Advanced reagent delivery systems for microfluidics

微流体技术之于化学和生命科学，就像微电子技术之于信息科学。通过在微观结构中操纵微小的流体等分试样，它扩大了生化分析的可能性，同时减少了试剂消耗、分析时间、设备尺寸、用户操作和总成本。在这一领域的进展一直与合理化的新的物理，化学和生物现象在微观尺度上观察到新的微流体“模块”的设计规则，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，微流体技术也面临着一些限制，这些限制减缓了其在主流医疗保健中的采用。首先，在即时诊断中，将试剂集成到芯片中以进行长期存储，并找到简单的方法来精确地重建它们是一个持续的挑战。其次，微流体通道与生物研究的工业标准（孔板和培养皿）的接口很差。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、免疫学和治疗随访的大规模组织分析不兼容。在运输方面，所有这些缺点都是单一挑战的不同方面：将试剂有效地输送到生物活性表面。 我的研究专长和兴趣是在基础流体物理学，传输理论，生物工程和先进的微制造之间的接口。在这个建议中，我们应用它来攻击试剂输送的挑战，在许多角度。更具体地说，我们将使用我们以前开发的理论框架来研究开放的2D微流体系统中的运输，以开发和利用使用平面流场而不是微通道运输试剂的全新微系统。我们小组最近引入的两个新的微流体概念，微流体多极和自聚结流动模块，将被扩展应用于研究信号通路中的快速动态瞬变，将组织暴露于多种精确的药物负载以研究药物反应机制，并在POC测试中产生不可克隆的安全功能以防止欺诈和伪造。一直以来，我们将加强我们的平面二维流动的知识，并开发新的传输模型，同时描述对流，扩散和反应在平面流动和多孔基质。这个多学科的研究计划将提供至少5个不同的高素质的人在运输科学，数学建模，过程工程和生物学之间的接口抢手的技能。所发现的解决方案将有助于微流体技术扩展到新兴市场，如自动液体处理、精密肿瘤学和医疗保健防伪，以期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.