Emulation of Colonic Oxygen Gradients in a Microdevice
Emulation of Colonic Oxygen Gradients in a Microdevice
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DOI：
10.1177/2472630317743425
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发表时间：
2018-04
期刊：
影响因子：
2.7
通讯作者：
David I. Walsh;E. Victoria Dydek;Jaclyn Y. Lock;Taylor L. Carlson;Rebecca L. Carrier;David S. Kong;Catherine R. Cabrera;T. Thorsen
中科院分区：
文献类型：
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作者：
David I. Walsh;E. Victoria Dydek;Jaclyn Y. Lock;Taylor L. Carlson;Rebecca L. Carrier;David S. Kong;Catherine R. Cabrera;T. Thorsen
芯片上肠道体外建模是一个新兴领域，因为人类肠道上皮和肠道微生物组最近已被确定为多种疾病的新型药物靶标。现实的体外肠道模型需要各种精确的环境线索，如化学和气体梯度，以及支持微生物群落生长的粘液等基质。本技术简介描述了一种微流体架构，其能够产生生理相关的氧气梯度，该氧气梯度模拟人类结肠上皮内层近端的氧气分布。该装置在数百微米的长度范围内产生从0%到4%分压O2的稳定和可重复的限定氧梯度，并用于研究氧合对结肠壁天然粘液结构的影响。使用模拟作为混合气-液微流体装置的设计工具使得能够在芯片上创建限定的生理氧气梯度。这些微流体架构在肠道生理学方面具有强大的潜在应用，包括为肠道衬里中哺乳动物上皮细胞的培养提供最佳氧合条件，以及为复杂的微生物组培养物创造肠腔中氧气梯度的逼真模拟。
Gut-on-a-chip in vitro modeling is an emerging field, as the human gut epithelium and gut microbiome have been recently identified as novel drug targets for a wide variety of diseases. Realistic in vitro gut models require a variety of precise environmental cues, such as chemical and gas gradients, in combination with substrates like mucus that support the growth of microbial communities. This technical brief describes a microfluidic architecture capable of developing a physiologically relevant oxygen gradient that emulates the oxygen profile proximal to the epithelial inner lining of the human colon. The device generates stable and repeatable defined oxygen gradients from 0% to 4 % partial pressure O2 over a length scale of hundreds of microns, and was applied to study the effects of oxygenation on the structure of native mucus that lines the colon wall. Using simulation as a design tool for hybrid gas–liquid microfluidic devices enables on-chip creation of defined, physiologically oxygen gradients. These microfluidic architectures have powerful potential applications for gut physiology, including providing optimal oxygenation conditions for the culture of mammalian epithelial cells in the gut lining, as well as creating a realistic mimic of the oxygen gradient found in the intestinal lumen for complex microbiome cultures.