# US 2014/0191430 A1 · Method and system for producing calibrated microcapsules

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- Number: US 2014/0191430 A1
- Document ID: US20140191430A1
- Status: Published application
- Kind: A1
- Application number: 14/113,210
- Filed: 2012-04-23
- Published: 2014-07-10
- Earliest claimed: 2011-04-22
- Assignees: Universite Technologie De Compiegne—UTC; Centre National de la Recherche Scientifique (CNRS)
- Inventors: Eric Leclerc; Anne-Virginie Salsac; Dominique Barthes-Biesel; Thi Xuan Chu
- Web page: https://patentgrep.com/patent/US20140191430A1

## CPC

- B01J 13/00: Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J 13/14: Polymerisation; cross-linking
- G05D 7/0694: {by action on throttling means or flow sources of very small size, e.g. microfluidics (microvalves F16K99/0001; microstructural devices per se B81B)}
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- G05D: SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES

## Abstract

The present invention relates to a method for producing microcapsules having a calibrated diameter and at least one parameter characteristic of the mechanical properties of an equally calibrated microcapsule, characterized in that the method includes the steps of: producing microcapsules by means of injection into a microsystem (10) of three fluids (f1, f2, f3); deforming the microcapsules by means generating a flow within a capillary tube (20); observing and acquiring the outline of at least one deformed microcapsule observed by an optical acquisition means (30); comparing the acquired outline with outlines from a collection of reference microcapsule outlines; determining the diameter and said at least one parameter characteristic of the mechanical properties of the observed microcapsule; and modifying the flow rates (Q1, Q2, and/or Q3) of the fluids (f1, f2, f3). The present invention also relates to a system for producing calibrated microcapsules.

## Claims

### Claim 1

Method for producing microcapsules having a calibrated diameter and at least one calibrated parameter characteristic of the mechanical properties of a microcapsule, method characterised in that it includes the steps of:
producing microcapsules by injecting into a microsystem (10):
a first fluid (f1) to be encapsulated, at a first flow rate (Q1).
a second fluid (f2) not miscible with the first fluid, at a second flow rate (Q2), and
a third fluid (f3) containing a precursor of the microcapsule membrane, at a third flow rate (Q3);
deforming the microcapsules by generating a flow of said microcapsules in a capillary (20), the diameter of the capillary (20) being of the same order of magnitude as the calibrated diameter;
observing and acquiring the outline of at least one deformed microcapsule observed by optical acquisition means (30);
comparing, by data processing means (40), the acquired outline with outlines from a collection of reference microcapsule outlines, the diameter and at least one parameter characteristic of the mechanical properties of a reference microcapsule being known for each reference microcapsule;
determining the diameter and the value of the at least one parameter characteristic of the mechanical properties of the observed microcapsule by the data processing means (40);
modifying the flow rates (Q1, Q2, and/or Q3) of to the fluids (f1, f2, f3) if the difference between:
the diameter of the determined observed microcapsule and an optimal diameter, and/or
the determined value of the at least one parameter characteristic of the mechanical properties of the observed microcapsule and an optimal value of the at least one parameter characteristic of the mechanical properties of a microcapsule, is above a predetermined threshold.

### Claim 2 (depends on 1)

Method according to claim 1, wherein the at least one parameter characteristic of the mechanical properties of a microcapsule is the modulus of elasticity of the membrane of the microcapsule.

### Claim 3 (depends on 2)

Method according to claim 2, wherein the at least one parameter characteristic of the mechanical properties of a reference microcapsule is the capillary number associated with the reference microcapsule.

### Claim 4

Method according to one of the preceding claims, wherein said predetermined threshold is 10% for the difference between the diameter of the determined observed microcapsule and the optimal diameter, and 30% for the difference between the determined value of the at least one parameter characteristic of the mechanical properties of the observed microcapsule and the optimal value of the at least one parameter characteristic of the mechanical properties of a microcapsule.

### Claim 5

Method according to one of the preceding to claims, wherein the microsystem (10) comprises a central microchannel (11), a first set of lateral microchannels (12) and a second set of lateral microchannels (13), the first fluid (f1) being injected into the central microchannel (11), the second fluid (f2) being injected into the first set of lateral microchannels (12), the third fluid (f3) being injected into the second set of lateral microchannels (13).

### Claim 6 (depends on 5)

Method according to claim 5, wherein each microchannel of the first set of lateral microchannels (12) and/or of the second set of lateral microchannels (13) intersects the central microchannel (11) with a same angle comprised between 45° and 90°.

### Claim 7

Method according to one of the preceding claims, wherein the second non miscible fluid (f2) is a biocompatible fatty ester.

### Claim 8

Method according to one of the preceding claims, wherein the precursor of the microcapsule membrane contained in the third fluid (f3) is a cross-linking agent.

### Claim 9 (depends on 8)

Method according to claim 8, wherein the microsystem (10) comprises a cross-linking coil (14) prolonging the microchannel (11).

### Claim 10 (depends on 8, 9)

Method according to one of claim 8 or 9, wherein the cross-linking is obtained by irradiation of the microdroplets in contact with the fluid (f3) by an infrared beam, an ultraviolet beam, or an electron beam.

### Claim 11

Method according to one of the preceding claims, wherein the microsystem (10) is made of transparent solidified polydimethylsiloxane.

### Claim 12

Method according to one of the preceding claims, wherein the capillary (20) is a glass tube of cylindrical section.

### Claim 13 (depends on 12)

Method according to claim 12, wherein the capillary (20) is inserted inside the central microchannel (11).

### Claim 14 (depends on 12, 13)

Method according to one of claim 12 or 13, wherein the capillary (20) has an internal diameter comprised between 25 and 150 μm, an external diameter comprised between 300 and 500 μm, and a length comprised between 10 and 100 mm.

### Claim 15

Method according to one of the preceding claims, wherein a reservoir (21) for storing microcapsules is placed at the output of the capillary (20).

### Claim 16

Method according to one of the preceding claims, wherein the step of acquiring the outline of at least one deformed microcapsule comprises the taking of at least one photograph of said microcapsule by the optical acquisition means (30), the acquired outline being constituted of a plurality of points materialising the membrane of the microcapsule placed on said photograph by the data processing means (40).

### Claim 17 (depends on 16)

Method according to claim 16, wherein the step of acquiring the outline of at least one deformed microcapsule comprises the successive taking of at least two photographs of the microcapsule by the optical acquisition means (30), said two photographs being compared by the data processing means (40) in order to measure the flow speed in the capillary (20) of the observed microcapsule, said speed being taken into account during the step of comparing the acquired outline with the outlines from a collection of reference microcapsule outlines.

### Claim 18 (depends on 16, 17)

Method according to one of claims 16 to 17, wherein the diameter of the observed microcapsule is directly calculated from the acquired outline, and wherein the step of comparing the acquired outline with a collection of reference microcapsule outlines deformed by said capillary (20) consists in the superposition of the plurality of points acquired with each reference deformed microcapsule outline having a diameter similar to the calculated diameter of the observed microcapsule, the value of the at least one parameter characteristic of the mechanical properties of the observed microcapsule being determined by the data processing means (40) from that associated with the reference microcapsule(s) having a diameter similar to the calculated diameter of the observed microcapsule whose outline comes nearest to said plurality of points.

### Claim 19 (depends on 16, 17)

Method according to one of claims 16 to 17, wherein the step of comparing the acquired outline with a collection of reference microcapsule outlines deformed by said capillary (20) consists in the superposition of the plurality of points acquired with each reference deformed microcapsule outline, the diameter and the value of the at least one parameter characteristic of the mechanical properties of the observed microcapsule being determined by the data processing means (40) from those associated with the reference microcapsule(s) whose outline comes nearest to said plurality of points.

### Claim 20

Method according to one of the preceding claims, wherein the optical acquisition means (30) comprise an inverted microscope and a high speed CCD camera.

### Claim 21

Method according to one of the preceding claims, wherein the outline acquisition step is implemented for each microcapsule produced by the microsystem (10).

### Claim 22

Method according to one of the preceding claims, wherein the outlines of the reference microcapsules are outlines acquired beforehand by the optical acquisition means (30), the reference microcapsules being deformed by means generating a flow within the capillary (20).

### Claim 23

System of producing calibrated microcapsules, characterised in that it comprises:
a microsystem (10);
a capillary (20);
optical acquisition means (30);
data processing means (40);
the microsystem (10) being adapted to produce microcapsules from a first fluid (f1) to be encapsulated injected at a first flow rate (Q1), a second fluid (f2) not miscible with the first fluid injected at a second flow rate (Q2) and a third fluid (f3) containing a precursor of the microcapsule membrane injected at a third flow rate (Q3);
the system being able to implement a method according to one of the preceding claims.