Microchip matrix device for duplicating and characterizing nucleic acids

• US 7,888,074 B2
• Filed: 01/02/2002
• Issued: 02/15/2011
• Est. Priority Date: 07/02/1999
• Status: Expired due to Fees

• Current Assignee: Clondiag Chip Technologies GmbH (Abbott Laboratories)
• Original Assignee: Clondiag Chip Technologies GmbH (Abbott Laboratories)
• Inventors: Ehricht, Ralf, Ellinger, Thomas, Tuchscherer, Jens, Poser, Siegfried, Ermantraut, Eugen, Schulz, Torsten
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US10/038,284
• Publication Number:
  US 20020150933A1
• Time in Patent Office: 3,331 Days
• Field of Search: 435/6, 435/283.1, 435/287.2, 435/288.4, 435/288.5, 422/68.1, 422/109, 422/129, 422/131, 422/138
• US Class Current: 435/91.2
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0809 rectangular shaped
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• 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 3/508 rigid containers not provided for above

Abstract

The aim of the invention is to provide a device for duplicating and characterizing nucleic acids almost simultaneously and with a high sample throughput rate. The device consists of a chamber body with a recess whose edge sealingly holds an optically transparent chip. Said chip holds nucleic acids in individual spots on a detection surface. The chamber body is placed on an optically transparent chamber support with a bearing surface, in such a way that a capillary gap, which can be filled with a liquid sample, is formed between the detection surface of the chip facing towards the chamber support and said chamber support. The chamber body is provided with an inlet and an outlet, which are spatially separate from each other, and has a space, which laterally encompasses the chip and which has a gas reservoir. The chamber support is provided with heating elements.

Claims

1. A device for duplicating and characterizing nucleic acids in a reaction chamber, comprising a reaction chamber defined by:

a chamber support having an optically permeable first surface facing the reaction chamber;

a chamber body sealingly and unreleasably placed on the chamber support and including;

a recess having an edge configured to support a chip; and

an inlet providing fluid communication between the reaction chamber and an environment external to the reaction chamber; and

a rigid optically permeable chip, sealingly supported by the edge of the recess, and having a second surface facing the reaction chamber, the second surface having an array of multiple different polynucleotide probes immobilized thereon, wherein the first and second surfaces are substantially parallel.

2. The device of claim 1, further comprising a temperature adjustment means connected with the chamber support and adapted to permit a rapid temperature control of the continuous cavity.

3. The device of claim 2, wherein the temperature adjustment means are situated on a side of the chamber support facing towards the chamber body.

4. The device of claim 2, wherein the temperature adjustment means are configured such that the optical transparency of the chip remains unaffected at least at the array.

5. The device of claim 4, wherein the temperature adjustment means comprise micro-structured heating elements.

6. The device of claim 1, wherein the chamber support comprises systems for thoroughly mixing a liquid sample, the systems being configured such that the chip remains optically transparent at least at the array;

and

a quadrupole system, adapted to induce an electro-osmotic flow, is associated with the chamber support.

7. The device of claim 6, wherein the quadrupole system includes gold-titanium electrodes.

8. The device of claim 1, wherein the chamber support and the chamber body consist of at least one of glass, synthetic material, and optically permeable synthetic materials.

9. The device of claim 1, wherein the chamber support consists of a thermally conducting material.

10. The device of claim 1, wherein the chip consists of optically permeable materials including at least one of glass, borofloat glass, quartz glass, monocrystalline CaF₂, sapphire, PMMA and silicon.

11. The device of claim 1, wherein the recess in the chamber body is an optically permeably conical recess aligned with the array.

12. The device of claim 1, wherein the chamber body includes an inlet and an outlet spatially separate from each other, for charging the reaction chamber.

13. The device of claim 12, wherein the inlet and the outlet are arranged unilaterally to the chip and are separated by a gas reservoir nose.

14. The device of claim 1, wherein the chamber body is sealingly and unreleasably connected with the chamber support by at least one of an adhesive and weld connection.

15. The device of claim 1, wherein the probes are immobilized through spacers.

16. The device of claim 1, wherein the reaction chamber is adapted to allow characterization by at least one of optical detection and spectroscopy.

17. The device of claim 1, wherein the chip is adapted to allow characterization by a silver precipitation reaction.

18. The device of claim 1, wherein the first surface is held opposite to the second surface by the chamber body.