Reactor and process for production thereof

• US 20020094303A1
• Filed: 09/13/2001
• Published: 07/18/2002
• Est. Priority Date: 09/13/2000
• Status: Active Grant

• Current Assignee: Riken, Hoechst Marion Roussel Deutschland GmbH (Sanofi )
• Original Assignee: Riken
• Inventors: Endo, Isao, Yamamoto, Takatoki, Hong, Jong Wook, Fujii, Teruo
• Granted Patent: US 7,189,367 B2
• Time in Patent Office: Days
• US Class Current: 422/130
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00873 Heat exchange
• CPC Class Codes: B01J 2219/00961 Temperature
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5027 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046

Abstract

In order to be capable of a chemical reaction, analysis or the like wherein a small amount of samples is used, a reactor comprises a flat plate-like first substrate the inside of which is provided with a heating means; and a flat plate-like second substrate, which is placed on the top of the above-described first substrate, and on a surface thereof to be placed on the top of the above-described first substrate a flow channel having a predetermined contour has been defined.

Claims

1. A reactor comprising:

a flat plate-like first substrate the inside of which is provided with a heating means; and

a flat plate-like second substrate, which is placed on the top of said first substrate, and on a surface thereof to be placed on the top of said first substrate a flow channel having a predetermined contour has been defined.

2. A reactor as claimed in claim 1 wherein:

said flow channel in said second substrate is provided with a plurality of inlets.

3. A reactor as claimed in claim 1 wherein:

a temperature sensor is disposed in between said heating means provided on the inside of said first substrate and the top of said first substrate.

4. A reactor as claimed in claim 2 wherein:

a temperature sensor is disposed in between said heating means provided on the inside of said first substrate and the top of said first substrate.

5. A reactor as claimed in claim 1 wherein:

said flow channel defined on said second substrate forms a concaved depression with respect to the top of said first substrate within a section opposed to the heating means provided on the inside of said first substrate in the case when said channel was defined on the top of said first substrate, and said concaved depression defines a chamber in the case when said second substrate is placed on the top of said first substrate.

6. A reactor as claimed in claim 2 wherein:

said flow channel defined on said second substrate forms a concaved depression with respect to the top of said first substrate within a section opposed to the heating means provided on the inside of said first substrate in the case when said channel was defined on the top of said first substrate, and said concaved depression defines a chamber in the case when said second substrate is placed on the top of said first substrate.

7. A reactor as claimed in claim 3 wherein:

said flow channel defined on said second substrate forms a concaved depression with respect to the top of said first substrate within a section opposed to the heating means provided on the inside of said first substrate in the case when said channel was defined on the top of said first substrate, and said concaved depression defines a chamber in the case when said second substrate is placed on the top of said first substrate.

8. A reactor as claimed in claim 5 wherein:

said heating means in said first substrate has a rectangle-shaped region along the top of said first substrate, while said concaved depression of said flow channel in said second substrate has a columnar shape, and a circle-shaped region of the bottom in the column-shaped concaved depression is narrower than the rectangle-shaped region of said heating means in said first substrate.

9. A reactor as claimed in claim 6 wherein:

said heating means in said first substrate has a rectangle-shaped region along the top of said first substrate, while said concaved depression of said flow channel in said second substrate has a columnar shape, and a circle-shaped region of the bottom in the column-shaped concaved depression is narrower than the rectangle-shaped region of said heating means in said first substrate.

10. A reactor as claimed in claim 7 wherein:

said heating means in said first substrate has a rectangle-shaped region along the top of said first substrate, while said concaved depression of said flow channel in said second substrate has a columnar shape, and a circle-shaped region of the bottom in the column-shaped concaved depression is narrower than the rectangle-shaped region of said heating means in said first substrate.

11. A reactor as claimed in claim 1 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

12. A reactor as claimed in claim 2 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

13. A reactor as claimed in claim 3 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

14. A reactor as claimed in claim 4 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

15. A reactor as claimed in claim 5 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

16. A reactor as claimed in claim 6 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

17. A reactor as claimed in claim 7 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

18. A reactor as claimed in claim 8 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

19. A reactor as claimed in claim 9 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

20. A reactor as claimed in claim 10 wherein:

all of said first substrate, said heating means provided on the inside of said first substrate, said temperature sensor, and said second substrate are transparent.

22. A reactor as claimed in claim 1 wherein:

both of said first substrate and said second substrate are micro chips.

23. A reactor as claimed in claim 2 wherein:

both of said first substrate and said second substrate are micro chips.

24. A reactor as claimed in claim 3 wherein:

both of said first substrate and said second substrate are micro chips.

25. A reactor as claimed in claim 4 wherein:

both of said first substrate and said second substrate are micro chips.

26. A reactor as claimed in claim 5 wherein:

both of said first substrate and said second substrate are micro chips.

27. A reactor as claimed in claim 6 wherein:

both of said first substrate and said second substrate are micro chips.

28. A reactor as claimed in claim 7 wherein:

both of said first substrate and said second substrate are micro chips.

29. A reactor as claimed in claim 8 wherein:

both of said first substrate and said second substrate are micro chips.

30. A reactor as claimed in claim 9 wherein:

both of said first substrate and said second substrate are micro chips.

31. A reactor as claimed in claim 10 wherein:

both of said first substrate and said second substrate are micro chips.

32. A reactor as claimed in claim 11 wherein:

both of said first substrate and said second substrate are micro chips.

33. A reactor as claimed in claim 12 wherein:

both of said first substrate and said second substrate are micro chips.

34. A reactor as claimed in claim 13 wherein:

both of said first substrate and said second substrate are micro chips.

35. A reactor as claimed in claim 14 wherein:

both of said first substrate and said second substrate are micro chips.

36. A reactor as claimed in claim 15 wherein:

both of said first substrate and said second substrate are micro chips.

37. A reactor as claimed in claim 16 wherein:

both of said first substrate and said second substrate are micro chips.

38. A reactor as claimed in claim 17 wherein:

both of said first substrate and said second substrate are micro chips.

39. A reactor as claimed in claim 18 wherein:

both of said first substrate and said second substrate are micro chips.

40. A reactor as claimed in claim 19 wherein:

both of said first substrate and said second substrate are micro chips.

41. A reactor as claimed in claim 20 wherein:

both of said first substrate and said second substrate are micro chips.

45. A reactor comprising:

pluralities of a reactor as claimed in any one of claims 1 through 42.

21. A reactor comprising:

a transparent first substrate having a flat plate-like glass layer made from glass, a flat plate-like first SiO₂ layer made from SiO₂ and laminated on said glass layer, and a flat plate-like second SiO₂ layer made from SiO₂ and laminated on said first SiO₂ layer, first ITO (Indium Tin Oxide) having a rectangle-shaped region and Al extending to said first ITO being disposed in between said glass layer and said first SiO₂ layer, besides, a second ITO drawing a serpentine line in a region corresponding to the rectangle-shaped region of said first ITO disposed in between said glass layer and said first SiO₂ layer being disposed in between said first SiO₂ layer and said second SiO₂ layer; and

a transparent second substrate made from PDMS (polydimethylsiloxane) in which when it is placed on the top of said second SiO₂ layer in said first substrate, a flow channel of a predetermined shape having a column-shaped concaved depression with respect to the top of said first substrate is formed on a surface faced in contact with the top of said second SiO₂ layer in said first substrate, said column-shaped concave depression having the bottom of a circle-shaped region narrower than the rectangle-shaped region of said first ITO in said first substrate within a section opposed to said first ITO in said first substrate;

a column-shaped chamber being formed with the top of said second SiO₂ layer in said first substrate and said concaved depression in said second substrate in the case when said transparent second substrate is placed on the top of said second SiO₂ layer in said first substrate.

42. A reactor as claimed in claim 21 wherein:

both of said first substrate and said second substrate are micro chips.

43. A process for the production of a reactor comprising:

a first process step for providing a heating means on a surface of a layer, which has been already formed in case of laminating a plurality of layers, and further laminating a new layer on said layer on which has been provided said heating means to form a first substrate the inside of which has been provided with a heating means;

a second process step for fabricating a master having a convex structure being a template of a flow channel having a predetermined shape and templating a material to form a second substrate by the use of said master; and

a third process step for bonding said first substrate prepared in accordance with said first process step to said second substrate prepared in accordance with said second process step in such that the surface on which has been defined said flow channel having the predetermined shape in said second substrate is placed on the top of said first substrate.

44. A process for the production of a reactor comprising:

a first process step for forming an ITO film on a surface of a glass substrate with a predetermined film thickness;

a second process step for patterning the ITO film formed on the surface of said glass substrate in accordance with said first process step into a rectangular shape to provide a heating means;

a third process step for patterning Al so as to extend to the heating means provided in accordance with said second process step to provide an electrical wiring;

a fourth process step for forming a SiO₂ layer on the surface of said glass substrate to which has been applied said third process step with a predetermined film thickness;

a fifth process step for forming an ITO film on the surface of the SiO₂ layer formed in accordance with said fourth process step with a predetermined film thickness;

a sixth process step for patterning the ITO film formed on the surface of said SiO₂ layer in accordance with said fifth process step so as to draw a serpentine line to provide a temperature sensor;

a seventh process step for patterning Al so as to extend to the temperature sensor provided in accordance with said sixth process step to provide an electrical wiring;

an eighth process step for forming a SiO₂ layer on the surface of said SiO₂ film, to which has been applied said seventh process step, with a predetermined film thickness to complete a fabrication of the glass substrate;

a ninth process step for spin-coating a photoresist SU-8 on a surface of a silicon wafer under a predetermined condition;

a tenth process step for transferring a pattern of a flow channel having a predetermined shape to said silicon wafer on which has been applied the SU-8 by said ninth process step in accordance with a manner of photolithography;

an eleventh process step for spin-coating the SU-8 on the surface of said silicon wafer to which has been applied said tenth process step and etching the same to form a master;

a twelfth process step for allowing the master formed in accordance with said eleventh process step to stand in a CHF₃ plasma atmosphere and treating the same with fluorocarbon to form a fluorocarbon layer on the surface of said master;

a thirteenth process step for pouring an unpolymerized PDMS (Dow Corning, Sylgard

     184) prepared by admixing the same with a curing agent in a ratio of 10;

1 into said master to which had been applied said twelfth process step and curing the same due to polymerization by heat treatment to fabricate a PDMS substrate replica;

a fourteenth process step for peeling off the PDMS substrate replica fabricated in accordance with said thirteenth process step from the master and defining an inlet and an outlet on said PDMS substrate replica to complete a fabrication of the PDMS substrate; and

a fifteenth process step for bonding the glass substrate fabricated in accordance with said eighth process step to the PDMS substrate fabricated in accordance with said fourteenth process step in such that the surface, on which has been defined said flow channel having the predetermined shape in said PDMS substrate, is placed on the top of said glass substrate.