Recent Developments in Using Scanning Radio-Frequency Impedance Measurements on Cell Culture Processes
John P Carvell, Aditya Bhat, Pareshkumar M Patel, Gerard H Markx
The viable cell concentration is of prime importance in monitoring cell culture manufacturing processes. Of the available online biomass assays, the radio-frequency impedance (RFI) method has some clear advantages for manufacturing
because it is an unambiguous reflection of viable cell biovolume rather than the total number of cells. This allows RFI to be used to control feeding rates or to maintain a constant level of biomass within the bioreactor. RFI is also suitable for measuring the live cell density in bioreactors when the cells are attached to microcarriers and to inert discs. Traditional RFI-based systems measure the capacitance at either one frequency (typically 0.5 MHz) or in a dual frequency mode. However, scanning the capacitance in a frequency range, typically between 0.1 and 20 MHz, also makes it possible to measure other
important parameters such as the cell size, the cell membrane capacitance, and the cell interior conductivity online.3,4
Online measurement of such properties can provide useful information regarding the physiological state of the cells, which can assist in better understanding and controlling the fermentation or cell culture process.
In this article, we introduce the concept, theory, and challenges of applying RFI frequency scanning using the Aber Biomass Monitor (Aberystwyth, UK) to cell culture processes, and show examples of how additional process parameters can be derived.