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Microfluidic approaches for precise in vitro control over temporal and spatial oxygenation.

机译:微流控方法可对体外时空氧合进行精确的体外控制。

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摘要

Oxygen is a key modulator of many cellular pathways and plays an important role in the pathogenesis of a number of diseases, such as in cancer metastasis and stroke. Unfortunately devices permitting in vitro oxygen modulation fail to meet the needs of biomedical research due to the inability to effectively mimic conditions found in vivo. In this work, a microfabricated technology has been developed to more accurately control the temporal and spatial oxygen concentration exposed to cell cultures. The platform consists of a polydimethylsiloxane (PDMS) insert that adapts to standard 6-well plates or Boyden chambers and their associated biological assays. The device operates by establishing an oxygen gradient between the cell culture media and a rapidly-perfused microfluidic gas network at the bottom of the pillar nested into the culture vessel, driving media equilibration towards a desired oxygen concentration. A 100 microm thick gas-permeable PDMS membrane separates the microfluidic network and culture media. Equilibration time is on the order of minutes and a wide variety of oxygen profiles can be attained based on the device design, including physiologically-relevant transient hypoxia regimes and oxygen gradients. The insert devices can be utilized for a variety of experiments, including migration, invasion, and proliferation assays. Utilizing the same microchannel-membrane design as for the insert devices, a tool for establishing steady-state concentration gradients across 3-D constructs has also been developed. This device will hopefully aid in fields where oxygen gradients across tissues are important biological determinants, such as in development and stem cell differentiation. The devices presented here are demonstrated to be viable tools to increase experimental throughput and permit novel experimental possibilities in any biomedical research lab.
机译:氧气是许多细胞途径的关键调节剂,并在许多疾病的发病机理中发挥重要作用,例如在癌症转移和中风中。不幸的是,由于无法有效地模拟体内条件,允许体外氧调节的设备无法满足生物医学研究的需求。在这项工作中,已经开发出一种微制造技术来更精确地控制暴露于细胞培养物中的时间和空间氧气浓度。该平台由适合标准6孔板或Boyden小室及其相关生物学测定的聚二甲基硅氧烷(PDMS)插入物组成。该设备通过在细胞培养基和嵌套在培养容器中的柱子底部的快速灌注微流体气体网络之间建立氧气梯度来运行,从而使培养基平衡达到所需的氧气浓度。 100微米厚的透气PDMS膜将微流体网络和培养基分开。平衡时间约为数分钟,可以根据设备设计获得各种氧气分布图,包括生理相关的瞬时低氧状态和氧气梯度。插入装置可用于多种实验,包括迁移,侵袭和增殖测定。利用与插入设备相同的微通道膜设计,还开发了一种用于建立跨3-D结构的稳态浓度梯度的工具。该设备有望在组织中氧梯度是重要的生物学决定因素的领域提供帮助,例如在发育和干细胞分化方面。此处展示的设备被证明是可行的工具,可以提高实验通量并在任何生物医学研究实验室中提供新颖的实验可能性。

著录项

  • 作者

    Oppergard, Shawn C.;

  • 作者单位

    University of Illinois at Chicago.;

  • 授予单位 University of Illinois at Chicago.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 199 p.
  • 总页数 199
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 遥感技术;
  • 关键词

  • 入库时间 2022-08-17 11:36:56

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