Microfluidic Fabrication of Compartmentalized Hydrogel Microparticles By Extractive Gelation

For successful application of compartmentalized microparticles in the therapeutic treatment several requirements have to be met, the size of the microparticles is definitely one of them.
Therefore this work is focusing on the reduction of a characteristic dimension of the composite hydrogel microparticles to that of the red blood cells.

In the present work, compartmentalized microparticles were synthesized from a calcium alginate gel matrix and contain several functional components, namely iron oxide nanoparticles for radiofrequency heating and MRI visualisation, liposomes for the storage and release of active molecules of their precursors. Liposomes are spherical structures formed by a phospholipid bilayer, which are able to release the active matter in response to temperature. The permeability of liposomes can be significantly increased once they are heated above its phase transition temperature. The needed temperature change is achieved by iron oxide nanoparticles upon exposure to external radio-frequency magnetic field.

Monodisperse microparticles were prepared by an extractive gelation process on a microfluidic chip. First, droplets of aqueous solution of alginate in the continuous oil phase are formed in a flow-focusing channel. Second, gelation of the droplets is established in a long wavy channel by diffusion of calcium ions from the continuous phase. At the same time, the volume of the droplets is reduced by partial extraction of water into the continuous phase. Depending on the volumetric flow-rates of the aqueous and the oil phase, different conditions of the production were mapped and the effect of extraction on the achievable size of the microparticles was evaluated. The ideal conditions to produce monodisperse microparticles and to encapsulate iron oxide nanoparticles and liposomes were found. The stability of liposome in the alginate microparticles was investigated and the remotely triggered released experiments were conducted. The possibilities to scale up the microfluidic chip, where the particles are synthesized one by one, to device with higher throughput was also investigated.