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

职业：用于药物输送的混合纳米粒子的可扩展制造的集成微流体系统

• 批准号: 1653006
• 负责人: YongTae Kim
• 金额: $ 50万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1653006&HistoricalAwards=false
• 关键词: CAREER; Integrated; Microfluidic; Systems; Scalable

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.

这项教师早期职业发展（职业）奖为研究和开发新型集成的微流体系统，用于制造具有控制的物理化学特性的治疗和诊断或治疗性纳米颗粒，用于精确释放药物提供药物递送。固定剂的卧床平移的成功率低主要是由于大量批处理变化和纳米颗粒性能在扩展生产中的可重复性较低。该奖项支持平行化微流体系统的设计和开发的基本研究，并与高精度反馈控制的集成，从而使纳米颗粒制造平台能够强大而可靠。一般而言，成功的大型，受控的多组分纳米颗粒的微流体合成将有可能提高广泛溶剂纳米颗粒的临床翻译中的成功率，并提高各种复杂纳米材料的制造能力。此外，可行的微流体系统在将高性能计算应用于各种制造运营（包括可用于快速产品生成的可重新配置运营）方面取得了最新进展。这项研究将促进代表性不足的少数群体的跨学科教育，这些教育是未来的科学家和工程师在机械/生物医学/化学工程以及化学和化学和材料科学领域的多个学科的领域。 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.研究团队将设计一个微vortex反应器系统，以最大化基于单个反应器的吞吐量，开发一个并行的MicroVortex反应器阵列平台，以通过数量级进一步增加吞吐量，并在生产过程中建立具有高级反馈控制的强大制造线，并建立具有高级反馈控制的强大制造线。微效应过程可以使纳米颗粒前体的强烈混合在一个比化学链形成的特征时间短的时间尺度内，从而导致稳定的组装动力学和同质纳米颗粒的产生。互补的迭代方法包括关于前体混合时间和效率，计算流体动力学模拟以及实验综合和表征的理论模型，将增强对高度控制的多组分纳米粒子自组装机制在高度控制的流动条件下的理解。这项研究将影响各种科学领域的基础科学，因为纳米颗粒涉及跨越生命科学，健康和能量的广泛应用中的无数物理和化学过程。

项目成果

High-precision microfluidic pressure control through modulation of dual fluidic resistances

• DOI: 10.1007/s40435-017-0378-7
• 发表时间: 2018-09
• 期刊: International Journal of Dynamics and Control
• 作者: Michael J. Toth;T. Kawahara;YongTae Kim

Microfluidics in nanoparticle drug delivery; From synthesis to pre-clinical screening

• DOI: 10.1016/j.addr.2018.04.001
• 发表时间: 2018-03-15
• 期刊: ADVANCED DRUG DELIVERY REVIEWS
• 影响因子: 16.1
• 作者: Ahn, Jungho;Ko, Jihoon;Jeon, Noo Li
• 通讯作者: Jeon, Noo Li