Measuring System and Manufacturing Process of Such a Measuring System

• US 20190310178A1
• Filed: 12/12/2017
• Published: 10/10/2019
• Est. Priority Date: 12/12/2016
• Status: Active Grant

• Current Assignee: Centre National De La Recherche Scientifique, NeuroInDx, Inc., The Foundation for the Promotion of Industrial Science
• Original Assignee: Centre National De La Recherche Scientifique, NeuroInDx, Inc., The Foundation for the Promotion of Industrial Science
• Inventors: Collard, Dominique, Fujita, Hiroyuki, Karsten, Stanislav
• Granted Patent: US 11,579,068 B2
• Time in Patent Office: Days
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: G01N 15/1023 Microstructural devices for non-optical measurement
• CPC Class Codes: G01N 15/1031 by measuring electrical or magnetic effects
• CPC Class Codes: G01N 2001/1056 Disposable (single-use) samplers
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1022 Measurement of deformation of individual particles by non-optical means
• CPC Class Codes: G01N 2015/1028 Sorting particles
• CPC Class Codes: G01N 2015/103 Particle shape
• CPC Class Codes: G01N 2203/0089 Biorheological properties
• CPC Class Codes: G01N 2203/0286 Miniature specimen; Testing on microregions of a specimen
• CPC Class Codes: G01N 3/08 by applying steady tensile or compressive forces G01N3/28 takes precedence
• CPC Class Codes: G01N 3/32 by applying repeated or pulsating forces
• CPC Class Codes: G01N 33/48728 Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10

Abstract

The invention relates to a system (10) adapted to measure multiple biophysical characteristics of cells, the system (10) comprising: a microfluidic chip (12) provided with a microfluidic channel (14) which allows cells to flow through, the microfluidic channel (14) having an inlet (14a), an outlet (14b), and a lateral opening (14c) situated between the inlet (14a) and the outlet (14b); and a capacitive sensor (30) integrated in the microfluidic chip, adapted to obtain biophysical characteristics of a single cell in the microfluidic channel (14) by directly manipulating the single cell by sensor elements (31, 32) through the lateral opening (14c) of the microfluidic channel (14), the sensor (30) comprising a stationary part and an electrostatically driven movable part which is movable relative to the stationary part, the stationary part being fixed to the microfluidic chip (12), the movable part being arranged in the lateral opening (14c) of the microfluidic channel (14), wherein a portion of the sensor elements (31, 32) provides an interface between fluid and air in the system.

Claims

1. A system adapted to measure multiple biophysical characteristics of cells, the system comprising:

a microfluidic chip provided with a microfluidic channel which allows cells to flow through, the microfluidic channel having an inlet, an outlet, and a lateral opening situated between the inlet and the outlet; and

a capacitive sensor integrated in the microfluidic chip, adapted to obtain biophysical characteristics of a single cell in the microfluidic channel by directly manipulating the single cell by sensor elements through the lateral opening of the microfluidic channel,

the sensor comprising a stationary part and an electrostatically driven movable part which is movable relative to the stationary part, the stationary part being fixed to the microfluidic chip, the movable part being arranged in the lateral opening of the microfluidic channel,

wherein a portion of the sensor elements provides an interface between fluid and air in the system.

2. The system of claim 1, wherein the sensor elements include a pair of arms extending toward each other, tips of the pair of arms (34) are arranged in the lateral openings formed on opposite side of the microfluidic channel, and at least one arm of the pair of arms is capable of moving closer to or away from the other arm.

3. The system of claim 2, wherein the lateral openings have a size selected to allow the tips of the arms to be introduced into the microfluidic channel through the respective opening while preventing a fluid within the microfluidic channel from leaking.

4. The system of claim 1, wherein the sensor is a programmable sensor adapted to selectively obtain one or more biophysical characteristics of the single cell.

5. The system of claim 1, wherein the microfluidic chip is further provided with at least one additional microfluidic channel arranged in parallel with the microfluidic channel.

6. The system of claim 1, wherein the sensor is adapted to obtain biophysical characteristics of the single cell by stimulating the single cell in the microfluidic channel mechanically and/or electrically.

7. The system of claim 1, wherein the sensor is adapted to obtain biophysical characteristics including at least one of size, rigidity, shape recovery time, viscosity, and electrical impedance, and/or frequency dependency of the biophysical characteristics.

8. The system of claim 1, further comprising a collecting means in fluid communication with the outlet of the microfluidic channel.

9. The system of claim 1, further comprising a sorting means for sorting the cells flowing in the microfluidic channel, depending on the biophysical characteristics of the cells obtained by the sensor.

10. The system of claim 9, wherein the microfluidic chip is further provided with at least one branch channel branching off from the microfluidic channel and downstream relative to the sensor.

11. The system of claim 10, wherein the sorting means comprises a valve adapted to direct the cell to the branch channel or downstream of the microfluidic channel, depending on the biophysical characteristics of the cell.

12. The system of claim 10, further comprising a dock in fluid communication with the branch channel.

13. The system of claim 9, wherein the sorting means is adapted to sort the cells by comparing the biophysical characteristics of the cell with a threshold.

14. The system of claim 13, wherein the threshold is programmable.

15. A process of manufacturing the system of claim 1, the process comprising:

applying a mask pattern corresponding to the shape of the microfluidic channel and the shape of the stationary part and the movable part of the sensor; and

forming the shape of the sensor together with the microfluidic channel.

16. A process of measuring multiple biophysical characteristics of cells, comprising:

providing a system according to claim 1;

flowing cells through the microfluidic channel between the inlet and the outlet;

directly manipulating a single cell by the sensor through the lateral opening of the microfluidic channel so as to obtain biophysical characteristics of said single cell.

17. The process of claim 16, further comprising stimulating the cell chemically and/or biologically in the microfluidic channel.

18. The process of claim 16, further comprising sorting the cells flowing in the microfluidic channel depending on the biophysical characteristics of the cells obtained by the sensor.

19. The process of claim 16, wherein the biophysical characteristics include at least one of size, rigidity, shape recovery time, viscosity, and electrical impedance, and/or frequency dependency of the biophysical characteristics.