Rapid and Highly Controlled Generation of Multiple Emulsions via a Hybrid Microfluidic Device
Date
2022-01
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Abstract
Multiple Emulsions (MEs) consist of droplets containing one or more microdroplets. Microfluidic approaches have been used to create monodisperse MEs in both a rapid and controlled manner. To generate monodisperse ME constructs, the design relies on the interaction between immiscible fluids in subsequent droplet formation steps. The microfluidic chip used to create the MEs consists of three liquid phases flowing through two subsequent compartments, each with a T-junction and a cross-junction. Creating high shear stress at the cross-junctions induces instability of liquid flow at the first junction, which splits the first immiscible phase into micrometer droplets surrounded by the second phase. The resulting structure is then supported by the third phase at the T-junction to generate and transport MEs. In this work, the ME formation within microfluidic chips is experimentally investigated and numerically simulated. Several critical parameters are examined concerning their effects on the physical properties of MEs. Dimensionless modelling is exploited to enable the change of one parameter at a time while assessing the system's sensitivity to that parameter. Following the optimization of ME formation, highly controlled and high-throughput MEs are formed within the microfluidic chips. It is shown that the consecutive MEs are monodisperse in size, allowing for the generation of controlled MEs for various applications, including bacterial and cell culture. Furthermore, polydimethylsiloxane (PDMS) microchannels are fabricated using conventional soft lithography techniques and coated with Tetraethyl Orthosilicate (TEOS) and Ethylamine (EA) to form a nanometer silicon oxide layer inside the microchannels. TEOS coated PDMS chips provide several advantages over bare PDMS chips. The first benefit of the TEOS coating is the prevention of fluid absorption by the PDMS bulk, which is a major challenge for long-term culture of cells in PDMS microchannels. Using the TEOS coating, bacteria successfully grow for several hours inside nanoliter-sized droplets in a controlled microenvironment, wherein the TEOS coating prevents droplets from being absorbed by the PDMS. Further engineering of this coating makes it a switchable coating, where its hydrophilic properties change to hydrophobic upon exposure to the ambient air. This feature provides selective hydrophobicity and hydrophilicity conditions and allows for the formation of diverse double and multiple emulsions. The hydrophilic property of the coating is further used for cell culture. As a proof-of-concept, MCF7 breast cancer cells and endothelium cells are cultured on the TEOS-coated PDMS chips, enabling further high-throughput drug screening on MEs containing multiple cell types and drugs.
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Keywords
Computational Fluid Dynamics, Multiphase flow, Droplet microfluidics, Bacteria culture in droplet, Surface modification of PDMS, Cell culture in microfluidics, Multiple emulsion, Double emulsion, Passive microinjection, Electrohydrodynamics for droplet formation
Citation
Azarmanesh, M. (2022). Rapid and highly controlled generation of Multiple Emulsions via a hybrid microfluidic device (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.