Integrated Electrochemical Sensor Array for On-Line Monitoring of Yeast Fermentations

Abstract

This paper describes the design, modeling, and experimental characterization of an electrochemical sensor array for on-line monitoring of fermentor conditions in both miniaturized cell assays and in industrial scale fermentations. The viable biomass concentration is determined from impedance spectroscopy. As a miniaturized electrode configuration with high cell constant is applied, the spectral conductivity variation is monitored instead of the permittivity variation. The dissolved oxygen concentration is monitored amperometrically using an ultramicroelectrode array, which is shown to have negligible flow dependence. pH is monitored using an ion-sensitive field effect transistor (ISFET), and a platinum thermistor is included for temperature measurements. All sensors were shown to be sufficiently accurate within the range relevant to yeast fermentations. The sensor array is shown to be very stable and durable and withstands steam-sterilization.

Aerobic batch cultivation in micro bioreactor with integrated electrochemical sensor array

“…Further details about the theoretical aspects, the design, the fabrication, packaging, and experimental characterization of the sensor arrays have been described previously. 22,23 Readout of the sensor array…”

“…The instability of the voltage drop over the salt bridge, including the Nafion junction, was measured to be less than 0.1 mV hr À1 within a 12 h period. Considering the fact that the ideal Nernstian sensitivity for an ISFET is À58.2 mV/pH unit at 20 C, 22 the stability of the voltage drop over the salt bridge was found to be acceptable for the intended application.…”

“…Recently, an integrated sensor array has been developed, based on the 96-well microtiter plate format, containing sensors for pH, dissolved oxygen, temperature, and viable biomass concentration. 22,23 Compatibility of a miniaturized bioreactor system to the current high-throughput cell cultivation platforms, i.e. the 24 and 96 (deep)well plates, is highly desirable because of the already available automation equipment.…”

“…Taking this into account, we developed a parallelized micro bioreactor system with a working volume of 100 lL based on the 96-well microtiter plate format. In each of the micro bioreactors, a recently developed electrochemical sensor array 22,23 was integrated for the online measurement of temperature, pH, dissolved oxygen concentration, and viable biomass concentration. The cumulative CO 2 production during the cultivations was measured with a conductometric sensor.…”

Soluble compound screening using microfluidic gradients for regenerative medicine research

“…Finally, Krommenhoek et al reported an integrated sensor device with a footprint of < 1 cm 2 to monitor in parallel different parameters in a bioreactor such as the temperature, the pH, the oxygen concentration, and the biomass. 149 Although this device has originally been developed for yeast culture, it could easily be employed in an integrated bioreactor for closely monitoring the growth environment of microtissues.…”