Thermal cycler including a temperature gradient block

• US 5,525,300 A
• Filed: 10/20/1993
• Issued: 06/11/1996
• Est. Priority Date: 10/20/1993
• Status: Expired due to Term

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Stratagene California
• Inventors: Shopes, Robert J., Danssaert, John L., Shoemaker, Daniel D.
• Primary Examiner(s): Snay, Jeffrey R.
• Assistant Examiner(s): Ludlow, Jan M.
• Application Number:
  US08/139,540
• Time in Patent Office: 965 Days
• Field of Search: 422/50, 422/68.1, 422/99, 422/104, 422/109, 422/67, 422/63, 435/290, 435/316, 435/809, 165/14, 165/26, 165/30, 436/43, 436/47, 436/49, 436/174, 935/85
• US Class Current: 422/552
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 2300/1844 using fans
• 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 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: B01L 7/5255 by moving sample containers
• CPC Class Codes: B01L 7/54 using spatial temperature gradients
• CPC Class Codes: G01N 2035/042 moved independently, e.g. by fork manipulator
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: Y10S 435/809 Incubators or racks or holders for culture plates or containers
• CPC Class Codes: Y10T 436/25 including sample preparation

Abstract

A method in which a temperature gradient is generated across a "gradient" block, and an apparatus comprising a block across which a temperature gradient can be generated. By setting up such a gradient, multiple reaction mixtures held in wells on the gradient block can be simultaneously run at temperatures which differ only slightly, thereby permitting an optimum temperature for the reaction to be quickly identified. In a preferred embodiment the gradient block is integrated into a thermal cycler used for nucleic acid amplification reactions.

Claims

1. An apparatus for generating a temperature gradient across a heat conducting block comprising:

a reaction mixture holder including a heat conducting block having top and bottom portions, first and second opposing end portions, and opposing side walls extending between said opposing end portions;

said heat conducting block having a plurality of reaction mixture wells formed in said top portion and spaced across said top portion in parallel rows;

said heat conducting block having holes bored therethrough between the rows of wells and extending through the block between said side walls;

a first block heater positioned adjacent to said first opposing end portion; and

a block cooler positioned adjacent to said second opposing end portion.

2. An apparatus as recited in claim 1 wherein said heat conducting block is composed of brass.

3. An apparatus as recited in claim 1 wherein said block cooler is a heat sink attached to the second opposing end portion of said heat conducting block.

4. An apparatus as recited in claim 3 wherein said block cooler further comprises a fan positioned adjacent to said heat sink.

5. An apparatus as recited in claim 1 further comprising a second block heater positioned adjacent to said bottom portion, and means for independently controlling said first and second block heaters.

6. An apparatus for performing molecular biological reactions comprising:

a temperature-gradient block having a plurality of rows of reaction mixture wells formed in a top portion thereof, wherein said temperature-gradient block has first and second opposing end portions and opposing side walls extending between said opposing end portions;

said temperature-gradient block having holes bored therethrough between the rows of wells and extending through the block between said side walls; and

means for generating a temperature gradient between said first and second opposing end portions of the temperature-gradient block.

7. An apparatus according to claim 6 wherein said temperature-gradient block is composed of brass.

8. An apparatus according to claim 6 further comprising a heating means for heating a bottom portion of said temperature-gradient block.