Peripheral events in olfaction involve odorant binding proteins (OBPs) whose role in the recognition of different volatile chemicals is yet unclear. Here we report on the sensitive and quantitative measurement of the weak interactions associated with neutral enantiomers differentially binding to OBPs immobilized through a self-assembled monolayer to the gate of an organic bio-electronic transistor. The transduction is remarkably sensitive as the transistor output current is governed by the small capacitance of the protein layer undergoing minute changes as the ligand–protein complex is formed. Accurate determination of the free-energy balances and of the capacitance changes associated with the binding process allows derivation of the free-energy components as well as of the occurrence of conformational events associated with OBP ligand binding. Capacitance-modulated transistors open a new pathway for the study of ultra-weak molecular interactions in surface-bound protein–ligand complexes through an approach that combines bio-chemical and electronic thermodynamic parameters.

Cow nasal tissue contains a protein which shows specific binding activity for ‘green’ smelling compounds such as 2‐isobutyl‐3‐methoxypyrazine. This protein has now been purified using anion‐exchange fast protein liquid chromatography. The protein has a relative molecular mass of 400000–44000, s= 3.1 ± 0.3 S, pI = 4.7 ± 0.1 with an absorbance maximum at 278 nm, and consists of two subunits with an identical relative molecular mass of 19000. It is localised in the soluble fraction of cells from the olfactory mucosa and respiratory mucosa from the middle part of the maxillary and nasal turbinates, and is absent from all other tissues tested.