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

组织工程和微流体技术的进步使得“芯片上的器官”设备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和药物发现方面具有很大的前景。尽管具有巨大的潜力，但芯片上器官平台的一个持续的局限性是，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、高通量和高含量的分析。引人注目的是，在将生物传感器集成到护理点和一些用于诊断和健康监测的可穿戴微流体设备方面已经取得了重大进展，但由于涉及的工程挑战，器官芯片平台的集成并没有跟上。在这里，我们提出了一个研究计划，通过利用我们新颖的微流控和传感器技术来设计具有片上生物传感能力的器官芯片平台和用于体液生物标志物检测的微流控设备，直接解决这些挑战。为此，我们将研究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；开发和适应敏感的片上传感器，以测量生物屏障完整性，显微组织收缩，溶解氧和其他分析物浓度在器官片上平台；设计用于尿量测量和生物标志物检测的软微流控装置。这些知识将被应用于创建血脑屏障和受伤心脏的增强器官芯片模型，并推进用于远程监测心力衰竭婴儿的可穿戴设备。在这个研究项目中训练的研究生和本科生将配备科学和专业技能，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。

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.