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A sharp-edge-based acoustofluidic chemical signal generator†
Lab on a Chip ( IF 6.1 ) Pub Date : 2018-04-18 00:00:00 , DOI: 10.1039/c8lc00193f
Po-Hsun Huang 1, 2, 3, 4 , Chung Yu Chan 4, 5, 6, 7 , Peng Li 4, 8, 9, 10 , Yuqi Wang 4, 5, 6, 7 , Nitesh Nama 4, 5, 6, 7 , Hunter Bachman 1, 2, 3, 4 , Tony Jun Huang 1, 2, 3, 4
Affiliation  

Resolving the temporal dynamics of cell signaling pathways is essential for regulating numerous downstream functions, from gene expression to cellular responses. Mapping these signaling pathways requires the exposure of cells to time-varying chemical signals; these are difficult to generate and control over a wide temporal range. Herein, we present an acoustofluidic chemical signal generator based on a sharp-edge-based micromixing strategy. The device, simply by modulating the driving signals of an acoustic transducer including the ON/OFF switching frequency, actuation time and duty cycle, is capable of generating both single-pulse and periodic chemical signals that are temporally controllable in terms of stimulation period, stimulation duration and duty cycle. We also demonstrate the device's applicability and versatility for cell signaling studies by probing the calcium (Ca2+) release dynamics of three different types of cells stimulated by ionomycin signals of different shapes. Upon short single-pulse ionomycin stimulation (∼100 ms) generated by our device, we discover that cells tend to dynamically adjust the intracellular level of Ca2+ through constantly releasing and accepting Ca2+ to the cytoplasm and from the extracellular environment, respectively. With advantages such as simple fabrication and operation, compact device design, and reliability and versatility, our device will enable decoding of the temporal characteristics of signaling dynamics for various physiological processes.

中文翻译:

基于尖端的声流体化学信号发生器

解决细胞信号通路的时间动态对于调节从基因表达到细胞反应的众多下游功能至关重要。绘制这些信号传导途径的图谱需要使细胞暴露于随时间变化的化学信号。这些很难在很宽的时间范围内生成和控制。在本文中,我们提出了一种基于锐利边缘微混合策略的声流体化学信号发生器。该设备仅通过调制声换能器的驱动信号(包括开/关切换频率,致动时间和占空比),就能够生成单脉冲和周期性化学信号,这些信号在刺激周期,刺激方面可在时间上控制持续时间和占空比。我们还演示了该设备的'2+)释放由不同形状的离子霉素信号刺激的三种不同类型细胞的动力学。在我们的设备产生短暂的单脉冲离子霉素刺激(约100毫秒)后,我们发现细胞倾向于通过不断地分别向细胞质和细胞外环境释放和接受Ca 2+来动态调节Ca 2+的细胞内水平。。凭借诸如简单的制造和操作,紧凑的设备设计以及可靠性和多功能性等优点,我们的设备将能够解码各种生理过程的信号动力学的时间特性。
更新日期:2018-04-18
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