Localized temperature control for spatial arrays of reaction media

• US 7,771,933 B2
• Filed: 05/21/2004
• Issued: 08/10/2010
• 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
• Primary Examiner(s): Benzion; Gary
• Assistant Examiner(s): Mummert; Stephanie K
• Application Number:
  US10/851,682
• Publication Number:
  US 20050009070A1
• Time in Patent Office: 2,272 Days
• Field of Search: None
• US Class Current: 435/6.11
• 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;

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; and

heat pipes arranged to provide thermal couplings between said thermoelectric modules and either said regions or heat sink means,

wherein said spatial array of reaction zones is defined by a plurality of wells joined in a fixed planar array, and wherein 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.

2. 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, said thermal coupling provided by a plurality of individually variable thermal coupling means;

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.

3. The apparatus of claim 2 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.

4. The apparatus of claim 2 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.

5. The apparatus of claim 2 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.

6. The apparatus of claim 5 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.

7. The apparatus of claim 5 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.