This article shows the development and testing of a microchip with integrated electrochemical sensors for measurement of pH, temperature, dissolved oxygen and viable biomass concentration under yeast cultivation conditions. Measurements were done both under dynamic batch conditions as well as under prolonged continuous cultivation conditions. The response of the sensors compared well with conventional measurement techniques. The biomass sensor was based on impedance spectroscopy. The results of the biomass sensor matched very well with dry weight measurements and showed a limit of detection of approximately 1 g/L. The dissolved oxygen concentration was monitored amperometrically using an ultra-microelectrode array, which showed an accuracy of approximately 0.2 mg/L and negligible drift. pH was monitored using an ISFET with an accuracy well below 0.1 pH unit. The platinum thin-film temperature resistor followed temperature changes with approximately 0.1 degrees C accuracy. The dimensions of the multi sensor chip are chosen as such that it is compatible with the 96-well plate format.
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.
This paper describes the design, modeling and experimental characterization of a micromachined impedance sensor for on-line monitoring of the viable yeast cell concentration (biomass) in a miniaturized cell assay. Measurements in Saccharomyces cerevisiae cell culture show that the characteristic frequency describing the -dispersion of S. cerevisiae cells is around 2.8 MHz. The permittivity change of the cell suspension was measured for the concentration range 0-9 g/l and depends linearly on the biomass concentration. In order to compensate the measurements for the electric properties of the background electrolyte, which increases the sensitivity and allows measurements in different media, the use of a three-electrode configuration in combination with a semi-permeable poly(2-hydroxyethyl methacrylate) (pHEMA) membrane was explored. Measurements show that the impedance of hydrated pHEMA varies with the background electrolyte conductivity only, and not with the concentration of cells, indicating that pHEMA is suitable for this purpose. The optimal pHEMA membrane thickness was determined using finite-element modelling and was found to be 1 m for the electrode configuration under study.
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