Biochemical reaction detection apparatus

• US 6,977,149 B2
• Filed: 01/03/2002
• Issued: 12/20/2005
• Est. Priority Date: 12/15/1999
• Status: Expired due to Fees

• Current Assignee: Hitachi, Ltd.
• Original Assignee: Hitachi, Ltd.
• Inventors: Kajiyama, Tomoharu, Miyahara, Yuji, Murakawa, Katsuji
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US10/034,075
• Publication Number:
  US 20020164778A1
• Time in Patent Office: 1,447 Days
• Field of Search: 435/4, 435/6, 435/7.1, 435/174, 435/283.1, 435/287.2, 435/288.4, 435/287, 422/68.1, 422/82.01, 422/82.02
• US Class Current: 435/6.19
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• 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
• CPC Class Codes: B01L 7/54 : using spatial temperature gradients
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2527/107 : Temperature of melting, i.e. Tm
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: Y10S 977/924 : using nanostructure as support of dna analysis

Abstract

A biochemical reaction detection chip capable of controlling the temperature for biochemical reactions including hybridizations and its substrate. The function of the chip is performed by comprising a plurality of islands of a heat conducting material on the membrane of the substrate, the islands being spaced from each other and individually provided with temperature controllers, and the probes immobilized on the substrate.

Claims

1. A biochemical reaction detection apparatus, comprising;

a first membrane of no more than 20 μ

m thick;

a heat draining layer shaped in a mesh having spaces provided on one side of said first membrane;

a plurality of islands provided on one said of said first membrane, each space of the mesh having at least one of said plurality of islands being formed therein;

probe cells for immobilizing probes for detecting biochemical reactions, each of said probe cells being provided on a side opposite to said one side of said first membrane corresponding to one of the islands directly through a cross section of the first membrane; and

a cover placed on top of the probe cells for accommodating a sample solution layer between the cover and said side opposite to said one side of said first membrane covering all of the probe cells,

wherein said islands are spaced from each other with intervals filled with air, and each of the islands includes a temperature controller for heating and temperature-controlling a corresponding one of said probe cells independently so that temperature of the sample solution is controlled independently probe cell by probe cell.

2. The biochemical reaction detection apparatus according to claim 1, wherein the interval between each of said islands is 50 μ

m or longer.

3. The biochemical reaction detection apparatus according to claim 1, wherein the interval between each of said islands is 100 μ

m or longer.

4. The biochemical reaction detection apparatus according to claim 1, wherein said first membrane has a heat conductivity of 10 w/mk (watt/(meter*kelvin)) or less.

5. The biochemical reaction detection apparatus according to claim 1, wherein said first membrane is made of a material or a composite material selected from a group consisting of silicon nitride, silicon oxide, aluminum oxide and Ta₂O₅.

6. The biochemical reaction detection apparatus according to claim 1, wherein said first membrane is 5 μ

m thick or thinner.

7. The biochemical reaction detection apparatus according to claim 1, wherein the heat draining layer functions as heat sinks provided among said islands.

8. The biochemical reaction detection apparatus to claim 1, wherein the heat draining layer includes a thermal conductor layers.

9. The biochemical reaction detection apparatus according to claim 7, wherein the heat draining layer is made from Si, Au, Ag or Cu.

10. The biochemical reaction detection apparatus according to claim 7, wherein a distance between one of said islands and one of the heat sinks is 10 -500 μ

m.

11. A biochemical reaction detection apparatus, comprising:

a first membrane of no more than 20 μ

m thick, a first side thereof being provided with a sample solution layer;

a heat draining layer shaped in a mesh having spaces provided on a second side of said first membrane opposite to the first side of said first membrane;

a plurality of islands provided on said second side of said first membrane, each space of the mesh having at least one of said plurality of islands being formed therein; and

probe cells for immobilizing probes for detecting biochemical reactions, each of said probe cells being provided on the first side of said first membrane corresponding to one of the islands directly through a cross section of said first membrane, each of said probe cells being set to contact with said sample solution layer,

wherein said islands are spaced from each other with intervals filled with air, and each of the islands includes a temperature controller for heating and temperature-controlling a corresponding one of said probe cells independently so that a temperature of the sample solution is controlled independently probe cell by probe cell.

12. The biochemical reaction detection apparatus according to claim 11, wherein the interval between each of said islands is 50 μ

m or longer.

13. The biochemical reaction detection apparatus according to claim 11, wherein the interval between each of said islands is 100 μ

m or longer.

14. The biochemical reaction detection apparatus according to claim 11, wherein said first membrane has a heat conductivity of 10 w/mk (watt/(meter*kelvin)) or less.

15. The biochemical reaction detection apparatus according to claim 11, wherein said first membrane is made of a material or a composite material selected from a group consisting of silicon nitride, silicon oxide, aluminum oxide and Ta₂O₅.

16. The biochemical reaction detection apparatus according to claim 11, wherein said first membrane is 5 μ

m thick or thinner.

17. The biochemical reaction detection apparatus according to claim 11, wherein the thermal conductor layer functions as heat sinks provided among said islands.

18. The biochemical reaction detection apparatus to claim 11, wherein the thermal conductor layer drains heat from said islands.

19. The biochemical reaction detection apparatus according to claim 17, wherein the thermal conductor layer is made from Si, Au, Ag or Cu.

20. The biochemical reaction detection apparatus according to claim 17, wherein a distance between one of said islands and one of the heat sinks is 10 -500 μ

m.