Apparatus and method for a nanocalorimeter for detecting chemical reactions

• US 7,141,210 B2
• Filed: 04/01/2002
• Issued: 11/28/2006
• Est. Priority Date: 04/01/2002
• Status: Active Grant

• Current Assignee: Xerox Corporation (Xerox Holdings Corp.)
• Original Assignee: Palo Alto Research Center, Inc. (Xerox Holdings Corp.)
• Inventors: Bruce, Richard H., Bell, Alan G., Peeters, Eric, Torres, Francisco E., Elrod, Scott A.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Siefke, Sam P.
• Application Number:
  US10/114,611
• Publication Number:
  US 20030186453A1
• Time in Patent Office: 1,702 Days
• Field of Search: 422/51, 422/68.1, 422/104, 422/82.01, 436/147
• US Class Current: 422/51
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: G01N 25/4846 for a motionless, e.g. solid sample
• CPC Class Codes: G01N 25/4866 by using a differential method
• CPC Class Codes: Y10S 977/957 Of chemical property or presence
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25625 Dilution
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A nanocalorimeter array for detecting chemical reactions includes at least one thermal isolation region residing on a substrate. Each thermal isolation region includes at least one thermal equilibration region, within which resides a thermal measurement device connected to detection electronics.

Claims

1. A nanocalorimeter array for detecting chemical reactions the nanocalorimeter array comprising:

a substrate;

at least two thermal isolation regions residing on said substrate, wherein said thermal isolation regions comprises a material having low thermal conductivity;

at least one reference region and at least one measurement region residing within said thermal isolation regions, wherein said at least one reference region is operatively associated with said at least one measurement region, and wherein said reference region receives reference reagents;

at least two drop merging electrodes residing within each said reference region and each said measurement region for mixing solutions on the nanocalorimeter array, wherein drops of said solutions are merged by application of a voltage to the electrodes;

at least one thermal equilibration region positioned within each said reference region and each said measurement region adjacent to and mechanically supported by said thermal isolation regions, wherein said drops of said solutions are brought to thermal equilibrium before being merged; and

at least one thermal measurement device residing as a layer within each said at least one thermal equilibration region, wherein said thermal measurement device is connected to detection electronics.

2. The nanocalorimeter array according to claim 1, wherein a least two thermal measurement devices reside within each of said thermal equilibration regions.

3. The nanocalorimeter array according to claim 1, wherein said thermal measurement device measures temperature change within each said thermal equilibration region, and wherein said detection electronics compare said measured temperatures for said at least one reference region and said at least one a measurement region, wherein said reference region and said measurement region are physically separate from each other.

4. The nanocalorimeter array according to claim 1, wherein said at least one thermal measurement device comprises a resistive thermometer.

5. The nanocalorimeter array according to claim 1, wherein said at least one thermal measurement device comprises a thermopile.

6. The nanocalorimeter array according to claim 1, further comprising means for depositing chemical samples on said nanocalorimeter array.

7. The nanocalorimeter array according claim 1, wherein said drop merging electrodes reside on a first layer and said at least one thermal measurement device resides on a second layer with an insulating layer interposed therein between, such that each said two drop merging electrodes are positioned adjacent to and physically touching said thermal measurement device.

8. The nanocalorimeter array according to claim 1, wherein said drop merging electrodes comprise said thermal measurement device.

9. The nanocalorimeter array according to claim 1, wherein said detection electronics comprise AC detection electronics.

10. The nanocalorimeter array according to claim 1, wherein said detection electronics comprise a software program.

11. The nanocalorimeter array according to claim 1, further comprising means for dispensing chemical samples within specific locations on said thennal equalization regions.

12. The nanocalorimeter array according to claim 1, wherein said nanocalorimeter array further comprises a plurality of thermal isolation regions residing on said substrate.

13. The nanocalorimeter array according to claim 1, wherein said substrate is in thermal contact with a first heat sink.

14. The nanocalorimeter array according to claim 13, wherein said first heat sink is a temperature controlled heat sink.

15. The nanocalorimeter array according to claim 1, wherein at least some of said detection electronics reside on a printed circuit board in thermal contact with a second temperature-controlled heat sink.

16. The nanocalonmeter array according to claim 4, wherein said resistive thermometer comprises amorphous silicon.

17. The nanocalorimeter array according to claim 4, wherein said resistive thermometer comprises silicon.

18. The nanocalorimeter array according to claim 4, wherein said resistive thermometer comprises yttrium barium copper oxide.

19. The nanocalorimeter array according to claim 4, wherein said resistive thermometer comprises vanadium oxide.

20. The nanocalorimeter array according to claim 4, wherein said resistive thennometer comprises, mercury cadmium telluride.

21. The nanocalorimeter array according to claim 1, wherein said detection electronics comprise:

at least one bridge;

at least one signal amplifier for amplifying bridge output;

at least one multiplexer for selecting from a plurality of said signal amplifiers; and

a lock-in circuit for producing a DC output equal to the amplitude of the detector signal.

22. The nanocalorimeter array according to claim 1, further comprising a detecting environment.

23. The nanocalorimeter array according to claim 22, wherein said detecting environment provides thermal isolation, electrical connections, and delivery of chemical samples and comprises:

at least one load lock chamber; and

at least one measurement chamber.

24. The nanocalorimeter array according to claim 23, wherein said detecting environment further comprises a temperature-controlled reservoir.

25. The nanocalorimeter array according to claim 1, wherein said detection electronics are detachably connected to the nanocalorimeter array.

26. The nanocalorimeter array according to claim 25, wherein pogo pins detachably connect said detection electronics and the nanocalorimeter array.

27. The nanocalorimeter array according to claim 1, wherein the chemical reactions comprise biochemical reactions.

28. A nanocalorimeter array for detecting chemical reactions the nanocalorimeter array comprising:

a substrate;

at least two thermal isolation regions residing on said substrate, wherein said thermal isolation regions comprises a material having low thermal conductivity;

at least one reference region and at least one measurement region residing within said thermal isolation regions, wherein said at least one reference region is operatively associated with said at least one measurement region, and wherein said reference region receives reference reagents;

at least one thermal equilibration region positioned within each said reference region and each said measurement region adjacent to and mechanically supported by said thermal isolation regions, wherein drops of said solutions are brought to thermal equilibrium before being merged; and

at least one thermal measurement device residing as a layer within each said at least one thermal equilibration region, wherein said thermal measurement device is connected to detection electronics, and wherein said detection electronics are detachably connected to the nanocalorimeter array.