Extracellular recording of glycine receptor chloride channel activity as a prototype for biohybrid sensors

There is a continuously growing scientific and technological interest to develop and improve the application of artificial sensors. Biological components which are capable to transduce neutral signals into specific, robust and reproducible indicators frame an attractive alternative to construct biohybrid sensors. Since naturally “occurring” biosensors are only sparsely compatible with artificial devices, genetic engineering of eukaryotic cells provides an attractive approach, where cells can be tailored such to detect target compounds with exquisite specificity and sensitivity. We have developed the prototype for a single-cell-based anion-selective biohybrid sensor. HEK293 cells were stably transfected with a gene encoding glycine receptor alpha1 subunits. These cells were employed as transducers for glycine-evoked chloride currents in a concentration-dependent way. Cultured on substrate-integrated micro-devices, anionic membrane currents of cells were monitored extracellularly with field-effect transistors (FETs) and gold microelectrode arrays (MEAs). The results supported predictions of state-of-the-art models for cell-sensor coupling mechanisms and confirmed that extracellularly recorded anion currents cause similar signals, regardless whether obtained with field-effect transistors or microelectrodes. The whole-cell sensor successfully tracked glycine concentrations differing by three orders of magnitude. To our knowledge this contribution for the first time marks the functional characterization of an anion-selective biohybrid sensor.