Thermal cycler

• US 5,795,547 A
• Filed: 10/23/1996
• Issued: 08/18/1998
• Est. Priority Date: 09/10/1993
• Status: Expired due to Term

• Current Assignee: Roche Diagnostics Corporation (Roche Holding AG)
• Original Assignee: Roche Diagnostic Systems Incorporated (Roche Holding AG)
• Inventors: Birrer, Lukas, Moser, Rolf
• Primary Examiner(s): LUDLOW, JAN M
• Application Number:
  US08/735,943
• Time in Patent Office: 664 Days
• Field of Search: 422/64, 422/67, 422/104, 422/105, 422/109, 422/99, 435/286.1, 435/303.1
• US Class Current: 422/64
• 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 9/06 Test-tube stands; Test-tube holders
• CPC Class Codes: G01N 35/1079 with means for piercing stoppers or septums

Abstract

An apparatus for automatic performance of temperature cycles in a number of test tubes in which each test tube is closed by a closure and contains a predetermined volume of a liquid reaction mixture. The apparatus includes a holder, a computer-controlled automatic control system, and a device for cyclic alteration of the holder temperature. The holder has an arrangement of chambers for holding test tubes with each chamber being adapted to receive one test tube. The holder is constructed of a material of high thermal conductivity, and has an upper surface, a bottom surface and a cylindrical outer wall. Each chamber has an opening located in the upper surface of the holder. The device for cyclic alteration of the temperature of the holder is actuated by the automatic control system. By reducing the dimensions of the device and the power required to operate it, numerous advantages are realized. Such advantages are achieved through the arcuate arrangement of chambers in the holder, and the test tube closure which is piercable by a pipetting needle.

Claims

1. An automatic analytical device, which comprises:

(a) a plurality of test tubes, each for containing a predetermined volume of a liquid reaction mixture, each of the plurality of test tubes being equipped with a pierceable closure;

(b) a pipetting needle configured and dimensioned for piercing the pierceable closures and removing liquid reaction mixture from the test tubes;

(c) means for moving the pipetting needle from a position outside of each test tube, through the piercable closure on the test tube, and into the test tube;

(d) means for applying suction to the pipetting needle so as to enable the pipetting needle to withdraw liquid reaction mixture out of a given test tube when the pipetting needle is inside the given test tube and reaction mixture is present within the given test tube; and

(e) a device for automatic performance of temperature cycles on the test tubes, which comprises;

(1) a holder formed of a thermally conductive material and having an upper surface, a lower surface and a cylindrical outer wall, the holder having an array of chambers for holding the test tubes equipped with piercable closures, the chambers being disposed along an arc with each chamber having an opening located in the upper surface of the holder, each chamber being configured and dimensioned to receive one test tube equipped with a piercable closure, the holder being configured and dimensioned so that when test tubes having piercable closures are held in the array of chambers, the piercable closures of the test tubes can be accessed by a pipetting needle;

(2) a computer-regulated automatic control system; and

(3) means actuated by the automatic control system for cyclic alteration of the temperature of the holder.

2. The device according to claim 1, wherein the means for cyclic alteration of the temperature of the holder includes a cold- and heat-producing element in the form of at least one Peltier element which is in thermal contact with the bottom surface of the holder.

3. The device according to claim 1, wherein the means for cyclic alteration of the temperature of the holder includes at least one Peltier element which is configured and dimensioned to operate as a cold-producing element and which is in thermal contact with the bottom surface of the holder.

4. The device according to claim 2, wherein the at least one Peltier element has a central part and is pressed against the holder by spring-biased securing means positioned at the central part, which securing means comprises a spring pressed by a screw, the tension on the spring being adjustable by means of the screw.

5. The device according to claim 3, wherein the at least one Peltier element has a central part and is pressed against the holder by spring-biased securing means positioned at the central part, which securing means comprises a spring pressed by a screw, the tension on the spring being adjustable by means of the screw.

6. The device according to claim 1 further comprising a hinged lid having a heating element for heating the test tubes having piercable closures when such test tubes are held in the array of chambers, the lid having an opening for each chamber so that the pipetting needle can traverse each opening to access the pierceable closure of the test tube in the chamber.

7. The device of claim 6, wherein the hinged lid contains a closing and pressure means for securing the test tubes having piercable closures when such test tubes are held in the array of chambers.

8. The device according to claim 1 further comprising a heating element disposed around the holder along the periphery of the cylindrical outer wall of the holder.

9. The device according to claim 1 further comprising means for recognizing a marking on an arrangement of test tubes.

10. The device according to claim 6 further comprising a lifting-out device for facilitating removal of the test tubes from the chambers in the holder, the lifting-out device comprising an ejection lever having one end connected to the hinge of the lid and the other end free.

11. The device according to claim 10 further comprising an ejection disc which is secured to the lever and is concentric with the axis of symmetry of the holder, the disc having a peripheral arrangement of recesses for removing the test tubes from the chambers.

12. The device of claim 1, wherein the chambers are disposed along an arc that forms a complete circle.

13. The device of claim 1, wherein the chambers are disposed along an arc that forms a semi-circle.