Continuous Flow Microfluidic Devices for High-Throughput Synthesis and Formulation of Multifunctional Nano-systems for Enhanced Drug Targeting and Imaging

用于高通量合成和配制用于增强药物靶向和成像的多功能纳米系统的连续流微流体装置

• 批准号: RGPIN-2016-05785
• 负责人: Tabrizian, Maryam
• 金额: $ 3.13万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709868
• 关键词: Continuous; Flow; Microfluidic; Devices; Throughput

The use of nanoparticles for therapy and imaging holds tremendous promise in regenerative medicine and nanomedicine. However, their translation into the clinic has been slow because it remains difficult to produce nanoparticles that are consistent 'batch-to-batch' and in sufficient quantities for clinical research. Moreover, platforms for rapid screening of nanoparticles are still lacking. Therefore, there is a need for improved preparation methods that are capable of yielding high quality nanoparticles of uniform size, geometry and stoichiometry. Advancements in the fields of microfluidic and lab-on-a-chip technologies now provide unique opportunities for the implementation of nanomaterial production processes. They offer a range of advantages compared to conventional batch reactors, including improved controllability and uniformity of nanomaterial characteristics and high throughput production. They also allow for one-step loading of biologically active molecules (drugs, proteins, genes, enzymes, etc.), independent of their chemical, hydrophilic or hydrophobic nature. In addition, fast mixing achieved within microchannels and the predictability of laminar flow conditions can be leveraged to investigate nanomaterial formation dynamics. To take advantage of our achievements in the development of nanoparticle drug delivery and imaging systems, and our acquired expertise in the fabrication of microfluidic (MF) devices, the overarching goal of our research in nanoparticle for delivery and imaging is to develop microfluidic platforms for “one-step” synthesis and preparation of highly complex and tuned multifunctional nanosystems while investigating cell-nanoparticle interactions on the same platform. During this 5 year discovery proposal, we particularly focus on 1) MF-assisted LbL self-assembly of chitosan-based NPs, 2) MF-assisted synthesis of hybrid and highly potent lipid NPs, 3) MF chip for synthesis of size-tunable multicomponent polymeric-lipid NPs and 4) MF-assisted synthesis of multi-featured Janus NPs, all for controlled release and in vitro imaging. To reach this goal, the sub-objectives of this proposal are: -) Design and fabrication of highly innovative 3D multilayer MF platform according to the required features for the specific NPs through simulation and using advanced microfabrication technology respectively; -) MF-assisted synthesis of aforementioned NPs; -) Physicochemical and biological characterization of NPs; and -) Investigation of MF-assisted NPscell interactions as a function of NPs characteristics and proof-of-concept study towards their intended use. We believe that microfluidic-enabled multifunctional nanoparticles could resolve multiple, prevalent issues in disease monitoring at an early stage with high-throughput bioassays and therapeutic delivery if persistent effort is devoted to this field of research.

纳米颗粒用于治疗和成像是再生医学和纳米医学的巨大希望。但是，它们转化为诊所的速度很慢，因为生产纳米颗粒仍然很难，这些纳米颗粒是一致的“批次到批次”，并且足够数量的临床研究。此外，仍缺乏快速筛查纳米颗粒的平台。因此，需要改进的制备方法，能够产生均匀尺寸，几何学和化学计量的高质量纳米颗粒。现在，微流体和实验室芯片技术领域的进步为实施纳米材料生产过程提供了独特的机会。与传统的批处理反应堆相比，它们具有一系列优势，包括提高纳米材料特征的可控性和均匀性和高吞吐量产生。它们还允许对生物活性分子（药物，蛋白质，基因，酶等）进行一步加载，与它们的化学，亲水性或疏水性无关。此外，可以利用微通道内实现的快速混合以及层流条件的可预测性来研究纳米材料形成动力学。要利用我们在纳米颗粒药物传递和成像系统开发中的成就，以及我们在制造微流体（MF）设备方面获得的专业知识，我们在纳米颗粒中进行研究的总体目标是为交付和成像进行研究，以开发“一步和调查的nnan nen”，以开发微流体的平台，并调查了nan的综合和调整的nan，同一平台。 During this 5 year discovery proposal, we particularly focus on 1) MF-assisted LbL self-assembly of chitosan-based NPs, 2) MF-assisted synthesis of hybrid and highly potential lipid NPs, 3) MF chip for synthesis of size-tunable multicomponent polymeric-lipid NPs and 4) MF-assisted synthesis of multi-featured Janus NPs, all for controlled release and in体外成像。为了实现这一目标，该提案的子目标是： - ）根据特定NP的所需功能，分别使用模拟并使用先进的微型制作技术，根据特定NP的所需功能设计和制造高度创新的3D多层MF平台； - ）MF辅助的综合NP； - ）NP的理化和生物学表征；和 - ）对MF辅助的NPSCEL相互作用的研究是NPS特征和概念验证研究的函数。我们认为，如果持续的努力致力于这一研究领域，则可以在早期的早期阶段，在早期阶段，在早期阶段，在早期阶段，在早期疾病监测中进行多个普遍的疾病监测问题，可以解决多个普遍的疾病监测问题。