Localized temperature control for spatial arrays of reaction media

• US 9,623,414 B2
• Filed: 12/11/2014
• Issued: 04/18/2017
• Est. Priority Date: 05/23/2003
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Ceremony, Jeff, Chu, Daniel Y.
• Primary Examiner(s): MUMMERT, STEPHANIE KANE
• Application Number:
  US14/567,121
• Publication Number:
  US 20150258547A1
• Time in Patent Office: 859 Days
• Field of Search: None
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/12 Specific details about materials
• 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 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 2300/1883 using thermal insulation
• CPC Class Codes: B01L 2400/0475 specific mechanical means and fluid pressure
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/049 vacuum
• 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: B01L 9/06 Test-tube stands; Test-tube holders

Abstract

Individual temperature control in multiple reactions performed simultaneously in a spatial array such as a multi-well plate is achieved by thermoelectric modules with individual control, with each module supplying heat to or drawing heat from a single region within the array, the region containing either a single reaction vessel or a group of reaction vessels.

Claims

1. Apparatus for performing polymerase chain reactions in a plurality of samples, said apparatus comprising:

a plurality of thermally conductive sample blocks for polymerase chain reactions, arranged in a fixed horizontal array, wherein each sample block comprises a plurality of sample wells and is configured to retain a plurality of samples;

a plurality of independently controlled thermoelectric modules, a thermoelectric module positioned underneath each said sample block, wherein the thermoelectric modules are configured to cycle the temperatures of the sample blocks for polymerase chain reactions;

a layer of thermally conductive material between each sample block and each thermoelectric module; and

a solid barrier of thermally insulating material positioned between each pair of adjacent sample blocks to thermally isolate the sample blocks of the pair from each other.

2. The apparatus of claim 1, wherein the thermally conductive material is selected from the group consisting of an adhesive, grease, putty, and paste.

3. The apparatus of claim 1 further comprising heat sink means thermally coupled to said plurality of thermoelectric modules to dissipate heat generated by said thermoelectric modules.

4. The apparatus of claim 3 wherein said heat sink means is a single heat sink common to all thermoelectric modules.

5. The apparatus of claim 3 wherein said heat sink means comprises an individual heat sink for each thermoelectric module.

6. The apparatus of claim 1 wherein said fixed horizontal array is a two-dimensional array.

7. The apparatus of claim 1 wherein the plurality of sample wells of each sample block is configured to receive a sample plate or portion thereof.

8. The apparatus of claim 1 wherein two or more thermoelectric modules are positioned underneath each said sample block.

9. A method for independently controlling temperatures of polymerase chain reactions in a plurality of samples retained in a plurality of thermally conductive sample blocks of the apparatus of claim 1, said method comprising:

supplying electric power to thermoelectric modules of the apparatus while controlling the magnitude of power supplied to each of said thermoelectric modules independently, thereby maintaining or changing the temperature of each sample block independently of other sample blocks.

10. The method of claim 9, wherein the thermally conductive material is selected from the group consisting of an adhesive, grease, putty, and paste.

11. The method of claim 9, further comprising drawing heat from said thermoelectric modules by heat sink means.

12. The method of claim 11, wherein said heat sink means is a single heat sink common to all thermoelectric modules.

13. The method of claim 11, wherein said heat sink means comprises an individual heat sink for each thermoelectric module.

14. The method of claim 9, wherein said sample blocks are arranged in a fixed horizontal two-dimensional array.

15. The method of claim 9, wherein the plurality of sample wells of each sample block is configured to receive a sample plate or portion thereof.

16. The method of claim 9, wherein two or more thermoelectric modules are positioned underneath each said sample block.