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A multi-purpose microfluidic perfusion system with combinatorial choice of inputs mixtures gradient patterns and flow rates

机译:一种多功能微流灌注系统可组合选择输入混合物梯度模式和流速

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摘要

Microfluidic perfusion systems, characterized by deterministic flow, low reagent consumption, small dead volumes, large integration in small footprints, high-throughput operation, and low-cost fabrication, are being increasingly used for cell culture studies in applications such as basic cell biology, molecular biological assays, tissue engineering, and systems biology. We report a multipurpose, pressure-driven and computer-controlled microfluidic perfusion device containing sixteen inlets and a large cell culture chamber. The user can choose, with sub-second temporal resolution, (a) to feed the chamber with one of 16 inlets, all 16 inlets, or one of 64 combinations of 2, 4, or 8 inlets using a binary multiplexer; (b) to introduce into the chamber a heterogeneous laminar flow of the inlets, a smoothened gradient, or a fully homogenized mixture; (c) to bypass the chamber in order to purge the inlet lines so as to minimize the dead volume; (d) to generate asymmetrical and curvilinear flow patterns within the chamber by opening side outlets; and (e) to slow down the flow by combinatorially adding segments of high fluid resistance (sixteen different levels of flow rates are possible using only four valves). All functionalities are combined to create complex gradient patterns and sequential perfusions within the central chamber.
机译:具有确定性的流量,较低的试剂消耗,较小的死体积,在较小的占位面积中具有较大的集成度,高通量的操作和低成本的制造等特征的微流体灌注系统正越来越多地用于基础细胞生物学等应用中的细胞培养研究,分子生物学测定,组织工程和系统生物学。我们报告了一个多功能,压力驱动和计算机控制的微流灌注设备,其中包含十六个入口和一个大的细胞培养室。用户可以选择亚秒级的时间分辨率,(a)使用二进制多路复用器为腔室提供16个入口之一,全部16个入口或2个,4个或8个入口的64种组合之一; (b)将不均匀的入口层流,平滑的梯度或完全均质的混合物引入腔室; (c)绕过腔室,以净化入口管线,以使死体积最小化; (d)通过打开侧面出口在腔室内产生不对称和曲线的流型; (e)通过组合增加高流体阻力段来减慢流量(仅使用四个阀就可以达到十六种不同的流速)。结合所有功能以在中央腔室内创建复杂的梯度模式和顺序灌注。

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