CAREER: Integrated Microfluidic Systems for Scalable Manufacturing of Hybrid Nanoparticles for Drug Delivery

该学院早期职业发展（Career）奖为研究和开发新型集成微流体系统提供资金，用于制造具有控制物理化学性质的治疗和诊断或治疗性纳米颗粒，用于精确释放药物。治疗学从实验室到床边转化的低成功率主要是由于批量到批量的大差异和大规模生产中纳米颗粒特性的低可重复性。该奖项支持并行微流体系统的设计和开发的基础研究，并与高精度反馈控制集成，使纳米颗粒制造平台坚固可靠。成功的大规模、可控的微流控合成多组分纳米颗粒将有可能提高广泛治疗性纳米颗粒临床转化的成功率，特别是增强各种复杂纳米材料的制造能力。此外，可并行微流控系统有助于高性能计算应用于各种制造操作的最新进展，包括用于快速产品生成的可重构操作。这项研究将有助于对未被充分代表的少数民族的跨学科教育，他们是未来几代在机械/生物医学/化学工程、化学和材料科学等多学科领域的科学家和工程师。具体来说，该奖项将开发涉及纳米技术、微流体、控制理论和制造的STEM课程。虽然大量的研究已经揭示了几种微流控平台中的纳米颗粒合成机制，但对于如何应用或扩展这些机制，以利用集成的微流控配置实现多组分或混合治疗纳米颗粒的大规模生产，人们知之甚少。研究小组将设计一个微涡反应器系统，以最大限度地提高单反应器的吞吐量，开发一个微涡反应器的并行阵列平台，以进一步提高吞吐量的数量级，并建立一个强大的治疗纳米颗粒生产线，高精度反馈控制，以解决生产过程中的扰动。微涡旋过程使纳米颗粒前体在比化学链形成的特征时间短的时间内进行强混合，从而导致稳定的组装动力学和均匀纳米颗粒的生产。互补迭代方法包括前驱体混合时间和效率的理论建模、计算流体动力学模拟以及实验合成和表征，将增强对微和毫米尺度下高度控制流动条件下多组分纳米颗粒自组装机制的理解。这项研究将影响各个科学领域的基础科学，因为纳米粒子在生命科学、健康和能源领域的广泛应用中涉及无数的物理和化学过程。

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.