This Faculty Early Career Development (CAREER) award provides funding to study and develop novel integrated microfluidic systems for manufacturing of therapeutic and diagnostic or theranostic nanoparticles with controlled physicochemical properties for precision-release drug delivery applications. The low success rate in the bench to bedside translation of theranostics is mainly due to large batch-to-batch variations and low reproducibility of nanoparticle properties in scaled-up production. This award supports fundamental research for the design and development of parallelized microfluidic systems and integration with high-precision feedback control enabling a nanoparticle manufacturing platform that is robust and reliable. Successful large-scale, controlled microfluidic synthesis of multicomponent nanoparticles will have the potential to improve the success rate in the clinical translation of a broad range of theranostic nanoparticles, in particular, and enhance the manufacturing ability of various complex nanomaterials, in general. Furthermore, parallelizable microfluidic systems lend themselves to the latest advances in the application of high-performance computing for a variety of manufacturing operations, including reconfigurable operations for rapid product generation. This research will contribute to cross-disciplinary education of underrepresented minorities who are future generations of scientists and engineers in areas interfacing multiple disciplines in mechanical/biomedical/chemical engineering and chemistry and materials sciences. Specifically, the award will develop STEM courses involving nanotechnology, microfluidics, control theory and manufacturing.
While substantial research has revealed nanoparticle synthesis mechanisms in several microfluidic platforms, extremely little is known about how to apply or extend the mechanisms to achieve large-scale production of multicomponent or hybrid theranostic nanoparticles using integrated microfluidic configurations. The research team will engineer a microvortex reactor system to maximize single reactor-based throughput, develop a parallelized array platform of microvortex reactors to further increase throughput by orders of magnitude, and establish a robust manufacturing line of theranostic nanoparticles with high-precision feedback control to address perturbations during production. The microvortex process enables strong mixing of the nanoparticle precursors within a timescale that is shorter than the characteristic time for chemical chain formation, leading to stable assembly kinetics and production of homogeneous nanoparticles. Complementary iterative approaches that consist of theoretical modeling on precursor mixing time and efficiency, computational fluid dynamics simulations, and experimental synthesis and characterization will enhance the understanding of multicomponent nanoparticle self-assembly mechanisms under highly controlled flow conditions at both micro- and millimeter scales. This study will impact the basic science of various scientific fields as nanoparticles are involved in a myriad of physical and chemical processes in a wide range of applications spanning life science, health, and energy.
