Miniaturized thermal cycler

• US 6,432,695 B1
• Filed: 02/16/2001
• Issued: 08/13/2002
• Est. Priority Date: 02/16/2001
• Status: Expired due to Fees

• Current Assignee: Agency For Science Technology and Research, National University of Singapore
• Original Assignee: Institute of Microelectronics
• Inventors: Chen, Yu, Sridhar, Uppili, Yan, Tie, Lim, Tit Meng, Zou, Quanbo, Zachariah, Emmanuel Selvanayagam
• Primary Examiner(s): Redding, David A.
• Application Number:
  US09/785,588
• Publication Number:
  US 20020115200A1
• Time in Patent Office: 543 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: 435/287.2
• 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.

Claims

1. A process for manufacturing a thermal cycler, comprising the sequential steps of:

providing a silicon wafer having upper and lower surfaces;

in said upper surface, etching two inner and two outer trenches to a first depth, said inner tenches having a first width and said outer trenches having second width;

forming a first dielectric layer on said upper surface, including said trenches;

depositing a layer of material suitable for use as a sensor and as a resistive heater;

patterning and etching the material layer to form temperature sensors and heater elements;

in said upper surface etching, to a second depth, two top preliminary trenches having a third width, each being located between an inner trench and an outer trench;

patterning and etching said upper surface whereby a chamber trench, having a fourth width and located between said inner trenches, is formed to a third depth and the top preliminary trenches have their depth increased to a fourth depth;

forming a second dielectric layer on said upper surface, including all trenches;

patterning and etching the lower surface of the wafer to form an under-trench that is wide enough to slightly overlap the top preliminary trenches, to a depth such that the top preliminary trenches extend through said lower surface and, within the chamber trench, the wafer has a thickness that is between about 30 and 100 microns;

providing a sheet of dielectric material and micro-machining said sheet to form holes in selected locations; and

bonding the sheet to the wafer thereby forming a hermetically sealed chamber that is thermally isolated from the wafer.

2. The process described in claim 1 wherein, at the start of the process the silicon wafer has a thickness between about 350 and 700 microns.

3. The process described in claim 1 wherein said first trench depth is between about 0.1 and 1 microns, said inner trenches'"'"' first width is between about 20 and 500 microns and said outer trenches'"'"' second width is between about 50 and 500 microns.

4. The process described in claim 1 wherein the first dielectric layer is selected from the group consisting of silicon oxide, phosphosilicate glass, silicon nitride, polymers, and plastics.

5. The process described in claim 1 wherein the layer of material suitable for use as a sensor and as a resistive heater is selected from the group consisting of monocrystalline silicon germanium and gallium arsenide, metals, and ceramics.

6. The process described in claim 1 wherein said second depth of the two top preliminary trenches is between about 30 and 100 microns and their third width is between about 20 and 100 microns and each top preliminary trench is about 100 microns from an inner trench.

7. The process described in claim 1 wherein said fourth width of the chamber trench is between about 100 and 10,000 microns and said increased fourth depth of the top preliminary trenches is between about 60 and 600 microns.

8. The process described in claim 1 wherein the second dielectric layer is formed to a thickness between about 0.1 and 0.5 microns.

9. The process described in claim 1 wherein said under-trench has a width between about 200 and 12,000 microns and a depth between about 50 and 500 microns.

10. The process described in claim 1 wherein said sheet of dielectric material is glass and bonding of the sheet to the wafer is achieved by means of anodic bonding.

11. The process described in claim 1 wherein said sheet of dielectric material is selected from the group consisting of rigid plastics, fused quartz, silicon, elastomers, and ceramics, and bonding is by means of glue or epoxy.