Integrated chemical microreactor with separated channels

• US 7,635,454 B2
• Filed: 11/24/2004
• Issued: 12/22/2009
• Est. Priority Date: 11/28/2003
• Status: Active Grant

• Current Assignee: STMicroelectronics SRL (STMicroelectronics NV)
• Original Assignee: STMicroelectronics SRL (STMicroelectronics NV)
• Inventors: Barlocchi, Gabriele, Mastromatteo, Ubaldo, Villa, Flavio Francesco
• Primary Examiner(s): Griffin; Walter D
• Assistant Examiner(s): Ramdhanie; Bobby
• Application Number:
  US10/997,235
• Publication Number:
  US 20050142597A1
• Time in Patent Office: 1,854 Days
• Field of Search: 422/130
• US Class Current: 422/130
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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

The microreactor is formed by a sandwich including a first body, an intermediate sealing layer and a second body. A buried channel extends in the first body and communicates with the surface of the first body through a first and a second apertures. A first and a second reservoirs are formed in the second body and are at least partially aligned with the first and second apertures. The sealing layer separates the first aperture from the first reservoir and the second aperture from the second reservoir, thereby avoiding contamination of liquids contained in the buried channel from the outside and from any adjacent buried channels. The sealing layer is perforated during use of the device, but a resilient plug can be used to reseal the device.

Claims

1. An integrated microreactor, comprising:

a) a first body including;

i) a surface;

ii) a buried channel;

iii) a first hole and a second hole and a third hole, each of said first, second and third holes at a distance from each other and extending between said buried channel and said surface;

b) a second body including;

i) a first opening and a second opening, at least a portion of said first opening being aligned with said first hole, and at least a portion of said second opening being aligned with said second hole;

ii) a sealing layer arranged between said first body and said second body and separating said first hole from said first opening and said second hole from said second opening; and

c) said third hole extending from said buried channel through said surface and said sealing layer, and wherein said second body closes and seals said third hole.

2. The integrated microreactor of claim 1, wherein said third hole is between said first hole and said second hole.

3. The integrated microreactor of claim 2, further comprising;

a) a plurality of buried channels;

b) a plurality of first holes and a plurality of second holes between said plurality of buried channels and said surface of said first body;

c) said first opening facing said plurality of first holes, and said second opening facing said plurality of second holes, to make a plurality of separate buried channels having a common inlet and a common outlet.

4. The integrated microreactor of claim 1, further comprising a resilient plug inserted in said first opening.

5. The integrated microreactor of claim 3, further comprising:

a) a plurality of buried channels;

b) a plurality of first holes and a plurality of second holes between said plurality of buried channels and said surface of said first body;

c) a plurality of first openings and a plurality of second openings in said second body;

d) said plurality of first openings facing said plurality of first holes, and said plurality of second openings facing said plurality of second holes; and

e) a plurality of resilient plugs in said plurality of first openings, to make a plurality of separate buried channels having separate inlets and outlets.

6. The integrated microreactor of claim 1, wherein said first body comprises semiconductor material and said second body comprises glass.

7. The integrated microreactor of claim 6, wherein said sealing layer comprises resist.

25. A method of performing a biological test, wherein a biological fluid is applied to the integrated microreactor of any of claims 1, 2-6 and 7, and a biological test is performed.

26. The method of claim 25, wherein the biological test is amplification.

27. The method of claim 26, wherein the amplification is DNA amplification.

8. A process for manufacturing an integrated microreactor, comprising the steps of:

a) forming a first wafer having a surface;

i) forming a buried channel in said first wafer;

ii) forming a first hole and a second hole and a third hole between said buried channel and said surface, each of said first, second and third holes at a distance from each other;

b) forming a second wafer and forming a first opening and a second opening in said second wafer;

c) forming a sealing layer on either the first or second wafer and having a connection opening in said sealing layer;

d) arranging said sealing layer between said first wafer and said second wafer and aligning said first wafer and said second wafer so that at least a portion of said first opening is aligned with said first hole and at least a portion of said second opening is aligned with said second hole and aligning said connection opening with said third hole so that said second wafer closes and seals said third hole; and

e) bonding said first wafer and said second wafer with said sealing layer and sealing said first hole and said second hole.

9. The process according to claim 8, wherein forming the sealing layer comprises:

a) applying a bonding layer on either said first wafer and said second wafer; and

b) forming a sandwich including said first wafer, said bonding layer and said second wafer; and

c) treating said sandwich to obtain a multiple wafer.

10. The process according to claim 9, wherein applying a bonding layer comprises laminating a dry resist layer on either said first wafer and said second wafer.

11. The process of claim 9, wherein applying a bonding layer comprises applying said bonding layer onto said second wafer.

12. The process of claim 9, wherein applying a bonding layer comprises applying said bonding layer onto said first wafer.

13. The process of claim 9, wherein applying said bonding layer comprises laminating said bonding layer on said first wafer and lithographically defining said connection opening in said bonding layer.

14. The process of claim 9, wherein said first opening and said second opening extend through said second wafer and said bonding layer is applied after forming said first opening and said second opening.

15. The process of claim 9, wherein bonding is carried out at a temperature of 140-180°

C.

16. The process according to claim 9, wherein bonding is carried out by applying a force to said sandwich.

17. The process of claim 9, wherein bonding said first wafer and said second wafer is carried out in vacuum conditions.

18. The process of claim 9, wherein bonding said first wafer and said second wafer is carried out at a pressure of 5×

10<sup>−

7</sup> to 5×

10<sup>−

6</sup> bar.

19. The process of claim 9, comprising:

a) forming a plurality of buried channels in said first wafer;

b) forming a plurality of first holes and a plurality of second holes between said plurality of buried channels and said surface;

c) aligning said first opening to said plurality of first holes;

d) aligning said second opening to said plurality of second holes, so as to create separate buried channels having a common inlet and a common outlet.

20. The process of claim 19, further comprising forming a resilient plug in said first opening.

21. The process of claim 9, further comprising:

a) forming a plurality of buried channels in said first wafer;

b) forming a plurality of first holes and a plurality of second holes between said plurality of buried channels and said surface;

c) forming a plurality of first openings facing said plurality of first holes, and a plurality of second openings facing said plurality of second holes; and

d) forming a plurality of resilient plugs in said plurality of first openings, so as to create separate channels having separate inlets and outlets.

22. A method of using of an integrated microreactor, a) the integrated microreactor comprising:

i) a first body having a surface;

a buried channel extending in said first body;

a first and a second hole and a third hole extending between said buried channel and said surface, each of said first, second and third holes at a distance from each other;

ii) a second body bonded to said first body;

a first and a second opening in said second body, with at least a portion of said first opening being aligned with said first hole and at least a portion of said second opening being aligned with said second hole; and

iii) a sealing layer having a connection opening and being arranged between said first and said second bodies and separating said first hole from said first opening and said second hole from said second opening and said connection opening is aligned with said third hole, and wherein said sealing layer is bonded to said first body and said second body at a low pressure,

b) the method comprising;

i) inserting a puncturing element in said first hole through said sealing layer, thereby perforating said sealing layer; and

ii) introducing a fluid into said buried channel, wherein said low pressure draws said fluid into said buried channel.

23. The method of claim 22, wherein introducing a fluid is carried out by said puncturing element and including removing said puncturing element after introducing a fluid.

24. The method according to claim 23, including, before inserting a puncturing element, arranging a resilient plug into said first opening, wherein perforating said sealing layer includes perforating said resilient plug, wherein said resilient plug sealingly closes said first hole after removing said puncturing element.