A High-Throughput Flow System to Probe Biomechanics of Pathophysiology

描述（由申请人提供）：用于探索病理生理学生物力学的高通量流动系统细胞培养模式和高通量筛选技术的最新进展极大地扩展了我们在生物学发现方面的潜力，并为开发新化合物和基于细胞的治疗方法打开了治疗进步的大门，用于治疗各种疾病。然而，目前的系统不具备在复杂的生物力学环境中探测细胞功能的能力，这些环境决定了体内多种组织环境中多种细胞类型的命运和功能表型。在这里，我们建议开发和实现一个动态的高通量流动系统，提供可编程的，时变的流体动力学波形，以培养细胞在单个孔的96孔板的市售。这个平台应该允许系统地研究生物系统中的信号通路，其功能和功能障碍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病理生理学，并导致发现新的治疗靶点或模式，用于各种疾病的临床干预以及临床和研究应用。

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.