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.

该学院早期职业发展（职业）奖为研究和开发新型集成微流体系统提供资金，用于制造具有受控物理化学性质的治疗和诊断或治疗诊断纳米颗粒，用于精确释放药物输送应用。治疗诊断学从实验室到床边转化的成功率较低，主要是由于批量生产中批次间差异较大以及纳米颗粒特性的再现性较低。该奖项支持并行微流体系统的设计和开发以及与高精度反馈控制集成的基础研究，从而实现稳健可靠的纳米颗粒制造平台。成功的大规模、受控微流体合成多组分纳米颗粒将有可能提高各种治疗诊断纳米颗粒的临床转化成功率，特别是，并总体上增强各种复杂纳米材料的制造能力。此外，可并行微流体系统有助于在各种制造操作中应用高性能计算的最新进展，包括用于快速产品生成的可重新配置操作。这项研究将有助于对代表性不足的少数群体进行跨学科教育，他们是机械/生物医学/化学工程以及化学和材料科学等多个学科交叉领域的未来科学家和工程师。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。虽然大量研究已经揭示了几种微流体平台中纳米粒子的合成机制，但对于如何应用或扩展这些机制来实现大规模生产却知之甚少。使用集成微流体配置的多组分或混合治疗诊断纳米颗粒。研究团队将设计一个微涡流反应器系统，以最大限度地提高基于单个反应器的吞吐量，开发微涡流反应器的并行阵列平台，以进一步将吞吐量提高几个数量级，并建立一个强大的具有高精度反馈控制的治疗诊断纳米粒子生产线，以实现解决生产过程中的干扰问题。微涡流过程能够在比化学链形成的特征时间更短的时间内强烈混合纳米颗粒前体，从而实现稳定的组装动力学和均匀纳米颗粒的生产。由前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组成的互补迭代方法将增强对微米和毫米尺度高度受控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，因为纳米颗粒参与生命科学、健康和能源等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