Monitoring of Cell Cultures With Biosensors and (Bio)Sensor Arrays

Abstract

The monitoring of cell cultures in terms of their viability and physiological state is extremely important in a wide range of applications, from basic research, through drug screening, cancer research, biocompatibility testing, and tissue engineering, to biotechnological industry. Traditionally, the physiological state of cell culture and its alterations are predominantly determined optically (microscopy and fluorescent cell-counting), while industrial bioproduction with the use of cells can be monitored controlling only single process variables like pH, pO2, temperature, and OD. These data can be supplemented with the information on changing concentrations of substrates consumed and metabolites produced during the culture and observed in cell microenvironment. For such purpose, biosensors and (bio)sensor arrays present great opportunity due to the possibility of detection of wide range of analytes, online and real-time measurements, and miniaturization for compatibility with cell microbioreactors/multiwell plates. In this article such devices are reviewed and their applications are discussed. First, single biosensors applied to the determination of key metabolites in cell cultures are presented, then their fusion in terms of biosensors arrays and sensors arrays incorporating pH, pO2, temperature sensing for cellular microphysiometry. Finally, soft sensing for cell-culture monitoring based on (bio)electrochemical imaging is introduced—applications of electronic tongues (i.e., sensor arrays with chemometric data analysis treatment) for cellular microphysiometry are presented.