Stimulation of cells with temporal waveforms can be used to observe the frequency-dependent nature of cellular responses. The ability to produce and maintain the temporal waveforms in spite of the broadening processes that occur as the wave travels through the microfluidic system is critical for observing dynamic behaviors. Broadening of waves in microfluidic channels has been examined, but the effect that large-volume cell chambers have on the waves has not. In this report, a sinusoidal glucose wave delivered to a 1 mm diameter cell chamber using various microfluidic channel structures was simulated by finite element analysis with the goal of minimizing the broadening of the waveform in the chamber and maximizing the homogeneity of the concentration in the chamber at any given time. Simulation results indicated that increasing the flow rate was the most effective means to achieve these goals, but at a given volumetric flow rate, geometries that deliver the waveform to multiple regions in the chamber while maintaining a high linear velocity produced sufficient results. A 4-inlet geometry with a 220 μm channel width gave the best result in the simulation and was used to deliver glucose waveforms to a population of pancreatic islets of Langerhans. The result was a stronger and more robust synchronization of the islet population as compared to when a non-optimized chamber was used. This general strategy will be useful in other microfluidic systems examining the frequency-dependence nature of cellular behavior.

中文翻译：

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在大体积微流体细胞室中保持刺激波形。

具有时间波形的细胞刺激可用于观察细胞反应的频率依赖性。尽管波在微流体系统中传播时会发生加宽过程，但产生和维持时间波形的能力对于观察动态行为至关重要。已经研究了微流体通道中波的展宽，但大容量细胞室对波的影响还没有。在本报告中，通过有限元分析模拟使用各种微流体通道结构输送到 1 mm 直径细胞室的正弦葡萄糖波，目的是最大限度地减少室中波形的展宽并最大限度地提高室中浓度的均匀性在任何给定的时间。仿真结果表明，增加流速是实现这些目标的最有效手段，但在给定的体积流速下，将波形传送到腔室中的多个区域同时保持高线速度的几何形状产生了足够的结果。具有 220 μm 通道宽度的 4 入口几何形状在模拟中给出了最佳结果，并用于将葡萄糖波形传递给朗格汉斯胰岛群。与使用非优化室时相比，结果是胰岛群的同步性更强、更稳健。这种通用策略将在其他微流体系统中有用，可检查细胞行为的频率依赖性。将波形传送到腔室中的多个区域同时保持高线速度的几何形状产生了足够的结果。具有 220 μm 通道宽度的 4 入口几何形状在模拟中给出了最佳结果，并用于将葡萄糖波形传递给朗格汉斯胰岛群。与使用非优化室时相比，结果是胰岛群的同步性更强、更稳健。这种通用策略将在其他微流体系统中有用，可检查细胞行为的频率依赖性。将波形传送到腔室中的多个区域同时保持高线速度的几何形状产生了足够的结果。具有 220 μm 通道宽度的 4 入口几何形状在模拟中给出了最佳结果，并用于将葡萄糖波形传递给朗格汉斯胰岛群。与使用非优化室时相比，结果是胰岛群的同步性更强、更稳健。这种通用策略将在其他微流体系统中有用，可检查细胞行为的频率依赖性。具有 220 μm 通道宽度的 4 入口几何形状在模拟中获得了最佳结果，并用于向朗格汉斯胰岛群提供葡萄糖波形。与使用非优化室时相比，结果是胰岛群的同步性更强、更稳健。这种通用策略将在其他微流体系统中有用，可检查细胞行为的频率依赖性。具有 220 μm 通道宽度的 4 入口几何形状在模拟中获得了最佳结果，并用于向朗格汉斯胰岛群提供葡萄糖波形。与使用非优化室时相比，结果是胰岛群的同步性更强、更稳健。这种通用策略将在其他微流体系统中有用，可检查细胞行为的频率依赖性。