BioFET Platforms Combined with PNA Probe for MicroRNA Detection: Current Trends and Future Perspectives

MicroRNAs (miRNAs) represent highly promising biomarkers for non-invasive clinical diagnostics. To overcome the limitations of conventional methods, Field-Effect Transistor biosensors (bioFETs) emerge as compelling alternatives by providing label-free and real-time readouts. However, bioFETs employing canonical DNA/RNA probes face fundamental limitations due to the Debye screening effect. Peptide Nucleic Acid (PNA), a synthetic nucleic acid analog featuring an uncharged peptide-like backbone, offers an effective solution. PNA’s electroneutrality allows for efficient hybridization at a low ionic strength, thereby mitigating Debye screening constraints. PNA also offers additional key advantages, including high specificity and enzymatic resistance. This work examines recent advancements in PNA–bioFETs, highlighting their potential for the development of robust platforms for clinical miRNA evaluation. Surface Plasmon Resonance (SPR) and Atomic Force Spectroscopy (AFS) are valuable tools to preliminarily characterize probe–target interactions. Key approaches, focused on implementing alternative PNA probe designs and optimizing Self-Assembled Monolayer (SAM) organization, are outlined. By presenting a cross-study comparison that correlates each strategy with the analytical outcomes of a custom-designed bioFET platform targeting miRNA 155, complemented by an overview of PNA–bioFETs across other miRNAs, we illustrate how the synergy between PNA and bioFET can approach reliable miRNA detection, paving the way for the development of Point-of-Care (POC) devices.