PNA-based biosensors for portable electrochemical diagnostics: Integration strategies and probe design

Portable and mobile biosensors are widely applied in point-of-care (POC) diagnostics due to their rapid response and suitability for decentralized testing. While DNA-based probes have been commonly used in electrochemical biosensors owing to their label-free operation, low cost, and sensitivity, their susceptibility to enzymatic degradation and low thermal stability has limited their broader utility. As an alternative, peptide nucleic acid (PNA) probes have gained increasing attention due to their synthetic backbone, which is based on an electrically neutral N-(2-aminoethyl)glycine (AEG) structure. This neutrality confers high resistance to nucleases and polymerases, while enabling stronger and more stable hybridization with negatively charged DNA targets. PNA probes also maintain structural integrity under low ionic strength conditions, improving signal stability compared to conventional DNA probes. These advantages have led to a growing body of research exploring PNA-based biosensors for portable applications. This mini-review surveys recent developments in this area, focusing on the physicochemical properties of PNA and their implications for biosensor design. Future directions for PNA biosensor development are also discussed. Representative studies on electrode architectures and detection strategies are highlighted, demonstrating the potential of PNA-based systems to support next-generation portable diagnostics. • PNA probes have enzymatic resistance due to their electrically neutral 2-(N-aminoethyl)glycine backbone. • Neutral charged PNA probes enable strong hybridization to DNA and RNA target fragments. • PNA probes maintain geometric consistency under both low and high ionic strength conditions