Granted Patent
B2
US 12,194,429 · App. 18/184,562 · Granted Jan 14, 2025
Exploiting oxygen inhibited photopolymerization within emulsion droplets for the fabrication of microparticles with customizable size, shape and interfacial and mechanical properties
Inventors:
John Oakey (Laramie, WY); Katie Dongmei Li-Oakey (Laramie, WY); Daniel Debroy (Laramie, WY); Carl Frick (Laramie, WY); Rajib Shaha (Laramie, WY)
Assignee:
University of Wyoming
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Abstract
Described are methods and devices for the generation of hydrogel particles with micrometer and submicrometer dimensions using oxygen-inhibited partial polymerization, and the particles generated therefrom. The described methods generate particles with dimensions independent of the starting polymerizable solution dimension, for example, a microdroplet. Further, microfluidic flow parameters (e.g. viscosity, flow rate) and photopolymerization process parameters (e.g. optical exposure intensity and duration) are controlled to generate particles with tunable crosslinking density-determined properties including elasticity, diffusivity, and biomolecular display for diverse applications such as drug delivery, tissue engineering cell scaffolds, and single- and multiple-cell therapeutics. Similarly, gradients of crosslinking density-determined properties can be created within single particles through the selection of optical exposure intensity and duration. In addition to conventional spherical shapes, a suite of non-spherical shapes may be generated by manipulating the dimensions of the microfluidic channels and other related physical and process parameters.
Claims (24)
1. A method of generating a plurality of microparticles comprising:
providing a continuous phase comprising a non-aqueous liquid and a dispersed phase comprising an aqueous solution having a monomer or a macromer and a photoinitiator;
forming a composition comprising microdroplets of said aqueous solution dispersed in said non-aqueous liquid, wherein oxygen is diffused through said non-aqueous phase into said microdroplets;
deforming a first microdroplet; and
partially polymerizing the deformed first microdroplet, thereby generating a non-spherical microparticle within the deformed first microdroplet.
2. The method of claim 1 , wherein said diffusion of oxygen into said microdroplets generates an oxygen concentration gradient in said aqueous solution.
3. The method of claim 2 , wherein said oxygen concentration gradient results in a crosslinking gradient in the non-spherical microparticle.
4. The method of claim 1 , wherein said step of partially polymerizing the deformed first microdroplet is oxygen inhibited.
5. The method of claim 1 , wherein said non-aqueous liquid comprises a fluorocarbon oil or a hydrocarbon oil.
6. The method of claim 1 , wherein the step of deforming the first microdroplet comprises flowing the first microdroplet through one or more channels of a microfluidic device.
7. The method of claim 6 , wherein said microfluidic device comprises PDMS, glass or any combination thereof.
8. The method of claim 7 , wherein said microfluidic device comprises PDMS and said PDMS has an oxygen concentration selected from the range of 4 mol/m 3 to 6 mol/m 3 .
9. The method of claim 7 , wherein said microfluidic device comprises PDMS and said PDMS has an oxygen diffusivity selected from the range of 0.001 mm 2 /s to 0.05 mm 2 /s.
10. The method of claim 1 , wherein said non-spherical microparticle has a primary cross-sectional dimension of less than or equal to 20 μm.
11. The method of claim 1 , wherein said microdroplets have an average primary cross-sectional dimension of less than or equal to 100 μm.
12. The method of claim 1 , wherein a surface of said non-spherical microparticle is bioactive.
13. The method of claim 1 further comprising contacting a surface of said non-spherical microparticle with a biological material.
14. The method of claim 1 , wherein a surface of said non-spherical microparticle has increased biocompatibility.
15. The method of claim 1 , wherein said aqueous solution further comprises a biological material.
16. The method of claim 1 , wherein the non-spherical microparticle has a shape selected from the group consisting of: oblong, a disk, a biconcave disk, a torus, a rod, a wire, a bullet, a caterpillar and a horseshoe.
17. The method of claim 1 , wherein the step of partially polymerizing the deformed first microdroplet results in an unpolymerized layer of aqueous solution covering the surface of the non-spherical microparticle.
18. The method of claim 17 , comprising removing the unpolymerized layer of aqueous solution from the surface of the non-spherical microparticle.
19. The method of claim 1 , wherein the non-spherical microparticle has an aspect ratio of at least 2:1.
20. The method of claim 1 , wherein the non-aqueous liquid has a viscosity of at least 130 cP.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 20, 2023
From: OAKEY, JOHN; LI-OAKEY, KATIE DONGMEI; DEBROY, DANIEL; FRICK, CARL; SHAHA, RAJIB
To: UNIVERSITY OF WYOMING
Reel/Frame 063031/0413 →
Continuity (4)
Continuation
16647869
Provisional Application
62586680
· Nov 15, 2017
Provisional Application
62573576
· Oct 17, 2017
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