Method and system for impedance-based quantification and microfluidic control

Patent metadata

Field	Value
Publication number	US-12031896-B2
Application number	US-202017425414-A
Country	US
Kind code	B2
Filing date	Jan 24, 2020
Priority date	Jan 24, 2019
Publication date	Jul 9, 2024
Grant date	Jul 9, 2024

Abstract

Disclosed herein are methods and systems that facilitate the integration of on-chip impedance sensors and measurement circuitries for quantifying the impedance/frequency response of microfluidic device under the same, or similar, conditions used for particle manipulation. The methods and systems can use a microfluidic chip comprising a microfluidic channel with one or more electric-field-generating structures located therein, including a first electric-field-generating structure, wherein the one or more electric-field-generating structures is configured to selectively polarize or manipulate biologic or particle components flowing within the microfluidic channel. The method and system can also employ a circuit configured for automated determination and quantification of parasitic voltage drops during AC electrokinetic particle manipulation, without the need to use valuable biological samples or model particles. The determined impedance response can be used to assess efficacy of the microfluidic device geometry as well as to provide control signals to inform downstream cell separation decisions.

First claim

What is claimed is:

1. A method comprising:
providing a microfluidic chip, the microfluidic chip comprising a microfluidic channel with one or more electric-field-generating structures located therein, including a first electric-field-generating structure, wherein the one or more electric-field-generating structures is configured to selectively polarize or manipulate biologic or particle components flowing within the microfluidic channel; and
measuring, via an on-chip impedance sensing element, impedance spectra associated with at least one internal capacitive structure of the first electric-field-generating structure or characteristic of the biologic or particle components, and determining, via a processor or logic circuit, one or more parameters associated with the at least one internal capacitive structure, wherein the one or more parameters is selected from the group consisting of:
an associated thickness of the at least one capacitive structure;
a surface area size of the at least one internal capacitive structure;
a surface charge property of the at least one internal capacitive structure;
an architecture feature of the at least one internal capacitive structure; and
a size of a portion of microfluidic channel to which the first electric-field-generating structure is located;

wherein the measured impedance spectra is used at least for one of i) control of the polarization or manipulation of the biologic or particle components when flowing through the microfluidic channel and ii) geometric or functional quantification of the at least one internal capacitive structure or of the microfluidic chip.

2. The method of claim 1 , further comprising:
triggering, by a processor or control circuit, controls of media conditions, polarization, or manipulation of the biologic or particle components when flowing through the microfluidic channel based on the measured impedance spectra.

3. The method of claim 2 , further comprising:
determining, via a processor or logic circuit, one or more parameters associated with the at least one internal capacitive structure or the characteristic of the biologic or particle components, wherein the determination is performed by a fitting operation, performed via the processor or logic circuit, of the measured impedance spectra to an equivalent circuit model that at least include the first electric-field-generating structure or a portion thereof.

4. The method of claim 1 , wherein the impedance spectra is measured by:
applying an impedance interrogating signal having a power level and a frequency range corresponding to those associated with the control of the media condition, polarization, or manipulation of the biologic or particle components; and
measuring a resulting voltage resulting from the applied impedance interrogating signal, wherein the measured resulting voltage has an amplitude and phase properties that defines the impedance spectra.

5. The method of claim 1 , wherein the first electric-field-generating structure comprises an electrode portion and an insulating barrier, wherein the insulating barrier corresponds to the at least one internal capacitive structure.

6. The method of claim 5 , wherein the electrode portion is configured as at least one of:
a contactless dielectrophoresis electrode;
a bi-polar dielectrophoresis electrode;
a passivated dielectrophoresis electrode;
an electrowetting on dielectric electrode; and
a droplet manipulating system electrode.

7. The method of claim 1 , wherein the impedance spectra is measured when the biologic or particle components are flowing within the microfluidic channel.

8. The method of claim 1 , wherein the impedance spectra is measured when the microfluidic channel is filled with a test media that does not have present biologic or particle components of interest.

9. The method of claim 1 ,
wherein the first electric-field-generating structure is used for electrokinetic trapping, acoustic trapping, or dielectrophoresis operation, and
wherein the functional quantification of at least one internal capacitive structure or the characteristic of the biologic or particle component comprises at least one of:
a quantification associated with efficacy of the electrokinetic trapping, acoustic trapping, or dielectrophoresis operation;
a quantification associated with a frequency response of the electrokinetic trapping, acoustic trapping, or dielectrophoresis operation;
a quantification of parasitic voltage drops of the first electric-field-generating structure;
a quantification associated with identifying a particle type and its position in the microfluidic channel; and
a quantification associated with sample transport post-trapping operation.

10. The method of claim 1 , wherein the first electric-field-generating structure and corresponding controls are configured for a target cell type selected from the group consisting of tumor cells, immune cells, and stem cells.

11. The method of claim 1 , wherein the first electric-field-generating structure and corresponding controls are configured for dielectrophoresis operation having a wide frequency range of at least 1 MHz.

12. The method of claim 1 , wherein the measured impedance spectra is used for the control of the selective polarization or manipulation of the biologic or particle components when flowing through the microfluidic channel.

13. The method of claim 1 , wherein the measured impedance spectra is used for the geometric or functional quantification of at least one internal capacitive structure of the first electric-field-generating structure or of the microfluidic chip.

14. The method of claim 13 , wherein the geometric or functional quantification is used to determine an initialized control setting value used in the control of the microfluidic chip.

15. The method of claim 1 , wherein the measured impedance spectra is used for the geometric or functional quantification of at least one internal capacitive structure of the first electric-field-generating structure or the microfluidic chip as part of a quality control assessment operation of the microfluidic chip.

16. The method of claim 1 , wherein the measured impedance spectra is used for the geometric or functional quantification of at least one internal capacitive structure of the first electric-field-generating structure or the microfluidic chip to determine a geometry or functional feature of the first electric-field-generating structure that is optimized for maximum trapping operation.

17. The method of claim 1 , wherein the microfluidic chip comprises a channeled structure made of a material selected from the group consisting of a polymer and a glass.

18. The method of claim 1 , wherein the impedance spectra is measured via active electronic components located on an electronic board that is electrically coupled to the on-chip impedance sensing elements.

19. The method of claim 3 , wherein the equivalent circuit model includes:
a first set of one or more impedance-associated parameters of at least one electrode of the first electric-field-generating structure,
a second set of one or more impedance-associated parameters of the microfluidic channel, and
a third set of one or more impedance-associated parameters of a capacitive structure that, at least, includes the at least one internal capacitive structure of the first electric-field-generating structure.

20. A method comprising:
providing a microfluidic chip, the microfluidic chip comprising a microfluidic channel with one or more electric-field-ge

Assignees

• Univ Virginia Patent Foundation

Inventors

• Swami Nathan
• Varhue Walter
• Farmehini Vahid

Classifications

• G01N15/01

  specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05) · CPC title

• G01R27/16

  Measuring impedance of element or network through which a current is passing from another source, e.g. cable, power line · CPC title

• G01N33/4833

  of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735) · CPC title

• B01L2300/0627

  Sensor or part of a sensor is integrated · CPC title

• B01L2200/0647

  Handling flowable solids, e.g. microscopic beads, cells, particles · CPC title