Design considerations to minimize the impact of drug absorption in polymer-based organ-on-a-chip platforms.
Design considerations to minimize the impact of drug absorption in polymer-based organ-on-a-chip platforms.
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DOI：
10.1039/c6lc01401a
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发表时间：
2017-02-14
期刊：
影响因子：
6.1
通讯作者：
George, S. C.
中科院分区：
文献类型：
--
作者：
Shirure, V. S.;George, S. C.
生物相容性聚合物，如聚二甲基硅氧烷（PDMS），是创建芯片上器官微流控平台的首选材料。理想的品质包括易于制造，光学清晰度和疏水性，后者有助于氧气运输到被包裹的细胞。器官芯片技术的一个新兴和重要应用是药物发现；然而，基于聚合物的微流体装置的一个潜在问题已经被最近的PDMS研究所强调，这些研究已经证明在某些实验条件下，疏水药物被PDMS吸收（从而损失）。聚合物中药物的吸收也会导致相邻微流控线之间药物的不良转移。考虑到聚合物的好处，对药物吸收有一个全面的了解是至关重要的。在这项研究中，我们考虑了药物在聚合物微流控装置内的对流、溶解和扩散，以定量的方式表征药物损失的动力学。我们通过COMSOL®的有限元分析解决了菲克第二扩散定律（非定常扩散-对流），并通过实验验证了PDMS中三种疏水分子（罗丹明B，花氨酸NHS酯和紫杉醇）损失的数值模型。药物损失，以及相邻微流控通道中药物的意外混合，在很大程度上取决于平台设计参数、实验条件和药物的物理化学性质，并且可以用四个可扩展的无量纲数的简单定量关系来捕获。这种简单的定量框架可用于设计各种基于聚合物的微流体装置，以最大限度地减少药物吸收的影响。我们描述了微流体中药物损失的动力学，并为设计用于药物发现的器官芯片提供了定量框架。
Biocompatible polymers, such as polydimethylsiloxane (PDMS), are the materials of choice for creating organ-on-a-chip microfluidic platforms. Desirable qualities include ease of fabrication, optical clarity, and hydrophobicity, the latter of which facilitates oxygen transport to encased cells. An emerging and important application of organ-on-a-chip technology is drug discovery; however, a potential issue for polymer-based microfluidic devices has been highlighted by recent studies with PDMS, which have demonstrated absorption (and thus loss) of hydrophobic drugs into PDMS under certain experimental conditions. Absorption of drug in the polymer can also lead to undesirable transfer of drug between adjacent microfluidic lines. Given the benefits of polymers, it is essential to develop a comprehensive understanding of drug absorption. In this study, we considered convection, dissolution, and diffusion of a drug within a polymer-based microfluidic device to characterize the dynamics of drug loss in a quantitative manner. We solved Fick’s 2nd Law of Diffusion (unsteady diffusion-convection) by finite element analysis in COMSOL®, and experimentally validated the numerical model for loss of three hydrophobic molecules (Rhodamine B, Cyanine NHS ester, and Paclitaxel) in PDMS. Drug loss, as well as the unintended mixing of drugs by adjacent microfluidic channels, depends strongly on platform design parameters, experimental conditions, and the physico-chemical properties of the drug, and can be captured in a simple quantitate relationship that employs four scalable dimensionless numbers. This simple quantitative framework can be used in the design of a wide range of polymer-based microfluidic devices to minimize the impact of drug absorption. We characterized the dynamics of drug-loss in microfluidics, and provide a quantitative framework for the design of organ-on-a-chip for drug discovery.
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DOI：
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发表时间：
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影响因子：
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