Fabrication of polymersomes using double-emulsion templates in glass-coated stamped microfluidic devices.

Polymersomes are vesicular self-assemblies of amphiphilic diblock copolymers; they consist of a spherical compartment enclosed by amacromolecular bilayer and have great potential as encapsulation and release systems. They offer enhanced mechanical and structural stability as compared to vesicles made from phospholipids or detergents. By tailoring block lengths, block chemistry and functionalization of the copolymers, polymersomes with controlled biological, chemical, and physicalproperties canbe formed.Typically, polymersomes are formed by techniques such as film rehydration, electroformation, phase transfer, and ultrasonication. These techniques rely on the undirected self-assembly of the copolymers, and typically lead to polymersomes with broad size distributions and low encapsulation efficiency. A promising alternative is the directed formation of polymersomes using copolymer-stabilized water/organic solvent/water (W/O/W) double emulsions inmicrofluidic devices. The assembly of the copolymers is directed by the double-emulsion droplets during evaporation of the organic solvent in which the copolymer is dissolved. A crucial aspect of this technique is the choice of the organic solvent; it must be highly volatile and the diblock copolymer must be highly soluble within it. Moreover, the use of mixed solvents provides additional control over the interaction between the block copolymers in the bilayer. However, many organic solvents either evaporate too quickly causing the copolymers to form precipitates that eventually clog the microfluidic device, or the organic solvent takes too long to be completely evaporated. These problems can be addressed by using mixtures of organic solvents for dissolving the copolymers. Organic solvents are typically premixed before injection into microfluidic devices for forming the double emulsion templates. As the concentration of the copolymers and the composition of the premixed solvents cannot be tuned inside the device, any copolymer precipitates cannot be easily removed without disruption of the emulsion generation. Thus, the ability to inject additional solvents during the operation of the device would enable in-situ removal of precipitates and eliminate the problem of fouling. Therefore, a microfluidic design that combines the ability to form double emulsions with the ability to inject and mix two organic solvents is desirable. This goal is difficult to achieve using glass capillarymicrofluidic devices, as the channel design is not easily customized. These limitations can be overcome using lithographic fabrication techniques to producemore sophisticatedmicrofluidic devices. A convenient fabrication technique is soft lithography using poly(dimethylsiloxane) (PDMS), which can be used to fabricate rather sophisticated devices; unfortunately however, PDMS has a low chemical resistance, and swells when it comes in contact with most organic solvents. The resistance of PDMS towards organic solvents can be significantly increased by depositing a glasslike coating using sol–gel chemistry.While thisapproachhasbeensuccessfully applied to generate single emulsion drops of organic solvents, its application to sophisticated devices for the fabrication of complex structures such as double emulsions has not been demonstrated. An optimal system for fabricating doubleemulsion-templated polymersomes would combine the versatility of stamped microfluidic devices with resistance against organic solvents. [!] J. Thiele, Dr. A. R. Abate, H. C. Shum, S. Bachtler, Prof. D. A. Weitz Department of Physics and School of Engineering and Applied Sciences Harvard University Cambridge, MA 02138 (USA) E-mail: [email protected]