Diagnostic Microperfusion Platfom for Functional Screening of Thick Preparations

用于浓制剂功能筛选的诊断微灌注平台

• 批准号: 7746905
• 负责人: Jelena Vukasinovic
• 金额: $ 19.5万
• 依托单位: LENA BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7746905
• 关键词: Adhesions; Afferent Pathways; Architecture; Beds; Benchmarking; Biomedical Research; Blood Vessels; Brain; Budgets; Cellular biology; Complex; Convection; Coupling; Development; Devices; Diagnostic; Diffusion; Electric Stimulation; Electrodes; Electronics; Electrophysiology (science); Elements; Environment; Failure; Functional Imaging; Gases; Goals; Heart Diseases; Hour; In Situ; In Vitro; Incubators; Manufacturer Name; Medical; Metabolic; Methods; Microelectrodes; Microscope; Monitor; Natural regeneration; Neurons; Nutrient; Optics; Perforation; Perfusion; Pharmacologic Substance; Pharmacology; Phase; Physiology; Preparation; Price; Process; Public Health; Regional Perfusion; Reproducibility; Research; Research Infrastructure; Sampling; Sampling Studies; Scheme; Screening procedure; Slice; System; Temperature; Testing; Therapeutic Studies; Thick; Time; Tissue Engineering; Tissue Sample; Tissues; Transplantation; base; cost; design; improved; innovation; instrument; interstitial; meetings; novel; novel diagnostics; premature; prevent; prototype; public health relevance; relating to nervous system; research study; tissue preparation; tool; user-friendly

DESCRIPTION (provided by applicant): The objective of the project Diagnostic Microperfusion Platform for Functional Screening of Thick Preparations is to develop a sophisticated, yet user friendly, high-throughput diagnostic instrument that provides long-term metabolic support of thick tissue samples and allows functional screening with unparallel control of culture parameters and diagnostic architecture. The first goal of the project is to extend the viability of greater than 500 ¿m thick tissue preparations and enable at least 5 days long, reproducible studies in vitro. Diffusion limited interstitial mass transport causes premature decay that is particularly exacerbated in thick samples. We propose to overcome diffusion limits by forced interstitial convection to achieve high concentration of nutrients and gas interstitially. At present, complex and expensive perfusion/recording chambers (Harvard Apparatus) allow ten-hour-long studies. Slices are thinning and their decay progress is questionable from study to study making it hard to repeat experiments, validate and interpret results. To enable successful completion of started experiments and increase the reproducibility of performed studies we will substantially mitigate culture decay, and, develop advanced fluidic architecture to aseptically isolate viable cultures and maintain unaltered perfusion if neighboring culture(s) fail. The second goal of the project is to overcome technological limitations in functional diagnostics in vitro by enabling unparallel access to thick tissue preparations. It will be up to users to select whether to monitor activity by functional imaging or electrical stimulation and recording using multi-electrode arrays. Long-term, reproducible studies will create a new benchmark for electrophysiology. Sample applications that may benefit from long-term perfusion and monitoring of neural activity are neuronal regeneration, development and plasticity as they involve processes that develop over extended periods of time. The third objective is to develop an economical fabrication approach that will turn this diagnostic platform into inexpensive, scalable, high-throughput devices with fluidic, gas, optical and electrical accessibility. Such approach will allow us to quickly and inexpensively change our designs, integrate different building blocks, and enable add-on-functionalities to satisfy specific user requirements. The end product will be a simple to use, miniature instrument whose modular architecture can be easily adjusted to suit various application challenges including but not limited to the understanding and treatment of neural and cardiac disorders, functional pharmacology in vitro, physiology, tissue engineering and transplantation. PUBLIC HEALTH RELEVANCE: Novel diagnostic platform proposed herein will advance public health by providing a simple, reliable and inexpensive test-bed for therapeutic studies. Ultimately, this development will facilitate medical and scientific discoveries that will benefit the treatment of neural and cardiac disorders.

描述（由申请人提供）：用于厚制剂功能筛选的诊断微灌注平台项目的目标是开发一种复杂且用户友好的高通量诊断仪器，为厚组织样本提供长期代谢支持，并允许功能性筛查对培养参数和诊断结构进行无与伦比的控制的筛选。 该项目的首要目标是延长超过 500 ¿厚的组织制剂，并能够进行至少 5 天的体外可重复研究。扩散限制的间质质量传输会导致过早腐烂，这种情况在厚样品中尤其加剧。我们建议通过强制间质对流来克服扩散限制，以实现高浓度的营养物质和目前，复杂且昂贵的灌注/记录室（哈佛装置）允许进行长达十小时的研究，并且它们的衰变进程从研究到结果都存在疑问。研究使得重复实验、验证和解释结果变得困难，为了成功完成已开始的实验并提高所进行研究的可重复性，我们将大大减轻培养物的腐烂，并开发先进的流体架构来无菌分离可行的培养物并保持不变的灌注。邻近文化失败。 该项目的第二个目标是通过提供无与伦比的厚组织制剂来克服体外功能诊断的技术限制。用户可以选择是否通过功能成像或电刺激和使用多电极阵列记录来监测活动。长期、可重复的研究将为电生理学创建一个新的基准，可能受益于长期灌注和神经活动监测的示例应用是神经再生、发育和可塑性，因为它们涉及长期发展的过程。 第三个目标是开发一种经济的制造方法，将该诊断平台转变为具有流体、气体、光学和电气可访问性的廉价、可扩展、高通量的设备，这种方法将使我们能够快速、廉价地改变我们的设计，集成不同的设计。最终产品将是一种易于使用的微型仪器，其模块化架构可以轻松调整以适应各种应用挑战，包括但不限于理解和处理。神经和心脏疾病，功能药理学体外、生理学、组织工程和移植。 公共健康相关性：本文提出的新型诊断平台将通过为治疗研究提供简单、可靠且廉价的测试平台来促进公共健康，最终，这一发展将促进有利于神经和心脏疾病治疗的医学和科学发现。