College of Engineering and Biodynamic Optical Imaging Center, Peking University, Beijing 100871, China.
Anal Chem. 2012 Feb 21;84(4):2088-93. doi: 10.1021/ac2032029. Epub 2012 Feb 8.
The interaction between tumor and endothelial cells is crucial to cancer metastasis and angiogenesis. We developed a novel microfluidic device to assess the cell-cell interaction quantitatively at the single cell resolution. This integrated chip offers 16 coculture experiments in parallel with controllable microenvironments to study interactions between cells dynamically. We applied this approach to model the tumor invasion using Hela cells and human umbilical vein endothelial cells (HUVECs) and monitored the migration of both. We observed the retreatment of HUVECs upon the approach of Hela cells during coculture, indicating that the interaction between two cells was mediated by soluble factors. This interaction was further analyzed through quantitatively processing the phase-contrast microscopic time-lapse images of each individual coculture chamber. We also confirmed this paracrine effect by varying the frequency of medium change. This microfluidic technique is highly controllable, contamination free, fully automatic, and inexpensive. This approach not only offers a unique way to quantitatively study the interaction between cells but also provides accurate spatial-temporal tunability of microenvironments for cell coculture. We believe this method, intrinsically high-throughput and quantitative, will greatly facilitate the study of cell-cell interactions and communications.
肿瘤细胞与内皮细胞的相互作用对癌症转移和血管生成至关重要。我们开发了一种新的微流控装置，能够以单细胞分辨率定量评估细胞间的相互作用。该集成芯片可提供 16 个共培养实验，具有可控的微环境，可动态研究细胞间的相互作用。我们应用这种方法模拟了 Hela 细胞和人脐静脉内皮细胞（HUVEC）的肿瘤侵袭，并监测了两者的迁移。我们观察到在共培养过程中 Hela 细胞接近时 HUVEC 的再处理，表明两种细胞之间的相互作用是由可溶性因子介导的。通过对每个共培养腔室的相差显微镜实时图像进行定量处理，进一步分析了这种相互作用。我们还通过改变培养基更换的频率来证实这种旁分泌效应。这种微流控技术具有高度可控性、无污染、全自动和低成本的特点。这种方法不仅提供了定量研究细胞间相互作用的独特方法，而且还为细胞共培养提供了准确的时空微环境可调性。我们相信，这种方法本质上具有高通量和定量的特点，将极大地促进细胞间相互作用和通讯的研究。
