Du Yanan, Shim Jaesool, Vidula Mahesh, Hancock Matthew J, Lo Edward, Chung Bong Geun, Borenstein Jeffrey T, Khabiry Masoud, Cropek Donald M, Khademhosseini Ali
Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Lab Chip. 2009 Mar 21;9(6):761-7. doi: 10.1039/b815990d. Epub 2008 Dec 10.
The ability to rapidly generate concentration gradients of diffusible molecules has important applications in many chemical and biological studies. Here we established spatially and temporally controllable concentration gradients of molecules (i.e. proteins or toxins) in a portable microfluidic device in an easy and rapid manner. The formation of the concentration gradients was initiated by a passive-pump-induced forward flow and further optimized during an evaporation-induced backward flow. The centimeter-long gradients along the microfluidic channel were shown to be spatially and temporally controlled by the backward flow. The gradient profile was stabilized by stopping the flow. Computational simulations of this dynamic process illustrated the combined effects of convection and diffusion on the gradient generation, and fit well with the experimental data. To demonstrate the applications of this methodology, a stabilized concentration gradient of a cardiac toxin, alpha-cypermethrin, along the microchannel was used to test the response of HL-1 cardiac cells in the micro-device, which correlated with toxicity data obtained from multi-well plates. The approach presented here may be useful for many biological and chemical processes that require rapid generation of long-range gradients in a portable microfluidic device.
在许多化学和生物学研究中，快速生成可扩散分子的浓度梯度的能力具有重要应用。在此，我们以简便快速的方式在便携式微流控装置中建立了分子（即蛋白质或毒素）在空间和时间上可控的浓度梯度。浓度梯度的形成由被动泵诱导的正向流动启动，并在蒸发诱导的反向流动过程中进一步优化。沿微流控通道的厘米级长梯度显示可通过反向流动在空间和时间上进行控制。通过停止流动使梯度分布稳定下来。对这一动态过程的计算模拟说明了对流和扩散对梯度生成的综合影响，并且与实验数据拟合良好。为了证明该方法的应用，沿微通道的心脏毒素α-氯氰菊酯的稳定浓度梯度被用于测试微装置中HL-1心脏细胞的反应，这与从多孔板获得的毒性数据相关。本文提出的方法可能对许多需要在便携式微流控装置中快速生成远程梯度的生物学和化学过程有用。
