Biological cells in vivo typically reside in a dynamic flowing microenvironment with extensive biomechanical and biochemical cues varying in time and space. These dynamic biomechanical and biochemical signals together act to regulate cellular behaviors and functions. Microfluidic technology is an important experimental platform for mimicking extracellular flowing microenvironment in vitro. However, most existing microfluidic chips for generating dynamic shear stress and biochemical signals require expensive, large peripheral pumps and external control systems, unsuitable for being placed inside cell incubators to conduct cell biology experiments. This study has developed a microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow. Further, based on the lumped-parameter and distributed-parameter models of multiscale fluid dynamics, the oscillatory flow field and the concentration field of biochemical factors has been simulated at the cell culture region within the designed microfluidic chip. Using the constructed experimental system, the feasibility of the designed microfluidic chip has been validated by simulating biochemical factors with red dye. The simulation results demonstrate that dynamic shear stress and biochemical signals with adjustable period and amplitude can be generated at the cell culture chamber within the microfluidic chip. The amplitudes of dynamic shear stress and biochemical signals is proportional to the pressure difference and inversely proportional to the flow resistance, while their periods are correlated positively with the flow capacity and the flow resistance. The experimental results reveal the feasibility of the designed microfluidic chip. Conclusively, the proposed microfluidic generator based on autonomously oscillatory flow can generate dynamic shear stress and biochemical signals without peripheral pumps and external control systems. In addition to reducing the experimental cost, due to the tiny volume, it is beneficial to be integrated into cell incubators for cell biology experiments. Thus, the proposed microfluidic chip provides a novel experimental platform for cell biology investigations.

中文翻译：

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基于自主振荡流的动态剪切应力和生化信号微流控发生器

体内的生物细胞通常存在于动态流动的微环境中，其广泛的生物力学和生化线索随时间和空间而变化。这些动态的生物力学和生化信号共同作用以调节细胞行为和功能。微流控技术是体外模拟细胞外流动微环境的重要实验平台. 然而，大多数现有的用于产生动态剪切应力和生化信号的微流控芯片需要昂贵的大型外围泵和外部控制系统，不适合放置在细胞培养箱内进行细胞生物学实验。本研究开发了一种基于自主振荡流的动态剪切应力和生化信号的微流体发生器。此外，基于多尺度流体动力学的集中参数和分布参数模型，在所设计的微流控芯片内模拟了细胞培养区域的振荡流场和生化因子浓度场。利用所构建的实验系统，通过用红色染料模拟生化因素，验证了所设计的微流控芯片的可行性。仿真结果表明，微流控芯片内的细胞培养室可以产生周期和幅度可调的动态剪切应力和生化信号。动态剪切应力和生化信号的幅值与压差成正比，与流动阻力成反比，而它们的周期与流量和流动阻力呈正相关。实验结果揭示了所设计的微流控芯片的可行性。总之，所提出的基于自主振荡流的微流体发生器可以在没有外围泵和外部控制系统的情况下产生动态剪切应力和生化信号。除了降低实验成本，由于体积小，集成到细胞培养箱中进行细胞生物学实验是有益的。因此，所提出的微流控芯片为细胞生物学研究提供了一个新的实验平台。