Integrated biosensors for organ-on-a-chip and physiological monitoring platforms

组织工程和微流控技术的进步使得“芯片上的器官”设备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。这些技术为疾病建模和药物发现带来了巨大的希望。尽管有巨大的潜力，但芯片上器官平台的一个持久限制是，它们依赖于手动的芯片外分析方法，这造成了分析瓶颈，限制了这些平台的价值。片上传感器的集成可以实现连续、更高吞吐量和更高含量的分析。引人注目的是，在将生物传感器整合到护理点和一些用于诊断和健康监测的可穿戴微流控设备方面取得了重大进展，但由于涉及的工程挑战，芯片上器官平台的集成没有跟上。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传感器技术来设计具有芯片上生物传感功能的芯片上器官平台和用于体液生物标记物检测的微流控设备，从而直接应对这些挑战。为此，我们将研究生物传输和生物传感的基本方面，以实现在动态微流控环境中检测生物分子；开发和改造敏感的芯片传感器，以测量芯片上器官的生物屏障完整性、微组织收缩、溶解氧和其他分析物浓度；以及设计用于尿量测量和生物标志物检测的软微流控设备。这些知识将被用于创建血脑屏障和受损心脏的增强芯片上器官模型，并将用于远程监测患有心力衰竭的婴儿的可穿戴设备。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。

Advances in tissue engineering and microfluidics have enabled the creation of "organ-on-a-chip" devices 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 and drug discovery. Despite their enormous potential, a persistent limitation of organ-on-a-chip 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 sensors could enable continuous, higher-throughput, and higher-content analyses. Strikingly, there have been significant advances in incorporating biosensors into point-of-care and some wearable microfluidic devices for diagnostics and health monitoring, but integration in organ-on-a-chip platforms has not kept up because of the engineering challenges involved. Here, we propose a research program to directly address these challenges by leveraging our novel microfluidic and sensor technologies to engineer organ-on-a-chip platforms with on-chip biosensing capabilities and microfluidic devices for body fluid biomarker detection. To do so, we will investigate fundamental aspects of biotransport and biosensing to enable biomolecule detection in dynamic microfluidic environments; develop and adapt sensitive on-chip sensors to measure biological barrier integrity, microtissue contraction, and dissolved oxygen and other analyte concentrations in organ-on-a-chip platforms; and design soft microfluidic devices for urine volume measurement and biomarker detection. This knowledge will be applied to create augmented organ-on-a-chip models of the blood-brain barrier and injured heart and to advance wearables for remote monitoring of infants with heart failure. 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.