Systems and methods for integrating sensors with pumps in a microfluidic device

Patent metadata

Field	Value
Publication number	US-2021069697-A1
Application number	US-202017013456-A
Country	US
Kind code	A1
Filing date	Sep 4, 2020
Priority date	Sep 5, 2019
Publication date	Mar 11, 2021
Grant date	—

Abstract

This disclosure provides systems and methods for integrating an array of electronic sensors capable of performing trans-epithelial electrical resistance (TEER) measurements into a microfluidic device that includes a well plate. In some implementations, the sensors can include electrodes that are submerged into fluidically connected wells of the microfluidic device, which can contain an electrically conductive fluid such as the cell culture media or a buffered salt solution. An array of such electrodes can be integrated into a lid of the system that includes the microfluidic device. These electrodes can be routed using a printed circuit board through a number of multiplex switches that can allow addressing of a desired unit of the device through a microprocessor in communication with a computer.

First claim

What is claimed is:

1 . A system, comprising:
a well plate having one or more wells; a plurality of probes having a source electrode and a respective sense electrode, the plurality of probes disposed within the one or more wells of the well plate; and a controller device configured to:
receive an identification of a well of the well plate for a measurement;
select a probe of the plurality of probes that corresponds to the identification of the well for measurement;
establish a connection from a sensor to the source electrode and the respective sense electrode of the probe;
determine a measurement of a fluid sample in the well from the probe using the sensor; and
store the measurement in memory.

2 . The system of claim 1 , further comprising one or more pumps each disposed within a respective well of the one or more wells, wherein the one or more pumps are electrically coupled to and controlled by the controller device.

3 . The system of claim 2 , wherein the source electrode and the respective sense electrode are each coupled to a respective pump.

4 . The system of claim 1 , further comprising:
an airtight enclosure enclosing the controller device; and a source of dry gas passing through the airtight enclosure to remove moisture from the controller device.

5 . The system of claim 1 , wherein the one or more wells of the well plate comprise up to 96 wells arranged in a rectangular pattern.

6 . The system of claim 3 , wherein the controller device further comprises one or more connectors configured to couple the controller device to the one or more pumps through mechanical force.

7 . The system of claim 6 , wherein the one or more connectors comprise at least one of a spring device, a conductive flexible material, or a deformable material that is pushed into place against the one or more pumps.

8 . The system of claim 1 , wherein the source electrode and the sense electrode of each of the one or more probes comprises at least one of silver, silver chloride, platinum, stainless steel, a polyimide polymer, or a polyether imide polymer.

9 . The system of claim 1 , further comprising:
a printed circuit board in electrical communication with the controller device and the one or more probes, comprising one or more multiplex switches; and wherein the controller device is further configured to establish the connection from a sensor to the source electrode and the respective sense electrode by addressing the selected probe using the one or more multiplex switches.

10 . The system of claim 6 , wherein the one or more connectors each comprise:
an opening configured to receive a portion of a pump of the one or more pumps; and a plurality of cantilevers arranged around the opening of the connector and configured to electrically couple the portion of the pump to the connector.

11 . A method, comprising:
receiving, by a controller device in electrical communication with a plurality of probes, an identification of a well of a well plate for a measurement; selecting, by the controller device, a probe of the plurality of probes that corresponds to the identification of the well for measurement; establishing, by the controller device via one or more switches, a connection from a sensor to a source electrode and a respective sense electrode of the probe; determining, by the controller device, a measurement of a fluid sample in the well using the sensor; and storing, by the controller device, the measurement in a memory.

12 . The method of claim 11 , wherein selecting the probe of the plurality of probes that corresponds to the identification of the well for measurement further comprises selecting a second source electrode and a second respective sense electrode.

14 . The method of claim 11 , wherein establishing the connection from the sensor to the probe further comprises electrically coupling, by the controller device, the sensor to the source electrode and the respective sense electrode of the probe, such that the sensor can receive one or more signals from the probe.

15 . The method of claim 11 , wherein the sensor is integrated with the controller device, and determining the measurement of the fluid sample in the well further comprises:
providing, by the controller device using the source electrode of the probe, a current source from the probe of the plurality of probes that corresponds to the identification of the well to a second probe of the plurality of probes; and sensing, by the controller device from the sense electrode of the probe, a voltage value between the sense electrode of the probe and the second probe of the plurality of probes.

16 . The method of claim 15 , wherein determining the measurement of the fluid sample comprises determining a resistance of a cell culture in the well using the voltage value.

17 . A system, comprising:
a plurality of current source electrodes of a first respective plurality of pump sippers disposed within a first respective plurality of wells in a well plate; a plurality of voltage sense electrodes of a second respective plurality of pump sippers disposed within a second respective plurality of wells, the second respective plurality of wells coupled to the first plurality of wells via a channel comprising a solution including cells; and a controller device configured to:
route an electric current through the cells in the channel using a first current source electrode and a second current source electrode of the plurality of current source electrodes;
measure a voltage level across the cells caused in part by the electric current;
determine a parameter of the solution using the voltage level; and
actuate a pump of one of the first plurality of pump sippers or the second plurality of pump sippers.

18 . The system of claim 17 , wherein the controller device is configured to determine an impedance of the solution including the cells as the parameter.

19 . The system of claim 17 , wherein the controller device is configured to generate one or more signals to one or more switches to cause the electric current to flow through the first current source, the cells, and the second current source.

20 . The system of claim 17 , wherein the plurality of current source electrodes and the plurality of voltage sense electrodes comprise at least one of:
round wires; flat wires; conductive tubes; or multi-lumen tubes.

Assignees

• Charles Stark Draper Laboratory Inc

Inventors

• Azizgolshani Hesham
• Coppeta Jonathan Robert
• Charest Joseph L
• Zorn Alex M
• Baldwin Keith B

Classifications

• C12M41/08

  Means for changing the orientation · CPC title

• C12M29/00

  Means for introduction, extraction or recirculation of materials, e.g. pumps (pumps per se F04B) · CPC title

• B01L2300/0645

  Electrodes · CPC title

• B01L3/5085 Primary

  for multiple samples, e.g. microtitration plates · CPC title

• C12M23/12 Primary

  Well or multiwell plates (C12M25/04 takes precedence) · CPC title