Methods and integrated devices and systems for performing temperature controlled reactions and analyses

• US 6,337,212 B1
• Filed: 11/02/2000
• Issued: 01/08/2002
• Est. Priority Date: 03/08/1999
• Status: Expired due to Term

• Current Assignee: Caliper Holdings Incorporated
• Original Assignee: Caliper Holdings Incorporated
• Inventors: Dubrow, Robert S., Nagle, Robert
• Primary Examiner(s): Beisner, William H.
• Application Number:
  US09/705,065
• Time in Patent Office: 432 Days
• Field of Search: 435/6, 435/91.2, 435/4, 435/287.2, 435/286.1, 435/288.4, 435/303.1, 435/305.2, 435/809, 435/288.5, 204/451, 204/453, 204/455, 204/601, 204/604, 204/605, 219/428, 219/436, 219/437, 219/438, 219/540, 422/102, 422/104, 422/943, 436/174, 436/176, 436/180
• US Class Current: 436/174
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• 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 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/50853 with covers or lids
• 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: C40B 60/14 for creating libraries
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Reactor systems that include a reaction receptacle that includes a plurality of reservoirs disposed in the surface of a substrate. The reactor system also typically includes a temperature control element having at least a first heat exchanger thermally coupled to it. The heat exchanger is, in turn, disposed within the at least one of the reservoirs whereby the heat exchanger transfers heat to or from a fluid disposed within the reservoir, which heat is conducted to or from the temperature control element.

Claims

1. A method of performing temperature dependent reactions, comprising:

providing a reactor system, which comprises a plurality of reservoirs disposed in a body structure, the reservoirs being fluidly connected to a microscale channel network disposed in an interior portion of the body structure, a temperature control element, and a heat exchanger thermally coupled with the temperature control element, the heat exchanger comprising a plurality of fins and further, the heat exchanger being inserted into the reservoir;

placing a first reactant into at least one of the reservoirs;

controlling a temperature within the reservoirs by modulating a temperature; and

transporting the at least one reactant from the at least first reservoir into the microscale channel network.

2. The method of claim 1, wherein the at least first reactant comprises a plurality of molecular species, and the channel network is configured to separate the plurality of molecular species into constituent components.

3. The method of claim 2, wherein the channel network comprises a sieving matrix disposed therein, the sieving matrix causing the constituent components of the plurality of molecular species to move through the channel network at different rate.

4. The method of claim 3, wherein the sieving matrix is selected from cellulose polymers, agarose polymers, and acrylamide polymers.

5. The method of claim 4, wherein the polymer comprises a liner polyacrylamide polymer.

6. The method of claim 5, wherein the polymer comprises a polydimethylacrylamide polymer.

7. The method of claim 1, wherein the step of controlling temperature comprises elevating a temperature within the reservoir to a preselected temperature.

8. The method of claim 1, wherein the step of controlling temperature comprises cycling a temperature within the reservoir between at least first and second preselected temperatures.

9. The method of claim 1, wherein the at least first reactant comprises nucleic acids.

10. The method of claim 1, wherein the reactant further comprises amplification reagents.

11. The method of claims 1, wherein the at least first reactant comprises an enzyme and its substrate.

12. The method of claim 1, wherein the at least first reactant is selected from a receptor or a ligand.

13. A method of performing temperature dependent reactions, comprising:

providing a reactor system, which comprises a plurality of reservoirs disposed in a body structure, the reservoirs being fluidly connected to a microscale channel network disposed in an interior portion of the body structure, a temperature control element, and a heat exchanger thermally coupled with the temperature control element, the heat exchanger comprising a coil and further, the heat exchanger being inserted into the reservoir;

placing a first reactant into at least one of the reservoirs;

controlling a temperature within the reservoirs by modulating a temperature; and

transporting the at least one reactant from the at least first reservoir into the microscale channel network.

14. The method of claim 13, wherein the at least first reactant comprises a plurality of molecular species, and the channel network is configured to separate the plurality of molecular species into constituent components.

15. The method of claim 14, wherein the channel network comprises a sieving matrix disposed therein, the sieving matrix causing the constituent components of the plurality of molecular species to move through the channel network at different rate.

16. The method of claim 15, wherein the sieving matrix is selected from cellulose polymers, agarose polymers, and acrylamide polymers.

17. The method of claim 16, wherein the polymer comprises a liner polyacrylamide polymer.

18. The method of claim 17, wherein the polymer comprises a polydimethylacrylamide polymer.

19. The method of claim 13, wherein the step of controlling temperature comprises elevating a temperature within the reservoir to a preselected temperature.

20. The method of claim 13, wherein the step of controlling temperature comprises cycling a temperature within the reservoir between at least first and second preselected temperatures.

21. The method of claim 13, wherein the at least first reactant comprises nucleic acids.

22. The method of claim 13, wherein the reactant further comprises amplification reagents.

23. The method of claim 13, wherein the at least first reactant comprises an enzyme and its substrate.

24. The method of claim 13, wherein the at least first reactant is selected from a receptor or a ligand.

25. A method of performing temperature dependent reactions, comprising:

providing a reactor system, which comprises a plurality of reservoirs disposed in a body structure, the reservoirs being fluidly connected to a microscale channel network disposed in an interior portion of the body structure, a temperature control element, and a heat exchanger thermally coupled with the temperature control element, the heat exchanger comprising a scintered metal element and further, the heat exchanger being inserted into the reservoir;

placing a first reactant into at least one of the reservoirs;

controlling a temperature within the reservoirs by modulating a temperature; and

transporting the at least one reactant from the at least first reservoir into the microscale channel network.

26. The method of claim 25, wherein the at least first reactant comprises a plurality of molecular species, and the channel network is configured to separate the plurality of molecular species into constituent components.

27. The method of claim 26, wherein the channel network comprises a sieving matrix disposed therein, the sieving matrix causing the constituent components of the plurality of molecular species to move through the channel network at different rate.

28. The method of claim 27, wherein the sieving matrix is selected from cellulose polymers, agarose polymers, and acrylamide polymers.

29. The method of claim 28, wherein the polymer comprises a liner polyacrylamide polymer.

30. The method of claim 29, wherein the polymer comprises a polydimethylacrylamide polymer.

31. The method of claim 25, wherein the step of controlling temperature comprises elevating a temperature within the reservoir to a preselected temperature.

32. The method of claim 25, wherein the step of controlling temperature comprises cycling a temperature within the reservoir between at least first and second preselected temperatures.

33. The method of claim 25, wherein the at least first reactant comprises nucleic acids.

34. The method of claim 25, wherein the reactant further comprises amplification reagents.

35. The method of claim 25, wherein the at least first reactant comprises an enzyme and its substrate.

36. The method of claim 25, wherein the at least first reactant is selected from a receptor or a ligand.

37. A method of performing temperature dependent reactions, comprising:

providing a reactor system, which comprises a plurality of reservoirs disposed in a body structure, the reservoirs being fluidly connected to a microscale channel network disposed in an interior portion of the body structure, a temperature control element, and a heat exchanger thermally coupled with the temperature control element, the heat exchanger comprising a randomly compressed wire and further, the heat exchanger being inserted into the reservoir;

placing a first reactant into at least one of the reservoirs;

controlling a temperature within the reservoirs by modulating a temperature; and

transporting the at least one reactant from the at least first reservoir into the microscale channel network.

38. The method of claim 37, wherein the at least first reactant comprises a plurality of molecular species, and the channel network is configured to separate the plurality of molecular species into constituent components.

39. The method of claim 38, wherein the channel network comprises a sieving matrix disposed therein, the sieving matrix causing the constituent components of the plurality of molecular species to move through the channel network at different rate.

40. The method of claim 39, wherein the sieving matrix is selected from cellulose polymers, agarose polymers, and acrylamide polymers.

41. The method of claim 40, wherein the polymer comprises a liner polyacrylamide polymer.

42. The method of claim 41, wherein the polymer comprises a polydimethylacrylamide polymer.

43. The method of claim 37, wherein the step of controlling temperature comprises elevating a temperature within the reservoir to a preselected temperature.

44. The method of claim 37, wherein the step of controlling temperature comprises cycling a temperature within the reservoir between at least first and second preselected temperatures.

45. The method of claim 37, wherein the at least first reactant comprises nucleic acids.

46. The method of claim 37, wherein the reactant further comprises amplification reagents.

47. The method of claim 37, wherein the at least first reactant comprises an enzyme and its substrate.

48. The method of claim 37, wherein the at least first reactant is selected from a receptor or a ligand.