Thermal Cycler for Microfluidic Array Assays

• US 20110003699A1
• Filed: 12/18/2009
• Published: 01/06/2011
• Est. Priority Date: 12/20/2002
• Status: Abandoned Application

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: BioTrove, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Yoder, Karl, Brenan, Colin, Katz, Arrin, Linton, John, Morrison, Tom, Fonseca, Jorge, Hasan, Leila, Ellis, Robert
• Application Number:
  US12/642,715
• Publication Number:
  US 20110003699A1
• Time in Patent Office: Days
• US Class Current: 506/7
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 2300/185 using a liquid as fluid
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: B01L 3/50857 using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: B01L 7/02 Water baths; Sand baths; Air baths
• 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

A system for thermal cycling a plurality of samples. The system includes a case having a fluid-tight cavity defining an interior volume. A microfluidic array is disposed in the interior volume, the array including a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces. A thermal cycler having at least one thermally controlled surface is adapted to thermally contact the case.

Claims

1. A system for thermal cycling a plurality of samples, the system comprising:

a case having a fluid-tight cavity defining an interior volume;

a microfluidic array disposed in the interior volume, the array including a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces; and

to a thermal cycler having at least one thermally controlled surface adapted to thermally contact the case.

2. The system according to claim 1, further comprising a positioning mechanism for retaining the case in a specified position and orientation when thermally contacting the thermally controlled surface.

3. The system according to claim 2, wherein the positioning mechanism includes on the thermally controlled surface one of a protrusion and an indention.

4. The system according to claim 3, wherein the indentation includes a graded surface, such that the microfluidic sample array can be slid into the indentation.

5. The system according to claim 1, wherein the thermal cycler includes a deck for placing the case prior to loading and/or removal from the thermally controlled surface.

6. The system according to claim 5, wherein the case is capable of being slid from the deck onto the thermally controlled surface.

7. The system according to claim 5, wherein the deck is capable of being rotated along a plane of the thermally controlled surface.

8. The system according to claim 1, wherein the thermal cycler includes a finger element for pressing the case against the thermally controlled surface.

9. The system according to claim 1, further comprising a heat transfer pad positioned between the case and the thermally controlled surface.

10. The system according to claim 1, further comprising an illumination source capable of illuminating at least one of the through-holes at one or more defined wavelengths.

11. The system according to claim 10, wherein the illumination source includes at least one LED.

12. The system according to claim 10, further comprising an imaging device for imaging one or more through-holes to provide imaging data, and wherein the illumination source includes at least two illuminations sources symmetrically positioned off-axis from the camera with reference to the array.

13. The system according to claim 1, further comprising an imaging device for imaging one or more through-holes to provide imaging data.

14. The system according to claim 13, wherein the imaging device is one of a camera and a a scanner, the camera for simultaneously imaging each of the through-holes to provide imaging data, the scanner for imaging one or more of the through-holes sequentially to provide imaging data.

15. The system according to claim 1, further comprising:

an immersion fluid disposed in the interior volume.

16. The system according to claim 1, wherein the array has greater than 100 through-holes.

17. The system according to claim 1, wherein the array has a through-hole density greater than one through-hole per 20 mm².

18. The system according to claim 1, further comprising:

an enclosure, the thermal cycler positioned within the enclosure;

an imaging device positioned within the enclosure for imaging the sample; and

an illumination system positioned with the enclosure for illuminated at least one sample at one or more predefined wavelengths.

19. A method of thermal cycling a plurality of samples, the method comprising:

holding a microfluidic array in a fluid-tight cavity in a case, the array including a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces; and

placing the case in thermal contact with a thermally controlled surface.

20. The method according to claim 19, further comprising covering the microfluidic array in the cavity with a volume of an immersion fluid.

21. The method according to claim 19, further comprising using a positioning mechanism for retaining the case in a specified position and orientation when thermally contacting the thermally controlled surface.

22. The method according to claim 19, further comprising illuminating the at least one of the through-holes at one or more defined wavelengths.

23. The method according to claim 22, further comprising imaging at least one through-hole.

24. The method according to claim 23, wherein illuminating includes providing illumination from at two illumination sources symmetrically positioned off-axis from the imaging device with reference to the array.

25. The method according to claim 23, wherein imaging includes sequentially imaging two or more through-holes.

26. The method according to claim 23, wherein imaging includes imaging each through-hole simultaneously.

27. The method according to claim 19, wherein the array has greater than 100 through-holes.

28. The method according to claim 19, wherein the array has a through-hole density greater than one through-hole per 20 mm².