Method and apparatus for concentrating and/or positioning particles or cells

• US 6,673,225 B1
• Filed: 01/12/2001
• Issued: 01/06/2004
• Est. Priority Date: 05/29/1998
• Status: Expired due to Fees

• Current Assignee: Industrial Research Limited
• Original Assignee: Industrial Research Limited
• Inventors: Arnold, William Michael
• Primary Examiner(s): Tung, T.
• Assistant Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US09/701,216
• Time in Patent Office: 1,089 Days
• Field of Search: 204/450, 204/547, 204/600, 204/643, 204/648, 204/553
• US Class Current: 204/547
• CPC Class Codes: B01D 57/02 by electrophoresis treatment of water, waste water, sewage or sludge by electrophoresis C02F1/469; electrophoretic production of compounds or non-metals C25B7/00; investigating or analysing materials by using electrophoresis G01N27/26
• CPC Class Codes: B03C 5/026 using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
• CPC Class Codes: C12M 33/00 Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus chemical or physical laboratory apparatus in general B01L, devices for taking cell samples A61B10/0045, withdrawing or distributing predetermined quantities of fluid B01L99/00
• CPC Class Codes: C12M 47/02 Separating microorganisms from the culture medium; Concentration of biomass separating microorganisms from their culture media C12N1/02
• CPC Class Codes: G01N 2001/4038 electric methods, e.g. electromigration, electrophoresis, ionisation

Abstract

A method for concentrating and/or positioning and/or separating particles or cells comprises placing a liquid medium containing the particles and/or cells over a surface having an electrode array associated with the surface, applying an alternating voltage to the electrode array to create an electric field above the surface within the medium to repel the particles or cells from the electrode array and thereby levitate the particles or cells above the surface, within the medium, by negative dielectrophoresis, and heating the liquid medium so as to cause convection currents to circulate within the medium which concentrate or relocate the levitated cells within the medium. Apparatus for concentrating and/or positioning and/or separating particles or cells are also disclosed.

Claims

1. A method for concentrating and positioning particles or cells in a liquid medium comprising:

subjecting the particles or cells to an electric field to levitate the particles or cells within the medium by negative dielectrophoresis, and

heating the medium to cause convection currents within the liquid medium which relocate the particles or cells substantially in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.

3. A method according to either of claims 1 and 2 including subjecting the particles or cells to an electric field created by an alternating voltage of a frequency in the range of 10 kHz to 300 kHz.

4. A method according to either of claims 1 or 2 wherein the strength of the electric field generated with the medium is in the range 10 V/mm-100 V/mm.

5. A method according to either of claims 1 or 2 wherein the medium is also heated to cause said convection currents by a radio frequency electric field.

2. A method for concentrating and positioning particles or cells comprising:

placing a liquid medium containing particles and/or cells over a surface having an electrode array associated with the surface,

applying an alternating voltage to the electrode array to create an electric field above the surface within the medium to repel the particles or cells from the electrode array and thereby levitate the particles or cells above the surface, within the medium, by negative dielectrophoresis, and

heating the liquid medium so as to cause convection currents to circulate within the medium which relocate the particles or cells substantially in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.

6. A method according to claim 2 wherein the electrode array comprises at least two comb-like rows of spaced interdigitated finger-like electrode elements.

7. A method according to claim 6 wherein the width of each finger-like electrode element is between about 2.5 and 50 times the average diameter of the particles or cells, and the spacing between adjacent electrode elements is between about 5 and 100 times the particle or cell diameter.

8. A method according to either of claims 6 or 7 wherein the electrode elements have a width in the range about 4 μ

m to about 1000 μ

m and a spacing between adjacent electrode elements of between about 2 μ

m and about 500 μ

m.

9. A method for concentrating particles and/or cells comprising:

placing a liquid medium containing the particles and/or cells over a surface having an electrode array associated with the surface,

applying an alternating voltage to the electrode array to repel the particles or cells from the electrode array and thereby levitate the particles or cells above the surface, within the medium, by negative dielectrophoresis, and

heating the liquid medium so as to cause convection currents to circulate within the medium including rising currents centrally within the medium over the electrode array which relocate the particles or cells in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.

10. A method according to claim 9 wherein the medium is also heated to cause said convection currents by the voltage applied to the electrode array.

11. A method for repositioning particles and/or cells within a liquid medium comprising:

subjecting the particles and/or cells to an electric field within the medium which repels the particles or cells to thereby levitate the particles or cells within the medium,

heating the liquid medium to cause convection currents within the medium which relocate the particles or cells in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium, and

applying a force to cause the concentrated particles or cells to move across the medium.

17. A method according to either of claims 11 or 12 including drawing off the particles or cells from the medium after relocation of the particles or cells within the medium.

12. A method for repositioning particles and/or cells within a liquid medium comprising:

subjecting the particles and/or cells to an alternating voltage to create an electric field within the medium which repels the particles or cells to thereby levitate the particles or cells within the medium,

heating the liquid medium to cause convection currents within the medium, and

subjecting the upper part of the medium to a second electric field which reshapes a part or parts of the upper surface of the medium to thereby cause the position at which the convection currents within the medium concentrate the cells to move within the medium.

13. A method according to claim 12 wherein said second electric field is applied via at least one electrode positioned above the top surface of the medium.

14. A method according to claim 12 including applying a voltage selectively to one or more of a series of electrodes positioned adjacent the upper part of the medium to cause movement of the particles or cells through the medium.

15. A method according to either of claims 13 and 14 wherein said electrode or electrodes are positioned within a layer of low conductivity above the liquid medium containing the particles or cells.

16. A method according to claim 15 wherein said layer of low conductivity comprises a layer of low conductivity fluid which is immiscible with the liquid medium containing the particles or cells and which extends above the liquid medium containing the particles or cells.

18. A method for separating particles or cells in a liquid medium comprising:

subjecting the particles or cells to an electric field to levitate two or more different types of particles or cells within the medium to two or more different heights within the medium, and

heating the medium to cause convection currents within the liquid medium which relocate the particles or cells substantially in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.

19. A method according to claim 18 wherein the electrode array comprises at least two comb-like rows of spaced interdigitated finger-like electrode elements.

21. A method according to either one of claims 18 and 20 including selectively drawing off at least one of the concentrated types of particles or cells.

22. A method according to either of claims 18 or 20 wherein the alternating voltage is of a frequency in the range 10 kHz to 30 MHz.

23. A method according to either of claims 18 or 20 wherein the field strength generated within the medium is in the range 10 V/mm-100 V/mm.

24. A method according to either of claims 18 ro 20 wherein the medium is also heated to cause said convection currents by a radio frequency electric field.

20. A method for separating particles or cells comprising:

placing a liquid medium containing the particles and/or cells over a surface having an electrode array associated with the surface,

applying an alternating voltage to the electrode array to create an electric field above the surface within the medium to repel the particles or cells from the electrode array and which thereby levitates at least two different types of particles or cells to two or more different heights above the surface, within the medium, by negative dielectrophoresis, and

heating the liquid medium so as to cause convection currents to circulate within the medium which relocate the particles or cells substantially in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.

25. Apparatus for concentrating and positioning particles or cells in a liquid medium comprising:

means to subject particles or cells to an electric field to levitate the particles or cells within the medium by negative dielectrophoresis, and

means to heat the medium to cause convection currents within the liquid medium which relocate the particles or cells substantially in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.

29. Apparatus according to either of claims 25 or 26 also comprising means for applying a force to cause the concentrated particles or cells to move across the medium.

30. Apparatus according to either of claims 25 or 26 also comprising means for subjecting the upper part of the medium to a second electric field which electrostatically attracts part or parts of the upper surface of the medium to thereby alter the position at which the convection currents within the medium concentrate the particles or cells to move the concentrated articles or cells within the medium.

31. Apparatus according to claim 30 wherein said means for applying a second electric field comprises at least one electrode positioned above the top surface of the medium.

32. Apparatus according to claim 30 wherein said means for applying a second electric field comprises a series of electrodes positioned adjacent the upper part of the medium and means to apply a voltage selectively to electrodes in the series to cause movement of the particles or cells through the medium.

26. Apparatus for concentrating and positioning particles or cells comprising:

a surface having an electrode array associated with the surface,

means for containing a liquid medium containing particles and/or cells over the surface,

means for applying an alternating voltage to the electrode array to create an electric field above the surface within the medium to repel the particles or cells from the electrode array and thereby levitate the particles or cells above the surface, within the medium by negative dielectrophoresis, and

means for heating the liquid medium so as to cause convection currents to circulate within the medium which relocate the particles or cells substantially in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.

27. Apparatus according to claim 26 wherein the electrode array comprises at least two comb-like rows of spaced interdigitated finger-like electrode elements.

28. Apparatus according to claim 27 wherein the electrode elements have a width in the range about 4 μ

m to about 1000 μ

m and a spacing between adjacent electrode elements of between about 2 μ

m and about 500 μ

m.

33. Apparatus for separating particles or cells in a liquid medium comprising:

means to subject the particles or cells to an electric field to levitate two or more different types of particles or cells within the medium to two or more different heights within the medium, and

means to heat the medium to cause convection currents within the liquid medium which relocate the particles or cells substantially in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.

34. Apparatus according to claim 33 wherein the electrode array comprises at least two comb-like rows of spaced interdigitated finger-like electrode elements.

36. Apparatus according to either one of claim 33 and 35 including means for selectively drawing off at least one of the concentrated types of particles or cells.

37. Apparatus according to either of claim 33 and 35 wherein the alternating voltage is of a frequency in the range of 10 kHz to 300 MHz.

38. Apparatus according to either of claims 33 or 35 wherein the field strength generated with the medium is in the range 10 V/mm-100 V/mm.

39. Apparatus according to either of claim 33 or 35 wherein the medium is also heated to cause said convection currents by a radio frequency electric field.

35. Apparatus for separating particles or cells comprising:

means to contain a liquid medium containing the particles and/or cells over a surface having an electrode array associated with the surface,

means for applying an alternating voltage to the electrode array to create an electric field above the surface within the medium to repel the particles or cells from the electrode array and which thereby levitates at least two different types of particles or cells to two or more different heights above the surface, within the medium, by negative dielectrophoresis, and

means for heating the liquid medium so as to cause convection currents to circulate within the medium which relocate the particles or cells substantially in a horizontal direction and thereby concentrate and position the levitated particles or cells within the medium.