# Nucleic Acid-Based Field-Effect Transistor Biosensors

**Authors:** Haoyu Fan, Dekai Ye, Xiuli Gao, Yuan Luo, Lihua Wang

PMC · DOI: 10.3390/bios16020095 · Biosensors · 2026-02-03

## TL;DR

This paper reviews recent advancements in nucleic acid-based FET biosensors for sensitive and rapid detection of biomolecules in health and environmental monitoring.

## Contribution

The paper provides a comprehensive review of design strategies and performance improvements in nucleic acid-based FET biosensors.

## Key findings

- NA-FET biosensors offer label-free and amplification-free detection of biomolecules at low concentrations.
- Integration of nucleic acid aptamers and framework nucleic acids enables multiplexed detection of diverse analytes.
- Advances in semiconductor materials improve signal transduction and device architecture for practical applications.

## Abstract

The demand for rapid and highly sensitive sensing technologies is increasing across diverse fields, including precise disease diagnosis, early-stage screening, and real-time environmental monitoring. Field-effect transistor (FET)-based sensing platforms have shown tremendous potential for detecting target molecules at extremely low concentrations, owing to their ultrahigh sensitivity, label-free and amplification-free operation, and rapid response. In recent years, the rapid advancement of nucleic acid probe design and interfacial engineering has markedly accelerated the development of FET sensors, leading to the emergence of nucleic acid-based FET (NA-FET) biosensors. Beyond their fundamental role in nucleic acid detection, the integration of nucleic acid aptamers and framework nucleic acids has greatly expanded NA-FET biosensors’ applicability to a wide range of analytes and multiplexed detection. At the same time, advances in semiconductor materials have endowed the NA-FET biosensor with highly efficient signal transduction and diverse device architectures, enabling successful proof-of-concept demonstrations for various clinically and environmentally relevant molecular biomarkers. Furthermore, the integration into portable, wearable, and implantable devices has laid a solid foundation for their future development into real-world applications. This review summarizes recent cutting-edge progress in NA-FET biosensors, highlights key design strategies and performance improvements, and discusses current challenges, future development directions, and their prospects for practical applications.

## Full-text entities

- **Genes:** MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, EPCAM (epithelial cell adhesion molecule) [NCBI Gene 4072] {aka Ber-Ep4, BerEp4, DIAR5, EGP-2, EGP314, EGP40}, NPEPPS (aminopeptidase puromycin sensitive) [NCBI Gene 9520] {aka AAP-S, MP100, PSA}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, ORF1ab (ORF1a polyprotein;ORF1ab polyprotein) [NCBI Gene 43740578], MIR141 (microRNA 141) [NCBI Gene 406933] {aka MIRN141, mir-141}, N (nucleocapsid phosphoprotein) [NCBI Gene 43740575], SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** sickle cell disease (MESH:D000755), breast cancer (MESH:D001943), sepsis (MESH:D018805), infectious disease (MESH:D003141), hepatocellular carcinoma (MESH:D006528), colon cancer (MESH:D015179), ALS (MESH:D000690), dry eye disease (MESH:D015352), COVID-19 (MESH:D000086382), anxiety disorders (MESH:D001008), PTSD (MESH:D013313), Cushing's syndrome (MESH:D003480), major depressive disorder (MESH:D003865), genetic diseases (MESH:D030342), Parkinson's disease (MESH:D010300), pancreatic cancer (MESH:D010190), cervical cancer (MESH:D002583), prostate cancer (MESH:D011471), injury to (MESH:D014947), inflammation (MESH:D007249), cancer (MESH:D009369), mental disorders (MESH:D001523), Alzheimer's (MESH:D000544)
- **Chemicals:** steroid (MESH:D013256), phosphonic acid (MESH:C570063), ATP (MESH:D000255), oxide (MESH:D010087), 5-HT (MESH:D012701), TIPS-pentacene (MESH:C522282), MXene (MESH:C000723374), PET (MESH:D011093), Mo (MESH:D008982), N-(2-aminoethyl)glycine (MESH:C028791), glutaraldehyde (MESH:D005976), dopamine (MESH:D004298), PBS (MESH:D007854), NA (MESH:D012964), potassium (MESH:D011188), S (MESH:D013455), ITO (MESH:C109984), Graphene (MESH:D006108), organosilane (MESH:D017646), Si (MESH:D012825), Framework (-), aluminum (MESH:D000535), oils (MESH:D009821), NH2 (MESH:D000588), 1-pyrenebutyric acid (MESH:C002218), carbon nanotubes (MESH:D037742), amino acids (MESH:D000596), thiol (MESH:D013438), PEDOT:PSS (MESH:C533756), Al2O3 (MESH:D000537), BPA (MESH:C006780), In2O3 (MESH:C047711), nucleotide (MESH:D009711), PMMA (MESH:D019904), ZnO (MESH:D015034), amide (MESH:D000577), water (MESH:D014867), cholesterol (MESH:D002784), copper (MESH:D003300), glutamate (MESH:D018698), biotin (MESH:D001710), sugar-phosphate (MESH:D013403), oxygen (MESH:D010100), sulfide (MESH:D013440), acid (MESH:D000143), salt (MESH:D012492), phosphate (MESH:D010710), black phosphorus (MESH:D010758), histamine (MESH:D006632), NaCl (MESH:D012965), Au (MESH:D006046), Metal (MESH:D008670), MoS2 (MESH:C082964), pyrene (MESH:C030984), Carbon (MESH:D002244), thymine (MESH:D013941), polymer (MESH:D011108), PNA (MESH:D020135), PVA (MESH:C063253), Cortisol (MESH:D006854)
- **Species:** Monkeypox virus (no rank) [taxon 10244], Respiratory syncytial virus (no rank) [taxon 12814], Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Enterovirus A71 (no rank) [taxon 39054], Hepatitis B virus (no rank) [taxon 10407], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** A35R
- **Cell lines:** PANC — Homo sapiens (Human), Pancreatic adenocarcinoma, Cancer cell line (CVCL_A658), MIHA — Homo sapiens (Human), Transformed cell line (CVCL_SA11), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027)

## Full text

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## Figures

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## References

144 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938189/full.md

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Source: https://tomesphere.com/paper/PMC12938189