A High-Throughput Flow System to Probe Biomechanics of Pathophysiology

用于探索病理生理学生物力学的高通量流系统

• 批准号: 8263037
• 负责人: Jeffrey T. Borenstein
• 金额: $ 24.37万
• 依托单位: CHARLES STARK DRAPER LABORATORY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8263037
• 关键词: Address; Automobile Driving; Behavior; Biological; Biological Assay; Biomechanics; Biomedical Research; Blood Vessels; Carbon Dioxide; Cardiovascular Diseases; Cell Count; Cell Culture System; Cell Culture Techniques; Cell Therapy; Cell physiology; Cells; Cellular Morphology; Clinical; Clinical Research; Columbidae; Complex; Cultured Cells; Development; Device or Instrument Development; Devices; Disease; Electronics; Elements; Endothelial Cells; Ensure; Environment; Fluorescence Microscopy; Functional disorder; Gases; Gene Expression; Health; Hematological Disease; Hematopoietic; Hematopoietic stem cells; Human; Humidity; Image; Imagery; Individual; Intervention; Investigation; Laboratories; Lead; Liquid substance; Malignant Neoplasms; Measurement; Mechanics; Mediating; Methods; Microscope; Modality; Modeling; Monitor; Motor; Mus; Optics; Output; Oxygen; Phenotype; Physiological; Printing; Process; Property; Proteins; RNA; Reagent; Real-Time Systems; Regenerative Medicine; Reporter; Reporting; Retinal Cone; Screening procedure; Signal Pathway; Signal Transduction; Simulate; Specific qualifier value; Staging; Stem cells; System; Techniques; Technology; Temperature; Therapeutic; Time; Tissues; Validation; Vascular Endothelial Cell; Visual; base; biological systems; cell behavior; cell type; design; design and construction; embryonic stem cell; fluorescence imaging; hemodynamics; high throughput screening; in vitro Model; in vivo; insight; instrument; miniaturize; new therapeutic target; operation; prototype; public health relevance; response; scale up; shear stress; stem cell differentiation

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.

描述（由申请人提供）：用于探测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的生物发现潜力，并为开发用于治疗各种疾病的新化合物和基于细胞的疗法的治疗进展打开了大门。然而，目前的系统不具有在复杂的生物力学环境的背景下探测细胞功能的能力，所述复杂的生物力学环境决定了体内包括不同组织环境的多种细胞类型的命运和功能表型。在此，我们提出开发和实施动态高通量流动系统，其将可编程的、时变的流体动力学波形递送至在市售96孔板的各个威尔斯孔中生长的培养细胞。该平台应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力学环境。该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目标或模式，用于广泛疾病的临床干预以及临床和研究应用。 公共卫生关系：叙述一个高通量的流动系统，以探索病理生理学的生物力学本项目旨在开发，第一次，一个高通量的仪器，能够培养细胞在一个传统的96孔板，并施加精确的机械力给他们。这一能力将使新的和更有效的方法，以调查心血管疾病，血液疾病，癌症和其他条件，使用更现实的实验室模型，并将加快发展更安全，更有效的治疗这些疾病的治疗方法。