Generalized serial dilution module for monotonic and arbitrary microfluidic gradient generators
Generalized serial dilution module for monotonic and arbitrary microfluidic gradient generators
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DOI：
10.1039/b813582g
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发表时间：
2009-01-01
期刊：
影响因子：
6.1
通讯作者：
Oh, Kwang W.
中科院分区：
文献类型：
--
作者：
Lee, Kangsun;Kim, Choong;Oh, Kwang W.
在本文中，我们提出了一个通用的微流控浓度梯度发生器，包括N级联混合阶段，在逐步的方式广义串行稀释模块。通过控制每个阶段中两种合并溶液的体积混合比来产生所需的浓度。通过控制通道长度来调节流速，通道长度与每个通道中的流体阻力成比例。基于微流控回路与电子回路之间的相似性，提出了一种用于产生任意复杂浓度和输出流速梯度的通用数学模型。压降对应于电压降，流速对应于电流，流阻对应于电阻。在此基础上，建立了一个简单的等效电路模型，每个通道段用一个电阻来表示。作为数学建模的结果，广义连续稀释模块中的唯一可变参数是通道长度。利用N4的广义连续稀释模块，成功地设计和测试了线性、对数和高斯梯度的三种类型的微流控梯度发生器。所提出的策略能够用单个模块生成通用单调梯度，或者用多个模块生成任意梯度，范围从线性到复杂的非线性形状的浓度梯度，以及以逐步的方式生成任意输出流速梯度。使用广义连续稀释模块的简单通用梯度生成技术将在更大的化学和生物界中得到广泛使用，并解决梯度依赖现象的许多挑战。
In this paper, we propose a generalized serial dilution module for universal microfluidic concentration gradient generators including N cascaded-mixing stages in a stepwise manner. Desired concentrations were generated by means of controlled volumetric mixing ratios of two merging solutions in each stage. The flow rates were adjusted by controlling channel length, which is proportional to fluidic resistance in each channel. A generalized mathematical model for generating any complex concentration and output flow rate gradients is presented based on the fact that there is an analogy between microfluidic circuits and electrical circuits. The pressure drop corresponds to a voltage drop, the flow rate to an electrical current, and the flow resistance to an electrical resistance. A simple equivalent electrical circuit model was generalized, and in the model each channel segment was represented by an electrical resistance. As a result of the mathematical modelling, the only variable parameter in the generalized serial dilution module was the channel length. By the use of the generalized serial dilution module with N 4, three types of microfluidic gradient generators for linear, logarithmic and Gaussian gradients were successfully designed and tested. The proposed strategy is capable of generating universal monotonic gradients with a single module or arbitrary gradients with multiple modules ranging from linear to complex non-linear shapes of concentration gradients as well as arbitrary output flow rate gradients in a stepwise manner. The simple universal gradient generation technology using the generalized serial dilution module will find widespread use in the greater chemical and biological community, and address many challenges of gradient-dependent phenomena.