Biosensing for organ-on-a-chip platforms

组织工程和微流体技术的最新进展使得“芯片上的器官”平台能够比传统的培养皿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台开发工程组织方面具有很大的前景。尽管具有巨大的潜力，但芯片上器官和微流体细胞培养平台的一个持续的局限性是它们依赖于人工的、芯片外的分析方法，这造成了分析瓶颈，限制了这些平台的价值。集成片上传感可以实现更高通量和更高含量的分析，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控设备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上，主要是因为涉及到工程挑战。******在这里，我们提出了一个研究计划，通过利用我们新的微流体和微组织技术来设计具有片上生物传感能力的器官芯片平台，直接解决这些限制。为此，我们研究了生物运输和生物传感的基本方面，以便在动态微流体环境中进行生物分子检测；开发灵敏的片上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健壮的组织。这些知识将被应用于生成新的器官芯片模型，用于监测血脑屏障的运输；用于在芯片上测量心肌收缩；以及优化机械刺激工程组织的方案。******在这个研究项目中训练的研究生和本科生将配备所需的科学和专业技能，以应用他们的研究产生的长期影响的知识，并在未来在生物传感，生物微流体和生物技术方面领导大胆的新举措

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.**