Microgel Generation and Encapsulation in Microdroplets

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In an article published by Chiara Martino, Daniele Vigolo, Xavier Casadevall i Solvas, Stavros Stavrakis, Andrew J. DeMello in Journal of Advanced Materials Technologies. The authors employed droplet-based microfluidics and microscope projection photolithography to produce PEGDA microgels and consecutive in-situ pico-droplet encapsulation.

ABSTRACT

PEGDA (poly (ethylene glycol) diacrylate) microgels were generated and encapsulated within pico-droplets by combining droplet-based microfluidics and microscope projection photolithography. A continuous-flow photolithography was set up within a cross junction to generate and simultaneously to in-situ encapsulate fiber-like structures in pico-droplets. Additionally, the microfiber length was tailored by studying various modes of UV excitation. Lastly, a new route leading to the production of 3D patterned micro-structures was explored by employing UV excitation within trapped droplets. 

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Fig.1 Combination of in-flow photolithography and droplet-based microfluidics. 2 configurations "all-in" and "in" PDMS configurations.

Fig.1 Combination of in-flow photolithography and droplet-based microfluidics. 2 configurations “all-in” and “in” PDMS configurations.

INTRODUCTION TO MICROGEL GENERATION & ENCAPSULATION IN MICRODROPLETS

Microgels can be described as cross-linked polymer networks that are employed in a broad range of biomedical applications [1] from the construction of scaffolds in tissue engineering [2, 3], drug delivery applications [4, 5], sensors in diagnostics [6,7] to artificial cells in therapeutic applications [8].

One key feature in microgel generation is the fine control of the particle morphology. The technique called “continuous flow lithography” allows to produce precisely shaped polymeric particles. It consists in forming polymerized hydrogels by projection photolithography within flow-based environments [9].

Here droplet-based microfluidics is combined with continuous flow lithography to study the effects of UV excitation on PEGDA solution in a cross-junction device. Furthermore, the application of microscope projection photolithography in trapped droplets was implemented for the first time. More precisely, the PEGDA polymerization is investigated in two ways: “in” and “all-in” manners depending on the presence of lack of bottom PDMS layer in the cross-junction device. Indeed, in the “all-in” version, the PEGDA polymerization is prevented from cross-linking onto the bottom glass slide but permits microgels to stay suspended after the polymerization within the channel.

AIM & OBJECTIVES

  • Technical challenge due to the combination of continuous flow lithography and droplet-based microfluidics to explore the effect of UV excitation on PEGDA solution within a cross junction.
  • Tailoring of PEGDA polymerization by varying the presence of bottom PDMS layer in the microfluidic reactor.

Single Fiber Alginate encapsulation. Courtesy of Daniele Vigolo.

Fig 3. PEGDA fiber production  via microfluidics and encapsulation into microdroplets.

Fig 3. PEGDA fiber production via microfluidics and encapsulation into microdroplets.

KEY FINDINGS

The set-up consisted in a PDMS cross-junction device for droplet generation followed by a trapping device for the PEGDA polymerization step via UV lamp through a high-resolution photomask as described in Fig 1.  Both continuous and pulse UV excitation were performed during the PEGDA droplet formation. From continuous flow lithography, fiber PEGDA were formed and further encapsulated within the forming droplet. The fine tuning of the pressure of the two phases via a pressure driven flow controller (OB1 Mk3 Elveflow) ensured at once the gradual flow of the dispersed phase and a steady and simultaneous droplet generation.

The two solutions were delivered at 60 mbar. Photopolymerization started as soon as UV illumination occurred. The fiber was produced and stretched until it detached and consecutively encapsulated into a droplet. The full process is described in Fig 3. and video 1.

It was observed that the position at which UV illumination occurs clearly affects the fiber length. For the first time, it has been proven that the combination of droplet-based microfluidics and continuous flow lithography allows for the generation of PEGDA-based microgels of controlled geometry readily encapsulated into pL-volume droplets.

Furthermore, it was shown that the dynamics of droplet generation were responsible for the self-regulation of the PEGDA fiber length produced by UV crosslinking.

The effects of UV excitation on trapped droplets under both static and dynamic conditions and proved that complex microgels geometries can be generated in a reproducible and high-throughput fashion.

It is believed that the method presented will be of great interest for a number of applications from scaffolds for artificial bio-inspired systems to cell-based studies for the easy production of biocompatible microgels of controlled geometries.

If you’re interested in reproducing what Chiara Martino and Daniele Vigolo have achieved in their work, feel free to contact our team of experts for additional information about the OB1 pressure-driven flow controller for fine tuning of your fluids flow!

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REFERENCES TO MICROGEL GENERATION & ENCAPSULATION IN MICRODROPLETS

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polymers. Chemical Society Reviews. 2009;38(8):2161-8. 10

[2] Chung BG, Lee K-H, Khademhosseini A, Lee S-H. Microfluidic fabrication of microengineered hydrogels and their application in tissue engineering. Lab on a Chip. 2012;12(1):45-59.

[3] Li C, Chen P, Shao Y, Zhou X, Wu Y, Yang Z, et al. A Writable Polypeptide–DNA Hydrogel with Rationally Designed Multi-modification Sites. Small. 2015;11(9-10):1138-43.

[4] Langer R, Tirrell DA. Designing materials for biology and medicine. Nature. 2004;428(6982):487-92.

[5] Kim S-H, Kim JW, Kim D-H, Han S-H, Weitz DA. Polymersomes Containing a Hydrogel Network for High Stability and Controlled Release. Small. 2013;9(1):124-31.

[6] Islam MR, Ahiabu A, Li X, Serpe MJ. Poly (N-isopropylacrylamide) Microgel-Based Optical Devices for Sensing and Biosensing. Sensors (Basel, Switzerland). 2014;14(5):8984-95.

[7] Rakickas T, Ericsson EM, Ruželė Ž, Liedberg B, Valiokas R. Functional Hydrogel Density Patterns Fabricated by Dip-Pen Nanolithography and Photografting. Small. 2011;7(15):2153-7.

[8] Chang TMS. Therapeutic applications of polymeric artificial cells. Nat Rev Drug Discov. 2005;4(3):221-35.

[9] Dendukuri D, Pregibon DC, Collins J, Hatton TA, Doyle PS. Continuous-flow lithography for high-throughput microparticle synthesis. Nat Mater. 2006;5(5):365-9.