In vitro biomimetic microfluidic models for toxicology studies

脂质双分子层是复杂而普遍存在的实体，调节细胞环境中的基本过程。特别是，脂质双分子层的复杂性以及它们如何介导药物和分子进入细胞的运输是生物学中一个重要的未解决问题，这对药物发现具有破坏性的影响。***化学和生物系统的小型化是自然科学领域最近出现的一个令人兴奋的趋势，它提供了许多优势，如提高分析通量，减少样本量和加强对实验参数的控制。特别是微流控平台，其技术被设计用于在微尺度上操纵流体，使得使用与真实细胞相当的体积和尺度的人工细胞型系统得以发展。***我的研究计划的目的是开发微型的自下而上的方法来形成仿生脂质双层，允许分析它们之间的运输并研究它们的性质。这些平台将允许完全控制双层系统的每个组件，从脂质组成到双层大小和结构。这个研究项目将利用微流体装置的力量来回答有关双层传输机制的基本问题。为了确保微流控技术在这些问题上的应用对制药行业开发新药的方式产生持久的影响，从一开始，这个研究项目将通过与领域专家的合作来了解行业的需求，以便所有的发展都有可能在制药环境中使用。因此，需要开发一系列模块，例如片上生物传感器，仿生脂质配方和使用允许批量生产的材料的微流控平台。这个研究项目的多学科性质对参与的研究人员有很多好处。他们将接受各种广泛应用的技术（如微流体装置的设计和制造）的培训，将善于解决各种科学研究领域（如分析化学、生物学和工程学）的问题，并将从与学术专家和行业联系的合作中受益。

Lipid bilayers are complex and ubiquitous entities that regulate fundamental processes within cellular environments. In particular, the complexity of lipid bilayers and how they mediate the transport of drugs and molecules into cells is an essential unsolved problem in biology, which has damaging ramifications for drug discovery. ***The miniaturisation of chemical and biological systems is a recent, but exciting trend in the natural sciences, providing a host of advantages such as enhanced analytical throughput, reduced sample sizes and heightened control over experimental parameters. Microfluidic platforms in particular, where the technology is designed to manipulate fluids on the microscale, have allowed the development of artificial cell-type systems using volumes and scales that are comparable to real cells.***The aim of my research program is to develop miniaturised bottom-up methods for the formation of biomimetic lipid bilayers that allow the analysis of transport across them and enable the study of their properties. These platforms will allow complete control over each component of a bilayer system, from lipid composition to bilayer size and architecture. ***This research program will harness the power of microfluidic devices to answer fundamental questions regarding the mechanism of bilayer transport. To ensure that the application of microfluidic technologies to these problems has a lasting effect on the way that the pharmaceutical industry develops new drugs, from the start, this research program will be informed by the needs of industry through collaborations with domain specialists so that all developments have the potential to be used in pharmaceutical environments. As such, there are a series of modules that need to be developed, such as on-chip biosensors, biomimetic lipid formulations, and microfluidic platforms using materials that allow mass-production.***The multidisciplinary nature of this research program has numerous advantages for the researchers involved. They will be trained in a variety of widely applicable techniques (such as microfluidic device design and fabrication), will become adept at problem solving in a variety of scientific research fields (such as analytical chemistry, biology and engineering) and will benefit from collaborations both with academic experts and industry contacts.