Enhancing the Detection of Long-Chain Aldehydes by Peptide-Based Biosensors Through Counter-Ion Exchange

<p>Long-chain aldehydes, particularly nonanal, are recognized as potential volatile biomarkers of lung cancer in exhaled breath. This study investigates the influence of peptide counter-ions on the performance of QCM-based biosensors using two odorant-binding protein-derived peptides (OBPP4 and OBPP4-GSGSGS) for selective gas-phase detection of these aldehydes. Exchanging the counter-ion from trifluoroacetate to chloride improves biosensor sensitivity and lowers the limit of detection within the set of biosensors investigated in this study. The OBPP4-GSGSGS with chloride exhibited the highest sensitivity to nonanal (0.153 Hz/ppm) and the lowest LOD (9.8 ppm), with excellent selectivity over other groups of volatiles. The novelty of this work lies in demonstrating, for the first time, that simple counter-ion exchange in synthetic peptides can significantly enhance the gas-phase binding of volatile aldehydes, classified as lung cancer biomarkers, without alteringthe peptide sequence, offering a straightforward and effective optimization strategy for peptide-based piezoelectric biosensors.</p>