Development of an integrated reference electrode for cell culture monitoring with large arrays of pH sensors

The possibility to monitor the metabolism of a in vitro extracellular activity, by monitoring the medium acidification rate, is of great interest in several fields of applications, where it can provide information on the culture status. To realise a highly integrated system with high throughput, ISFET sensors are good candidates. One drawback of this solution is the need of bulky external reference electrodes, which limits the actual integration of the system. Recently, reference electrodes based on polymeric layers doped with lipophilic salts to provide electrical conductivity, have provided promising results in term of potential stability and long term viability of the device. In this paper, we present the development of an “all-solid state” integrated reference electrode based on a PVC solid electrolyte with different types of lipophilic salts for the integration of an ISFET sensor array with Si3N4 gate dielectric used as sensitive material.