In vitro biomimetic microfluidic models for toxicology studies

用于毒理学研究的体外仿生微流体模型

• 批准号: RGPIN-2017-04844
• 负责人: Elvira, Katherine
• 金额: $ 1.6万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=650156
• 关键词: vitro; biomimetic; microfluidic; models; toxicology

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.

脂质双分子层是复杂的和普遍存在的实体，调节细胞环境中的基本过程。特别是，脂质双层的复杂性以及它们如何介导药物和分子转运到细胞中是生物学中一个基本的未解决的问题，这对药物发现具有破坏性影响。*** 化学和生物系统的自动化是自然科学中最近出现的一个令人兴奋的趋势，它提供了许多优势，例如提高分析通量，减少样品量和加强对实验参数的控制。特别是微流体平台，该技术被设计为在微尺度上操纵流体，已经允许使用与真实的细胞相当的体积和规模来开发人工细胞类型系统。我的研究计划的目的是开发用于形成仿生脂质双层的自下而上的方法，该方法允许分析它们之间的运输并研究它们的特性。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。* 这项研究计划将利用微流体设备的力量来回答有关双层运输机制的基本问题。为了确保微流体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，该研究计划将通过与领域专家的合作来了解行业的需求，以便所有开发都有可能用于制药环境。因此，有一系列模块需要开发，例如芯片生物传感器，仿生脂质制剂和使用允许大规模生产的材料的微流体平台。该研究项目的多学科性质对于相关研究人员来说具有许多优势。他们将接受各种广泛适用的技术（如微流体设备设计和制造）的培训，将擅长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，并将受益于与学术专家和行业联系人的合作。