A High-Throughput Flow System to Probe Biomechanics of Pathophysiology

描述(申请人提供)：探索病理生理学生物力学的高通量流动系统细胞培养方式和高通量筛选技术的最新进展极大地扩展了我们的生物发现潜力，并为开发新化合物和基于细胞的治疗方法以治疗多种疾病打开了大门。然而，目前的系统还不能在复杂的生物力学环境中探索细胞功能，这种环境决定了体内多种细胞类型的命运和功能表型。在这里，我们建议开发和实施一种动态高通量流动系统，该系统向在商业上可获得的96孔板的单个孔中生长的培养细胞提供可编程的、时变的流体动态波形。这个平台应该允许对生物系统中的信号通路进行系统研究，生物系统的功能和功能严重依赖于流体机械环境。这一仪器的开发将使人们能够更好地了解人类的病理生理学，并为广泛疾病的临床干预以及临床和研究应用发现新的治疗目标或方式。 公共卫生相关性：叙事用于探索病理生理学生物力学的高通量流动系统该项目旨在首次开发一种能够在常规96孔板中培养细胞并对其施加精确机械力的高通量仪器。这一能力将使新的、更有效的方法能够使用更现实的实验室模型来调查心血管疾病、血液疾病、癌症和其他疾病，并将加快开发针对这些疾病的更安全、更有效的治疗方法。

DESCRIPTION (provided by applicant): A High-Throughput Flow System to Probe Biomechanics of Pathophysiology Recent advances in cell culture modalities and high-throughput screening technology have vastly expanded our potential for biological discovery, and have opened the door toward therapeutic advances in the development of new compounds and cell-based therapies for treatment of a wide range of diseases. Nevertheless, current systems do not have the capability to probe cellular function in the context of the complex biomechanical environments that dictate the fate and functional phenotype of multiple cell types comprising diverse tissue milieus in vivo. Here we propose to develop and implement a dynamic high-throughput flow system that delivers programmable, time- varying fluid dynamic waveforms to cultured cells grown in individual wells of a commercially available 96-well plate. This platform should allow the systematic investigation of signaling pathways in biological systems whose function and dysfunction critically depends on the fluid mechanical environment. Development of this instrument will enable better understanding of human pathophysiology and lead to the discovery of new therapeutic targets or modalities for clinical interventions for a broad range of diseases and clinical and research applications. PUBLIC HEALTH RELEVANCE: Narrative A High-Throughput Flow System to Probe Biomechanics of Pathophysiology This project aims to develop, for the first time, a high-throughput instrument capable of culturing cells in a conventional 96-well plate and applying precise mechanical forces to them. This capability will enable new and more efficient methods to investigate cardiovascular diseases, blood disorders, cancer and other conditions using more realistic laboratory models, and will accelerate the development of safer and more efficacious therapeutic treatments for these diseases.