Synthesis of Particles in Microfluidics

The synthesis of particles in microfluidics refers to chemical assembly of particles typically of micron or nanometer size inside fluid-containing channels, chambers, or flow cells of micron scale. The particles assembled may include polymers, metal particles, gels, emulsions, and clusters of smaller particles. The microfluidics typically operates with very low energy, handles very low volumes of fluid in the range of pL-fL, and involves specific fluid effects only seen in the micro domain. 

Once formed, microgel particles can be useful as scaffolds in the constructimi of other particles. A useful variant on the emulsification/ gelation approach to microfluidic synthesis of particles is the use of double emulsions in which it is possible to carefully adjust the size, monodispersity, and chemical composition within a microfluidic framework [3]. fri this case, microgel particles may form a stmctural scaffold to shift the relative position of the inner droplet in the emulsion and thus help to control the morphology of the particles subsequently produced. 

Lewis PC, Graham RR, Nie Z, Xu S, Seo M, Kumacheva E. 2005. Continuous synthesis of copolymer particles in microfluidic reactors. Macromolecules 38 4536-4538. 

A number of elegant studies over the past few years have also addressed the need to minimize particle size distributions through the use of segmented flow microfluidic systems. Such an approach removes the possibility of particle deposition on channels and eliminates the problems of residence time distributions that occur in single phase systems (where drag at the channel walls sets up a velocity distribution inside the channel). For example, Shestopalov et al. reported the two-step synthesis... 

Microfluidic techniques have been recently used for the synthesis of microgel particles with dimensions of 1-30 pm. In these methods, microfluidic devices are used that provide emulsification of polymer solutions followed by physical [27, 28] or chemical [29] crosslinking. 

Besides the synthesis of bulk polymers, microreactor technology is also used for more specialized polymerization applications such as the formation of polymer membranes or particles [119, 141-146] Bouqey et al. [142] synthesized monodisperse and size-controlled polymer particles from emulsions polymerization under UV irradiation in a microfluidic system. By incorporating a functional comonomer, polymer microparticles bearing reactive groups on their surface were obtained, which could be linked together to form polymer beads necklaces. The ability to confine and position the boundary between immiscible liquids inside microchannels was utilized by Beebe and coworkers [145] and Kitamori and coworkers [146] for the fabrication of semipermeable polyamide membranes in a microfluidic chip via interfacial polycondensation. 

In an attempt to use PG microgels as scaffolds for the synthesis of ceU-laden microparticles, Steinhilber et al. [29] applied the microfluidic approach to fabricate miaogels that were highly loaded with yeast cells. The polymer matrix allowed the cells to metabolize so that a good percentage of the cells stayed alive for more than 12h after the particle formation. 

In a continuous flow system, reactions are performed at steady state, which makes it possible to achieve better control and reproducibility. Furthermore, the ability to manipulate reactant concentrations in both space and time also provides a high level of reaction control than that of bulk stirred reactors. The spatial and temporal controls of chemical reactions in microfluidic devices are useful to control and alter chemical reactivity according to the prefiminary design. And usually multistep synthesis can produce particles with fairly complex shapes and functionalities. However, the coalescence between droplets, the stability of flows after several times of mixing, and the controllability of the fluid by multistep stiU remain to be improved. 

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