Abstract
Miniaturized, reusable, and scalable biosensors are key enablers of precision diagnostics and accessible healthcare. Among emerging liquid biopsy cancer biomarkers, microRNAs (miRNAs) have demonstrated transformative potential; however, conventional detection methods rely on expensive enzymes, labels, and bulky instrumentation, limiting clinical utility. Field effect transistor (FET) biosensors offer a promising alternative owing to their miniaturized size, intrinsic amplification capacity, user-friendliness, and scalability. This study introduces a probe-functionalized thin film transistor-based miRNA biosensor, called miR-TFT, enabling label-free, enzyme-free, ultrasensitive, and specific detection of miRNA. The highly scalable device features a tri-channel heterojunction thin-film transistor (HJ-TFT) with an In2O3/ZnO channel, functionalized with bespoke peptide nucleic acid (PNA) probes via phosphonic acid anchor groups. Compared to conventional oligonucleotides, PNAs offer superior specificity, stability, and resistance to degradation. Sequence-specific binding between the target miRNA and PNA probes induces charge modulation at the buried heterointerface, altering the transistor's electrical properties. This interaction produces an amplified signal, yielding an ultra-low 0.6 fM limit-of-detection with single-nucleotide specificity. Moreover, the device supports facile surface regeneration through O2 plasma treatment, enabling device reuse without compromising performance. In addition to its exceptional analytical performance, miR-TFT offers portability, reusability, and compatibility with wafer-scale manufacturing, positioning it as a transformative solution to drive decentralized precision diagnostics.