Advanced reagent delivery systems for microfluidics

微流体学之于化学和生命科学，犹如微电子学之于信息科学。通过在微观结构中操作微小的等分流体，它扩展了生化分析的可能性领域，同时减少了试剂消耗、分析时间、设备尺寸、用户操作和总体成本。这一领域的进展一直与在微观尺度上观察到的新的物理、化学和生物现象的合理化联系在一起，这些现象被设计成新的微流体“模块”，可以执行新的“单元操作”，以解决生物学、化学和生命科学中的关键问题。然而，微流体也面临着一些限制，这些限制减缓了它在主流医疗保健领域的应用。首先，在即时诊断中，将试剂集成到芯片中以进行长期存储，并找到简单的方法精确地重组它们是一项持续的挑战。其次，微流体通道与生物研究的工业标准：孔板和培养皿的界面很差。最后，在个性化医疗中，基于芯片的解决方案通常与用于诊断、预后和治疗随访的大规模组织分析不兼容。在运输方面，所有这些缺点都是一个挑战的不同方面：将试剂有效地运送到生物活性表面。

Microfluidics is to chemistry and the life sciences what microelectronics is to information science. By manipulating tiny aliquots of fluids in microstructures, it has expanded the realm of possibilities for biochemical analyses, all the while reducing reagent consumption, analysis times, device size, user manipulations, and overall costs. Progress in this field has always been linked to the rationalization of new physical, chemical and biological phenomena observed at the microscale into design rules for new microfluidics “modules” that can perform new “unit operations” to solve critical problems in biology, chemistry, and the life sciences. Yet, microfluidics also faces several limitations that have slowed down its adoption in mainstream healthcare. First, in point-of-care diagnostics, integrating reagents into chips for long time storage, and finding simple ways to reconstitute them precisely is an on-going challenge. Secondly, microfluidic channels interface poorly with the industrial standards of biological research: the well plate, and the petri dish. Finally, in personalized medicine, chip-based solutions are not typically compatible with large scale tissue analysis for diagnostics, prognostics, and treatment follow-up. In transport terms, all these shortcomings are the different facets of a single challenge: to deliver reagents effectively to biologically-active surfaces. My research expertise and interests are set at the interface between fundamental fluid physics, transport theory, bioengineering, and advanced micromanufacturing. In this proposal, we apply it to attack the reagent delivery challenge under many angles. More specifically, we will use our previously developed theoretical framework to study transport in open 2D microfluidic systems to develop and exploit fundamentally new microsystems that transport reagents using planar flow fields rather than microchannels. Two new microfluidic concepts recently introduced by our group, microfluidic multipoles and self-coalescence flow modules, will be expanded an applied to study fast dynamic transients in signalling pathways, to expose tissue to multiple precise drug loads to study drug response mechanisms, and to generate unclonable security features in POC tests to prevent fraud and counterfeiting. All the while, we will strengthen our knowledge of planar 2D flow and develop new transport models to describe simultaneously convection, diffusion and reaction in both planar flows and porous matrices. This multidisciplinary research programme will provide at least 5 different highly qualified people with sought-after skills at the interface between transport-science, mathematical modelling, process engineering, and biology. The solutions found will help microfluidics expand into new emerging markets, such as automated liquid handling, precision oncology, and healthcare anticounterfeiting, in the hope of improving health care and quality of life for all Canadians.