Impedance based feedback control of microfluidic valves

Patent metadata

Field	Value
Publication number	US-11059043-B2
Application number	US-201715491743-A
Country	US
Kind code	B2
Filing date	Apr 19, 2017
Priority date	Apr 19, 2017
Publication date	Jul 13, 2021
Grant date	Jul 13, 2021

Abstract

A microfluidic system includes a microfluidic chip including a channel layer and a fluid control layer operatively connected to the channel layer, the channel layer having one or more fluid channels. The one or more channels are configured to contain a plurality of droplets. A valve control system is provided to control flow of fluid through the one or more fluid channels in the channel layer. The microfluidic system also includes a droplet impedance detection and feedback control system operatively connected to the valve control system. The droplet impedance detection and feedback control system is configured to detect at least a position of at least one droplet in a fluid channel and to send a signal to the valve control system to operate a particular valve at a particular time based on the detected position of the at least one droplet.

First claim

We claim:

1. A microfluidic system having feedback valve control, comprising:
a microfluidic chip comprising a channel layer and a fluid control layer operatively connected to the channel layer, the channel layer comprising one or more fluid channels and one or more fluid input ports connected to the one or more fluid channels;
a fluid input system fluidly connected to the one or more fluid input ports of the channel layer, the fluid input system being configured to input at least a sample solution, buffer solution and at least one reagent, wherein said one or more fluid channels are configured to contain a plurality of droplets, the plurality of droplets comprising at least the sample solution and separated from each other by the buffer solution;
a valve control system operatively connected to the fluid control layer to selectively open and close a plurality of valves in the channel layer to control flow of fluid through the one or more fluid channels in the channel layer; and
a droplet detection and feedback control system operatively connected to said valve control system and comprising an electrical impedance-based droplet detection system,
wherein said droplet detection and feedback control system comprises at least one pair of spaced apart electrodes arranged proximate said one or more fluid channels of said channel layer to detect at least one droplet in a fluid channel in the one or more fluid channels due to a measured change of electrical impedance of said at least one droplet compared to said buffer solution,
wherein the droplet detection and feedback control system is configured to detect at least a position of the at least one droplet in the fluid channel in the one or more fluid channels when the droplet travels over the at least one pair of spaced apart electrodes based on the measured change of electrical impedance of the at least one droplet passing across the at least one pair of spaced apart electrodes and to send a signal to the valve control system to operate a particular valve in the plurality of valves at a time calculated by the droplet detection and feedback control system based on the detected position of the at least one droplet and a velocity of the at least one droplet in the fluid channel.

2. The microfluidic system according to claim 1 , further comprising a droplet generator configured to generate the plurality of droplets in the one or more fluid channels in the channel layer.

3. The microfluidic system according to claim 2 , further comprising a fluid reservoir containing the sample solution, wherein the droplet generator comprises one or more valves in communication with the fluid reservoir containing the sample solution and with the one or more fluid input ports, the one or more valves being configured to open and close sequentially to introduce the sample solution in a form of the plurality of fluid droplets into the one or more fluid channels.

4. The microfluidic system according to claim 1 , wherein an electrical impedance of a material between the at least one pair of electrodes is measured using an impedance measurement circuit comprising:
a voltage source electrically connected to the at least one pair of electrodes, the voltage source being configured to supply a voltage signal to the at least one pair of electrodes;
a voltage measurement device electrically connected to the at least one pair of electrodes, the voltage measurement device being configured to measure a voltage change across the at least one pair of electrodes; and
a current measurement device electrically connected to the at least one pair of electrodes, the current measurement device being configured to measure a current across the at least one pair of electrodes,
wherein the electrical impedance of the material between the at least one pair of electrodes is determined based on current and voltage change across the at least one pair of electrodes.

5. The microfluidic system according to claim 4 , wherein the material comprises the sample solution or the buffer solution, or both.

6. The microfluidic system according to claim 4 , wherein the voltage signal is a direct current (DC) voltage or an alternating current (AC) voltage.

7. The microfluidic system according to claim 1 , wherein the at least one pair of electrodes are arranged in a coplanar configuration, wherein the at least one pair of electrodes are spaced apart from each other along a length of the one or more fluid channels in a direction of movement of the at least one droplet.

8. The microfluidic system according to claim 1 , wherein the at least one pair of electrodes are arranged in a parallel configuration wherein the at least one pair of electrodes are disposed on opposite sides of the one or more fluid channels such that the at least one pair of electrodes are spaced apart from each other by at least a thickness of the one or more fluid channels.

9. The microfluidic system according to claim 1 , wherein said droplet detection and feedback control system is configured to calculate a time delay between detection of said at least one droplet and operation of said particular valve based on a known droplet-travel distance between the detected position of the at least one droplet and the position of the particular valve and the velocity of the at least one droplet detected.

10. The microfluidic system according to claim 9 , wherein the velocity of the detected at least one droplet is determined using a calibration method prior to manually inputting the velocity of the detected at least one droplet into the detection and feedback control system.

11. The microfluidic system according to claim 1 , wherein the droplet detection and feedback control system comprises a first pair of electrodes and a second pair of electrodes arranged proximate said fluid channel in the one or more fluid channels of said channel layer to detect said at least one droplet due to a change of electrical impedance of said at least one droplet compared to said buffer solution, wherein the velocity of the at least one droplet is determined using a measured distance between the first pair of electrodes and the second pair of electrodes and a transit time of the at least one droplet between the first pair of electrodes and the second pair of electrodes.

12. The microfluidic system according to claim 1 , wherein the droplet detection and feedback control system is further configured to calculate a length of said at least one droplet using a speed of said at least one droplet and a time period between a change of electrical impedance from an electrical impedance of the buffer solution to an electrical impedance of the sample solution of said at least one droplet to a change of electrical impedance back from the electrical impedance of the sample solution to the electrical impedance of the buffer solution.

Assignees

• Univ Johns Hopkins
• Pioneer Hi Bred Int

Inventors

• Wang Tza-Huei
• Axt Brant
• Hsieh Yi-Fan
• Zec Helena C
• Kaushik Aniruddha
• Hsieh Kuangwen
• Yun Yue

Classifications

• B01L2200/061

  Counting droplets · CPC title

• B01L2400/06

  Valves, specific forms thereof · CPC title

• F16K2099/0084

  Chemistry or biology, e.g. "lab-on-a-chip" technology · CPC title

• B01L2300/0883

  Serpentine channels · CPC title

• B01L2300/0645

  Electrodes · CPC title