Multiaperture sample positioning and analysis system

• US 20030052002A1
• Filed: 03/07/2002
• Published: 03/20/2003
• Est. Priority Date: 12/17/1997
• Status: Active Grant

• Current Assignee: Molecular Devices, Ecole polytechnique fãdãrale de lausanne epfl (Schweizerische Eidgenossenschaft)
• Original Assignee: MDS Analytical Technologies US Incorporated (Danaher Corporation)
• Inventors: Schmidt, Christian, Vogel, Horst
• Granted Patent: US 7,201,836 B2
• Time in Patent Office: Days
• US Class Current: 204/403.01
• 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 3/5088 confining liquids at a location by surface tension, e.g. virtual wells on plates, wires B01L3/50857 takes precedence
• CPC Class Codes: G01N 33/48728 Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10

Abstract

Systems for positioning and/or analyzing samples such as cells, vesicles, cellular organelles, and fragments, derivatives, and mixtures thereof, for electrical and/or optical analysis, especially relating to the presence and/or activity of ion channels.

Claims

1. A multiaperture system for analyzing samples such as cells, vesicles, and cellular organelles, and fragments, derivatives, and mixtures thereof, comprising:

a carrier having a plurality of apertures, the carrier being adapted so that at least one of the samples can be sealed across at least one of the apertures;

at least two fluid compartments, connected via at least one of the apertures; and

at least two electrodes in electrical contact with at least one of the fluid compartments, wherein the electrodes are adapted to measure at least one of an electrical potential and a current, across at least a portion of the at least one of the samples.

2. The system of claim 1, wherein the samples are selected from the group consisting of cells, vesicles, and biological organelles, and fragments thereof.

3. The system of claim 1, wherein the samples are selected from the group consisting of natural, artificial, and modified lipid membranes.

4. The system of claim 1, wherein at least one electrode is used for measurement over more than one aperture.

5. The system of claim 1, wherein several or all of the electrodes on one side of the carrier have a common electrical potential.

6. The system of claim 1, wherein the compartments and electrodes are separated on one side of the carrier to allow independent measurements.

7. The system of claim 1, wherein the system is configured for sequential measurements over at least two apertures.

8. The system of claim 1, wherein the system is configured for parallel measurements over at least two apertures.

9. The system of claim 1, wherein the diameter of the aperture is between about 0.3 μ

m and about 7 μ

m.

10. The system of claim 1, further comprising a sample-handling mechanism for adding, manipulating, exchanging, storing, and/or removing samples and sample components from at least one compartment.

11. The system of claim 10, wherein the sample-handling mechanism is configured to add and/or store fluid on one or both sides of the carrier.

12. The system of claim 10, wherein the sample-handling mechanism is configured to add cells, vesicles, and other biological organelles or particles on one or both sides of the carrier.

13. The system of claim 10, wherein the sample-handling mechanism is configured to check the fluid level in the compartments.

14. The system of claim 10, wherein the sample-handling system is configured to introduce samples into a compartment through an inlet opening arranged concentrically above the aperture.

15. The system of claim 1, wherein the carrier is at least substantially planar.

16. The system of claim 1, wherein the carrier has an electrically charged surface that attracts biological membranes.

17. The system of claim 1, wherein the carrier has a surface that provides a molecule-specific bonding of cells, vesicles, membrane fragments, or biological organelles on it.

18. The system of claim 1, wherein the carrier is formed at least in part of materials selected from the group consisting of silicon, silicon derivatives, glass, and plastic.

19. The system of claim 1, wherein the carrier comprises a silicon chip or a silicon wafer.

20. The system of claim 1, wherein the compartments on at least one side of the carrier are open.

21. The system of claim 1, wherein the compartments on at least one side of the carrier have no physical boundary on the side.

22. The system of claim 1, wherein at least two fluid compartments are disposed on one side of the carrier, each of those compartments being in contact, via the apertures, with a single fluid compartment disposed on the other side of the carrier.

23. The system of claim 1, further comprising an optical-analysis mechanism for optical analysis samples positioned about at least one aperture, configured for optical analysis of electrical measurement using the positioning and measurement system.

24. The system of claim 1, wherein the sample-analysis mechanism is configured for fluorescence measurements.

25. The system of claim 1, further comprising a holder adapted to support the carrier.

26. The system of claim 1, wherein the number of apertures is selected from the group consisting of 96, 384, and 1536.

27. The system of claim 1, wherein the application of a voltage difference, mediated by the electrodes, creates an inhomogeneous electric field around the aperture, which becomes larger as the aperture is approached.

28. A method for analyzing samples such as cells, vesicles, and cellular organelles, and fragments, derivatives, and mixtures thereof, comprising:

selecting a multiaperture system according to claim 1;

adding a sample to one of the fluid compartments; and

measuring at least one of an electrical potential difference and a current across at least a portion of the sample, using the electrodes.

29. The method of claim 28, further comprising:

adding a second sample to a second one of the fluid compartments; and

measuring at least one of an electrical potential difference and a current across at least a portion of the second sample, using the electrodes.

30. The method of claim 29, the sample being a first sample, where the steps of measuring are performed sequentially for the first and second samples.

31. The method of claim 29, the sample being a first sample, where the steps of measuring are performed simultaneously for the first and second samples.

32. A multiaperture system for analyzing samples such as cells, vesicles, and cellular organelles, and fragments, derivatives, and mixtures thereof, comprising:

a holder; and

a plurality of measurement sites disposed in the holder, each measurement site having a carrier that separates from one another two fluid compartments;

wherein the carrier contains an aperture that connects the two compartments, the carrier being adapted so that a sample can be sealed across the aperture; and

wherein each compartment is in electrical contact with at least one electrode, the electrodes being adapted to measure at least one of an electrical potential and a current, across at least a portion of the sample.

33. The system of claim 32, wherein the samples are selected from the group consisting of cells, vesicles, and biological organelles, and fragments thereof.

34. The system of claim 32, wherein the system is configured for sequential measurements over at least two measurement sites.

35. The system of claim 32, wherein the system is configured for parallel measurements over at least two measurement sites.

36. The system of claim 32, wherein the diameter of the aperture is between about 0.3 μ

m and about 7 μ

m.

37. The system of claim 32, further comprising a sample-handling mechanism for adding, manipulating, exchanging, storing, and/or removing samples and sample components from at least one compartment.

38. The system of claim 32, wherein each carrier is at least substantially planar.

39. The system of claim 32, wherein each carrier is formed at least in part of materials selected from the group consisting of silicon, silicon derivatives, glass, and plastic.

40. The system of claim 32, wherein the number of measurement sites is selected from the group consisting of 96, 384, and 1536.

41. The system of claim 32, the holder being substantially rectangular, wherein the length of the holder ranges between about 125 mm and about 130 mm, and wherein the width of the holder ranges between about 80 mm and about 90 mm.

42. The system of claim 32, wherein the measurement sites correspond at least in part to microplate wells.

43. A method for analyzing samples such as cells, vesicles, and cellular organelles, and fragments, derivatives, and mixtures thereof, comprising:

selecting a multiaperture system according to claim 32;

adding a sample to one of the fluid compartments; and

measuring at least one of an electrical potential difference and a current across at least a portion of the sample, using the electrodes.

44. A multiaperture system for positioning and/or analyzing samples such as cells, vesicles, and cellular organelles, and fragments, derivatives, and mixtures thereof, comprising:

a carrier having a plurality of apertures, the carrier being adapted so that at least one of the samples can be sealed across at least one of the apertures;

at least one sample fluid compartment and at least one reference fluid compartment, in contact via the apertures; and

at least one sample electrode and at least one reference electrode, each sample electrode in contact with at least one of the sample fluid compartments, and each reference electrode in contact with at least one of the reference fluid compartments, wherein the at least one sample electrode and the at least one reference electrode are adapted to apply and/or measure an electrical potential across the apertures.

45. The multiaperture system of claim 44, where the at least one sample fluid compartment and the at least one reference fluid compartment are disposed on opposite sides of the carrier.

46. The system of claim 44, wherein the samples are selected from the group consisting of cells, vesicles, and biological organelles, and fragments thereof.

47. A method for analyzing samples, comprising:

selecting a multiaperture system according to claim 44;

adding a sample to one of the sample fluid compartments; and

measuring at least one of an electrical potential difference and a current across at least a portion of the sample, using the electrodes.