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: 8116992
• 负责人: Jeffrey T. Borenstein
• 金额: $ 21.68万
• 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 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8116992
• 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; 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）：一种高通量流量系统，用于探测病理生理学的生物力学，最新的细胞培养方式和高通量筛查技术的进步已大大扩展了我们的生物学发现潜力，并为基于新的化合物和基于细胞的细胞治疗范围治疗范围范围的治疗疗法打开了治疗性进步。然而，当前系统在复杂的生物力学环境的背景下没有能力探测细胞功能，该环境决定了包括体内各种组织环境的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个动态的高通量流系统，该系统可将可编程，变化的流体动态波形传递到在市售96孔板的单个井中生长的培养细胞。该平台应允许对功能和功能障碍严重取决于流体机械环境的生物系统中的信号通路进行系统的研究。该仪器的开发将使人们能够更好地了解人类病理生理学，并导致为广泛疾病以及临床和研究应用的临床干预发现新的治疗靶标或方式。 公共卫生相关性：叙事一种高通量流系统，用于探测病理生理学的生物力学该项目旨在首次开发一种能够在常规96孔板中培养细胞的高通量仪器，并向其施加精确的机械力。这种能力将实现新的，更有效的方法，以使用更现实的实验室模型来研究心血管疾病，血液疾病，癌症和其他疾病，并加快针对这些疾病的更安全，更有效的治疗治疗方法。