Electrochemical FETs Toward Nucleotide Detection With Emphasis on Clinical Translation: A Review

The rapid and accurate diagnosis of diseases is critical for timely remedial intervention and recurrence prevention. Nucleic acid-based biomarkers have emerged as pivotal diagnostic tools due to their high specificity and the capability for signal amplification from minimal sample quantities. Despite the widespread use of polymerase chain reaction (PCR) as the gold-standard technique, its limitations, including high costs, complex infrastructure requirements, and reduced effectiveness in complex biological matrices, underscore the need for alternative methods. Field-effect transistor (FET)-based biosensors have garnered significant attention as a transformative technology in this space, offering high sensitivity, miniaturization potential, and real-time detection. This review provides a focused and critical assessment of recent advancements in the application of nanostructured FET-based platforms for ultrasensitive nucleotide detection. It discusses cutting-edge amplification mechanisms, surface functionalization strategies, and signal modulation techniques that collectively enhance biosensor performance. This article also summarizes the attempts toward integration of microfluidic systems for efficient sample handling and highlights the use of machine learning (ML) models to improve diagnostic accuracy in clinical settings. Furthermore, it addresses prevailing challenges such as device stability, signal standardization, and reproducibility, offering strategic insights for overcoming these hurdles. By synthesizing recent progress and outlining pathways for clinical implementation, this article aims to accelerate the development of robust, point-of-care FET biosensors for nucleic acid diagnostics.