Capillary electrophoresis device

• US 8,512,538 B2
• Filed: 05/23/2011
• Issued: 08/20/2013
• Est. Priority Date: 05/28/2010
• Status: Active Grant

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Majlof, Lars, Van Gelder, Ezra
• Primary Examiner(s): Ball, J. Christopher
• Application Number:
  US13/113,968
• Publication Number:
  US 20110290648A1
• Time in Patent Office: 820 Days
• Field of Search: 204450-455, 204601-605, 236/1.F, 165267-269, 165287-293, 137/341, 219476-480, 219482-489
• US Class Current: 204/602
• CPC Class Codes: G01N 27/44708 Cooling

Abstract

This invention provides a capillary electrophoresis device in which capillaries are thermally regulated on a thermally responsive electrical path attached to an electrically insulating circuit board. This invention also provides an optical scanner useful for scanning an array of capillaries. A laser, optical detector and optical selector are in an arrangement that allows the optical detector to selectively detect an optical signal from any one or more of the plurality of electrophoresis capillaries.

Claims

1. An apparatus, comprising:

an electrically insulating circuit board;

at least one electrical path comprising at least one conductive trace attached to the circuit board, said at least one electrical path generating Joule energy responsive to electrical current through said at least one electrical path, wherein the at least one electrical path forms at least one thermal area; and

at least one electrophoresis capillary in thermal contact with said at least one thermal area, such that said at least one electrophoresis capillary is thermally regulated responsive to electrical current through said at least one electrical path.

2. The apparatus of claim 1, further comprising:

at least one temperature sensor in thermal contact with said at least one electrophoresis capillary, such that said at least one temperature sensor provides temperature data of said at least one electrophoresis capillary; and

a controller of a temperature of said at least one electrophoresis capillary, the controller changing the electrical current through said at least one electrical path responsive to the temperature data from said at least one temperature sensor.

3. The apparatus of claim 1, wherein said at least one electrical path has at least one resistance providing temperature data of said at least one electrophoresis capillary in thermal contact with said at least one electrical path, and the apparatus further comprises:

a controller of a temperature of said at least one electrophoresis capillary, the controller changing the electrical current through said at least one electrical path responsive to the temperature data from said at least one resistance of said at least one electrical path.

4. The apparatus of claim 1, further comprising:

at least one thermal insulation member attached to the circuit board and positioned by said at least one electrical path and said at least one electrophoresis capillary, said at least one thermal insulation member reducing heat transfer between a part of the circuit board attached to said at least one electrical path and said at least one electrophoresis capillary and a remainder of the circuit board.

5. The apparatus of claim 1, further comprising:

at least one aperture in the circuit board attached to the circuit board and positioned by said at least one electrical path and said at least one electrophoresis capillary, said at least one aperture reducing heat transfer between a part of the circuit board attached to said at least one electrical path and said at least one electrophoresis capillary and a remainder of the circuit board.

6. The apparatus of claim 1, wherein said at least one electrical path includes a plurality of electrical paths in thermal contact with different sections of said at least one electrophoresis capillary, such that the different sections of said at least one electrophoresis capillary are separately thermally regulated by different electrical paths of the plurality of electrical paths.

7. The apparatus of claim 6, wherein the apparatus further comprises:

a plurality of temperature sensors in thermal contact with the different sections of said at least one electrophoresis capillary, such that the plurality of temperature sensors provides temperature data of the different sections of said at least one electrophoresis capillary; and

a controller of temperatures of the different sections of said at least one electrophoresis capillary, the controller changing the electrical currents through the plurality of electrical paths responsive to the temperature data from the plurality of temperature sensors.

8. The apparatus of claim 6,

wherein said plurality of electrical paths have resistances providing temperature data of the different sections of said at least one electrophoresis capillary in thermal contact with the plurality of electrical paths, and

the apparatus further comprises:

a controller of temperatures of the different sections of said at least one electrophoresis capillary, the controller changing the electrical currents through the plurality of electrical paths responsive to the temperature data from the resistances of the plurality of electrical paths.

9. The apparatus of claim 1, wherein said at least one electrophoresis capillary is attached to the circuit board.

10. The apparatus of claim 1, wherein said at least one electrophoresis capillary is attached to the circuit board with adhesive material.

11. The apparatus of claim 1, wherein said at least one electrical path includes an electrical path that runs back and forth in said at least one thermal area or an electrical path configured as two electrical nodes connected by a plurality of electrical paths.

12. The apparatus of claim 1, wherein said at least one thermal area has a width no less than 5 mm.

13. The apparatus of claim 1, wherein the thermal area widens by a part of said at least one electrophoresis capillary entering the electrically insulating circuit board.

14. The apparatus of claim 1, wherein said electrically insulating circuit board has an aperture through the electrically insulating circuit board, the aperture facilitating optical interaction with said at least one electrophoresis capillary.

15. The apparatus of claim 1, wherein said at least one electrical path has at least one bend.

16. The apparatus of claim 1, wherein said at least one electrical path overall has an S-shape.

17. An apparatus, comprising:

(a) an electrophoresis thermal assembly, including;

an electrically insulating circuit board;

at least one electrical path comprising at least one conductive trace attached to the circuit board, said at least one electrical path generating Joule energy responsive to electrical current through said at least one electrical path;

at least one electrophoresis capillary in thermal contact with said at least one electrical path, such that said at least one electrophoresis capillary is thermally regulated responsive to electrical current through said at least one electrical path;

(b) at least one analyte injector coupled to inject at least one electrophoresis analyte into said at least one electrophoresis capillary;

(c) a voltage source coupled to opposite ends of said at least one electrophoresis capillary providing an electrophoretic voltage difference between the opposite ends of said at least one electrophoresis capillary;

(d) a laser device positioned to deliver a beam from the laser device to said at least one electrophoresis capillary;

(e) an optical detector optically coupled to receive an optical signal from said at least one electrophoresis capillary.

18. A method, comprising:

providing an apparatus comprising;

an electrically insulating circuit board;

at least one electrical path comprising at least one conductive trace attached to the circuit board, said at least one electrical path generating Joule energy responsive to electrical current through said at least one electrical path, wherein the at least one electrical path forms at least one thermal area; and

at least one electrophoresis capillary in thermal contact with said at least one thermal area, such that said at least one electrophoresis capillary is thermally regulated responsive to electrical current through said at least one electrical path;

electrophoretically moving analytes through at least one electrophoresis capillary; and

thermally heating said at least one electrophoresis capillary via thermal contact with said at least one thermal area with Joule energy generated by passing electrical current through said at least one electrical path attached to said electrically insulating circuit board.

19. The method of claim 18, further comprising:

generating temperature data of said at least one electrophoresis capillary in thermal contact with said at least one thermal area; and

changing the electrical current through said at least one electrical path, responsive to the temperature data of said at least one electrical path.

20. The method of claim 18, further comprising:

generating, via at least one temperature sensor of said at least one electrophoresis capillary, temperature data of said at least one electrophoresis capillary in thermal contact with said at least one thermal area; and

changing the electrical current through said at least one electrical path responsive to the temperature data from said at least one temperature sensor.

21. The method of claim 18, further comprising:

generating, via at least one resistance of said at least one electrophoresis capillary, temperature data of said at least one electrophoresis capillary in thermal contact with said at least one thermal area; and

changing the electrical current through said at least one electrical path responsive to the temperature data from said at least one resistance.

22. The method of claim 18, further comprising:

reducing heat transfer between a part of the circuit board attached to said at least one electrical path and said at least one electrophoresis capillary, and a remainder of the circuit board.

23. The method of claim 18, further comprising:

reducing heat transfer with at least one aperture between a part of the circuit board attached to said at least one electrical path and said at least one electrophoresis capillary, and a remainder of the circuit board.

24. The method of claim 18, wherein said thermally heating includes:

separately thermally heating different sections of said at least one electrophoresis capillary via thermal contact with a plurality of electrical paths carrying electrical currents through the electrically insulating circuit board.

25. The method of claim 24, further comprising:

generating temperature data of the different sections of said at least one electrophoresis capillary; and

changing the electrical currents through the plurality of electrical paths, responsive to the temperature data from the different sections of said at least one electrophoresis capillary.

26. The method of claim 24, further comprising:

generating temperature data of the different sections of said at least one electrophoresis capillary, via different temperature sensors of the different sections of said at least one electrophoresis capillary; and

changing the electrical currents through the plurality of electrical paths, responsive to the temperature data from the different sections of said at least one electrophoresis capillary.

27. The method of claim 24, further comprising:

generating temperature data of the different sections of said at least one electrophoresis capillary, via resistances of the plurality of electrical paths; and

changing the electrical currents through the plurality of electrical paths, responsive to the temperature data from the different sections of said at least one electrophoresis capillary.

28. The method of claim 18, further comprising:

injecting at least one analyte into said at least one electrophoresis capillary.

29. The method of claim 18, further comprising:

optically exciting at least one analyte in said at least one electrophoresis capillary; and

detecting an optical signal from said excited at least one analyte.

30. A method, comprising:

separately regulating temperature in different sections of at least one capillary via thermal contact with different thermal areas formed from different electrical paths carrying electrical currents through an electrically insulating circuit board, wherein each of said different electrical paths comprise different conductive traces attached to the circuit board, said different electrical paths generating Joule energy responsive to electrical current through said different electrical paths, wherein the different electrical path forms said thermal areas; and

moving analytes through said at least one capillary supporting a biochemical activity in the separately thermally regulated different sections of said at least one electrophoresis capillary.

31. The method of claim 30 wherein the biochemical activity is polymerase chain reaction or a sandwich assay using affinity reagents.

32. The method of claim 31 wherein the capillary contains at least one DNA polymerase dNTPs and primers.

33. The method of claim 30 comprising moving the analytes through thermal areas adapted for PCR including thermal areas adapted for a denaturation step;

an annealing step and an extension/elongation step.

34. The method of claim 33 wherein the thermal area adapted for a denaturation step has a temperature between 94-98°

C., the thermal area adapted for an annealing step has a temperature between 50-65°

C.; and

the thermal area adapted for extension/elongation step has a temperature around 72°

C.

35. The method of claim 30 comprising moving the analytes through thermal areas adapted for PCR including a thermal area adapted for an initialization step having a temperature between 94-96°

C.;

a thermal area adapted for a denaturation step having a temperature between 94-98°

C., a thermal area adapted for an annealing step having a temperature between 50-65°

C.;

a thermal area adapted for extension/elongation step has a temperature around 72°

C.;

a thermal area adapted for final elongation having a temperature between 70-74°

C. and a thermal area adapted for final hold having a temperature between 4-15°

C.