Optimizing peptide detection using FET-based sensors: Integrating non-linearities of surface functionalization

• Proposed a novel method for improving peptide interaction with the ATPES/linker system. This method utilizes tert -Butyloxycarbonyl (BOC) protection for the N-terminal, effectively preventing undesirable reactions and boosting overall detection efficiency. • A noise-filtering technique is developed to address noise interference that can hinder peptide recognition. This technique works by leveraging the full pH titration spectrum, enabling accurate retrieval of peptide signatures even under low signal-to-noise ratio (SNR) conditions. • The research delves into the critical role of BOC protection levels on how amine surfaces are functionalized with APTES. • This work bridges the gap between peptide synthesis/sequencing and bioanalytical applications. This study presents a method for enhancing peptide interaction with ATPES/linkers, utilizing tert -Butyloxycarbonyl to protect the N-terminal and prevent undesirable reactions. Addressing noise interference in peptide recognition, we devised a noise-filtering technique that enables accurate peptide signature retrieval even at low signal-to-noise ratio (SNR) by leveraging the full pH titration spectrum. Additionally, our research explores the impact of BOC protection levels on the functionalization of amine surfaces with APTES, highlighting how silanol sites influence the isoelectric point, surface potential, and capacitance. These findings underscore the necessity of considering chemical protection and surface chemistry in peptide synthesis and sequencing, offering valuable insights for bioanalytical applications.