Microfluidic system for handling biological cells

Patent metadata

Field	Value
Publication number	US-12179198-B2
Application number	US-201816475901-A
Country	US
Kind code	B2
Filing date	Jan 5, 2018
Priority date	Jan 6, 2017
Publication date	Dec 31, 2024
Grant date	Dec 31, 2024

Abstract

A system for handling biological cells includes a main channel having an inlet end and an outlet end, and, at least over a first portion from the inlet end, including a cross section such that a cell circulating in the portion undergoes mechanical stresses. The system further includes first means for detecting the presence of a cell at the inlet end of the main channel and at least one access zone opening into the main channel between its inlet end and its outlet end in the first portion, in order to make it possible to exert an action on the cell. The system also includes means for displacing the cell in order to control the displacement of the cell between the inlet end and the outlet end.

First claim

The invention claimed is:

1. A handling system for handling biological cells, comprising:
n main channels, n being a whole number at least equal to 1, with each main channel comprising an inlet end, an outlet end, and at least on a first portion starting from the inlet end;
at least a first detector configured to detect presence of a cell on the inlet end of said each main channel;
at least one access zone opening into the main channel between the inlet end and the outlet end in said first portion, in order to exert an action on said detected cell; and
a device configured to displace said detected cell for controlling the displacement of the detected cell between the inlet end and the outlet end, said device being configured in such way that the detected cell enters into the main channel by the inlet end and exits from the main channel by the outlet end, wherein
said each main channel further comprises a transverse section that is smaller than a transverse section of the detected cell, such that the detected cell circulating in said first portion undergoes mechanical stresses applied by the first portion,
the at least said first detector comprises a support forming a portion of a wall of the main channel, and
at least one actuator is configured to put said support into vibration, wherein
the access zone comprises a secondary channel and a device configured to interrupt a fluidic communication between the secondary channel and the main channel,
the device configured to interrupt a fluidic communication between the secondary channel and the main channel comprises a closing element, which is configured to be subjected in the secondary channel to two pressures being exerted in opposite directions, said device configured to interrupt a fluidic communication between the secondary channel and the main channel controlling said pressures in order to displace the closing element, and
the closing element is a fluid that is immiscible with at least a liquid that contains the detected cell.

2. The handling system according to claim 1 , wherein the at least said first detector is configured to provide information on at least one property of the detected cell.

3. The handling system according to claim 1 , further comprising at least a second detector between the access zone and the outlet end.

4. The handling system according to claim 1 , wherein the secondary channel is configured to be supplied with one or several substances to be delivered to the detected cell.

5. The handling system according to claim 1 , wherein the secondary channel is configured to be connected to a zone for collecting one or several substances ejected by the detected cell.

6. The handling system according to claim 5 , wherein the secondary channel is configured to be connected to an analyzer configured to analyze the substance or substances ejected by the detected cell.

7. The handling system according to claim 1 , wherein
at least one portion of a side wall of the main channel is transparent, and
the handling system further comprises an imaging system arranged on a transparent portion.

8. The handling system according to claim 1 , further comprising control circuitry connected at least to the at least said first detector, to the access zone, and to the device configured to displace said detected cell, said control circuitry being configured to act at least on the access zone and/or on the device configured to displace said detected cell in order to apply an action to the detected cell.

9. The handling system according to claim 1 , wherein n is equal to at least two.

10. The handling system according to claim 1 , wherein
the at least said first detector comprises a support forming a portion of a wall of the main channel, and
said at least one actuator is a piezoelectric actuator.

11. The handling system according to claim 1 , wherein the detected cell undergoes the mechanical stresses while passing through the main channel.

12. The handling system according to claim 1 , wherein the mechanical stresses are modified by a section of the main channel.

13. A method for implementing a handling system for handling biological cells, the handling system comprising: n main channels, n being a whole number at least equal to 1, with each main channel comprising an inlet end, an outlet end, and at least on a first portion starting from the inlet end, a transverse section of said each main channel such that a cell circulating in said first portion undergoes mechanical stresses, the transverse section of the main channel being smaller than a transverse section of the cell; at least a first detector configured to detect presence of said cell on the inlet end of said each main channel; at least one access zone opening into the main channel between the inlet end and the outlet end in said first portion, in order to exert an action on said cell; and a device configured to displace said cell for controlling the displacement of the cell between the inlet end and the outlet end, said device being configured in such way that the cell enters into the main channel by the inlet end and exits from the main channel by the outlet end, the method comprising:
supplying of a solution that contains at least one cell at the inlet end of the main channel;
displacing of the cell in the main channel;
detecting of the presence of the cell at the inlet of the main channel;
determining of at least one property of the cell and optionally the determining of said cell;
deciding whether to apply an action to the cell;
if an action is to be applied to the cell, controlling the device configured to displace said cell in order to immobilize the cell at the access zone and controlling the access zone in order to apply an action; and

controlling the device configured to displace said cell in order to bring the cell to the outlet end, wherein
the handling system comprising at least a second detector between the access zone and the outlet end, and
a comparison of signals emitted by the at least said first detector and signals emitted by the at least said second detector is carried out in order to detect a modification in at least one property of the cell following the action that has been applied to the cell.

14. The method for handling according to claim 13 , wherein the action is a delivery of macromolecules.

15. The method for handling according to claim 13 , wherein said at least one property of the cell being a deformability, the determining takes a measurement of said deformability of the cell and determines whether the cell has a metastatic potential.

16. The method for handling according to claim 13 , wherein at least the deciding, controlling the device configured to displace said cell in order to immobilize the cell, and controlling the device configured to displace said cell in order to bring the cell to the outlet end are controlled by control circuitry.

17. The method for handling according to claim 13 , wherein the action is collection of one or several substances ejected by the cell, including secretome.

Assignees

• Commissariat Energie Atomique

Inventors

• Agache Vincent
• Casset Fabrice
• Fanget Stephane
• Fouillet Yves
• Millet Arnaud

Classifications

• G01N2015/1021

  Measuring mass of individual particles · CPC title

• G01N15/01

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

• G01N15/10

  Investigating individual particles · CPC title

• C12Q1/04

  Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} · CPC title

• B01L2300/0645

  Electrodes · CPC title