System and method for heating, cooling and heat cycling on microfluidic device

• US 7,648,835 B2
• Filed: 08/27/2008
• Issued: 01/19/2010
• Est. Priority Date: 06/06/2003
• Status: Active Grant

• Current Assignee: Revvity Health Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Micronics Inc. (Sony Group Corp.)
• Inventors: Tonn, Jeffrey F., Bardell, Ronald L., Breidford, Wayne L., Lancaster, Christy A., Hayenga, Jon W., Weigl, Bernhard H.
• Primary Examiner(s): Griffin; Walter D
• Assistant Examiner(s): EDWARDS, LYDIA E
• Application Number:
  US12/199,613
• Publication Number:
  US 20090081771A1
• Time in Patent Office: 510 Days
• Field of Search: 435/288.5
• US Class Current: 435/288.5
• 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 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/185 using a liquid as fluid
• CPC Class Codes: B01L 2300/1877 using chemical reactions
• 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

An integrated heat exchange system on a microfluidic card. According to one aspect of the invention, the portable microfluidic card has a heating, cooling and heat cycling system on-board such that the card can be used portably. The microfluidic card includes one or more reservoirs containing exothermic or endothermic material. Once the chemical process of the reservoir material is activated, the reservoir provides heat or cooling to specific locations of the microfluidic card. Multiple reservoirs may be included on a single card to provide varying temperatures. The assay chemicals can be moved to the various reservoirs to create a thermal cycle useful in many biological reactions, for example, Polymerase Chain Reaction (PCR) or rtPCR. According to another aspect of the invention, the integrated heat exchanger is an adjacent microfluidic circuit containing fluid that is either independently heated or cooled, or is an exothermic or endothermic material, such that the fluid in the adjacent circuit imparts a change in temperature to the assay fluid in an independent circuit. According to yet another aspect of the invention, a thermal electric cooler (TEC) is used for thermocycling the amplification chamber of a disposable microfluidic card.

Claims

1. A microfluidic device for amplifying a nucleic acid comprising:

a) a first plate with a first surface and a second surface;

b) a first amplification chamber formed in said first surface;

c) a microfluidic assay fluid circuit fluidly connected to said first amplification chamber; and

d) a heat exchange film covering and sealing over said first amplification chamber, said heat exchange film with interior surface facing said first surface of said first plate and with oppositely facing exterior surface, wherein said interior surface of said heat exchange film is an optically transparent polyethylene terephthalate roll stock film.

2. The microfluidic device of claim 1 wherein said optically transparent polyethylene terephthalate roll stock film has a thickness of less than or equal to 0.004 inches.

3. The microfluidic device of claim 1 wherein said optically transparent polyethylene terephthalate roll stock film has a thickness of less than or equal to 0.002 inches.

4. The thermocycling apparatus of claim 1 wherein said heat exchange film is sealed to said first surface with a double-sided ACA adhesive layer.

5. The microfluidic device of claim 1, wherein said device is configured for performing an enzymatic reaction selected from the group consisting of PCR, NASBA, reverse transcription, and LAMP.

6. A microfluidic device for amplifying a nucleic acid comprising:

a) a first plate with a first surface and a second surface;

b) a first amplification chamber formed in said first surface;

c) a microfluidic assay fluid circuit fluidly connected to said first amplification chamber; and

d) a heat exchange film covering and sealing over said first amplification chamber, said heat exchange film with interior surface facing said first surface of said first plate and with oppositely facing exterior surface, wherein said interior surface of said heat exchange film is an optically transparent polyethylene terephthalate roll stock film, and wherein said heat-exchange film is joined to said first plate by a double sided ACA adhesive layer with laser cutout to seal around but not cover said amplification chambers.

7. The microfluidic device of claim 6, wherein said device is configured for performing an enzymatic reaction selected from the group consisting of PCR, NASBA, reverse transcription, and LAMP.

8. A microfluidic product for amplifying a nucleic acid, wherein:

a) said product comprises a first plate having at least one amplification chamber and a microfluidic assay circuit;

b) said product is manufactured by a process comprising a step of coveringly joining an optically transparent polyethylene terephthalate heat exchange film to said first plate with a sandwich comprising a double-sided ACA layer of pressure sensitive adhesive, thereby sealingly enclosing said amplification chamber, and

c) said ACA layer in said product is further characterized as having at least one laser cutout configured to expose the internal surface of the heat exchange film forming the cap of said amplification chamber.

9. The microfluidic device of claim 8, further wherein said polyethylene terephthalate film and said ACA adhesive layer are supplied as roll stock and said process is a continuous process.

10. A microfluidic device for amplifying a nucleic acid comprising:

a) a first plate with a first surface and a second surface;

b) a first amplification chamber formed in said first surface;

c) a microfluidic assay fluid circuit fluidly connected to said first amplification chamber; and

d) a heat exchange film covering and sealing over said first amplification chamber, said heat exchange film with interior surface facing said first surface of said first plate and with oppositely facing exterior surface, wherein said interior surface of said heat exchange film is an optically and UV transparent cyclic polyolefin roll stock film, and wherein said heat-exchange film is joined to said first plate by a double sided ACA adhesive layer with laser cutout to seal around but not cover said amplification chambers.

11. The microfluidic product of claim 10, wherein said device is configured for performing an enzymatic reaction selected from the group consisting of PCR, NASBA, reverse transcription, and LAMP.

12. A microfluidic product for amplifying a nucleic acid, wherein

a) said product comprises a first plate having at least one amplification chamber and a microfluidic assay circuit;

b) said product is manufactured by a process comprising a step of coveringly joining an optically and UV transparent cyclic polyolefin heat exchange film to said first plate with a sandwich comprising a double-sided ACA layer of pressure sensitive adhesive, thereby sealingly enclosing said amplification chamber; and

c) said ACA layer in said product is further characterized as having at least one laser cutout configured to expose the internal surface of the heat exchange film forming the cap of said amplification chamber.