Localized temperature control for spatial arrays of reaction media

• US 20050009070A1
• Filed: 05/21/2004
• Published: 01/13/2005
• Est. Priority Date: 05/23/2003
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Ragsdale, Charles W., Chu, Daniel Y., Ceremony, Jeff, Arciniegas, German
• Granted Patent: US 7,771,933 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 independently controlling temperature in discrete regions of a spatial array of reaction zones, said apparatus comprising:

a plurality of thermoelectric modules thermally coupled to said regions with a separate module for each region;

an electric power supply electrically coupled to said thermoelectric modules; and

means for independently controlling the magnitude of electric power delivery from said electric power supply to each thermoelectric module, thereby maintaining the temperature of each region independently of other regions.

2. The apparatus of claim 1 further comprising thermal insulating means separating each of said regions from adjacent regions.

3. The apparatus of claim 1 further comprising heat pipes arranged to provide thermal couplings between said thermoelectric modules and either said regions or heat sink means.

4. The apparatus of claim 2 wherein said heat pipes are arranged to provide thermal couplings between said thermoelectric modules and said regions.

5. The apparatus of claim 2 wherein said heat pipes are arranged to provide thermal couplings between said thermoelectric modules and said heat sink means.

6. The apparatus of claim 2 wherein each said heat pipe comprises

a heat receiving end,

a heat dissipating end,

a working fluid, and

fluid conveying means for conveying said working fluid from said heat dissipating end to said heat receiving end.

7. The apparatus of claim 6 wherein each said heat pipe further comprises fluid transport control means for independently controlling the rate of conveyance of said working fluid from said heat dissipating end to said heat receiving end in each heat pipe independently of other heat pipes.

8. The apparatus of claim 1 further comprising a single heat sink common to all thermoelectric modules.

9. The apparatus of claim 1 further comprising an individual heat sink for each thermoelectric module.

10. The apparatus of claim 1 wherein said thermal insulating means is an air gap.

11. The apparatus of claim 1 wherein said thermal insulating means comprises solid barriers of thermally insulating material positioned between each adjacent pair of regions.

12. The apparatus of claim 1 wherein said thermal coupling between said thermoelectric modules and said regions is provided by a plurality of individually variable thermal coupling means.

13. The apparatus of claim 12 wherein said individually variable thermal coupling means comprises a dispersion of electrically conductive non-magnetic particles in a fluid medium and means for producing localized AC electrical fields within said dispersion and thereby electrical repulsion among said particles, one such field for each region, and for independently controlling the magnitudes of said electrical fields thereby providing each region with independently controlled thermal coupling to said thermoelectric modules.

14. The apparatus of claim 12 wherein said individually variable thermal coupling means comprises a magnetic fluid whose thermal conductivity varies with a magnetic field, and means for producing localized magnetic fields within said magnetic fluid, with one such field for each region, and for independently controlling the magnitudes of said localized magnetic fields thereby providing each region with independently controlled thermal coupling to said thermoelectric modules.

15. The apparatus of claim 12 wherein said individually variable thermal coupling means comprises means for applying localized pressure to urge said thermoelectric modules toward said regions, and independent control means for independently controlling the magnitudes of said localized pressure thereby providing each region with independently controlled thermal coupling to said thermoelectric modules.

16. The apparatus of claim 15 wherein said means for applying localized pressure are comprised of magnetic material and means for applying localized magnetic fields to said magnetic material, and said independent control means are means for independently controlling said localized magnetic fields.

17. The apparatus of claim 15 wherein said means for applying localized pressure are comprised of piezoelectric elements and means for supplying a voltage to each said piezoelectric element, and said independent control means are means for independently controlling said voltages.

18. The apparatus of claim 1 in which said spatial array of reaction zones is defined by a plurality of wells joined in a fixed planar array.

19. The apparatus of claim 18 further in which said wells are discrete open-top receptacles having heat conductive walls and joined by filaments of thermally insulating material.

20. The apparatus of claim 18 in which each of said wells has a serpentine cross-section profile.

21. The apparatus of claim 18 in which each of said wells has a base with an elastic closure, and said apparatus further comprises a thermally conductive support block with indentations complementary in shape and spatial distribution to said wells except for a protrusion within each indentation positioned such that when said wells are pressed against said support block said protrusions press against said elastic closures and thereby stretch said elastic enclosures around said protrusions to provide each said well with an internal surface area that is increased by an amount corresponding to said protrusion.