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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=666370
• 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 NPs–cell 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.**

使用纳米颗粒进行治疗和成像在再生医学和纳米医学领域具有巨大的前景，但是，它们向临床的转化进展缓慢，因为仍然难以生产“批次间”一致且数量充足的纳米颗粒用于临床。此外，仍然缺乏快速筛选纳米颗粒的平台，因此需要改进的制备方法，以产生具有均匀尺寸、几何形状和化学计量的高质量纳米颗粒。微流体和芯片实验室技术领域现在为实施纳米材料生产工艺提供了独特的机会，与传统的间歇式反应器相比，它们具有一系列优势，包括提高纳米材料特性的可控性和均匀性以及高通量生产。它们还允许生物活性分子（药物、蛋白质、基因、酶等）的一步加载，无论其化学、亲水或疏水性质如何。此外，在微通道内实现快速混合以及可预测性。可以利用层流条件来研究纳米材料的形成动力学，利用我们在纳米颗粒药物输送和成像系统开发方面取得的成就，以及我们在微流体 (MF) 设备制造方面获得的专业知识，这是我们研究的总体目标。用于传输和成像的纳米颗粒的目标是开发高度微流体的平台，用于“一步”合成和制备复杂且可调的多功能纳米系统，同时在同一平台上研究细胞-纳米颗粒的相互作用。特别关注 1) MF 辅助的基于壳聚糖的 NP 的 LbL 自组装，2) MF 辅助的混合和高效脂质 NP 的合成，3) 用于合成尺寸可调的多组分聚合物脂质 NP 的 MF 芯片和 4) MF 辅助合成多功能 Janus NP，全部用于控释和体外成像 为了实现这一目标，该提案的子目标是： -) 分别通过模拟和使用先进的微加工技术，根据特定纳米粒子的所需特性设计和制造高度创新的 3D 多层纳米粒子平台； -) 纳米粒子的物理化学和生物表征； -) 研究 MF 辅助的 NPs-细胞相互作用作为 NPs 特性的函数，并对其预期用途进行概念验证研究。如果在这一研究领域持续努力，纳米粒子可以通过高通量生物测定和治疗递送来解决早期疾病监测中的多个普遍问题。**