Biosensing for organ-on-a-chip platforms

组织工程和微流控技术的最新进展使得“芯片上的器官”平台能够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台来开发工程组织方面大有可为。尽管芯片上器官和微流控细胞培养平台具有巨大的潜力，但它们依赖于手动的芯片外分析方法，这造成了分析瓶颈，限制了这些平台的价值。集成芯片传感可以实现更高吞吐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。值得注意的是，尽管在将生物传感器纳入护理点式微流控设备方面取得了重大进展，但生物传感器尚未被集成到微组织和芯片上的器官平台中，这主要是因为涉及的工程挑战。 在这里，我们提出了一项研究计划，通过利用我们的新型微流控和微组织技术来设计具有芯片上生物传感功能的芯片上器官平台，从而直接解决这些限制。为此，我们研究了生物运输和生物传感的基本方面，以实现在动态微流体环境中检测生物分子；开发灵敏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，以设计机械功能强大的组织。这些知识将被用于产生新的芯片上器官模型，用于监测血脑屏障的传输；用于在芯片上测量心肌收缩；以及用于优化工程组织的机械刺激方案。 在这项研究计划中培训的研究生和本科生将具备必要的科学和专业技能，以应用他们的研究产生的知识产生长期影响，并在未来在生物传感、生物微流体和生物技术领域领导大胆的新举措。

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.