(357s) Microfluidic Devices for Pharmaceutical Development: Lipid-Based Drug Production & Target-Directed Ligand Screening | AIChE

(357s) Microfluidic Devices for Pharmaceutical Development: Lipid-Based Drug Production & Target-Directed Ligand Screening

Authors 

Lin, W. Z. - Presenter, University of Southern California
Malmstadt, N., University of Southern California
Microfluidics technology processes fluids that are geometrically constrained within a micrometer-scaled channel, typically within 10-900 µm. The distinct behavior of fluids at this scale allows precise control of small volumes of fluids and convenient manipulation of fluid interfaces. The well-controlled microscale mixing has been adopted for nanodrug fabrication, such as the recent messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aside from the enhanced mixing, unique advantages of microfluidics include reduced material consumption, precise fluidic control, and compatibility with fluidic control systems for automation. These qualities are particularly appealing for pharmaceutical development due to the inherently sophisticated biochemical procedures that often deplete precious analytical samples. This presentation summarizes my work on developing microfluidics devices for biopharmaceutical applications, including lipid-based nanodrug production and a continuous-flow ligand screening device for high-throughput cancer drug discovery and development.

Lipid nanoparticles encapsulating mRNA were produced at high throughput using a 3D microfluidic mixer. The 3D microscale mixing produces nanodrugs with low polydispersity and high nucleic acids encapsulation efficiency. For liposomes production, a microfluidic hydrodynamic flow focusing device was developed. The device enables one-step production of hydrophobic and hydrophilic drug-loaded liposomes with precise control over particle size and drug encapsulation efficiencies. For target-directed ligand screening, a 3D-printed microfluidic enrichment device was developed for affinity peptide selection using mRNA display technology. The device utilizes continuous flow to enable flow-based kinetic off-rate selections, achieving a 4-fold improvement in enrichment compared to standard selection for affinity reagents.

Through my PhD, I am skilled at microfluidics design and fabrication (3D printing, soft lithography, computer-aided design, COMSOL), process automation (Python, MATLAB, microcontrollers, process control, design of experiment), and nanoparticles characterization (cryogenic electron microscopy, transmission electron microscopy, dynamic light scattering, nanoparticle tracking analysis, fluorescence-based assay), and fundamental in-vitro biochemical reactions (PCR, DNA transcription, mRNA translation, and more). I am passionate about delivering better diagnosis and treatment tools using creative and feasible solutions.

Research Interests: microfluidics, nanomedicine, drug discovery, nanotechnology

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