A High-Throughput Impedance Sensing System for 3D Cell Drug Permeability Gradient Effect Real-Time Monitoring

摘要

3D cells are encapsulated in the thick matreigel, drugs can not penetrate the matrigel evenly, resulting in the gradient effect. The gradient effect would affects the accuracy of the 3D cell-based biosensor response to drug screening. Traditional 3D cell impedance sensors is difficult to measure the gradient of 3D cell drug permeation effectively. In this study, a high-throughput 3D parallel impedance chip has been constructed for real-time drug gradient effect monitoring. Adenocarcinomic human alveolar basal epithelial cell lines (A549) are encapsulated in matrigel to construct 3D lung cancer model. The system consist of 3D parallel impedance chip with 16 vertically aligned gold electrodes, a homemade detecting instrument and a PC software based on LabVIEW. Computational finite element (FE) analysis was used to explore the interactions of adjacent electrodes. In our previous study, cell proliferation or apoptosis in the matrigel would cause variation of cell density, which shown to be inverse proportional to the impedance magnitude of the cell/matrigel entire construct. By using this system, long-term, non-invasive, real-time monitoring of cell proliferation and viability can be achieved. Moreover, after the cell proliferation reached to plateau phase, 3D cell culture system was dosed with different kind of anti-cancer drugs under diverse concentration and the viability of 3D cells at different spatial location sites can be monitored. The experiment results show that drug permeability gradient can be detected by our sensing system. This high-throughput impedance sensing system has a high potential to develop a powerful analytical platform for cancer research and drug screening.