Microfluidic devices and methods based on measurements of electrical admittance

• US 7,250,775 B1
• Filed: 11/12/2004
• Issued: 07/31/2007
• Est. Priority Date: 11/12/2003
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Collins, John, Lee, Abraham
• Primary Examiner(s): Deb; Anjan
• Application Number:
  US10/987,179
• Time in Patent Office: 991 Days
• Field of Search: 738/610.8, 738/611.2, 324/425, 324/439, 324/444, 324/71.4, 324/446, 324/449, 324/692, 324/693, 324/713
• US Class Current: 324/692
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• 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 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: G01F 1/64 by measuring electrical currents passing through the fluid flow; measuring electrical potential generated by the fluid flow, e.g. by electrochemical, contact or friction effects G01F1/58 takes precedence

Abstract

Microfluidic devices and methods that use electrical admittance as the basis for measuring flow rate of fluids and/or for distinguishing (e.g., characterizing, sorting, separation, etc.) different particles, chemical compositions or biospecies (e.g., different cells, cells containing different substances, different particles, different chemical compositions, etc.).

Claims

1. A method of measuring the flow rate of a conducting fluid in a microchannel, comprising:

a) applying a voltage across a pair of electrodes placed in the microchannel;

b) determining the current flowing across the electrodes;

c) comparing the current determined in Step B to a base current with no flow between the electrodes; and

d) determining the flow-induced electrical admittance at different frequencies by calculating the change in flow rate as a function of the change in current.

2. The method according to claim 1, wherein the step of applying a voltage comprises applying an ac voltage across the electrodes in series with a resistor.

3. The method according to claim 2, wherein the step of calculating the current comprises measuring the rms voltage across the resistor.

4. The method according to claim 1, wherein the electrodes are placed parallel to the line of flow.

5. The method according to claim 2, wherein the step of applying an ac voltage comprises applying the voltage at an optimized frequency.

6. The method according to claim 5, wherein the frequency is approximately 500 Hz.

7. The method according to claim 6, wherein the step of applying an ac voltage comprises applying an optimized voltage.

8. The method according to claim 7, wherein the ac voltage is approximately 400 mV.

9. The method according to claim 1, wherein the conducting fluid comprises an electrolyte solution or suspension, and further comprising a step of selecting an optimum concentration of the electrolyte.

10. The method according to claim 9, wherein the electrolyte is NaOH and the concentration is about 0.2 M.

11. A transducer or other device for measuring the flow rate of a conducting fluid in a microchannel, comprising:

a) electrodes positioned substantially parallel to the line of flow;

b) means for applying a voltage across the electrodes; and

c) means for measuring the current across the electrodes and for determining electrical admittance at different frequencies based on measurement of current across the electrodes.

12. A transducer or other device according to claim 11, wherein the transducer comprises a microfluidic device including a substrate formed of a first material and an upper layer formed of a second material.

13. A transducer or other device according to claim 11, wherein the electrodes are located on one of the layers and the microchannel is located on or in the other layer.

14. A transducer or other device according to claim 12, wherein the first material is a glass.

15. A transducer or other device according to claim 12, wherein the second material is polydimethylsiloxane (PDMS).

16. A transducer or other device according to claim 11, wherein the means for applying a voltage comprises means for applying an ac voltage.

17. A transducer or other device according to claim 11, wherein the means for measuring the current comprises:

a) a resistor placed in series with the electrodes; and

b) means for measuring the rms voltage across the resistor.

18. A method for characterizing or distinguishing between different types of particles, different chemical compositions or different biospecies, said method comprising the steps of:

a) providing a device for measuring flow-induced electrical admittance spectra of the different types of flowing particles or different biospecies;

b) using the device to measure the flow-induced electrical admittance spectra of the different types of particles or different biospecies; and

c) characterizing different flowing particles or different biospecies on the basis of differences in their respective flow-induced electrical admittance spectra.

19. A method according to claim 18 further comprising the step of:

d) sorting the different particles, compositions or biospecies.

20. A method according to claim 18 wherein the device provided in Step a comprises:

a flow channel through which the particles, compositions or biospecies may flow in a direction of flow;

electrodes positioned substantially parallel to the line of flow;

a power source for applying a voltage across the electrodes; and

measuring apparatus for measuring the current across the electrodes and for determining electrical admittance spectra based on such current measurements.

21. A method according to claim 19 wherein the sorting is carried out through the use of fluidic switches.

22. A method according to claim 18 wherein the different particles, compositions or biospecies comprise biological cells of different type.

23. A method according to claim 22 wherein the method is employed to distinguish or sort stem cells from other cells.

24. A method according to claim 18 wherein the different particles, compositions or biospecies comprise different chemical compositions.

25. A method according to claim 18 wherein the different particles, compositions or biospecies comprise different prions.

26. A method according to clam 18 wherein the different particles, compositions or biospecies comprise different microorganisms.

27. A method according to clam 18 wherein the different particles, compositions or biospecies comprise cells containing different contents or substances.

28. A method according to claim 27 wherein the cells containing different contents or substances are selected from the group consisting of:

cells containing different drugs;

cells containing different therapeutic substances;

cells containing different markers or diagnostic agents;

cells containing different dyes;

cells containing different drug delivery substances;

cells containing different toxins; and

cells containing different metabolites.