REVERSIBLE MICROFLUIDIC CHIP

Abstract

The invention relates to a reversible microfluidic chip comprising at least one lower part and at least one upper part configured to come into contact with said lower part and to close said chip, said lower part and/or said upper part comprising a microfluidic structure, and said upper part comprising at least one layer of a flexible epoxide polymer material and at least one layer of a rigid epoxide polymer material, at least one part of the flexible layer being directly in physical contact with the lower part of the chip when said chip is in the closed configuration, to the method for the fabrication thereof, to the use of said upper part in a reversible microfluidic chip, to said upper part for producing said chip, and to the uses of said chip in various applications.

Claims

1. A reversible microfluidic chip comprising: at least one lower part and at least one upper part configured to come into contact with said lower part and to close said chip, characterized in that: said lower part and/or said upper part comprises a microfluidic structure, said upper part comprises at least a first layer of an epoxide polymer material having a Young's modulus Y.sub.1, and at least a second layer of an epoxide polymer material having a Young's modulus Y.sub.2, said first and second layers being such that: the Y.sub.1/Y.sub.2 ratio is greater than or equal to 50, Y.sub.2 is less than or equal to 50 MPa, and at least one part of said second layer is directly in physical contact with the lower part of said chip when the chip is in the closed configuration.

2. The chip according to claim 1, wherein the Young's modulus Y.sub.1 of the first layer (201) is at least 0.1 GPa.

3. The chip according to claim 1, wherein: the epoxide polymer material of the first layer is obtained by polyaddition of a crosslinkable composition A comprising at least a first epoxide precursor chosen from the products of the condensation reaction of epichlorohydrin with a polyphenol, at least a second epoxide precursor chosen from diglycidyl ether aliphatic epoxy resins and the products of the condensation reaction of epichlorohydrin with a polyphenol, and at least one hardener, and the epoxide polymer material of the second layer is obtained by polyaddition of a crosslinkable composition B comprising at least a first epoxide precursor chosen from the products of the condensation reaction of epichlorohydrin with a polyphenol, at least a second epoxide precursor chosen from diglycidyl ether aliphatic epoxy resins and the products of the condensation reaction of epichlorohydrin with a polyphenol, and at least one hardener.

4. The chip according to claim 1, wherein the lower part comprises a rigid material having a Young's modulus Y′.sub.3 such that Y′.sub.3≥Y.sub.1, Y.sub.1 being as defined in claim 1 or 2.

5. The chip according to claim 1, wherein the upper part is a transparent element.

6. The chip according to claim 1, wherein the upper part comprises mechanical means configured for manually opening the microfluidic chip, preferably by the lever effect.

7. The chip according to claim 6, wherein the upper part comprises an upper face which corresponds to the upper face of the chip, and a lower face which corresponds to the face that comes into contact with the lower part of the chip and closes said chip, and in that the mechanical means are chamfers oriented in such a way that the upper face of the upper part of the chip is of larger dimension than the lower face of said upper part.

8. The chip according to claim 1, wherein the lower part of the chip comprises a microfluidic structure.

9. The chip according to claim 8, wherein the upper part of the chip comprises an upper face which corresponds to the upper face of the chip, and a lower face which corresponds to the face that comes into contact with the lower part of the chip and closes said chip, and in that the lower face of the upper part has a planar surface.

10. The chip according to claim 8, wherein the upper part of the chip comprises an upper face which corresponds to the upper face of the chip, and a lower face which corresponds to the face that comes into contact with the lower part of the chip and closes said chip, and in that the upper part comprises an open cavity on the lower face.

11. The chip according to claim 1, wherein the upper part of the chip comprises a microfluidic structure.

12. The chip according to claim 11, wherein the upper part comprises patterns of microfluidic channels having an aspect ratio ranging from 1 to 1600.

13. A method for fabricating a microfluidic chip as defined in claim 1, wherein said method comprises at least the following steps: i) depositing a crosslinkable composition B capable of forming said epoxide polymer material having a Young's modulus Y.sub.2, in a suitable polymer mould of the upper part, ii) initiating the crosslinking of the crosslinkable composition B, iii) depositing a crosslinkable composition A capable of forming said epoxide polymer material having a Young's modulus Y.sub.1, on the crosslinkable composition B before complete crosslinking of the crosslinkable composition B, iv) leaving the crosslinkable compositions A and B to crosslink for a time sufficient to form respectively the first and second layers of the upper part, v) demoulding the upper part of the chip comprising the first layer and the second layer, and vi) optionally assembling the upper part of the chip with a lower part, such that at least one part of said second layer is directly in physical contact with the lower part of said chip.

14. The method according to claim 13, wherein said method also comprises, before step i), a step a) of fabricating the polymer mould of the upper part, comprising at least one substep a.sub.1) of preparing a polymer model of the upper part, and a substep a.sub.2) of moulding with said polymer model.

15. An upper part in a reversible microfluidic chip comprising: at least a first layer of an epoxide polymer material having a Young's modulus Y.sub.1, and at least a second layer of an epoxide polymer material having a Young's modulus Y.sub.2, said first and second layers being such that: the Y.sub.1/Y.sub.2 ratio is greater than or equal to 50, and Y.sub.2 is less than or equal to 50 MPa.

16. An upper part for producing a microfluidic chip as defined in claim 1, wherein said upper part comprises at least a first layer of an epoxide polymer material having a Young's modulus Y.sub.1, and at least a second layer of an epoxide polymer material having a Young's modulus Y.sub.2, said first and second layers being such that: the Y.sub.1/Y.sub.2 ratio is greater than or equal to 50, and Y.sub.2 is less than or equal to 50 MPa, and in that said upper part also comprises mechanical means configured for manually opening said microfluidic chip.

17. A microfluidic chip as defined in claim 1, wherein said microfluidic chip is configured to be applied the any one of the group consisting of medical, biotechnological, biological, analysis, chemical synthesis, and clinical diagnosis applications.

18. The microfluidic chip according to claim 17, wherein said microfluidic chip is configured to be applied in any one of the group consisting of automating biological tests, new generation sequencing, point-of-care diagnostic tests, genetic analysis, capillary electrophoresis, DNA amplification, cell biology, proteomics, diagnostics, drug research, and the synthesis of molecules or nanomaterials, or kinetic studies.

Description

EXAMPLES

[0245] FIG. 1 shows a diagrammatic representation of the opening and closing of a chip 1 in accordance with the first subject of the invention. In particular, FIG. 1A is a view from above of the closing [FIG. A-1)] and opening [FIG. A-2)] of a chip 1 in accordance with the first subject of the invention, and FIG. 1B is a sectional view of the closing [FIG. B-1)] and opening [FIG. B-2)] of a chip 1 in accordance with the first subject of the invention.

[0246] The chip 1 comprises an upper part 2, and a lower part 3 comprising a microfluidic structure 4. The lower part 3 comprises a support 3s on which a microfluidic structure 4 is deposited. The upper part 2 is configured for coming into contact with said lower part 3 and closing said chip 1. The upper part 2 comprises chamfers 5 which allow manual opening of the microfluidic chip, in particular by the lever effect. The chamfers 5 are oriented in such a way that the upper face 2-Fsup of the upper part 2 of the chip is of larger dimension than the lower face 2-Finf of said upper part 2 [cf. Figures B-1) and B-2)].

[0247] The opening and closing of the chip 1 can be carried out by simple manual pressure (vertical arrows in Figure A-1)) by virtue of the adhesion capacity of the flexible second layer of the upper part 2 of the chip 1, and optionally the presence of chamfers 5. Sealed and uniform closing is thus ensured by the adhesion of at least one part of the second layer with the lower part 3, after application of a uniform pressure over the entire surface of the closed chip [Figures A-1) and B-1)]. Opening is permitted by application of a local manual pressure (vertical arrows in Figure A-2)) at the edge of the chip by the lever effect with the chamfers 5 [Figures A-2) and B-2)]. This reversibility makes it possible to deposit for example a sample in the chip for the monitoring of a reaction by the microfluidic route, and then to recover it at the end of reaction monitoring and subsequently re-use the upper part 2 and lower part 3 of the chip. Since the geometry of the chamfers 5 is adjustable for creating the upper part 2, it is possible to modulate the adhesion between the two parts of the chip 1 and therefore the working pressure during monitoring of a reaction (e.g. pressure ranging approximately from 0 to 1.5 bar). The chamfers 5 are mechanical means that are much simpler and much less bulky than a conventional tightening system. In particular, they do not prevent observation of the interior of the chip. They also make it possible to limit the number of constituents of the chip 1 and to work more rapidly. The chip can be completely transparent, thereby enabling in-situ observations with wavelengths throughout the visible range with a minimum value of 400 nm. It is thus possible to envisage monitoring a reaction by photoluminescence under excitation at 450 nm.

[0248] FIG. 2 shows three chips 10, 11, and 12 in accordance with the invention respectively according to the “cavity version”, “planar version” and “microfluidic structure version” embodiments. The chips 10, 11 and 12 comprise an upper part 20 optionally comprising a microfluidic structure 40′, and a lower part 30 comprising a support 30s on which a microfluidic structure 40 is optionally deposited. The upper part 20 is configured for coming into contact with said lower part 30 and closing said chip 10, 11 or 12. The upper part 20 comprises chamfers 50 which allow manual opening of the microfluidic chip, in particular by the lever effect. The chamfers 50 are oriented in such a way that the upper face 20-Fsup of the upper part 20 of the chip is of larger dimension than the lower face 20-Finf of said upper part 20. The surface 70, termed “surface of adhesion”, denotes the surface of the lower face 20-Finf of the upper part 20 which is directly in physical contact with the lower part 30 of the chip when said chip is in the closed configuration. The surface of adhesion 70 corresponds to the part of the second layer of the upper part directly in physical contact with the lower part of the chip.

[0249] In the chip 10, the upper part 20 comprises a cavity 60 open on the lower face 20-Finf, and the lower part 30 comprises a support 30s on which a microfluidic structure 40 is deposited (“cavity version” chip). In the chip 11, the lower face 20-Finf of the upper part 20 has a planar surface, and the lower part 30 comprises a support 30s on which a microfluidic structure 40 is deposited (“planar version” chip). In the chip 12, the upper part 20 comprises a microfluidic structure 40′ and the lower part 30 has a planar surface and consists of a support 30s.

[0250] FIG. 3 is a sectional diagrammatic representation of a chip 100 in accordance with the invention.

[0251] The chip 100 comprises an upper part 200, and a lower part 300 comprising a support 300s on which a microfluidic structure 400 comprising at least one microfluidic channel 401 is deposited. The upper part 200 is configured for coming into contact with said lower part 300 and closing said chip 100. The upper part 200 comprises chamfers 500 which allow manual opening of the microfluidic chip, in particular by the lever effect. The chamfers 500 are oriented in such a way that the upper face 200-Fsup of the upper part 200 of the chip is of larger dimension than the lower face 200-Finf of said upper part 200. The upper part 200 comprises at least a first layer 201 of an epoxide polymer material having a Young's modulus Y.sub.1, and at least a second layer 202 of an epoxide polymer material having a Young's modulus Y.sub.2, said Young's moduli Y.sub.1 and Y.sub.2 being as defined in the invention. At least one part of said second layer 202 (surface of adhesion) is directly in physical contact with the lower part 300 of said chip 100 when the chip is in the closed configuration.

[0252] The angle α of the chamfers, relative to the upper face 200-Fsup of the upper part 200 of the chip 100, is preferentially between 130 and 160°.

[0253] P is defined as being the “pivot point”, and A is defined as being the chip opening pressure point. The width D of the chamfers is defined as the distance between the pivot point P and the resultant (or projection) of the opening pressure point A on the lower part 300. The width D is approximately 5 mm, when the angle α is 130°, and approximately 1 cm when the angle α is 160°.

[0254] The adhesion width Da is defined as the distance between the pivot point P and the beginning of a microfluidic channel 401.

[0255] Other chips can be envisaged according to the invention, in particular a chip in which the lower and upper parts each comprise a microfluidic structure and/or microfluidic structures on several stages.

Example 1: Fabrication of a “Planar Version” Chip

1.1 Fabrication of a “Planar Version” Upper Part Model

[0256] A first rectangular piece PMMA with dimensions of 76×26×5 mm is prepared and trimmed using a drill with router heads (of Dremel type), so as to create chamfers. This first piece of PMMA represents the “planar version” upper part model.

1.2 Fabrication of a “Planar Version” Upper Part Mould

[0257] A second rectangular piece of PMMA with dimensions of 96×46×5 mm is prepared. A piece of adhesive tape approximately 5 cm wide is stuck to a part of the piece of PMMA, so as to act as formwork for the mould. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is then poured over the piece of PMMA, so as to form a first layer of PDMS with a thickness of approximately 5 to 10 mm deposited on the piece of PMMA. The assembly is left at 60° C. for 40 to 60 minutes, then a crosslinkable composition of PDMS sold under the reference Sylgard 184 is poured onto the previously formed layer of PDMS, so as to form a second layer of PDMS. While this second layer is still liquid, the “planar version” upper part model previously obtained is incorporated into the second layer of PDMS until it is totally immersed, the chamfered face of the model facing downwards. The assembly is then left at 60° C. for 24 h. The surplus PDMS above the model is then cut away and the model is demoulded using compressed air.

1.3 Fabrication of a “Planar Version” Upper Part

[0258] 2 g of an epoxy resin sold under the tradename EC251 is mixed with 1 g of a hardener sold under the tradename W242.

[0259] The crosslinkable composition B obtained is degassed, then 2 g are poured into the mould obtained in example 1.2 above, so as to totally cover the bottom of the mould. The crosslinkable composition B is left to crosslink at ambient temperature for 4 hours.

[0260] In parallel, 6 g of an epoxy resin sold under the tradename EC161 is mixed with 3 g of a hardener sold under the tradename W242. The crosslinkable composition A obtained is degassed, then 6 g of this crosslinkable composition A are poured onto the crosslinkable composition B in the mould before the composition B has finished crosslinking. The crosslinkable compositions A and B are then left to crosslink for 24 h.

[0261] The upper part thus obtained is demoulded using compressed air, then pierced to form flow inlet and outlet orifices, using a tool of Dremel type.

1.4 Fabrication of a “Planar Version” Chip

[0262] The lower part is fabricated by lamination of a photosensitive resin on a glass slide and photolithography, under non-actinic conditions. To do this, a microscope slide with dimensions of 76×26×1.2 mm is cleaned, then heated for 1 to 2 minutes at 100° C. It is then cleaned with a plasma. A photosensitive resin sold under the reference DF-3050 by Engineered Materials Systems Inc. is deposited on the glass slide by laminating at a speed of approximately 1 cm/s and at a temperature of 98° C. A glass slide covered with a mask containing the patterns of the microchannels is then deposited on the laminated glass slide, and the assembly is insolated using a device sold under the tradename UV-KUB 3, for 9 seconds at 100% power. The mask is then removed, and the laminated slide is annealed at 100° C. for 10 minutes, and developed in cyclohexanone between 9 and 11 minutes. The assembly obtained is annealed at 175° C. for 1 h.

[0263] The surface of adhesion of the upper part intended to be in contact with the lower part of the chip is sprinkled with acetone and then dried with compressed air. The upper part is then positioned on the lower part comprising the microfluidic structure. The chip is then closed by simple pressure of the fingers on the upper part.

Example 2: Fabrication of a “Microfluidic Structure Version” Chip

2.1 Fabrication of a “Microfluidic Structure Version” Upper Part Model

[0264] A microscope slide with dimensions of 76×26×1.2 mm is cleaned, then heated for 1 to 2 minutes at 100° C. It is then cleaned with a plasma. A photosensitive resin sold under the reference DF-3050 by Engineered Materials Systems Inc. is deposited on the glass slide by lamination at a speed of a few cm/s and at a temperature of 98° C. A glass slide covered with a mask containing the patterns of the microchannels is then deposited on the laminated glass slide, and the assembly is insolated using a device sold under the tradename UV-KUB 3, for 9 seconds at 100% power. The mask is then removed, and the laminated slide is annealed at 100° C. for 10 minutes, and developed in cyclohexanone for between 9 and 11 minutes. The assembly obtained is annealed at 175° C. for 1 h. A glass slide comprising reliefs of the photosensitive resin representing the negative of the fluid microfluidic structure is obtained.

[0265] In parallel, a rectangular piece of PMMA with dimensions of 96×46×5 mm is prepared. A piece of adhesive tape approximately 5 cm wide is stuck on a part of the piece of PMMA, so as to act as formwork for the mould. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is then poured onto the piece of PMMA, so as to form a first layer of PDMS with a thickness of approximately 5 to 10 mm deposited on the piece of PMMA. The assembly is left at 60° C. for 40 to 60 minutes and then it is left to cool at ambient temperature. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is poured onto the layer of PDMS previously formed, so as to form a second layer of PDMS. While this second layer is still liquid, the glass slide comprising reliefs of the photosensitive resin previously obtained is deposited on the first layer of PDMS, until it is totally immersed, the reliefs being positioned facing downwards (i.e. photolithography face downwards). The assembly is then left at ambient temperature for 48 h. The surplus PDMS above the glass slide and the reliefs is then cut away, and removed with the glass slide, and a premould is obtained.

[0266] A crosslinkable composition comprising an epoxy resin sold under the reference EC 161 and a hardener sold under the tradename W242, the hardness/epoxy resin weight ratio being 1/2, is then poured into the premould. The assembly is left at ambient temperature for 48 h, then the part made of epoxy resin is demoulded using compressed air. This part made of epoxy resin is trimmed using a drill with router heads (Dremel type), so as to create chamfers, in order to form a “microfluidic structure version” upper part model.

2.2 Fabrication of a “Microfluidic Structure Version” Upper Part Mould

[0267] A rectangular piece of PMMA with dimensions of 96×46×5 mm is prepared. A piece of adhesive tape approximately 5 cm wide is stuck on a part of the piece of PMMA, so as to act as formwork for the mould. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is then poured onto the piece of PMMA, so as to form a first layer of PDMS deposited on the piece of PMMA. The assembly is left at 60° C. for 40 to 60 minutes before being left to cool to ambient temperature, then a crosslinkable composition of PDMS sold under the reference Sylgard 184 is poured onto the layer of PDMS previously formed, so as to form a second layer of PDMS. While this second layer is still liquid, the “microfluidic structure version” upper part model previously obtained is incorporated into the second layer of PDMS until it is totally immersed, the lower face of the upper part model facing downwards. The assembly is then left at ambient temperature for 48 h. The surplus PDMS above the model is then cut away and the model is demoulded using compressed air.

2.3 Fabrication of a “Microfluidic Structure Version” Upper Part

[0268] 2 g of an epoxy resin sold under the tradename EC251 are mixed with 1 g of a hardener sold under the tradename W242. The crosslinkable composition B obtained is degassed, then 2 g are poured into the mould obtained in example 2.2 above, so as to totally cover the bottom of the mould. The crosslinkable composition B is left to crosslink at ambient temperature for 4 hours.

[0269] In parallel, 6 g of an epoxy resin sold under the tradename EC161 is mixed with 3 g of a hardener sold under the tradename W242. The crosslinkable composition A obtained is degassed, then 6 g of this crosslinkable composition A are poured onto the crosslinkable composition B in the mould. The crosslinkable compositions A and B are left to crosslink for 24 h at ambient temperature.

[0270] The upper part thus obtained is demoulded using compressed air, then pierced to form flow inlet and outlet orifices.

2.4 Fabrication of a “Microfluidic Structure Version” Chip

[0271] A simple glass slide with dimensions of 26×76×1.2 mm is used as lower part.

[0272] The surface of adhesion of the upper part intended to be in contact with the lower part of the chip is sprinkled with acetone for a few seconds, then dried with compressed air. The upper part comprising the microfluidic structure is then positioned on the lower part. The chip is then closed by simple pressure of the fingers on the upper part.

Example 3: Fabrication of a “Cavity Version” Chip

3.1 Fabrication of a “Cavity Version” Upper Part Model

[0273] The “planar version” upper part mould as fabricated in example 1.2 above is used as premould for preparing the “cavity version” upper part model. To do this, an object with dimensions of 10×10×3 mm comprising a magnetized part (the dimensions of the object are those that it is then desired to obtain for the cavity) is positioned in the premould at the desired position. A magnet is positioned under the premould in order to ensure contact of the object with the premould. Since the two magnets attract one another, the passage under the object of the crosslinkable composition as described hereinafter is limited.

[0274] Next, a crosslinkable composition comprising an epoxy resin sold under the reference EC 161 and a hardener sold under the tradename W242, the hardness/epoxy resin weight ratio being 1/2, is poured into the premould, so as to immerse the object. The assembly is left for 48 h at ambient temperature, the magnet under the premould is removed, the part made of epoxy resin surrounding the object and the object are demoulded together using compressed air, and the object is removed using a magnet so as to form a “cavity version” upper part model.

3.2 Fabrication of a “Cavity Version” Upper Part Mould

[0275] A rectangular piece of PMMA with dimensions of 96×46×5 mm is prepared. A piece of adhesive tape approximately 5 cm wide is stuck on a part of the piece of PMMA, so as to serve as formwork for the mould. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is then poured onto the piece of PMMA, so as to form a first layer of PDMS deposited on the piece of PMMA. The assembly is left at 60° C. for 40 to 60 minutes, then a crosslinkable composition of PDMS sold under the reference Sylgard 184 is poured onto the layer of PDMS previously formed, so as to form a second layer of PDMS. While this second layer is still liquid, the “cavity version” upper part model previously obtained is incorporated into the second layer of PDMS until it is totally immersed, the lower face of the upper part model facing downwards. The assembly is then left at 60° C. for 24 h. The surplus PDMS above the model is then cut away and the model is demoulded using compressed air.

3.3 Fabrication of a “Cavity Version” Upper Part

[0276] 2 g of an epoxy resin sold under the tradename EC251 are mixed with 1 g of a hardener sold under the tradename W242. The crosslinkable composition B obtained is degassed, then 2 g are poured into the mould obtained in example 3.2 above, so as to totally cover the bottom of the mould. The crosslinkable composition B is left to crosslink at ambient temperature for 4 hours.

[0277] In parallel, 6 g of an epoxy resin sold under the tradename EC161 are mixed with 3 g of a hardener sold under the tradename W242. The crosslinkable composition A obtained is degassed, then 6 g of this crosslinkable composition A are poured onto the crosslinkable composition B in the mould. The crosslinkable compositions A and B are left to crosslink for 24 h.

[0278] The upper part of the chip thus obtained is demoulded using compressed air, then pierced to form flow inlet and outlet orifices, using a tool of Dremel type.

3.4 Fabrication of a “Cavity Version” Chip

[0279] The lower part is fabricated by spin coating of a photosensitive resin on a glass slide and photolithography, under non-actinic conditions. The method used in example 1 can also be carried out.

[0280] To do this, a microscope slide with dimensions of 76×26×1.2 mm is used. A compound sold under the reference AZ1512HS by MicroChemicals is deposited by spincoating at a speed of 5000 revolutions per minute and at ambient temperature. The spin-coated slide is annealed at 100° C. for 2 minutes and insolated using a device sold under the tradename digital SmartPrint, equipped with a 1× objective: 10.2 mW/cm.sup.2 for 15 seconds at 150 mJ/cm.sup.2 of power. The spin-coated slide is then developed in an aqueous solution containing 50% by volume of AZ1500 for 45 seconds, and washed in a bath of demineralized water. The assembly obtained is dried and then annealed at 110° C. for 1 min.

[0281] The surface of adhesion of the upper part intended to be in contact with the lower part of the chip is sprinkled with acetone for a few seconds and then dried with compressed air. The object or sample to be analysed is placed in the cavity with a magnet of the same format as that used to make the model. The upper part comprising the cavity is then positioned on the lower part. The chip is then closed by simple pressure of the fingers on the upper part.

Example 4: Fabrication of a “Planar Version” Chip

4.1 Fabrication of a “Planar Version” Upper Part Model

[0282] A first rectangular piece of PMMA of dimensions of 76×26×5 mm is prepared and trimmed using a drill with router heads (of Dremel type), so as to create chamfers. This first piece of PMMA represents the “planar version” upper part model.

4.2 Fabrication of a “Planar Version” Upper Part Mould

[0283] A second rectangular piece of PMMA with dimensions of 96×46×5 mm is prepared. A piece of adhesive tape approximately 5 cm wide is stuck on a part of the piece of PMMA, so as to serve as formwork for the mould. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is then poured onto the piece of PMMA, so as to form a first layer of PDMS with a thickness of approximately 5 to 10 mm deposited on the piece of PMMA. The assembly is left at 60° C. for 40 to 60 minutes, then a crosslinkable composition of PDMS sold under the reference Sylgard 184 is poured onto the layer of PDMS previously formed, so as to form a second layer of PDMS. While this second layer is still liquid, the “planar version” upper part mould previously obtained is incorporated into the second layer of PDMS until it is totally immersed, the chamfered face of the model facing downwards. The assembly is then left at 60° C. for 24 h. The surplus PDMS above the model is then cut away and the model is demoulded using compressed air.

4.3 Fabrication of a “Planar Version” Upper Part

[0284] 2 g of an epoxy resin sold under the tradename WWAS are mixed with 0.54 g of a hardener sold under the tradename WWB4.

[0285] The crosslinkable composition B obtained is degassed, then 2 g are poured into the mould obtained in example 4.2 above, so as to totally cover the bottom of the mould. The crosslinkable composition B is left to crosslink at ambient temperature for 1 hour.

[0286] In parallel, 6 g of an epoxy resin sold under the tradename WWAS is mixed with 2.4 g of a hardener sold under the tradename WWB4. The crosslinkable composition A obtained is degassed, then 6 g of this crosslinkable composition A are poured onto the crosslinkable composition B in the mould before the composition B has finished crosslinking. The crosslinkable compositions A and B are then left to crosslink for 24 h.

[0287] The upper part thus obtained is demoulded using compressed air, then pierced to form flow inlet and outlet orifices, using a tool of Dremel type.

4.4 Fabrication of a “Planar Version” Chip

[0288] The lower part is fabricated by lamination of a photosensitive resin on a glass slide and photolithography, under non-actinic conditions. To do this, a microscope slide with dimensions of 76×26×1.2 mm is cleaned, then heated for 1 to 2 minutes at 100° C. It is then cleaned with a plasma. A photosensitive resin sold under the reference DF-3050 by Engineered Materials Systems Inc. is deposited on the glass slide by lamination at a speed of approximately 1 cm/s and at a temperature of 98° C. A glass slide covered with a mask containing the patterns of the microchannels is then deposited on the laminated glass slide, and the assembly is insolated using a device sold under the tradename UV-KUB 3, for 9 seconds at 100% power. The mask is then removed, and the laminated slide is annealed at 100° C. for 10 minutes, and developed in cyclohexanone for between 9 and 11 minutes. The assembly obtained is annealed at 175° C. for 1 h.

[0289] The surface of adhesion of the upper part intended to be in contact with the lower part of the chip is sprinkled with acetone and then dried with compressed air. The upper part is then positioned on the lower part comprising the microfluidic structure. The chip is then closed by simple pressure of the fingers on the upper part.

Example 5: Fabrication of a “Microfluidic Structure Version” Chip

5.1 Fabrication of a “Microfluidic Structure Version” Upper Part Model

[0290] A microscope slide with dimensions of 76×26×1.2 mm is cleaned, then heated for 1 to 2 minutes at 100° C. It is then cleaned with a plasma. A photosensitive resin sold under the reference DF-3050 by Engineered Materials Systems Inc. is deposited on the glass slide by lamination at a speed of a few cm/s and at a temperature of 98° C. A glass slide covered with a mask containing the patterns of the microchannels is then deposited on the laminated glass slide, and the assembly is insolated using a device sold under the tradename UV-KUB 3, for 9 seconds at 100% power. The mask is then removed, and the laminated slide is annealed at 100° C. for 10 minutes, and developed in cyclohexanone for between 9 and 11 minutes. The assembly obtained is annealed at 175° C. for 1 h. A glass slide comprising reliefs of the photosensitive resin representing the negative of the final microfluidic structure is obtained.

[0291] In parallel, a rectangular piece of PMMA with dimensions of 96×46×5 mm is prepared. A piece of adhesive tape approximately 5 cm wide is stuck on a part of the piece of PMMA, so as to serve as formwork for the mould. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is then poured onto the piece of PMMA, so as to form a first layer of PDMS with a thickness of approximately 5 to 10 mm deposited on the piece of PMMA. The assembly is left at 60° C. for 40 to 60 minutes, and is then left to cool at ambient temperature. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is poured onto the layer of PDMS previously formed, so as to form a second layer of PDMS. While this second layer is still liquid, the glass slide comprising reliefs of the photosensitive resin previously obtained is deposited on the first layer of PDMS, until it is totally immersed, the reliefs being positioned facing downwards (i.e. photolithography face downwards). The assembly is then left at ambient temperature for 48 h. Next, the surplus PDMS above the glass slide and the reliefs is cut away, and removed with the glass slide, and a premould is obtained.

[0292] Next, a crosslinkable composition comprising an epoxy resin sold under the reference WWAS and a hardener sold under the tradename WWB4, the hardness/epoxy resin weight ratio being 100/40, is poured into the premould. The assembly is left for 48 h at ambient temperature, then the part made of epoxy resin is demoulded using compressed air. This part made of epoxy resin is trimmed using a drill with router heads (of Dremel type), so as to create chamfers, in order to form a “microfluidic structure version” upper part model.

5.2 Fabrication of a “Microfluidic Structure Version” Upper Part Mould

[0293] A rectangular piece of PMMA with dimensions of 96×46×5 mm is prepared. A piece of adhesive tape approximately 5 cm wide is stuck on a part of the piece of PMMA, so as to serve as formwork for the mould. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is then poured onto the piece of PMMA, so as to form a first layer of PDMS deposited on the piece of PMMA. The assembly is left at 60° C. for 40 to 60 minutes before being left to cool to ambient temperature, then a crosslinkable composition of PDMS sold under the reference Sylgard 184 is poured onto the layer of PDMS previously formed, so as to form a second layer of PDMS. While this second layer is still liquid, the “microfluidic structure version” upper part model previously obtained is incorporated into the second layer of PDMS until it is totally immersed, the lower face of the upper part model facing downwards. The assembly is then left at ambient temperature for 48 h. The surplus PDMS above the model is then cut away and the model is demoulded using compressed air.

5.3 Fabrication of a “Microfluidic Structure Version” Upper Part

[0294] 2 g of an epoxy resin sold under the tradename WWAS is mixed with 0.54 g of a hardener sold under the tradename WWB4. The crosslinkable composition B obtained is degassed, then 2 g are poured into the mould obtained in example 5.2 above, so as to totally cover the bottom of the mould. The crosslinkable composition B is left to crosslink at ambient temperature for 1 hour.

[0295] In parallel, 6 g of an epoxy resin sold under the tradename WWAS are mixed with 2.4 g of a hardener sold under the tradename WWB4. The crosslinkable composition A obtained is degassed, then 6 g of this crosslinkable composition A are poured onto the crosslinkable composition B in the mould. The crosslinkable compositions A and B are left to crosslink for 24 h at ambient temperature.

[0296] The upper part thus obtained is demoulded using compressed air, then pierced to form flow inlet and outlet orifices.

5.4 Fabrication of a “Microfluidic Structure Version” Chip

[0297] A simple glass slide with dimensions of 26×76×1.2 mm is used as lower part.

[0298] The surface of adhesion of the upper part intended to be in contact with the lower part of the chip is sprinkled with acetone for a few seconds, then dried with compressed air. The upper part comprising the microfluidic structure is then positioned on the lower part. The chip is then closed by simple pressure of the fingers on the upper part.

Example 6: Fabrication of a “Cavity Version” Chip

6.1 Fabrication of a “Cavity Version” Upper Part Model

[0299] The mould of the “planar version” upper part as fabricated in example 4.2 above is used as premould for preparing the model of the “cavity version” upper part model. To do this, an object with dimensions of 10×10×3 mm comprising a magnetized part (the dimensions of the object are those that it is subsequently desired to obtain for the cavity) is positioned in the premould in the desired place. A magnet is positioned under the premould in order to ensure contact of the object with the premould. Since the two magnets attract one another, the passage under the object of the crosslinkable composition as described hereinafter is limited.

[0300] Next, a crosslinkable composition comprising an epoxy resin sold under the reference WWAS and a hardener sold under the tradename WWB4, the hardness/epoxy resin weight ratio being 100/40, is poured into the premould, so as to immerse the object. The assembly is left for 48 h at ambient temperature, the magnet under the premould is removed, the part made of epoxy resin surrounding the subject and the subject are demoulded together using compressed air, and the object is removed using a magnet so as to form a “cavity version” upper part model.

6.2 Fabrication of a “Cavity Version” Upper Part Mould

[0301] A rectangular piece of PMMA with dimensions of 96×46×5 mm is prepared. A piece of adhesive tape approximately 5 cm wide is stuck on a part of the piece of PMMA, so as to serve as formwork for the mould. A crosslinkable composition of PDMS sold under the reference Sylgard 184 is then poured onto the piece of PMMA, so as to form a first layer of PDMS deposited on the piece of PMMA. The assembly is left at 60° C. for 40 to 60 minutes, then a crosslinkable composition of PDMS sold under the reference Sylgard 184 is poured onto the layer of PDMS previously formed, so as to form a second layer of PDMS. While this second layer is still liquid, the “cavity version” upper part model previously obtained is incorporated into the second layer of PDMS until it is totally immersed, the lower face of the upper part model facing downwards. The assembly is then left at 60° C. for 24 h. The surplus PDMS above the model is then cut away and the model is demoulded using compressed air.

6.3 Fabrication of a “Cavity Version” Upper Part

[0302] 2 g of an epoxy resin sold under the tradename WWAS are mixed with 0.54 g of a hardener sold under the tradename WWB4. The crosslinkable composition B obtained is degassed, then 2 g are poured into the mould obtained in example 6.2 above, so as to totally cover the bottom of the mould. The crosslinkable composition B is left to crosslink at ambient temperature for 1 hour.

[0303] In parallel, 6 g of an epoxy resin sold under the tradename WWAS are mixed with 2.4 g of a hardener sold under the tradename WWB4. The crosslinkable composition A obtained is degassed, then 6 g of this crosslinkable composition A are poured onto the crosslinkable composition B in the mould. The crosslinkable compositions A and B are left to crosslink for 24 h.

[0304] The upper part of the chip thus obtained is demoulded using compressed air, then pierced to form flow inlet and outlet orifices, using a tool of Dremel type.

6.4 Fabrication of a “Cavity Version” Chip

[0305] The lower part is fabricated by spin coating of a photosensitive resin on a glass slide and photolithography, under non-actinic conditions. The method used in example 4 can also be carried out.

[0306] To do this, a microscope slide with dimensions of 76×26×1.2 mm is used. A compound sold under the reference AZ1512HS by MicroChemicals is deposited by spincoating at a speed of 5000 revolutions per minute and at ambient temperature. The spin-coated slide is then annealed at 100° C. for 2 minutes and insolated using a device sold under the tradename digital SmartPrint, equipped with a 1× objective: 10.2 mW/cm.sup.2 for 15 seconds at 150 mJ/cm.sup.2 of power. The spin-coated slide is then developed in an aqueous solution containing 50% by volume of AZ1500 for 45 seconds, and washed in a bath of demineralized water. The assembly obtained is dried and then annealed at 110° C. for 1 min.

[0307] The surface of adhesion of the upper part intended to be in contact with the lower part of the chip is sprinkled with acetone for a few seconds and then dried with compressed air. The object or sample to be analysed is placed in the cavity with a magnet of the same format as that used to make the model. The upper part comprising the cavity is then positioned on the lower part. The chip is then closed by simple pressure of the fingers on the upper part.

[0308] When it is desired to fabricate other chips as described in examples 1, 2, 3, 4, 5 and 6, the first two steps are not necessary since the moulds of the upper parts have already been fabricated. This considerably reduces the chip fabrication time. Moreover, if it is desired to work with an identical chip several times, the chip is reusable, thereby further reducing the microfabrication times.

[0309] To open the chips as fabricated in examples 1, 2, 3, 4, 5 and 6, it is sufficient to disconnect the chip from any fluid inlet and outlet, and to place the chip on a horizontal support, such that the lower part lies on said support (workbench, table, etc.). Then, with both thumbs, a uniform pressure on one of the sides of the chip is applied so that the chamfers make a lever arm. The pressure is maintained until the chip has opened.