Development of a prototype micro fluidic device for the study of cell function within a tissue environment

开发用于研究组织环境内细胞功能的原型微流体装置

• 批准号: BB/E002722/1
• 负责人: Steve Haswell
• 金额: $ 76.06万
• 依托单位: University of Hull
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE002722%2F1
• 关键词: Development; prototype; micro; fluidic; device

The Micro Reactor Research Group at Hull has now carried out over 200 man-years of research, to establish the fundamental design and operational parameters e.g. channel shape, size, flow methodology and surface functionalisation, that give micro fluidic devices significant advantages in the field of analytical chemistry. Recently this work has been extended into the field of cell biology and now features a number of ongoing collaborative projects with the Cellular Processes Group at Hull. In general the main practical advantages of micro fluidic methodology, apart from requiring small sample sizes, can be summarised as devices which offer (i) a very high degree of spatial (nano meter) and temporal (micro second) control of processes originating from diffusive mixing processes occurring within a laminar flow regime; (ii) the possibility of generating extremely high surface to volume ratios to intensify liquid/surface or surface/surface interactions and (iii) the opportunity to integrate complex processes with non-invasive analytical measurements in order to achieve significantly better temporal and spatial resolution of dynamic processes than is currently possible. At present the main thrust of the work at Hull is to develop integrated process/measurement devices for forensic/environmental and drug discovery based processes which involves approximately 28 research staff drawn from a range of scientific and engineering disciplines. Given the support at Hull to develop integrated cellular processing and measurement technology it would seem timely and advantageous to align this current proposal with ongoing work whilst developing a unique focus in tissue based research. Thus by combining new science with a significant critical mass of research and know-how considerable added value will be achieved with the proposed funding. We propose therefore to use the expertise that resides within the pool of researchers at Hull to establish (micro fluidic) and exploit (biomedical) micro fluidic methodology in the area of tissue processing and by doing so establish a unique link between research scientists and clinicians. Biological tissue obtained, for example, from a small biopsy, represents a complex aggregation of cell types arranged within an intricate non-cellular structure which supports intercellular connections. However, maintaining a stable tissue sample for study in the laboratory has proved to be very difficult as nutrient delivery, removal of waste products and gaseous exchange all need to be achieved. In nature these processes are carried out via a complex network of blood and lymphatic vessels which give dynamic perfusion of the tissue. Micro fluidic systems mimic nature with their high surface to volume ratio, inherent fast perfusion and localised (single cell) interrogation capability, and so offer an ideal microenvironment for the development of novel technology encompassing integrated measurement capability. The proposed micro fluidic devices will enable the study of cell function and the role of the extracellular (EC) matrix in normal and diseased tissues to be carried out in a novel way. This in turn will lead to significant scientific advances in the understanding of cell and tissue biology. In this project the EC environment between cells will be conditioned using a selection of reagents that will modify the chemical and biological interactions in a defined and controlled way. By then testing the conditioned tissue with a drug-like compound, the effect of conditioning (i.e. modified EC environment) can be used to identify the importance of individual cell interactions. For example, tissue could be conditioned with a calcium inhibitor e.g. EDTA which will disrupt integrin function (a family of cell surface molecules involved in cell binding) allowing the tissue, which is otherwise unchanged, to be tested for responses to cytotoxic drugs in order to identify the role of integrins in mediating drug activity.

船体的微反应器研究小组现已进行了超过200人年的研究，以建立基本的设计和操作参数，例如通道形状，尺寸，流动方法和表面功能化，使微流体装置在分析化学领域具有显着的优势。最近，这项工作已扩展到细胞生物学领域，目前正在与船体的细胞过程组进行一些合作项目。通常，除了需要小的样品尺寸之外，微流体方法的主要实际优点可以概括为提供以下的装置：（i）非常高程度的空间分辨率，（纳米）和时间（微秒）控制源自层流状态内发生的扩散混合过程的过程;（ii）产生极高的表面与体积比以加强液体/表面或表面/表面相互作用的可能性，以及（iii）将复杂过程与非表面相互作用结合的机会。侵入性分析测量，以实现比目前可能的更好的动态过程的时间和空间分辨率。目前，船体的主要工作是为法医/环境和药物发现过程开发综合过程/测量设备，涉及来自一系列科学和工程学科的约28名研究人员。鉴于船体的支持，以开发集成的细胞处理和测量技术，这似乎是及时和有利的，以调整目前的建议与正在进行的工作，同时开发一个独特的重点，在组织为基础的研究。因此，通过将新的科学与大量的研究和专门知识相结合，拟议的供资将实现相当大的附加值。因此，我们建议利用船体研究人员的专业知识，在组织处理领域建立（微流体）和利用（生物医学）微流体方法，并通过这样做建立研究科学家和临床医生之间的独特联系。例如，从小活检获得的生物组织代表了排列在支持细胞间连接的复杂非细胞结构内的细胞类型的复杂聚集。然而，在实验室中保持稳定的组织样品用于研究已被证明是非常困难的，因为营养输送、废物的去除和气体交换都需要实现。在自然界中，这些过程是通过复杂的血管和淋巴管网络进行的，这些血管和淋巴管提供组织的动态灌注。微流体系统以其高表面积与体积比、固有的快速灌注和局部（单细胞）询问能力模仿自然，因此为开发包括集成测量能力的新技术提供了理想的微环境。所提出的微流体装置将使细胞功能的研究和细胞外（EC）基质在正常和患病组织中的作用能够以一种新的方式进行。这反过来将导致细胞和组织生物学的理解的重大科学进步。在这个项目中，细胞之间的EC环境将使用选择的试剂进行调节，这些试剂将以定义和受控的方式改变化学和生物相互作用。然后，通过用药物样化合物测试经调理的组织，调理的效果（即经修饰的EC环境）可用于鉴定单个细胞相互作用的重要性。例如，可以用钙抑制剂例如EDTA调节组织，所述钙抑制剂将破坏整联蛋白功能（参与细胞结合的细胞表面分子家族），从而允许测试在其他方面未改变的组织对细胞毒性药物的应答，以鉴定整联蛋白在介导药物活性中的作用。