User-defined local stimulation of live tissue through a movable microfluidic port
User-defined local stimulation of live tissue through a movable microfluidic port
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DOI：
10.1039/c8lc00204e
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发表时间：
2018-07-21
期刊：
影响因子：
6.1
通讯作者：
Pompano, Rebecca R.
中科院分区：
文献类型：
--
作者：
Catterton, Megan A.;Dunn, Austin F.;Pompano, Rebecca R.
许多体内组织反应是局部开始的，然而大多数体外刺激是整体施加的。微流控技术具有独特的能力，能够对组织样本进行局部刺激，并精确控制流体位置、流速和成分。然而，先前在组织下方使用固定端口的装置需要手动将组织对准端口，这增加了机械损伤的风险。在此我们介绍一种新型微流控装置，它允许使用者确定向活组织切片输送流体的位置，而无需操作组织本身。该装置采用双组件滑动芯片设计，在组织切片下方创建一个可移动端口。一个由一系列端口穿孔的培养室容纳组织切片，并通过一层氟碳油与单个输送端口隔开，该输送端口由下方可移动层中的微流控通道供液。我们推导并验证了一个基于界面张力和流动阻力的物理模型，以预测在何种条件下流体输送不会泄漏到层间间隙。水溶液可重复地输送到组织和凝胶样本中，输送区域的宽度主要由对流控制。组织切片的活性不受该装置上刺激的影响。作为原理验证，我们表明淋巴结组织的活切片可以依次被精确刺激。未来，该装置可能作为一个平台，用于研究组织中流体流动的影响以及进行局部药物筛选。
Many in vivo tissue responses begin locally, yet most in vitro stimuli are delivered globally. Microfluidics has a unique ability to provide focal stimulation to tissue samples with precise control over fluid location, flow rate, and composition. However, previous devices utilizing fixed ports beneath the tissue required manual alignment of the tissue over the ports, increasing the risk of mechanical damage. Here we present a novel microfluidic device that allows the user to define the location of fluid delivery to a living tissue slice without manipulating the tissue itself. The device utilized a two-component SlipChip design to create a mobile port beneath the tissue slice. A culture chamber perforated by an array of ports housed a tissue slice and was separated by a layer of fluorocarbon oil from a single delivery port, fed by a microfluidic channel in the movable layer below. We derived and validated a physical model, based on interfacial tension and flow resistance, to predict the conditions under which fluid delivery occurred without leakage into the gap between layers. Aqueous solution was delivered reproducibly to samples of tissue and gel, and the width of the delivery region was controlled primarily by convection. Tissue slice viability was not affected by stimulation on the device. As a proof-of-principle, we showed that live slices of lymph node tissue could be sequentially targeted for precise stimulation. In the future this device may serve as a platform to study the effects of fluid flow in tissues and to perform local drug screening.