Thermal cycling reaction apparatus and reactor therefor

• US 5,736,106 A
• Filed: 01/25/1996
• Issued: 04/07/1998
• Est. Priority Date: 01/26/1995
• Status: Expired due to Fees

• Current Assignee: Tosoh Corporation
• Original Assignee: Tosoh Corporation
• Inventors: Fukunaga, Shingo, Mitoma, Yasutami, Ishiguro, Takahiko
• Primary Examiner(s): Jones, W. Gary
• Assistant Examiner(s): REES, DIANE
• Application Number:
  US08/591,270
• Time in Patent Office: 803 Days
• Field of Search: 435/91.1, 435/91.2, 435/285.1, 435/287.2, 435/288.7, 165/133, 165/64, 422/99, 422/68.1, 422/131
• US Class Current: 422/131
• 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

Abstract

A thermal cycling reaction apparatus comprises a reactor having a reactor body made of a thin heat-conductive plate having a cavity as a reaction chamber with an opening of the chamber sealed with a transparent heat-resistant sheet. The apparatus further includes, delivery rollers for delivering the reactor along a delivery path and stopping it at stopping positions in a predetermined order; plural temperature-controlling blocks having respectively a temperature-controlling surface to be brought into contact with a heat-transfer face of the reactor and being placed at the stopping positions separately so as not to thermally affect each other; and a temperature-controlling mechanism for keeping the fixed temperature-controlling surfaces respectively at prescribed temperatures.

Claims

1. A reactor for a thermal cycling reaction, the reactor being able to be delivered along a delivery path having plural and separate temperature-controlling blocks fixed thereon, each of said temperature controlling blocks respectively having a fixed temperature-controlling surface of a prescribed area at a controlled temperature, the reactor being capable of repeatedly contacting successively in a predetermined order with a selected temperature controlling block, said reactor comprising a reactor body being in a shape of a plate, said reactor body having a heat-transferring area on at least one face of the plate to be brought into face-to-face contact with the respective temperature-controlling surfaces, said reactor body further having a cavity which forms a reaction chamber, said cavity having an opening on at least one face of the plate, wherein a heat-resistant sealing sheet for sealing the reaction chamber covers the opening of the chamber;

wherein the reactor further comprises a delivery-assisting member which carries the reactor body, said delivery-assisting member being composed of a poor heat-conductive material, the reactor body and the delivery-assisting member being formed in a plate shape.

2. The reactor of claim 1, wherein the sealing sheet is a heat-resistant transparent sheet which forms a transparent window for optically detecting a change in the reaction chamber from the outside.

3. The reactor of any one of claims 1 to 2, wherein said reaction chamber has a sealable liquid-filling opening for filling the reaction chamber with a reaction liquid.

4. The reactor of any of claims 1 to 2, wherein the reactor body is in a shape of a plate which has a thickness ranging from 0.2 to 3 mm.

5. A thermal cycling reaction apparatus, comprising a reactor of any one of claims 1 to 2;

the thermal cycling reaction apparatus comprising said delivery path which guides the reactor;

said plural temperature-controlling blocks placed apart from each other so as not to cause a thermal interaction along the delivery path and having respectively said fixed temperature-controlling surface of a prescribed area to be brought into contact with the reactor;

a temperature controlling means for maintaining the temperature-controlling surfaces of the temperature-controlling blocks at respectively prescribed temperatures; and

a driving means for delivering the reactor to each of the temperature controlling blocks so as to repeatedly contact each of the fixed temperature-controlling surfaces of the temperature-controlling blocks in a predetermined order.

6. The thermal cycling reaction apparatus of claim 5, wherein said delivery path includes a stopping position for the reactor that is different from positions of the temperature-controlling blocks on the delivery path;

and further comprising an optical detecting means for detecting optically a change in the sealed reactor from the outside through the sealing sheet.

7. The thermal cycling reaction apparatus of claim 5, wherein the plural temperature-controlling blocks are placed separately along the delivery path.

8. The thermal cycling reaction apparatus of claim 5, for use for PCR, wherein a first temperature-controlling block of said temperature controlling blocks has a fixed first temperature-controlling surface kept at a dissociation temperature for a DNA having a target DNA sequence to dissociate a double-stranded DNA into a single-stranded DNA, a second temperature-controlling block of said temperature controlling blocks has a fixed second temperature-controlling surface kept at an annealing temperature for the single-stranded DNA to anneal thereto a forward primer and a reverse primer, and a third temperature-controlling block of said temperature controlling blocks has a fixed third temperature-controlling surface kept at a temperature for synthesizing another DNA strand complementary to the single-stranded DNA;

and the delivery means is constructed so as to deliver the reactor to the first, second and third fixed temperature-controlling surfaces, and repeats this cycle a number of times.

9. The reactor according to claim 1, wherein said delivery-assisting member comprises a hole, said reactor body being fitted in said hole of said delivery-assisting member.

10. A reactor for a thermal cycling reaction, the reactor being able to be delivered along a delivery path having plural and separate temperature-controlling blocks fixed thereon, each of said temperature controlling blocks respectively having a fixed temperature-controlling surface of a prescribed area at a controlled temperature, the reactor repeatedly contacting successively in a predetermined order with a selected temperature controlling block, said reactor comprising a reactor body being in a shape of a plate, said reactor body having a heat-transferring area on at least one face of the plate to be brought into face-to-face contact with the respective temperature-controlling surfaces, said reactor body further having a cavity which forms a reaction chamber, said cavity having an opening on at least one face of the plate, wherein a heat-resistant sealing sheet for sealing the reaction chamber covers the opening of the chamber, and the reactor body has a thickness ranging from 0.2 to 3 mm.

11. A thermal cycling reaction apparatus comprising:

a reactor for a thermal cycling reaction, said reactor comprising a reactor body with a heat-transferring area, said reactor body comprising a cavity which forms a reaction chamber, wherein a heat-resistant sealing sheet covers the reaction chamber so as to seal the reaction chamber;

a delivery path for guiding the reactor past a plurality of temperature controlling blocks which make contact with the reactor, wherein the plurality of temperature controlling blocks are positioned along said delivery path, each of said temperature controlling blocks having a temperature controlling surface of a prescribed area;

a temperature controlling means for maintaining the temperature controlling surfaces of the temperature controlling blocks at prescribed temperatures; and

driving means for conveying the reactor along said delivery path so as to bring the heat-transferring area of the reactor body into contact in a predetermined order with each of the temperature-controlling surfaces of each of the temperature controlling blocks.