Method and system for producing calibrated microcapsules

Patent metadata

Field	Value
Publication number	US-9737864-B2
Application number	US-201214113210-A
Country	US
Kind code	B2
Filing date	Apr 23, 2012
Priority date	Apr 22, 2011
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

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 (f 1 , f 2 , f 3 ); 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 (Q 1 , Q 2 , and/or Q 3 ) of the fluids (f 1 , f 2 , f 3 ). The present invention also relates to a system for producing calibrated microcapsules.

First claim

The invention claimed is:

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:
a first fluid to be encapsulated, at a first flow rate
a second fluid not miscible with the first fluid, at a second flow rate, and
a third fluid containing a precursor of the microcapsule membrane, at a third flow rate;

deforming the microcapsules by generating a flow of said microcapsules in a capillary, the diameter of the capillary being of the same order of magnitude as the calibrated diameter, said flow having a flow rate and said diameter being such that said microcapsules are purposely deformed by said flow rate and said diameter;
observing and acquiring the outline of at least one deformed microcapsule within said capillary observed by optical acquisition means;
comparing, by data processing means, 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;
modifying the flow rates of the fluids if at least one of:
the difference between the diameter of the determined observed microcapsule and an optimal diameter is above a predetermined threshold, and
the difference between 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.

2. 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.

3. 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.

4. Method according to claim 1 , claim 2 or claim 3 , 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.

5. Method according to claim 1 , wherein the microsystem comprises a central microchannel, a first set of lateral microchannels and a second set of lateral microchannels, the first fluid being injected into the central microchannel, the second fluid being injected into the first set of lateral microchannels, the third fluid being injected into the second set of lateral microchannels.

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

7. Method according to claim 1 , wherein the second non miscible fluid is a biocompatible fatty ester.

8. Method according to claim 1 , wherein the precursor of the microcapsule membrane contained in the third fluid is a cross-linking agent.

9. Method according to claim 8 , wherein the microsystem comprises a cross-linking coil prolonging the microchannel.

10. 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 by an infrared beam, an ultraviolet beam, or an electron beam.

11. Method according to claim 1 , wherein the microsystem is made of transparent solidified polydimethylsiloxane.

12. Method according to claim 1 , wherein the capillary is a glass tube of cylindrical section.

13. Method according to claim 12 , wherein the capillary is inserted inside the central microchannel.

14. Method according to one of claim 12 or 13 , wherein the capillary 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.

15. Method according to claim 1 , wherein a reservoir for storing microcapsules is placed at the output of the capillary.

16. Method according to claim 1 , 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, 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.

17. 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, said two photographs being compared by the data processing means in order to measure the flow speed in the capillary 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.

18. Method according to claim 16 or 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.

19. Method according to claim 16 or 17 , wherein the step of comparing the acquired outline with a collection of deformed by said reference capillary microcapsule ( 20 ) consists outlines 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 microcapsules(s) whose outline comes nearest to said plurality of points.

20. Method according to claim 1 , wherein the optical acquisition means comprise an inverted microscope and a high speed CCD camera.

21. Method according to claim 1 , wherein the outline acquisition step is implemented for each microcapsule produced by the microsystem.

22. Method according to claim 1 , wherein the outlines of the reference microcapsules are outlines acquired beforehand by the optical acquisition means, the reference microcapsules being deformed by means genera

Assignees

• Leclerc Eric
• Salsac Anne-Virginie
• Barthes-Biesel Dominique
• Chu Thi Xuan
• Univ Tech De Compiegne-Utc
• Centre Nat De La Rech Scient (Cnrs)

Inventors

• Leclerc Eric
• Salsac Anne-Virginie
• Barthes-Biesel Dominique
• Chu Thi Xuan

Classifications

• B01J13/14

  Polymerisation; cross-linking · CPC title

• B01J13/00 Primary

  Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons · CPC title

• G05D7/0694

  by action on throttling means or flow sources of very small size, e.g. microfluidics (microvalves F16K99/0001; microstructural devices per se B81B) · CPC title