Design of a Multiparametric Biosensing Platform and Its Validation in a Study on Spontaneous Cell Detachment from Temperature Gradients

This article reports on a bioanalytical sensor device that hosts three different transducer principles: impedance spectroscopy, quartz-crystal microbalance with dissipation monitoring, and the thermal-current-based heat-transfer method. These principles utilize a single chip, allowing one to perform either microbalance and heat transfer measurements in parallel or heat transfer and impedance measurements. When taking specific precautions, the three measurement modalities can even be used truly simultaneously. The probed parameters are distinctly different, so that one may speak about multiparametric or “orthogonal” sensing without crosstalk between the sensing circuits. Hence, this sensor allows one to identify which of these label-free sensing principles performs best for a given bioanalytical application in terms of a high signal amplitude and signal-to-noise ratio. As a proof-of-concept, the three-parameter sensor was validated by studying the spontaneous, collective detachment of eukaryotic cells in the presence of a temperature gradient between the QCM chip and the supernatant liquid. In addition to heat transfer, detachment can also be monitored by the impedance- and QCM-related signals. These features allow for the distinguishing between different yeast strains that differ in their flocculation genes, and the sensor device enables proliferation monitoring of yeast colonies over time.