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We present for the first time biofunctionalization and biocompatibibility studies of solution-processable organic semiconductors. Furthermore, low-operating voltage organic thin-film transistor devices have been fabricated, which can be used as sensors in electrolytes. The devices are based on regioregular poly(3-hexylthiophene), being both a reasonably conductive and optically active polymer. To overcome biocompatibility problems protein-based coatings and oxygen-plasma treatments have been adopted to enable growth of adherent living cells on those modified surfaces. With the demonstration of biocompatible semiconducting polymeric layers, we have overcome a substantial hurdle for the realizations of low-cost and mass-produced sensors in life science, opening new possibilities of biological sensing with organic electronic devices.