Apparatus for conducting electrophysiological measurements on cells

• US 6,815,197 B2
• Filed: 02/16/2001
• Issued: 11/09/2004
• Est. Priority Date: 02/16/2001
• Status: Expired due to Fees

• Current Assignee: Multi Channel Systems Mcs GmbH (Harvard Bioscience, Inc.)
• Original Assignee: Multichannel Systems MCS GmbH
• Inventors: Boven, Karl-Heinz, Möller, Andreas
• Primary Examiner(s): Beisner, William H.
• Application Number:
  US09/785,559
• Publication Number:
  US 20020115196A1
• Time in Patent Office: 1,362 Days
• Field of Search: 435/285.1, 435/285.2, 435/286--28, 435/287.1, 435/287.3, 435/287.2, 435/288.4, 435/288.7, 600/345, 436/63
• US Class Current: 435/285.1
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12M 41/46 of cellular or enzymatic activity or functionality, e.g. cell viability

Abstract

Apparatus for conducting electrophysiological measurements on cells wherein a measuring head is provided with at least one electrode in a common support for impaling the cells.

Claims

1. An apparatus for conducting electrophysiological measurements on cells comprising a measuring head provided with at least one measuring electrode for impaling said cells, with at least one reference electrode, with at least one perfusion conduit made as a perfusion inlet having a first end opening, wherein said at least one measuring electrode and said at least one reference electrode are molded into a common support, said at least one perfusion inlet being arranged essentially parallel with said at least one measuring electrode, and said first end opening being located above a lower end of said at least one measuring electrode.

2. The apparatus of claim 1 wherein said at least one measuring electrode and said at least one reference electrode are inserted into recesses within said support.

3. The apparatus of claim 1 wherein said at least one measuring electrode and said at least one reference electrode consist of pulled glass tubes.

4. The apparatus of claim 1 wherein said at least one measuring electrode and said at least one reference electrode have an electrical resistance of between 5 MΩ

and 100 MΩ

.

5. The apparatus of claim 1 wherein said electrodes have an electrical resistance of between 500 kΩ

and 5 MΩ

.

6. The apparatus of claim 1 wherein said at least one measuring electrode and said at least one reference electrode are configured as wire electrodes.

7. The apparatus of claim 6 wherein said at least one measuring electrode and said at least one reference electrode are configured as silver wire electrodes.

8. The apparatus of claim 7 wherein said at least one measuring electrode and said at least one reference electrode are configured as silver wire electrodes provided with a chloride coating.

9. The apparatus of claim 1 wherein least one electrode has a straight section.

10. The apparatus of claim 1 wherein least one electrode is provided with a tip at its front terminal end.

11. The apparatus of claim 1 wherein two electrodes are arranged essentially symmetrical relative to a longitudinal axis of said support.

12. The apparatus of claim 11 wherein said electrodes have a distance d at their free terminal end being between 50 μ

m and 800 μ

m.

13. The apparatus of claim 12 wherein said distance d is between 200 μ

m and 500 μ

m.

14. The apparatus of claim 11 wherein at least one electrode has a straight section, said straight section enclosing an acute angle α

with a longitudinal axis of said support.

15. The apparatus of claim 14 wherein said acute angle α

is between 3° and

10°

.

16. The apparatus of claim 15 wherein said acute angle α

is 5°

.

17. The apparatus of claim 1 wherein said at least one measuring electrode is coupled to a measuring amplifier.

18. The apparatus of claim 17 wherein said measuring amplifier is adapted to be adjusted.

19. The apparatus of claim 1 wherein said at least one measuring electrode is connected to a current source.

20. The apparatus of claim 19 wherein said current source is adapted to be adjusted.

21. The apparatus of claim 1 wherein said reference electrode is connected to ground.

22. The apparatus of claim 21 wherein two measuring electrodes and two reference electrodes are provided.

23. The apparatus of claim 22 wherein at least two reference electrodes are arranged in a second common plane.

24. The apparatus of claim 1 wherein at least two measuring electrodes are arranged in a first common plane.

25. The apparatus of claim 24 wherein said first and a second plane extend parallel to each other and wherein at least two reference electrodes are arranged in said second common plane.

26. The apparatus of claim 25 wherein, as viewed on first plane, said perfusion inlet is located in front of said first plane and a perfusion outlet is located behind said second plane and wherein at least one perfusion conduit is said perfusion outlet.

27. The apparatus of claim 1 wherein said perfusion inlet is arranged essentially on a symmetry axis between two measuring electrodes, said perfusion inlet being arranged essentially parallel with said two measuring electrodes said first end opening being located above a lower end of said two measuring electrodes.

28. The apparatus of claim 1 wherein said perfusion inlet is connected to a conveyor pump.

29. The apparatus of claim 28 wherein said pump is adapted to be adjusted.

30. The apparatus of claim 1 wherein said perfusion inlet is adapted to be connected to a plurality of storage containers via a controllable valve system.

31. The apparatus of claim 30 wherein said storage containers are arranged above said perfusion inlet.

32. The apparatus of claim 30 wherein said storage containers contain a test liquid.

33. The apparatus of claim 30 wherein said storage containers contain a rinsing liquid.

34. The apparatus of claim 1 wherein at least one perfusion conduit is a perfusion outlet.

35. The apparatus of claim 34 wherein said perfusion outlet has a second end opening said second end opening being located above the first end opening.

36. The apparatus of claim 35 wherein said end openings are oriented along opposite directions.

37. The apparatus of claim 34 wherein said perfusion outlet is connected to a suction pump.

38. The apparatus of claim 37 wherein said suction pump is adapted to be adjusted.

39. The apparatus of claim 1 further comprising a receptacle for said cells wherein said measuring head is arranged on an actuator, said actuator being adapted to be displaced long a coordinate system above said receptacle.

40. The apparatus of claim 39 wherein said actuator carries a plurality of measuring heads.

41. The apparatus of claim 40 wherein said measuring heads are adapted to be displaced individually relative to said actuator along said axis z directed towards said cell.

42. The apparatus of claim 39 wherein said measuring head is affixed to said actuator by plugging or screwing.

43. The apparatus of claim 39 wherein said receptacle for said cell is configured as a standardized multi-well-plate.

44. The apparatus of claim 43 wherein individual wells within said plate are provided with a readable code, said actuator comprising means for reading said code.

45. The apparatus of claim 44 wherein said code is a bar code, said means being a bar code reading head.

46. The apparatus of claim 1 wherein means are provided for injecting cDNA and/or mRNA into said cell.

47. The apparatus of claim 46 wherein said means are located on an actuator.

48. An apparatus for conducting electrophysiological measurements on cells comprising a measuring head provided with at least two electrodes for impaling said cells of which at least one electrode is configured as a measuring electrode, and at least one perfusion conduit made as a perfusion inlet, wherein said electrodes and said at least one perfusion conduit are molded into a common support, said electrodes are arranged essentially symmetrical relative to a longitudinal axis of said support, and wherein at least one electrode has a straight section enclosing an acute angle α

with said longitudinal axis of said support, and wherein said perfusion inlet is arranged essentially on a symmetry axis between said electrodes, and wherein said perfusion inlet has a first end opening, said perfusion inlet being arranged essentially parallel with said electrodes, and said first end opening being located above a lower end of said at least one measuring electrode.

49. An apparatus For conducting electrophysiological measurements on cells comprising a measuring head provided with at least one measuring electrode for impaling said cells with at least one reference electrode, with one first perfusion conduit made as a perfusion inlet, with a second perfusion conduit made as a perfusion outlet, wherein said at least one measuring electrode and said at least one reference electrode and said perfusion conduits are molded into a common support, said perfusion inlet has a first end opening and is arranged essentially parallel with said at least one measuring electrode, said first end opening being located above a lower end of said at least one measuring electrode, and said perfusion outlet has a second end opening being located above the first end opening.

50. An apparatus for conducting electrophysiological measurements on cells comprising a measuring head provided with at least two measuring electrodes for impaling said cells, at least two reference electrodes, a first perfusion conduit made as a perfusion inlet having a first end opening, a second perfusion conduit made as a perfusion outlet, said at least two measuring electrodes are molded into a common support, said at least two measuring electrodes are arranged in a first common plane and said at least two reference electrodes are arranged in a second common plane, said first and said second plane extend parallel to each other, and as viewed on said first plane, said perfusion inlet, is located in front of said first plane and said perfusion outlet is located behind said second plane, said perfusion inlet being arranged essentially parallel with said at least two measuring electrodes, said first end opening being located above a lower end of said at least two measuring electrodes.

51. An apparatus for conducting electrophysiological measurements on cells comprising a plurality of measuring heads arranged on an actuator, said measuring heads are provided with at least one electrode for impaling said cells, said at least one electrode is integrated into a support, wherein said measuring heads are adapted to be displaced individually relative to said actuator along said axis z directed towards said cells.

52. An apparatus for conducting electrophysiological measurements on cells with at least one measuring electrode for impaling said cells, with at least one reference electrode, with a first perfusion conduit made as a perfusion inlet having a first end opening for supplying perfusate to the cells, said perfusion inlet being arranged essentially parallel with said at least one electrode, said first end opening being located above a lower end of said at least one electrode, a second perfusion conduit made as a perfusion outlet having a second end opening for purging perfusate away from the cells, said second end opening being located above the first end opening, wherein said at least one measuring electrode is molded together with said at least one reference electrode and with said perfusion conduits into a common support of a measuring head.

53. An apparatus for conducting electrophysiological measurements on cells comprising a measuring head provided with at least one measuring electrode for impaling said cells, with at least one perfusion conduit made as a perfusion inlet having a first end opening, with at least one perfusion conduit made as a perfusion outlet having a second end opening being located above said first end opening, wherein said end openings are oriented along opposite directions, wherein said at least one measuring electrode is integrated into a support, said at least one perfusion inlet being arranged essentially parallel with said at least one measuring electrode, and said first end opening being located above a lower end of said at least one measuring electrode.

54. An apparatus for conducting electro-physiological measurements on cells comprising a measuring head provided with at least one measuring electrode for impaling said cells, with at least one perfusion conduit made as a perfusion inlet having a first end opening, wherein said at least measuring electrode is integrated into a support, said at least one perfusion inlet being arranged essentially parallel with said at least one measuring electrode, and said first end opening being located above a lower end of said at least one measuring electrode, said apparatus further comprising a receptacle for said cells wherein said measuring head is arranged on an actuator, said actuator being adapted to be displaced along a coordinate system above said receptacle, wherein said actuator carries a plurality of measuring heads, wherein said measuring heads are adapted to be displaced individually relative to said actuator along said axis z directed towards said cell.