基于微流控芯片的乳腺癌细胞微环境酸化检测

建立了基于微流控芯片的乳腺癌微环境酸化模型和动态检测微环境酸化情况的分析方法。设计了一种多层复合式微流控芯片，将乳腺癌细胞悬液引入含有水凝胶前体的芯片培养室后，在硝酸纤维素薄膜上固化形成3D培养支架。芯片通道连续灌流模拟血流供应，并将非电化学的pH检测器引入芯片，通过图像分析得到实时的pH变化。通过观察癌细胞的存活率、增殖率、乳酸水平及pH值，分析微环境的酸化情况，同时与正常细胞进行比较。结果表明，连续灌流培养7 d，乳腺癌细胞的存活率保持在90%以上；随着培养天数的增加，芯片上癌细胞微环境的pH值逐渐降低，且灌流速度越低，pH值下降越明显，而正常细胞微环境的pH值无明显变化。基于微流控芯片的微环境酸化检测平台可实时动态检测微环境的pH值，有望成为相关肿瘤研究的有力工具。

Detection of microenvironment acidification in breast cancer cells by microfluidic chips

An analytical method was established for dynamic detection of microenvironment acidification in a breast cancer cell model based on microfluidic chips. A multilayer hybrid microfluidic chip was designed. When the suspension of the breast cancer cells entered the chips the hydrogel grids would become skeleton for 3D cultures. Continuous perfusion in microfluidic chip channels was used to mimic blood flow in vivo. And the non-electrochemical pH sensor was introduced into the chips to give the real-time changes of pH by image analysis. Cell viabilities, cell proliferations, lactic acid levels and pH values of cancer cells were detected to analyze microenvironment acidification, while comparing with the normal cells. Continuous perfusion for 7 d, the cell viability remained above 90%. With the increase of culturing days, the pH of the tumor microenvironment decreased gradually. The lower perfusion rates, the lower pH values, but the pH of the normal cells microenvironment had no obvious change. The microenvironment acidification detection platform of the microfluidic chip could detect microenvironment pH in real time, and it is a useful tool for cancer research.