Thermal cycler for PCR

Patent metadata

Field	Value
Publication number	US-9776187-B2
Application number	US-22940408-A
Country	US
Kind code	B2
Filing date	Aug 22, 2008
Priority date	Mar 28, 1997
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

An instrument for performing highly accurate PCR employing an assembly, a heated cover, and an internal computer, is provided. The assembly is made up of a sample block, a number of Peltier thermal electric devices, and a heat sink, clamped together. A control algorithm manipulates the current supplied to thermoelectric coolers such that the dynamic thermal performance of a block can be controlled so that pre-defined thermal profiles of sample temperature can be executed. The sample temperature is calculated instead of measured using a design specific model and equations. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block/heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics.

First claim

What is claimed is:

1. An apparatus for performing the polymerase chain reaction in a plurality of liquid reaction mixtures, said apparatus comprising:
an assembly adapted for cycling a plurality of vials through a series of temperature excursions, the assembly comprising:
a sample block for receiving a microtiter plate having the plurality of vials, wherein in a position of the microtiter plate received by the sample block, the vials are optically accessible by an optical reader without opening the vials;
a heated cover having a platen and a skirt surrounding a perimeter of and extending from the platen, the platen comprising a plurality of recesses sized to allow optical access to the vials, and the skirt being configured to engage and align to the microtiter plate in the position of the microtiter plate received by the sample block;
a plurality of thermoelectric devices,
a heatsink, and
a seal element surrounding and contacting a perimeter of the sample block and configured to seal off the plurality of thermoelectric devices, wherein the seal element is in contact with an inner surface of the heated cover surrounding the sample block; and

a computing apparatus configured for controlling said temperature excursions of said assembly.

2. The apparatus of claim 1 wherein the plurality of thermoelectric devices comprise a plurality of Peltier thermoelectric devices, and the assembly further comprises: a clamping mechanism that applies pressure to the sample block to clamp the thermoelectric devices between the sample block and the heatsink.

3. The apparatus of claim 2 wherein said sample block comprises: a plurality of sample wells, for receiving the vials of the microtiter plate, each well having a top and bottom; and an upper support plate connecting the tops of said sample wells.

4. The apparatus of claim 3 wherein said upper support plate and said sample wells are electroformed as a single piece.

5. The apparatus of claim 1 , further comprising a cover for applying a seating force directly to said plurality of vials and for applying a constant temperature to the upper portions of said plurality of vials.

6. The apparatus of claim 1 , wherein the assembly further comprises a heater positioned loosely around the perimeter of said sample block.

7. The apparatus of claim 2 , wherein said plurality of Peltier thermoelectric devices are matched to provide a temperature within 0.2 C for a given input current.

8. The apparatus of claim 2 , wherein each of the plurality of Peltier thermoelectric devices comprise:
a first ceramic layer having bonded copper traces;
a second ceramic layer having bonded copper traces, said second ceramic layer comprising a plurality of ceramic elements; and
a plurality of bismuth telluride pellets positioned between said first ceramic layer and said second ceramic layer and soldered to said bonded copper traces on said first and second ceramic layers.

9. The apparatus of claim 2 , wherein said heatsink comprises:
a plate having a top side and a bottom side;
a plurality of fins extending perpendicularly from said bottom side;
a trench extending around the perimeter of said top side to impede heat loss from said perimeter;
a fan placed in close proximity to said fins to control air flow through said fins; and
a recess within said plate for receiving a temperature sensor.

10. The assembly of claim 2 , wherein said clamping mechanism comprises:
a spine and said spine having a plurality of openings in said spine for receiving fasteners; and
a plurality of fingers extending laterally from said spine.

11. The apparatus of claim 10 , wherein said fingers have a first end protruding laterally from said spine and a protrusion extending downward from said first end.

12. The apparatus of claim 2 , wherein said heater comprises an electrically resistive path embedded in a frame-shaped film carrier.

13. The apparatus of claim 12 , wherein said electrically resistive path comprises a first set of sections located on opposite sides of said frame-shaped film carrier having a first power density and a second set of sections located on opposite sides of said frame-shaped film carrier having a second power density.

14. The apparatus of claim 2 further comprising an associated memory device capable of storing data related to said assembly.

15. The apparatus of claim 5 , wherein
the platen is vertically and horizontally displaceable in relationship to said vials, said platen including:
an array of openings corresponding to locations of said vials, said openings having a perimeter corresponding to a perimeter of said vials;
wherein the skirt extends downward around the perimeter of said platen, said skirt having dimensions corresponding to the perimeter of a standard microtiter tray, said skirt constructed to
engage said perimeter of said tray during vertical displacement of said platen,
cause said openings in said platen to engage said perimeter of said vials, and
apply a seating force on said vials for maintaining a snug fit between walls of said sample vials and said assembly for receiving said sample vials;

a mechanism configured for forcibly lowering said platen to maintain said seating force; and
a heater positioned in close contact with said platen to maintain said platen at a constant temperature.

16. The apparatus of claim 1 , wherein the skirt and platen define a volume.

Assignees

• Atwood John G
• Fawcett Adrian
• Ferrara Keith S
• Hetherington Paul M
• Noreiks Richard W
• Olsen Douglas E
• Widomski John R
• Wittmer Charles M
• Applied Biosystems Llc

Inventors

• Atwood John G
• Fawcett Adrian
• Ferrara Keith S
• Hetherington Paul M
• Noreiks Richard W
• Olsen Douglas E
• Widomski John R
• Wittmer Charles M

Classifications

• B01L2300/1822

  using Peltier elements · CPC title

• G05D23/1919

  characterised by the type of controller · CPC title

• B01L2300/1827

  using resistive heater · CPC title

• B01L3/50853

  with covers or lids (closures for test tubes B01L3/50825) · CPC title

• C12Q1/686

  Polymerase chain reaction [PCR] · CPC title