Differential Inductive Sensor for Continuous Non-Invasive Cell Growth Monitoring in Disposable Bioreactors

Abstract

Abstract:In this work, we present a low-cost sensor system for continuous non-invasive cell growth monitoring, especially for single use bioreactor (SUB) applications. The sensor system is based on a differential transformer. Using this differential setup, the influence of the primary magnetic flux is eliminated from the measuring signal, enabling highly sensitive non-invasive detection of permittivity changes in the culture medium. To evaluate the sensor, E. coli cultivations are performed and the cell density is measured through the polymer foil of a SUB. We found a linear dependency with low data scattering between measuring signal and cell density.

How Geometry Affects Sensitivity of a Differential Transformer for Contactless Characterization of Liquids

“…Therefore, this measuring method is well suited for the contactless determination of the electrical and dielectric properties of liquids located inside a plastic or glass measuring (flow-through) chamber. Therefore, this measurement method has potential in biotechnology and medical technology for the contactless determination of biomass within single-use bioreactors [1,18] or for obtaining tissue information [19][20][21][22][23]. In addition, the differential transformer approach is investigated with respect to continuous in-line monitoring of the sodium concentration in human blood, by measuring the blood plasma conductivity, mainly influenced by the sodium concentration [24][25][26][27].…”

P2.05 - Continuous non-invasive cell growth monitoring in disposable bioreactors using an active compensated differential transformer

“…The measuring voltage Us is zero for an ideally symmetrical, unloaded sensor, as the primary magnetic flux passes through identically both receiver coils. However, due to small geometric asymmetries and resonance effects, caused by parasitic coupling between the coils the measuring voltage Us is not fully zero balanced in real differential transformers [8]. As shown in Figure 2, in the unloaded state, the real part of the measuring voltage Us' significantly exceeds zero depending on the frequency.…”

“…The receiver coils Ls1 and Ls2 have a similar inductance of Ls = 10 mH (2 mm high, 33 mm in diameter). In order to reach an increased sensitivity, a high turn ratio is realized by choosing a 100-fold lower inductance for the excitation coil Lp = 0.1 mH (10 mm high, 15 mm in diameter) [8].…”

“…According to [7], zero balancing of the measuring voltage can be achieved by vertical displacement of the outer receiver coil Ls2. However, this also affects the parasitic coupling between the coils and shifts the resonance frequencies which can lead to decreased sensitivity when operating at a fixed measuring frequency [8]. Hence, we developed another zero balancing method of the measuring voltage.…”

“…Preliminary measurements show a good correlation between the biomass concentration in the cell culture medium and the sensor signal [7]. However, due to high offset voltages caused by geometric asymmetries and resonance effects, complex measuring electronics is required for the detection of small sensor signal variations caused by permittivity changes of the cell culture medium [8]. Here, we present a very promising approach to compensate such disturbing offset voltages without loss of sensitivity allowing the use of simple measuring electronics and eventually a low-cost sensor.…”