Advanced reagent delivery systems for microfluidics

微流体学之于化学和生命科学，就像微电子学之于信息科学。通过在微结构中操作微小的等分液体，它扩大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、化学和生物现象合理化，并纳入新的微流体“模块”的设计规则有关，这些“模块”可以执行新的“单元操作”，以解决生物、化学和生命科学中的关键问题。然而，微流控也面临着几个限制，这些限制减缓了它在主流医疗保健中的采用。首先，在医疗诊断中，将试剂集成到芯片中进行长期存储，并找到简单的方法精确重建它们是一个持续不断的挑战。其次，微流控通道与生物学研究的工业标准--井板和培养皿--的对接很差。最后，在个性化医学中，基于芯片的解决方案通常与用于诊断、预后和治疗后续治疗的大规模组织分析不兼容。在运输方面，所有这些缺点都是单一挑战的不同方面：将试剂有效地输送到具有生物活性的表面。我的研究专长和兴趣集中在基础流体物理、运输理论、生物工程和先进的微制造之间。在这个方案中，我们从多个角度应用它来应对试剂传递的挑战。更具体地说，我们将使用我们之前开发的理论框架来研究开放的2D微流控系统中的传输，以开发和从根本上开发使用平面流场而不是微通道来传输试剂的新的微系统。我们团队最近推出的两个新的微流控概念，微流控多极和自聚合流模块，将被扩展和应用于研究信号通路中的快速动态瞬变，将组织暴露在多个精确的药物负荷下以研究药物响应机制，并在POC测试中产生不可克隆的安全特征，以防止欺诈和假冒。同时，我们将加强我们对平面二维流动的了解，并发展新的输运模型来同时描述平面流动和多孔基质中的对流、扩散和反应。这一多学科的研究计划将为至少5名不同的高素质人才提供在交通科学、数学建模、过程工程和生物学之间的热门技能。找到的解决方案将帮助微流控扩展到新的新兴市场，如自动液体处理、精确肿瘤学和医疗保健防伪，希望改善所有加拿大人的医疗保健和生活质量。

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.