Miniaturized thermal cycler

• US 6,509,186 B1
• Filed: 05/01/2001
• Issued: 01/21/2003
• Est. Priority Date: 02/16/2001
• Status: Expired due to Fees

• Current Assignee: Agency For Science Technology and Research (Government of Singapore), National University of Singapore
• Original Assignee: Institute of Microelectronics
• Inventors: Zachariah, Emmanuel Selvanayagam, Chen, Yu, Sridhar, Uppili, Yan, Tie, Lim, Tit Meng, Zou, Quanbo
• Primary Examiner(s): Redding, David A.
• Application Number:
  US09/846,126
• Time in Patent Office: 630 Days
• Field of Search: 435/286.1, 435/287.2, 435/287.3, 435/288.3, 435/288.4, 435/289.1, 435/303.1, 435/305.2, 422/102, 422/109, 422/113, 422/131, 216/2
• US Class Current: 435/286.1
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1883 using thermal insulation
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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

The invention describes a thermal cycler which permits simultaneous treatment of multiple individual samples in independent thermal protocols, so as to implement large numbers of DNA experiments simultaneously in a short time. The chamber is thermally isolated from its surroundings, heat flow in and out of the unit being limited to one or two specific heat transfer areas. All heating elements are located within these transfer areas and at least one temperature sensor per heating element is positioned close by. Fluid bearing channels that facilitate sending fluid into, and removing fluid from, the chamber are provided. The chambers may be manufactured as integrated arrays to form units in which each cycler chamber has independent temperature and fluid flow control. Two embodiments of the invention are described together with a process for manufacturing them as well as two schemes for making connections to the outside world.

Claims

1. A multi-chamber thermal cycler system, comprising:

a multi-chamber thermal cycler chip;

a layer of a material having high thermal conductivity as well as a high level of softness, said layer being uniquely located between the thermal cycler chip and a heat sink, whereby good thermal contact and conductance between the chip and the heat sink are provided;

a controller board, having opposing sides, that includes electrically conductive lines and tracks and electric connectors;

means for connecting and disconnecting bond-pads on the chip to the controller board; and

a control system for multi-channel independent parallel protocol control, including;

electronic circuits for multi-channel analogue and digital signals communication between the controller board and a processor having programmed multiple channel parallel proportional-integral-derivative control.

2. The multi-chamber thermal cycler system described in claim 1 wherein said layer is selected from the group consisting of thermal conductive tapes, greases, glues, polymers, elastomers, rubber, and plastics.

3. The multi-chamber thermal cycler system described in claim 1 wherein said layer has a thickness between about 1 and 100 microns.

4. The multi-chamber thermal cycler system described in claim 1 wherein said layer has a thermal conductivity between about 0.2 and 20 W/m.K.

5. The multi-chamber thermal cycler system described in claim 1 wherein said layer has a softness value between about 1 and 100 shore D Durometer units.

6. The multi-chamber thermal cycler system described in claim 1 wherein said electric connectors are on both sides of the board or on either side of the board.

7. The multi-chamber thermal cycler system described in claim 1 wherein said means for connecting and disconnecting bond-pads on the chip to the controller board is selected from the group consisting of wire-bonding, probing-cards and flextural electric connectors.

8. The multi-chamber thermal cycler system described in claim 1 wherein said multiple channel parallel proportional-integral-derivative control contains between 2 and 384 channels.