microsystème d'analyse biologique ou biochimique selon l'invention, - les figures 4A à 4C sont des vues en coupe illustrant la réalisation d'un quatrième composant pour microsystème d'analyse biologique ou biochimique selon l'invention.- Figures 3A and 3B are sectional views illustrating the production of a third component for a biological or biochemical analysis microsystem according to the invention, - Figures 4A to 4C are sectional views illustrating the production of a fourth component for microsystem for biological or biochemical analysis according to the invention.
DESCRIPTION DETAILLEE DE MODES DE RÉALISATION DE L• INVENTIONDETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION
Les figures 1A et 1B illustrent la réalisation d'un composant pour microsystème d'analyse biologique ou biochimique en utilisant un support à empreinte . La figure 1A montre un support 10, par exemple en silicium, dont la face supérieure a été usinée ou gravée pour former une empreinte consistant en une dépression 11 prolongée par des tranchées 12. Sur l'empreinte, on vient couler un mélange d'un matériau composite liquide 13 constitué d'un polymèreFIGS. 1A and 1B illustrate the production of a component for a biological or biochemical analysis microsystem using an imprint support. FIG. 1A shows a support 10, for example made of silicon, the upper face of which has been machined or engraved to form an imprint consisting of a depression 11 extended by trenches 12. On the imprint, a mixture of a liquid composite material 13 consisting of a polymer
(par exemple du poly (diméthylsiloxane) ) et de microbilles (par exemple des billes de silice de 1 μm de diamètre) . La quantité de matériau composite liquide est prévue pour remplir l'empreinte dans sa totalité.(e.g. poly (dimethylsiloxane)) and microbeads (for example silica beads 1 μm in diameter). The quantity of liquid composite material is provided to fill the entire impression.
Le support et son contenu sont . alors disposés dans une étuve maintenue à 60°C pendant 4 heures .The medium and its content are. then placed in an oven maintained at 60 ° C for 4 hours.
Après évacuation des solvants contenus dans le polymère, le matériau composite est démoulé du support . Le composant 16 obtenu est représenté à la figure 1B. Il comprend une base 14 complémentaire de la dépression 11 et des parois 15 perpendiculaires à la base et complémentaires des tranchées 12. Deux parois consécutives définissent un canal. Le composant obtenu est prêt à subir des protocoles chimiques et/ou électriques permettant de le fonctionnaliser.After removal of the solvents contained in the polymer, the composite material is removed from the support. The component 16 obtained is shown in FIG. 1B. It comprises a base 14 complementary to the depression 11 and walls 15 perpendicular to the base and complementary to the trenches 12. Two consecutive walls define a channel. The component obtained is ready to undergo chemical and / or electrical protocols allowing it to be functionalized.
Les figures 2A et 2B illustrent la réalisation d'un composant pour microsystème d'analyse biologique ou biochimique à partir d'un matériau composite photosensible. Des motifs en polymère ou en résine photosensible peuvent être réalisés sur des substrats plans, ce qui évite l'utilisation de machines de gravure complexe. Par exemple, la réalisation de plots ou de canaux dans une lame de verre ou de silicium est remplacée par une simple photo-1ithographie .FIGS. 2A and 2B illustrate the production of a component for a microsystem for biological or biochemical analysis from a photosensitive composite material. Polymer or photosensitive resin patterns can be produced on flat substrates, which avoids the use of complex engraving machines. For example, the production of studs or channels in a glass or silicon slide is replaced by a simple photo-1ithography.
La gravure profonde du verre est délicate. Elle ne peut être réalisée par plasma à cause du blocage de la gravure par les impuretés ioniques et métalliques contenues dans le verre. Le verre est donc gravé par voie chimique isotrope, ce qui interdit la réalisation de motifs fins à faibles pas. L'invention permet de réaliser de telles structures en utilisant un matériau composite photosensible.The deep etching of the glass is delicate. It cannot be produced by plasma because of the blocking of the etching by the ionic and metallic impurities contained in the glass. The glass is therefore etched by isotropic chemistry, which prevents the production of fine patterns with low steps. The invention allows to realize such structures using a photosensitive composite material.
La figure 2A montre un support 20 en silicium de 100 mm de diamètre dont la face supérieure est recouverte d'une couche de matériau composite 21. Le matériau composite est constitué d'un polyimide photosensible commercialisé sous l'appellation "Probimide 7510" dans lequel sont dispersées des microbilles, par exemple des billes de silice de 1 μm de diamètre. Le mélange est déposé à la tournette sur le support 20 à une vitesse de 3000 tours/minute puis recuit à 110°C sur une plaque chauffante.FIG. 2A shows a silicon support 20 with a diameter of 100 mm, the upper face of which is covered with a layer of composite material 21. The composite material consists of a photosensitive polyimide sold under the name "Probimide 7510" in which microbeads are dispersed, for example silica beads 1 μm in diameter. The mixture is deposited with the spinner on the support 20 at a speed of 3000 revolutions / minute then annealed at 110 ° C. on a hot plate.
Le matériau composite est insolé par des rayons ultra-violets à travers un masque puis développé afin d'obtenir le composant souhaité, par exemple celui représenté à la figure 2B où des tranchées 22 sont visibles dans le matériau composite 21. Ensuite, le matériau composite est recuit à 150°C sur une plaque chauffante, puis à 300°C dans un four de traitement thermique.The composite material is exposed by ultraviolet rays through a mask and then developed in order to obtain the desired component, for example that shown in FIG. 2B where trenches 22 are visible in the composite material 21. Next, the composite material is annealed at 150 ° C on a hot plate, then at 300 ° C in a heat treatment oven.
Les figures 3A et 3B illustrent la réalisation d'un composant pour microsystème d'analyse biologique ou biochimique pour lequel le matériau composite est localisé dans un canal. La figure 3A montre un support 30 en polymère dont une face présente une empreinte 31 réalisée par une technique classique telle que l'emboutissage, le moulage ou l'ablation laser. Une couche 32 de matériau composite est déposée sur la face présentant une empreinte en recouvrant les parois de l'empreinte. Le matériau composite est constitué d'un polyimide photosensible commercialisé sous l'appellation "Probimide 7510" dans lequel sont dispersées des microbilles, par exemple des billes de silice de 1 μm de diamètre. Le matériau composite est déposé par trempage puis recuit à 110°C sur une plaque chauffante.FIGS. 3A and 3B illustrate the production of a component for a biological or biochemical analysis microsystem for which the composite material is located in a channel. FIG. 3A shows a polymer support 30, one face of which has an imprint 31 produced by a conventional technique such as stamping, molding or laser ablation. A layer 32 of composite material is deposited on the face having an imprint by covering the walls of the imprint. The composite material consists of a photosensitive polyimide sold under the name "Probimide 7510" in which microbeads are dispersed, for example silica beads of 1 μm in diameter. The composite material is deposited by soaking and then annealed at 110 ° C on a heating plate.
Le matériau composite déposé est insolé, à travers un masque, par des rayons ultra-violets puis développé afin d'obtenir le composant souhaité, représenté à la figure 3B. Pour ce composant, seules les parois de l'empreinte 31 sont recouvertes d'une couche 33 de matériau composite. Le matériau composite est ensuite recuit à 150°C sur une plaque chauffante puis à 300°C dans un four de traitement thermique. Les figure 4A à 4C illustrent la réalisation d'un composant pour microsystème d'analyse biologique ou biochimique où le matériau composite est obtenu par dépôt de matériau inerte sur un lit de billes . La figure 4A montre un support 40, par exemple un support en silicium de 100 mm de diamètre, dont la face supérieure a été usinée ou gravée pour former une empreinte consistant en une série de tranchées parallèles 41. On dépose au fond des tranchées 41 des billes 42 en silice de 100 μm de diamètre .The deposited composite material is exposed, through a mask, by ultraviolet rays and then developed in order to obtain the desired component, shown in FIG. 3B. For this component, only the walls of the imprint 31 are covered with a layer 33 of composite material. The composite material is then annealed at 150 ° C on a heating plate and then at 300 ° C in a heat treatment oven. FIGS. 4A to 4C illustrate the production of a component for a biological or biochemical analysis microsystem where the composite material is obtained by depositing inert material on a bed of beads. FIG. 4A shows a support 40, for example a silicon support 100 mm in diameter, the upper face of which has been machined or engraved to form an imprint consisting of a series of parallel trenches 41. Trenches 41 are deposited at the bottom 42 silica beads 100 μm in diameter.
Comme le montre la figure 4B un matériau inerte 43, par exemple un poly(diméthylsiloxane) , est coulé sur le support 40. Le matériau inerte remplit les tranchées 41 et se mélange avec les billes 42 au fond des tranchées . L'ensemble est disposé dans une étuve à 60°C pendant 4 heures. Après évacuation des solvants contenus dans le polymère, on procède au démoulage. On obtient le composant représenté à la figure 4C constitué d'une base 44 et de parois 45, le sommet 46 des parois étant en matériau composite. Le composant est prêt à subir des protocoles chimiques permettant de le fonctionnaliser.As shown in FIG. 4B, an inert material 43, for example a poly (dimethylsiloxane), is poured onto the support 40. The inert material fills the trenches 41 and mixes with the balls 42 at the bottom of the trenches. The whole is placed in an oven at 60 ° C for 4 hours. After evacuation of the solvents contained in the polymer, the mold is removed. We obtain the component shown in Figure 4C consisting of a base 44 and walls 45, the top 46 of the walls being of composite material. The component is ready to undergo chemical protocols allowing it to be functionalized.
On peut utiliser des billes préalablement fonctionnalisées comme celles que l'on trouve dans le commerce. Ces billes possèdent à leur surface des fonctions chimiques (acide, aminé, aldéhyde) ou des groupements biologiques (avidine, biotine) . Ces billes fonctionnalisées sont alors mélangées au matériau inerte afin de réaliser un matériau composite comprenant une phase inerte et une phase fonctionnalisée .One can use previously functionalized beads like those found on the market. These beads have chemical functions (acid, amino, aldehyde) or biological groups on their surface (avidin, biotin). These functionalized beads are then mixed with the inert material in order to produce a composite material comprising an inert phase and a functionalized phase.
Selon la nature du matériau fonctionnalisable, différentes techniques peuvent être employées pour le fonctionnaliser. Pour des matériaux tels que le silicium, l'oxyde de silicium, le nitrure de silicium ou la silice synthétique, un traitement de silanisation permet de fixer à la surface de ces matériaux des fonctions chimiques qui assureront ultérieurement la fixation d'éléments biologiques ou de fonctions chimiques.Depending on the nature of the functionalizable material, different techniques can be used to functionalize it. For materials such as silicon, silicon oxide, silicon nitride or synthetic silica, a silanization treatment makes it possible to fix chemical functions on the surface of these materials which will subsequently ensure the attachment of biological elements or chemical functions.
Différents types de silanes peuvent être utilisés. Chacun possède son propre protocole de fixation à la surface du matériau à fonctionnaliser. Le choix du silane à employer dépend de la fonction chimique que l'on veut utiliser soit directement, soit pour la réalisation ultérieure d'une réaction chimique ou de la fixation d'un élément biologique. Parmi les silanes les plus couramment utilisés, on peut citer 1' aminopropyltriéthoxysilane, l' aminopropyldiméthylé- thoxysilane, le silane époxy, le 2- (hydroxyéthyl) -3- aminopropyltriéthoxysilane .Different types of silanes can be used. Each has its own fixing protocol on the surface of the material to be functionalized. The choice of silane to use depends on the chemical function that you want to use either directly or for the subsequent carrying out of a chemical reaction or the fixation of a biological element. Among the most commonly used silanes, mention may be made of aminopropyltriethoxysilane, aminopropyldimethylethoxysilane, epoxy silane, 2- (hydroxyethyl) -3- aminopropyltriethoxysilane.
A titre d'exemple, le protocole de silanisation utilisé pour l' aminopropyltriéthoxysilane est le suivant : - traitement de la surface concernée par un plasma d'oxygène (Nextral 310) à 150 watts pendant 30 secondes pour créer sur la surface des fonctions silanol ;For example, the silanization protocol used for aminopropyltriethoxysilane is as follows: treatment of the surface concerned with an oxygen plasma (Nextral 310) at 150 watts for 30 seconds to create silanol functions on the surface;
- incubation dans une solution de silane à 10% dans de l'éthanol à 95% pendant 12 heures ;- incubation in a 10% silane solution in 95% ethanol for 12 hours;
- rinçage à l'eau distillée ;- rinsing with distilled water;
- rinçage à l'éthanol à 95%- 95% ethanol rinse
- recuit à 110°C pendant 3 heures en étuve . On peut fixer directement des oligonucleotides synthétisés avec une fonction aldéhyde ou par l'intermédiaire d'un glutaraldéhyde si les oligonucleotides sont synthétisés avec une fonction NH2.- annealing at 110 ° C for 3 hours in an oven. Oligonucleotides synthesized with an aldehyde function can be fixed directly or via a glutaraldehyde if the oligonucleotides are synthesized with an NH 2 function.
Cette technique de silanisation permet de fixer des oligonucleotides, des protéines ou tout élément biologique ou chimique compatible avec les fonctions présentes sur le silane fixé au matériau fonctionnalisé (fonctions aminé, acide aldéhyde, ester activé,...) . Si le matériau à fonctionnaliser est une couche d'or, on utilise la fixation de thiols ou de composés disulfurês sur la surface de cette couche métallique. Comme pour les silanes, différents thiols permettent d'obtenir à la surface de la couche à fonctionnaliser les fonctions chimiques nécessaires aux réactions chimiques voulues. Les techniques de fixation des thiols sur une surface métallique sont connues, par exemple par le document suivant : « Formation of Monolayer Films by the Spontaneous Assembly of Organic Thiols from Solution onto Gold » de C. D. BAIN et al., J. Am. Chem. Soc. 1989, Vol. 111, N° 1, pages 321 à 335.This silanization technique makes it possible to fix oligonucleotides, proteins or any biological or chemical element compatible with the functions present on the silane attached to the functionalized material (amino functions, aldehyde acid, activated ester, etc.). If the material to be functionalized is a layer of gold, the fixing of thiols or of disulfurized compounds on the surface of this metallic layer. As with silanes, different thiols make it possible to obtain on the surface of the layer to functionalize the chemical functions necessary for the desired chemical reactions. The techniques for fixing thiols on a metal surface are known, for example by the following document: “Formation of Monolayer Films by the Spontaneous Assembly of Organic Thiols from Solution onto Gold” by CD BAIN et al., J. Am. Chem. Soc. 1989, Vol. 111, No. 1, pages 321 to 335.
Toujours à titre d'exemple, on peut citer le greffage d'acide mercapto-propionique ou de cystamine en incubant une solution à Im pendant 3 heures dans de l'éthanol absolu à température ambiante.Still by way of example, mention may be made of the grafting of mercaptopropionic acid or of cystamine by incubating a solution at Im for 3 hours in absolute ethanol at room temperature.
Pour une fonctionnalisation électrique, on peut obtenir des charges électriques en surface de silice synthétique, de silicium, de nitrure de silicium et d'oxyde de silicium en greffant un aminopropyltriéthoxysilane sur la couche à fonctionnaliser selon le protocole présenté ci-dessus. Un traitement en milieu acide (par exemple HCl 0,2M) permet de protéger le groupement aminé du silane et d'obtenir des charges électriques en surface du matériau fonctionnalisé. For electrical functionalization, electrical charges can be obtained on the surface of synthetic silica, silicon, silicon nitride and silicon oxide by grafting an aminopropyltriethoxysilane onto the layer to be functionalized according to the protocol presented above. A treatment in an acid medium (for example 0.2M HCl) makes it possible to protect the amino group of the silane and to obtain electrical charges on the surface of the functionalized material.

Claims

REVENDICATIONS
1. Composant pour microsystème d'analyse biologique ou biochimique formé à partir d'un support et possédant au moins une zone de surface fonctionnalisée chimiquement, pour y permettre la formation d'une chimie d'accrochage d'éléments biologiques ou biochimiques, et/ou électriquement, pour y permettre la formation de charges électriques, caractérisé en ce que le support comprend au moins une partie (16, 21, 33, '46) réalisée en matériau composite, le matériau composite étant un mélange d'au moins un matériau inerte et d'au moins un matériau fonctionnalisable chimiquement et/ou électriquement pour fournir ladite zone de surface fonctionnalisée.1. Component for biological or biochemical analysis microsystem formed from a support and having at least one chemically functionalized surface area, to allow the formation of a chemistry for attachment of biological or biochemical elements, and / or electrically, to allow the formation of electrical charges, characterized in that the support comprises at least one portion (16, 21, 33, '46) made of composite material, the composite material being a mixture of at least one material inert and at least one chemically and / or electrically functionalizable material to provide said functionalized surface area.
2. Composant selon la revendication 1, caractérisé en ce que le matériau inerte du matériau composite est un matériau choisi parmi un polymère, un plastique, une résine et une colle.2. Component according to claim 1, characterized in that the inert material of the composite material is a material chosen from a polymer, a plastic, a resin and an adhesive.
3. Composant selon la revendication 2, caractérisé en ce que le polymère est un polyimide, un poly (diméthylsiloxane) ou une résine photosensible de type époxy..3. Component according to claim 2, characterized in that the polymer is a polyimide, a poly (dimethylsiloxane) or a photosensitive resin of epoxy type.
4. Composant selon la revendication 1, caractérisé en ce que ladite partie (16) forme le support dans sa totalité. 4. Component according to claim 1, characterized in that said part (16) forms the support in its entirety.
5. Composant selon la revendication 1, caractérisé en ce que le support comprend un substrat (20, 30) supportant ladite partie.5. Component according to claim 1, characterized in that the support comprises a substrate (20, 30) supporting said part.
6. Composant selon la revendication 5, caractérisé en ce que le substrat (20, 30) est en un matériau choisi parmi le verre, la silice, le silicium, un polymère et un métal .6. Component according to claim 5, characterized in that the substrate (20, 30) is made of a material chosen from glass, silica, silicon, a polymer and a metal.
7. Composant selon l'une quelconque des revendications 1 à 6, caractérisé en ce que ladite partie (21) est structurée.7. Component according to any one of claims 1 to 6, characterized in that said part (21) is structured.
8. Composant selon l'une quelconque des revendications 1 à 7, caractérisé en ce que le matériau fonctionnalisable est choisi parmi la silice, la silice synthétisée, le nitrure de silicium, un métal et un polymère fonctionnalisable.8. Component according to any one of claims 1 to 7, characterized in that the functionalizable material is chosen from silica, synthesized silica, silicon nitride, a metal and a functionalizable polymer.
9. Composant selon l'une quelconque des revendications 1 à 8, caractérisé en ce que le matériau composite est un mélange comprenant une phase de matériau inerte et une phase de matériau fonctionnalisable .9. Component according to any one of claims 1 to 8, characterized in that the composite material is a mixture comprising a phase of inert material and a phase of functionalizable material.
10. Composant selon l'une quelconque des revendications 1 à 8, caractérisé en ce que le matériau composite est constitué d'éléments d'un matériau fonctionnalisable dispersés dans le matériau inerte. 10. Component according to any one of claims 1 to 8, characterized in that the composite material consists of elements of a functionalizable material dispersed in the inert material.
11. Composant selon la revendication 10, caractérisé en ce que le matériau fonctionnalisable se présente sous la forme de billes (42) .11. Component according to claim 10, characterized in that the functionalizable material is in the form of balls (42).
12. Composant selon l'une quelconque des revendications l à 11, caractérisé en ce que ladite zone de surface supporte des fonctions chimiques aptes à assurer la fixation d'éléments biologiques ou d'autres fonctions chimiques sur ladite zone de surface.12. Component according to any one of claims l to 11, characterized in that said surface area supports chemical functions capable of ensuring the fixation of biological elements or other chemical functions on said surface area.
13. Composant selon l'une quelconque des revendications 1 à 11, caractérisé en ce que ladite zone de surface supporte des fonctions chimiques aptes à assurer la présence de charges électriques sur ladite zone de surface .13. Component according to any one of claims 1 to 11, characterized in that said surface area supports chemical functions capable of ensuring the presence of electrical charges on said surface area.
14. Procédé de réalisation d'un composant pour microsystème d'analyse biologique ou biochimique à partir d'un support, le support devant présenter au moins une zone de surface fonctionnalisée chimiquement pour y permettre la formation d'une chimie d'accrochage d'éléments biologiques ou biochimiques, et/ou électriquement, pour y permettre la formation de charges électriques, caractérisé en ce qu'il comprend la réalisation d'un support comprenant au moins une partie (16, 21, 33, 46) en matériau composite, le matériau composite étant un mélange d'au moins un matériau inerte et d'au moins un matériau fonctionnalisable chimiquement et/ou électriquement pour fournir ladite zone de surface fonctionnalisée. 14. Method for producing a component for a biological or biochemical analysis microsystem from a support, the support having to present at least one surface area chemically functionalized to allow the formation of a bonding chemistry of biological or biochemical elements, and / or electrically, to allow the formation of electric charges therein, characterized in that it comprises the production of a support comprising at least one part (16, 21, 33, 46) of composite material, the composite material being a mixture of at least one inert material and at least one chemically and / or electrically functionalizable material to provide said functionalized surface area.
15. Procédé selon la revendication 14, caractérisé en ce que le matériau composite est obtenu par mélange en phases liquides du matériau inerte et du15. The method of claim 14, characterized in that the composite material is obtained by mixing in liquid phases the inert material and
5 matériau fonctionnalisable, le mélange étant ensuite solidifié pour fournir ladite partie en matériau composite .5 functionalizable material, the mixture then being solidified to provide said part in composite material.
16. Procédé selon la revendication 14, 10 caractérisé en ce que le matériau composite est obtenu par dispersion d'éléments en matériau fonctionnalisable dans le matériau inerte en phase liquide, le mélange étant ensuite solidifié pour fournir ladite partie en matériau composite. 1516. The method of claim 14, 10 characterized in that the composite material is obtained by dispersing elements of functionalizable material in the inert material in the liquid phase, the mixture then being solidified to provide said part in composite material. 15
17. Procédé selon la revendication-- 16, caractérisé en ce que lesdits éléments en matériau fonctionnalisable sont sous forme de billes (42) .17. The method of claim-- 16, characterized in that said elements of functionalizable material are in the form of balls (42).
20 18. Procédé selon l'une des revendications18. Method according to one of claims
16 ou 17, caractérisé en ce que le matériau inerte en phase liquide dans lequel sont dispersés lesdits éléments est coulé sur un support à empreinte (s) (10) avant d'être solidifié.16 or 17, characterized in that the inert liquid phase material in which the said elements are dispersed is poured onto an impression support (10) before being solidified.
2525
19. Procédé selon la revendication 18, caractérisé en ce que le support à empreinte (s) (10) est retiré après solidification du mélange.19. The method of claim 18, characterized in that the imprint support (s) (10) is removed after solidification of the mixture.
30. 30.
20. Procédé selon l'une des revendications20. Method according to one of claims
16 ou 17, caractérisé en ce que le matériau inerte en phase liquide dans lequel sont dispersés lesdits éléments est déposé sur un support (20, 30) avant d'être solidifié.16 or 17, characterized in that the inert material in liquid phase in which said elements are dispersed is deposited on a support (20, 30) before being solidified.
21. Procédé selon la revendication 20, caractérisé en ce que le matériau inerte étant un matériau photosensible, ladite partie en matériau composite (21) est, après solidification, structurée par photo-lithographie.21. The method of claim 20, characterized in that the inert material being a photosensitive material, said part made of composite material (21) is, after solidification, structured by photo-lithography.
22. Procédé selon la revendication 20, caractérisé en ce que le dépôt se faisant sur une surface du support (30) présentant au moins une empreinte (31) , le matériau composite (32) est, après solidification, éliminé hors de l'empreinte.22. Method according to claim 20, characterized in that the deposition being made on a surface of the support (30) having at least one imprint (31), the composite material (32) is, after solidification, removed from the imprint .
23. Procédé selon la revendication 22, caractérisé en ce que le matériau inerte étant un matériau photosensible, l'élimination du matériau composite hors de l'empreinte se fait par photolithographie .23. The method of claim 22, characterized in that the inert material being a photosensitive material, the removal of the composite material from the imprint is done by photolithography.
24. Procédé selon la revendication 14, caractérisé en ce que le support (40) présentant une face avec au moins une empreinte (41) , des éléments en matériau fonctionnalisable (42) sont déposés au fond de l'empreinte, puis le matériau inerte (43) en phase liquide est coulé sur ladite face du support, ensuite le matériau inerte est solidifié pour fournir le matériau composite (46) au fond de l'empreinte, le support étant enfin retiré. 24. The method of claim 14, characterized in that the support (40) having a face with at least one imprint (41), elements of functionalizable material (42) are deposited at the bottom of the imprint, then the inert material (43) in the liquid phase is poured onto said face of the support, then the inert material is solidified to provide the composite material (46) at the bottom of the impression, the support finally being removed.
25. Procédé selon la revendication 24, caractérisé en ce que lesdits éléments en matériau fonctionnalisable (42) sont sous forme de billes.25. The method of claim 24, characterized in that said elements of functionalizable material (42) are in the form of balls.
26. Procédé selon l'une quelconque des revendications 15 à 25, caractérisé en ce que ladite solidification est obtenue par un traitement thermique. 26. Method according to any one of claims 15 to 25, characterized in that said solidification is obtained by a heat treatment.
EP03717419A 2002-02-21 2003-02-20 Composite material for a biological or biochemical analysis microfluidic system Ceased EP1476755A1 (en)

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FR0202206 2002-02-21
FR0202206A FR2836072B1 (en) 2002-02-21 2002-02-21 COMPONENT USING COMPOSITE MATERIAL FOR MICROSYSTEM FOR BIOLOGICAL OR BIOCHEMICAL ANALYSIS
PCT/FR2003/000567 WO2003071277A1 (en) 2002-02-21 2003-02-20 Composite material for a biological or biochemical analysis microfluidic system

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FR2836072A1 (en) 2003-08-22
US20040126779A1 (en) 2004-07-01
FR2836072B1 (en) 2004-11-12
JP2005517958A (en) 2005-06-16
WO2003071277A1 (en) 2003-08-28

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