Research Center for Analytical Sciences, Northeastern University, Shenyang 110819, China.
Lab Chip. 2011 Oct 7;11(19):3305-12. doi: 10.1039/c1lc20123a. Epub 2011 Aug 15.
An integrated microfluidic concentration gradient chip was developed for generating stepwise concentrations in high-density channels and applied to high-throughput apoptosis analysis of human uterine cervix cancer (HeLa) cells. The concentration gradient was generated by repeated splitting-and-mixing of the source solutions in a radial channel network which consists of multiple concentric circular channels and an increasing number of branch channels. The gradients were formed over hundreds of branches with predictable concentrations in each branch channel. This configuration brings about some distinctive advantages, e.g., more compact and versatile design, high-density of channels and wide concentration ranges. This concentration gradient generator was used in perfusion culture of HeLa cells and a drug-induced apoptosis assay, demonstrated by investigating the single and combined effects of two model anticancer drugs, 5-fluorouracil and Cyclophosphamide, which were divided into 65 concentrations of the two drugs respectively and 65 of their combinatorial concentrations. The gradient generation, the cell culture/stimulation and staining were performed in a single chip. The present device offers a unique platform to characterize various cellular responses in a high-throughput fashion.
一种集成的微流控浓度梯度芯片被开发出来，用于在高密度通道中产生逐步浓度，并应用于高通量分析人子宫颈癌细胞（HeLa）的细胞凋亡。浓度梯度通过在由多个同心圆形通道和数量不断增加的分支通道组成的径向通道网络中对源溶液进行反复分裂和混合来产生。梯度在数百个分支中形成，每个分支通道都具有可预测的浓度。这种配置带来了一些独特的优势，例如更紧凑和通用的设计、高密度的通道和广泛的浓度范围。该浓度梯度发生器用于 HeLa 细胞的灌注培养和药物诱导的细胞凋亡检测，通过研究两种模型抗癌药物 5-氟尿嘧啶和环磷酰胺的单一和联合作用来证明，这两种药物分别分为 65 种浓度和 65 种组合浓度。梯度生成、细胞培养/刺激和染色都在单个芯片中进行。该装置提供了一个独特的平台，可高通量地描述各种细胞反应。
