WO2003071277A1 - Materiau composite pour microsysteme d'analyse biologique ou biochimique - Google Patents
Materiau composite pour microsysteme d'analyse biologique ou biochimique Download PDFInfo
- Publication number
- WO2003071277A1 WO2003071277A1 PCT/FR2003/000567 FR0300567W WO03071277A1 WO 2003071277 A1 WO2003071277 A1 WO 2003071277A1 FR 0300567 W FR0300567 W FR 0300567W WO 03071277 A1 WO03071277 A1 WO 03071277A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composite material
- support
- functionalizable
- inert
- elements
- Prior art date
Links
- 239000002131 composite material Substances 0.000 title claims abstract description 58
- 238000012742 biochemical analysis Methods 0.000 title claims abstract description 18
- 239000000463 material Substances 0.000 claims abstract description 86
- 239000000126 substance Substances 0.000 claims abstract description 18
- 239000000203 mixture Substances 0.000 claims abstract description 17
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 19
- 229920000642 polymer Polymers 0.000 claims description 19
- 239000000377 silicon dioxide Substances 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 239000011521 glass Substances 0.000 claims description 11
- 239000007791 liquid phase Substances 0.000 claims description 11
- 229910052710 silicon Inorganic materials 0.000 claims description 9
- 239000010703 silicon Substances 0.000 claims description 9
- 239000012071 phase Substances 0.000 claims description 8
- 239000000758 substrate Substances 0.000 claims description 8
- 229920005989 resin Polymers 0.000 claims description 7
- 239000011347 resin Substances 0.000 claims description 7
- 238000007711 solidification Methods 0.000 claims description 7
- 230000008023 solidification Effects 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000004033 plastic Substances 0.000 claims description 6
- 229920003023 plastic Polymers 0.000 claims description 6
- 239000004642 Polyimide Substances 0.000 claims description 4
- 229910052581 Si3N4 Inorganic materials 0.000 claims description 4
- 238000000206 photolithography Methods 0.000 claims description 4
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 4
- 229920001721 polyimide Polymers 0.000 claims description 4
- HQVNEWCFYHHQES-UHFFFAOYSA-N silicon nitride Chemical compound N12[Si]34N5[Si]62N3[Si]51N64 HQVNEWCFYHHQES-UHFFFAOYSA-N 0.000 claims description 4
- 239000004593 Epoxy Substances 0.000 claims description 3
- 239000000853 adhesive Substances 0.000 claims description 3
- 230000001070 adhesive effect Effects 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000000151 deposition Methods 0.000 claims description 2
- -1 poly (dimethylsiloxane) Polymers 0.000 claims description 2
- 230000008021 deposition Effects 0.000 claims 1
- 239000011324 bead Substances 0.000 description 11
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 8
- 239000010410 layer Substances 0.000 description 7
- 238000002444 silanisation Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 229910000077 silane Inorganic materials 0.000 description 5
- 150000003573 thiols Chemical class 0.000 description 4
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 238000007306 functionalization reaction Methods 0.000 description 3
- 239000011325 microbead Substances 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- 150000004756 silanes Chemical class 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000005530 etching Methods 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 229910052814 silicon oxide Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- DLOSDQIBVXBWTB-UHFFFAOYSA-N 1-[dimethyl(propyl)silyl]oxyethanamine Chemical compound CCC[Si](C)(C)OC(C)N DLOSDQIBVXBWTB-UHFFFAOYSA-N 0.000 description 1
- FYJBSSZUXFVIDH-UHFFFAOYSA-N 3-(aminomethyl)-4-triethoxysilylbutan-1-ol Chemical compound CCO[Si](OCC)(OCC)CC(CN)CCO FYJBSSZUXFVIDH-UHFFFAOYSA-N 0.000 description 1
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 241001082241 Lythrum hyssopifolia Species 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- OOTFVKOQINZBBF-UHFFFAOYSA-N cystamine Chemical compound CCSSCCN OOTFVKOQINZBBF-UHFFFAOYSA-N 0.000 description 1
- 229940099500 cystamine Drugs 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000005370 electroosmosis Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000000608 laser ablation Methods 0.000 description 1
- 239000002991 molded plastic Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000000678 plasma activation Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000005372 silanol group Chemical group 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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.
Abstract
Description
Claims
Priority Applications (3)
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JP2003570129A JP2005517958A (ja) | 2002-02-21 | 2003-02-20 | 生物又は生化学分析マイクロシステム用に集積され、コンポジット材料を用いるコンポーネント |
EP03717419A EP1476755A1 (fr) | 2002-02-21 | 2003-02-20 | Materiau composite pour microsysteme d'analyse biologique ou biochimique |
US10/475,634 US7214478B2 (en) | 2002-02-21 | 2003-02-20 | Composite material for biological or biochemical analysis microfluidic system |
Applications Claiming Priority (2)
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FR02/02206 | 2002-02-21 | ||
FR0202206A FR2836072B1 (fr) | 2002-02-21 | 2002-02-21 | Composant utilisant un materiau composite et destine a un microsysteme d'analyse biologique ou biochimique |
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WO2003071277A1 true WO2003071277A1 (fr) | 2003-08-28 |
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PCT/FR2003/000567 WO2003071277A1 (fr) | 2002-02-21 | 2003-02-20 | Materiau composite pour microsysteme d'analyse biologique ou biochimique |
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US (1) | US7214478B2 (fr) |
EP (1) | EP1476755A1 (fr) |
JP (1) | JP2005517958A (fr) |
FR (1) | FR2836072B1 (fr) |
WO (1) | WO2003071277A1 (fr) |
Cited By (3)
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US8585971B2 (en) | 2005-04-05 | 2013-11-19 | The General Hospital Corporation | Devices and method for enrichment and alteration of cells and other particles |
US8895298B2 (en) | 2002-09-27 | 2014-11-25 | The General Hospital Corporation | Microfluidic device for cell separation and uses thereof |
US8921102B2 (en) | 2005-07-29 | 2014-12-30 | Gpb Scientific, Llc | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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FR2836071B1 (fr) * | 2002-02-21 | 2005-02-04 | Commissariat Energie Atomique | Composant pour microsysteme d'analyse biologique ou biochimique |
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- 2003-02-20 JP JP2003570129A patent/JP2005517958A/ja active Pending
- 2003-02-20 WO PCT/FR2003/000567 patent/WO2003071277A1/fr active Application Filing
- 2003-02-20 US US10/475,634 patent/US7214478B2/en not_active Expired - Fee Related
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Cited By (9)
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US8895298B2 (en) | 2002-09-27 | 2014-11-25 | The General Hospital Corporation | Microfluidic device for cell separation and uses thereof |
US8986966B2 (en) | 2002-09-27 | 2015-03-24 | The General Hospital Corporation | Microfluidic device for cell separation and uses thereof |
US10081014B2 (en) | 2002-09-27 | 2018-09-25 | The General Hospital Corporation | Microfluidic device for cell separation and uses thereof |
US11052392B2 (en) | 2002-09-27 | 2021-07-06 | The General Hospital Corporation | Microfluidic device for cell separation and uses thereof |
US8585971B2 (en) | 2005-04-05 | 2013-11-19 | The General Hospital Corporation | Devices and method for enrichment and alteration of cells and other particles |
US9174222B2 (en) | 2005-04-05 | 2015-11-03 | The General Hospital Corporation | Devices and method for enrichment and alteration of cells and other particles |
US9956562B2 (en) | 2005-04-05 | 2018-05-01 | The General Hospital Corporation | Devices and method for enrichment and alteration of cells and other particles |
US10786817B2 (en) | 2005-04-05 | 2020-09-29 | The General Hospital Corporation | Devices and method for enrichment and alteration of cells and other particles |
US8921102B2 (en) | 2005-07-29 | 2014-12-30 | Gpb Scientific, Llc | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
Also Published As
Publication number | Publication date |
---|---|
EP1476755A1 (fr) | 2004-11-17 |
US20040126779A1 (en) | 2004-07-01 |
FR2836072A1 (fr) | 2003-08-22 |
JP2005517958A (ja) | 2005-06-16 |
US7214478B2 (en) | 2007-05-08 |
FR2836072B1 (fr) | 2004-11-12 |
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