3D cell-based biosensor for cell viability and drug assessment by 3D electric cell/matrigel-substrate impedance sensing

Preclinical efficacy and toxicity assessment of drug candidates plays a significant role in drug discovery and development. Traditional planar cell culture is a common way to perform the preclinical drug test, but it is difficult to correctly predict the drug efficacy and toxicity due to the simple two-dimensional (2D) extracellular microenvironment. Compared to the planar cell culture, three-dimensional (3D) cell culture system can better mimic the complex extracellular microenvironment where cells reside in the 3D tissues/organs in vivo. However, the conventional imaging techniques are difficult to achieve the dynamic and label-free monitoring of cellular behavior in thick sample by 3D cell culture. Here, 3D electric cell/matrigel-substrate impedance sensing (3D-ECMIS) is developed for real-time and non-invasive monitoring of 3D cell viability and drug susceptibility. In this study, human hepatoma cells (HepG2) are encapsulated in the matrigel scaffold and cultured in a 3D ECMIS chip which involves a pair of vertical golden electrodes on the opposite sidewalls of the culture chamber for the in-situ impedance measurement. Moreover, a portable multichannel system is developed to monitor the 3D cell/matrigel construct. The number of 3D-cultured cells was inversely proportional to the impedance magnitude of the entire cell/matrigel construct. Furthermore, anti-cancer drug screening will be conducted on the 3D-cultured cells when the cell proliferation reaches to a plateau phase. To validate the performance of 3D-ECMIS for the cell viability and drug susceptibility, the cell live/dead staining are utilized to confirm the results of drug susceptibility by this 3D-cell-based biosensor system. It is demonstrated that the 3D cell-based biosensor and 3D-ECMIS system will be a promising platform to improve the accuracy of cell-based anti-cancer drug screening in vitro.