Biosensing for organ-on-a-chip platforms

器官芯片平台的生物传感

• 批准号: RGPIN-2016-06026
• 负责人: Simmons, Craig
• 金额: $ 3.86万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=710101
• 关键词: Biosensing; organ; chip; platforms

Recent advances in tissue engineering and microfluidics have enabled the creation of “organ-on-a-chip” platforms that mimic the functions of human organs and tissues better than conventional Petri dish-based cell culture systems. These technologies hold great promise for disease modeling, drug discovery, and as bioreactor test beds to develop engineered tissues. Despite their great potential, a persistent limitation of organ-on-a-chip and microfluidic cell culture platforms is that they rely on manual, off-chip analytical methods, which creates an analysis bottleneck and limits the value of these platforms. Integration of on-chip sensing could enable higher-throughput and higher-content analyses, real-time measurement of cell and tissue function, and even feedback control of dynamic culture microsystems. Strikingly, while there have been significant advances in incorporating biosensors into point-of-care microfluidic devices, biosensors have not been integrated into microtissue and organ-on-a-chip platforms largely because of the engineering challenges involved. Here, we propose a research program to directly address these limitations by leveraging our novel microfluidic and microtissues technologies to engineer organ-on-a-chip platforms with on-chip biosensing capabilities. To do so, we investigate fundamental aspects of biotransport and biosensing to enable biomolecule detection in dynamic microfluidic environments; develop sensitive on-chip strain sensors to measure cell contraction forces; and identify process control strategies to engineer mechanically robust tissues. This knowledge will be applied to generate novel organ-on-a-chip models for monitoring transport across the blood-brain-barrier; for measuring heart muscle contraction on-chip; and for optimizing protocols for mechanical stimulation of engineered tissues. The graduate and undergraduate students trained in this research program will be equipped with the scientific and professional skills required to apply the knowledge generated by their research for long-term impact and to lead bold new initiatives in biosensing, biomicrofluidics, and biotechnology in the future.

组织工程和微流体技术的最新进展使得能够创建“器官芯片”平台，其比传统的基于培养皿的细胞培养系统更好地模拟人体器官和组织的功能。这些技术在疾病建模、药物发现以及作为生物反应器试验床开发工程组织方面具有很大的前景。尽管它们具有巨大的潜力，但器官芯片和微流体细胞培养平台的持续限制是它们依赖于手动的芯片外分析方法，这造成了分析瓶颈并限制了这些平台的价值。芯片上传感的集成可以实现更高通量和更高内容的分析，实时测量细胞和组织功能，甚至动态培养微系统的反馈控制。引人注目的是，虽然在将生物传感器集成到即时微流体设备中方面取得了重大进展，但生物传感器尚未集成到微组织和器官芯片平台中，主要是因为所涉及的工程挑战。 在这里，我们提出了一个研究计划，以直接解决这些限制，利用我们的新的微流体和微组织技术，工程器官芯片平台与芯片上的生物传感能力。为此，我们研究了生物运输和生物传感的基本方面，以实现动态微流体环境中的生物分子检测;开发敏感的芯片应变传感器来测量细胞收缩力;并确定过程控制策略来设计机械坚固的组织。这些知识将被应用于生成新的器官芯片模型，用于监测跨血脑屏障的运输;用于测量芯片上的心肌收缩;以及用于优化工程组织的机械刺激方案。 在本研究计划中接受培训的研究生和本科生将具备应用其研究产生的知识以产生长期影响所需的科学和专业技能，并在未来引领生物传感，生物微流体和生物技术的大胆新举措。