SUMMARY

A wide range of nanoparticles (NPs) have been developed with the potential to revolutionize therapeutics and diagnostics through targeted delivery of drugs, genes, and selective combination of imaging agents to specific cells. The expanding field of microfluidics has been utilized in the development of NPs, and developed as a platform to accelerate the translation of nanomedicines. Microfluidic approaches facilitate the micro- and nano- scale interactions of precursor components to produce NPs more reproducibly than conventional bulk synthesis approaches. Many microfluidic approaches have been developed over the last decade; however, these microfluidics-based NP syntheses have been largely limited to small-scale production of specific single component NPs. There is not a reliable and practical approach available for scalable manufacturing of multicomponent and multifunctional NPs to industrially relevant level (~kg/h or even higher as needed).
To address the challenge of nanomanufacturing, this proposal focuses on the development of a microvortex reactor (MVR) for NP synthesis and optimized for lipid-polymer nanoparticles (LPNPs). A plurality of MVR will be parallelized by minimizing identified key parameters of MVR LPNP synthesis optimization, to maintain NP quality on a manufacturing scale. The development of a high precision, high-throughput, and long-term feedback pressure control system microfluidic inlet pressure control, mitigating internal and external disturbances, for robust NP manufacturing. Finally, to improve the versatility and accessibility of the parallelized microvortex array, a multi-layer parallelized microfluidic device is proposed allowing for interchangeable parallelized arrays. These approaches will impact the field of nanomedicine by enabling robust NP manufacturing and accelerating the clinical translation.