Development of a micro-scale perfusion 3D cell culture biochip with an incorporated electrical impedance measurement scheme for the quantification of cell number in a 3D cell culture construct

This article reports a perfusion 3D cell culture biochip with an incorporated electrical impedance measurement-based scheme for the quantification of cell number in the 3D cell culture construct. The biochip consists of culture chamber and fluidic channel for perfusion 3D cell culture followed by assembling the electrodes for impedance measurement. In this study, breast cancer cell line culture was performed using the proposed biochip. The perfusion 3D cell culture model was compared with a conventional static cell culture model in terms of environmental pH and metabolic activities of cells. Results revealed that the real value of the proposed biochip has its ability to maintain a stable and thus quantifiable culture condition. In addition, the metabolic activities of cells in the two culture models compared showed statistically different. It is concluded that the choice of a cell culture format can influence assay results. Moreover, after performing the 3D cell culture, electrical impedance measurement was conducted for the quantification of cell number in the 3D cell culture construct. The results indicated that the change in impedance was directly proportional to the cell number from 10 ⁴ to 10 ⁷ cells ml ^-1 in the culture construct. As a whole, the proposed biochip not only can provide a stable, well-defined, and biologically meaningful culture environment, but also integrates the work of cell number quantification in a simple, economy, and time efficient manner. All of these traits are particularly useful for high-precision and high-throughput 3D cell culture-based assays.