All-aqueous water-in-water droplet microfluidics

拟议研究的性质：产生被油包围的水滴(所谓的油包水液滴)的微流控系统已经使用了十多年来产生单分散液滴，并实现了诸如药物颗粒合成、单细胞分析和细胞递送等重要应用。然而，油包水液滴在生物应用中面临的一个根本挑战是，由于油相的毒性，需要对液滴进行广泛的后处理，这使得无油、生物兼容的液滴微流控技术变得非常必要。一种用于无油液滴微流体的替代流体系统是双水相系统(ATPS)，它是由于至少两种不相容的聚合物溶液的高浓度混合而形成的。ATPS中的两种水基液体被界面分开，类似于水和油之间的界面，尽管界面张力要低得多。2016年，我的团队首次展示了在微流体中被动产生水中的水滴可以通过使用微弱的静水压力作为驱动力来实现，并且这种微流体中的水中的水滴可以用来在全生物兼容的环境中包裹和可控地释放细胞。这些结果使得一种新的微流控平台得以实现，该平台利用水中的水而不是油中的水液滴用于生物技术应用。NSERC的这一发现计划通过1)增加功能、2)改进性能和3)实现生物应用来推进水中水滴微流控平台。具体地说，该计划致力于增加按含量分选水中水的功能，并实现水中水中水的双重乳化。此外，该计划将重点放在液滴生成能力的数量级改进上，以帮助实现该技术的临床应用。最后，该项目正在开发水中水滴，用于药物输送和体内细胞相分离过程的体外建模。预期结果：由这笔赠款支持的研究正在扩展我的团队近年来帮助发起的水中水滴微流体的新兴范例。成熟后，这一水滴微流控平台将改变生物技术应用，例如全生物兼容的药物输送颗粒形成，以及用于细胞治疗的细胞封装，从而改善健康结果，并推动加拿大的生物技术产业。我们解决的基本流体力学问题将对微流体社区产生深远的影响。接受该计划培训的高素质人员(HQP)将在芯片实验室设备设计和开发方面拥有独特的技能，使他们适合加拿大生物技术行业的许多职业道路。

Nature of Proposed Research: Microfluidic systems that generate droplets of water surrounded by oil (so-called, water-in-oil droplets) have been used for more than a decade to produce monodisperse droplets, and realize important applications such as drug particle synthesis, single cell analysis, and cellular delivery. However, one of the fundamental challenges associated with water-in-oil droplets in biological applications is the need for extensive post-processing of the droplets due to the toxicity of the oil phase, which makes an oil-free, biocompatible droplet microfluidic technology highly desirable. An alternative fluid system for oil-free droplet microfluidics is an aqueous two-phase system (ATPS), which forms due to the mixture of high concentrations of at least two incompatible polymer solutions. The two water-based liquids in an ATPS are separated by an interface, similar to that observed between water and oil, albeit with much lower interfacial tension. My group showed for the first time, in 2016, that passively generating water-in-water droplets in microfluidics is achievable by using weak hydrostatic pressure as the driving force, and that such water-in-water droplets in microfluidics can be used to both encapsulate and controllably release cells in an all-biocompatible environment. These results enabled a new microfluidic platform that utilizes water-in-water as opposed to water-in-oil droplets for biotechnological applications. This NSERC Discovery program is advancing the water-in-water droplet microfluidics platform by 1) increasing functionality, 2) improving performance, and 3) realizing bio-applications. Specifically, this program is working towards adding the functionalities of water-in-water droplet sorting by content, and achieving double-emulsions of water-in-water-in-water droplets. Furthermore, this program is focusing on orders-of-magnitude improvements in droplet generation throughput, to help realize clinical applications of the technology. Finally, this program is developing the water-in-water droplets for applications in drug delivery and in vitro modeling of in vivo cellular phase separation processes. Anticipated Outcomes: The research supported by this grant is expanding the emerging paradigm of water-in-water droplet microfluidics that my group helped initiate in recent years. Upon maturation, this water-in-water droplet microfluidics platform will transform biotechnological applications, such as all-biocompatible drug delivery particle formation, and cellular encapsulation for cellular therapy, leading to improved health outcomes, and advancing the biotechnology industry in Canada. The fundamental fluid mechanics questions that we address will profoundly impact the microfluidics community. Highly qualified personnel (HQP) trained in this program will possess a unique skillset in lab-on-a-chip device design and development that makes them suitable for many career paths in Canada's biotechnology sector.