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）的微流体系统已经被用于产生单分散液滴超过十年，并且实现了重要的应用，例如药物颗粒合成、单细胞分析和细胞递送。然而，在生物应用中与油包水液滴相关的基本挑战之一是由于油相的毒性而需要对液滴进行大量的后处理，这使得无油的生物相容性液滴微流体技术非常理想。用于无油液滴微流体的替代流体系统是水性两相系统（ATPS），其由于高浓度的至少两种不相容的聚合物溶液的混合物而形成。ATPS中的两种水基液体被界面分开，类似于水和油之间观察到的界面，尽管界面张力低得多。我的团队在2016年首次证明，通过使用弱静水压力作为驱动力，可以在微流体中被动产生水包水滴，并且微流体中的这种水包水滴可以用于在全生物相容性环境中封装和可控释放细胞。这些结果使得一种新的微流体平台成为可能，该平台利用水包水而不是油包水液滴用于生物技术应用。这个NSERC发现计划正在通过1）增加功能，2）提高性能和3）实现生物应用来推进水包水滴微流体平台。具体而言，该计划正在努力增加水包水滴按内容物分类的功能，并实现水包水包水滴的双重乳液。此外，该计划专注于液滴生成吞吐量的数量级改进，以帮助实现该技术的临床应用。最后，该项目正在开发水包水液滴，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：这项资助支持的研究正在扩展我的团队近年来帮助发起的水包水微流体的新兴范式。成熟后，这种水包水滴微流体平台将改变生物技术应用，例如全生物相容性药物递送颗粒形成和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深刻影响微流体社区。在该计划中接受培训的高素质人员（HQP）将拥有芯片实验室设备设计和开发方面的独特技能，这使他们适合加拿大生物技术领域的许多职业道路。

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.