Microfluidic flow-encoded switching for parallel control of dynamic cellular microenvironments
Microfluidic flow-encoded switching for parallel control of dynamic cellular microenvironments
复制标题
DOI：
10.1039/b716962k
复制
发表时间：
2008-01-01
期刊：
影响因子：
6.1
通讯作者：
Toner, Mehmet
中科院分区：
文献类型：
--
作者：
King, Kevin R.;Wang, Sihong;Toner, Mehmet
生物刺激的时间模式是细胞反应的重要决定因素。我们提出了一种微流体平行灌注培养系统，用于控制可溶性细胞微环境的动力学，同时进行细胞反应的活细胞成像。一种“流编码开关”（FES）设计策略被开发出来，同时提供许多不同的时间刺激，包括脉冲序列的宽度，长度和频率，下游贴壁细胞使用一个单一的输入控制。设计策略采用层流和限制扩散混合的原理，将网络的状态（每个通道中的瞬时刺激浓度）编码为两个流速的比值，该比率由单个压差控制。为了证明该实验系统的实用性，我们研究了动态刺激对NFkB转录激活和细胞命运决定的影响。我们的研究结果表明，转录反应和细胞命运的决定在数量和质量上都取决于刺激的时间。总之，通过在单一输入压力下编码动态刺激，微流控流编码开关为系统地探测时间模式细胞环境的功能意义提供了一种可扩展的实验方法。
The temporal pattern of a biological stimulus is an important determinant of the resulting cellular response. We present a microfluidic parallel perfusion culture system for controlling the dynamics of soluble cell microenvironments while simultaneously performing live-cell imaging of cellular responses. A "Flow-encoded Switching'' (FES) design strategy is developed to simultaneously deliver many different temporal profiles of stimuli, including pulse train widths, lengths, and frequencies, to downstream adherent cells using a single input control. The design strategy uses principles of laminar flow and diffusion-limited mixing to encode the state of the network (the instantaneous stimulus concentrations in each channel) into the ratio of two flow rates, which is controlled by a single differential pressure. To demonstrate the utility of this experimental system, we investigated the effect of dynamic stimuli on NFkB transcriptional activation and cell fate determination. Our results illustrate that transcriptional responses and cell fate decisions depend both quantitatively and qualitatively on the timing of the stimulus. In summary, by encoding dynamic stimuli in a single input pressure, microfluidic flow-encoded switching offers a scalable experimental method for systematically probing the functional significance of temporally patterned cellular environments.