场效应晶体管生物传感器在核酸检测中的应用进展

doi:10.19586/j.2095-2341.2024.0204

生物技术进展 ›› 2025, Vol. 15 ›› Issue (4): 597-605.DOI: 10.19586/j.2095-2341.2024.0204

• 进展评述 • 上一篇

场效应晶体管生物传感器在核酸检测中的应用进展

施玥¹^,²(), 韩尧², 李浩², 孙岩松¹^,²()

^1.牡丹江医科大学公共卫生学院，黑龙江牡丹江 157011
^2.军事科学院军事医学研究院，病原微生物生物安全全国重点实验室，北京 100071

收稿日期:2024-12-23 接受日期:2025-03-05 出版日期:2025-07-25 发布日期:2025-09-08
通讯作者: 孙岩松
作者简介:施玥E-mail: shiyoo22@163.com；
基金资助:
国家重点研发计划项目(2023YFC2605100)

Application Progress of Biosensors Based on Field-effect Transistors in Nucleic Acid Detection

Yue SHI¹^,²(), Yao HAN², Hao LI², Yansong SUN¹^,²()

^1.College of Public Health，Mudanjiang Medical University，Heilongjiang Mudanjiang 157011，China
^2.State Key Laboratory of Pathogen and Biosecurity，Academy of Military Medical Sciences，Beijing 100071，China

Received:2024-12-23 Accepted:2025-03-05 Online:2025-07-25 Published:2025-09-08
Contact: Yansong SUN

摘要/Abstract

摘要：

场效应晶体管生物传感器是一种基于场效应晶体管原理检测生物分子或生物标志物的传感器，由于其电场效应的信号放大特性可以检测到极低浓度的生物分子相互作用，进一步实现生物分子识别，在核酸检测领域具有无需核酸扩增的独特优势，核酸检测时间更短。此外，场效应晶体管生物传感器在核酸检测性能、便携性和成本效益等方面也有优势。总体而言，场效应晶体管生物传感器可实现超快速、超高灵敏度的病毒基因靶向识别，其结合微流控技术、纳米材料、柔性电子材料等，在食品安全、临床诊断、基因分型、生物安全等领域具有巨大的应用潜力。为了更好地将场效应晶体管传感器应用于生物检测领域，回顾了场效应晶体管生物传感器在核酸检测中的应用，从生物识别层方面对场效应晶体管生物传感器进行了分类讨论，以期为场效应晶体管生物传感器在核酸检测中的应用研究提供参考。

关键词: 场效应晶体管, 核酸检测, 传感器

Abstract:

The field-effect transistor （FET） biosensor is a type of sensor based on the principle of detecting biomolecules or biomarkers. Due to the signal amplification characteristics of its electric field effect， it enables the detection of biomolecular interactions at extremely low concentrations， further enabling biomolecular recognition. In the field of nucleic acid detection， this approach offers the unique advantage of eliminating the need for nucleic acid amplification， resulting in shorter detection times. Additionally， FET biosensors also excel in nucleic acid detection performance， portability， and cost-effectiveness. Overall， FET biosensors can achieve ultra-rapid and ultra-sensitive targeted identification of viral genes. Combined with microfluidic technology， nanomaterials， or flexible electronic materials， they hold significant promise for application in food safety， clinical diagnosis， genotyping， biosafety， and other fields. To facilitate the better application of FET sensors in biological detection， this review summarized the current applications of FET biosensors in nucleic acid detection and provided a classification and discussion based on the biological recognition layer， aiming to offer insights for future research in this area.

Key words: field-effect transistors, nucleic acid, biosensors

中图分类号:

施玥, 韩尧, 李浩, 孙岩松. 场效应晶体管生物传感器在核酸检测中的应用进展[J]. 生物技术进展, 2025, 15(4): 597-605.

Yue SHI, Yao HAN, Hao LI, Yansong SUN. Application Progress of Biosensors Based on Field-effect Transistors in Nucleic Acid Detection[J]. Current Biotechnology, 2025, 15(4): 597-605.

图/表 3

参考文献 44

[1]	世界卫生组织. 国际卫生条例(2005)突发事件委员会第十四次会议关于新型冠状病毒肺炎(COVID-19)大流行的声明[EB/OL]. (2023-01-30) [2024-12-20]. .
[2]	MERCER A. Protection against severe infectious disease in the past[J]. Pathog. Glob. Health, 2021, 115(3): 151-167.
[3]	LAZCKA O, DEL CAMPO F J, MUÑOZ F X. Pathogen detection: a perspective of traditional methods and biosensors[J]. Biosens. Bioelectron., 2007, 22(7): 1205-1217.
[4]	GRACIAS K S, MCKILLIP J L. A review of conventional detection and enumeration methods for pathogenic bacteria in food[J]. Can. J. Microbiol., 2004, 50(11): 883-890.
[5]	CESEWSKI E, JOHNSON B N. Electrochemical biosensors for pathogen detection[J/OL]. Biosens. Bioelectron., 2020, 159: 112214[2025-03-25]. .
[6]	张春雷.病原微生物检测技术研究进展[J].生物技术进展,2024,14(2):189-195.
	ZHANG C L. Pathogens detection technology: a review[J]. Curr. Biotechnol., 2024, 14(2): 189-195.
[7]	AHMAD W, GONG Y, ABBAS G, et al.. Evolution of low-dimensional material-based field-effect transistors[J]. Nanoscale, 2021, 13(10): 5162-5186.
[8]	SADIGHBAYAN D, HASANZADEH M, GHAFAR-ZADEH E. Biosensing based on field-effect transistors (FET): recent progress and challenges[J/OL]. Trends Analyt. Chem., 2020, 133: 116067[2025-03-25]. .
[9]	KAISTI M. Detection principles of biological and chemical FET sensors[J]. Biosens. Bioelectron., 2017, 98: 437-448.
[10]	WANG J, CHEN D, HUANG W, et al.. Aptamer-functionalized field-effect transistor biosensors for disease diagnosis and environmental monitoring[J/OL]. Exploration, 2023, 3(3): 20210027[2025-03-25]. .
[11]	ZHANG X, LIU T, BOYLE A, et al.. Dielectric-modulated biosensing with ultrahigh-frequency-operated graphene field-effect transistors[J/OL]. Adv. Mater., 2022, 34(7): e2106666[2025-03-25]. .
[12]	KONG D, WANG X, GU C, et al.. Direct SARS-CoV-2 nucleic acid detection by Y-shaped DNA dual-probe transistor assay[J]. J. Am. Chem. Soc., 2021, 143(41): 17004-17014.
[13]	ZHANG Y, CHEN B, CHEN D, et al.. Electrical detection assay based on programmable nucleic acid probe for efficient single-nucleotide polymorphism identification[J]. ACS Sens., 2023, 8(5): 2096-2104.
[14]	WANG X, KONG D, GUO M, et al.. Rapid SARS-CoV-2 nucleic acid testing and pooled assay by tetrahedral DNA nanostructure transistor[J]. Nano Lett., 2021, 21(22): 9450-9457.
[15]	WU Y, JI D, DAI C, et al.. Triple-probe DNA framework-based transistor for SARS-CoV-2 10-in-1 pooled testing[J]. Nano Lett., 2022, 22(8): 3307-3316.
[16]	LIANG Y, XIAO M, XIE J, et al.. Amplification-free detection of SARS-CoV-2 down to single virus level by portable carbon nanotube biosensors[J/OL]. Small, 2023, 19(34): e2208198[2025-03-25]. .
[17]	WANG L, WANG X, WU Y, et al.. Rapid and ultrasensitive electromechanical detection of ions, biomolecules and SARS-CoV-2 RNA in unamplified samples[J]. Nat. Biomed. Eng., 2022, 6(3): 276-285.
[18]	LI J, WU D, YU Y, et al.. Rapid and unamplified identification of COVID-19 with morpholino-modified graphene field-effect transistor nanosensor[J/OL]. Biosens. Bioelectron., 2021, 183: 113206[2025-03-25]. .
[19]	MEI J, LI Y T, ZHANG H, et al.. Molybdenum disulfide field-effect transistor biosensor for ultrasensitive detection of DNA by employing morpholino as probe[J]. Biosens. Bioelectron., 2018, 110: 71-77.
[20]	CAI B, HUANG L, ZHANG H, et al.. Gold nanoparticles-decorated graphene field-effect transistor biosensor for femtomolar microRNA detection[J]. Biosens. Bioelectron., 2015, 74: 329-334.
[21]	LI J, TANG L, LI T, et al.. Tandem Cas13a/crRNA-mediated CRISPR-FET biosensor: a one-for-all check station for virus without amplification[J]. ACS Sens., 2022, 7(9): 2680-2690.
[22]	李加好.基于石墨烯场效应晶体管生物传感器的病毒核酸免扩增、高灵敏检测[D].武汉: 湖北中医药大学, 2022.
[23]	LI H, YANG J, WU G, et al.. Amplification-free detection of SARS-CoV-2 and respiratory syncytial virus using CRISPR Cas13a and graphene field-effect transistors[J/OL]. Angew. Chem. Int. Ed., 2022, 61(32): e202203826[2025-03-25]. .
[24]	USLU F, INGEBRANDT S, MAYER D, et al.. Labelfree fully electronic nucleic acid detection system based on a field-effect transistor device[J]. Biosens. Bioelectron., 2004, 19(12): 1723-1731.
[25]	HAN Y, OFFENHÄUSSER A, INGEBRANDT S. Detection of DNA hybridization by a field-effect transistor with covalently attached catcher molecules[J]. Surf. Interface Anal., 2006, 38(4): 176-181.
[26]	HUA Y, MA J, LI D, et al.. DNA-based biosensors for the biochemical analysis: a review[J/OL]. Biosensors, 2022, 12(3): 183[2025-03-25]. .
[27]	HONG S, JIANG W, DING Q, et al.. The current progress of tetrahedral DNA nanostructure for antibacterial application and bone tissue regeneration[J]. Int. J. Nanomedicine, 2023, 18: 3761-3780.
[28]	NING Y, HU J, LU F. Aptamers used for biosensors and targeted therapy[J/OL]. Biomed. Pharmacother., 2020, 132: 110902[2025-03-25]. .
[29]	戴邵亮.基于适配体的沙门氏菌检测方法研究进展[J].食品安全质量检测学报,2019,10(14):4589-4596.
	DAI S L. Research progress of detection method of Salmonella based on aptamer[J]. J. Food Saf. Qual., 2019, 10(14): 4589-4596.
[30]	MA H, LIU J, ALI M M, et al.. Nucleic acid aptamers in cancer research, diagnosis and therapy[J]. Chem. Soc. Rev., 2015, 44(5): 1240-1256.
[31]	ZHANG G J, ZHANG G, CHUA J H, et al.. DNA sensing by silicon nanowire: charge layer distance dependence[J]. Nano Lett., 2008, 8(4): 1066-1070.
[32]	PELLESTOR F, PAULASOVA P. The peptide nucleic acids, efficient tools for molecular diagnosis (review)[J]. Int. J. Mol. Med., 2004, 13(4): 521-525.
[33]	GUO D, ZHUO M, ZHANG X, et al.. Indium-tin-oxide thin film transistor biosensors for label-free detection of avian influenza virus H5N1[J]. Anal. Chim. Acta, 2013, 773: 83-88.
[34]	LIANG Y, XIAO M, WU D, et al.. Wafer-scale uniform carbon nanotube transistors for ultrasensitive and label-free detection of disease biomarkers[J]. ACS Nano, 2020, 14(7): 8866-8874.
[35]	RAJAN A, SHRIVASTAVA S, JANHAW I, et al.. CRISPR-Cas system: from diagnostic tool to potential antiviral treatment[J]. Appl. Microbiol. Biotechnol., 2022, 106(18): 5863-5877.
[36]	ZHAO L, QIU M, LI X, et al.. CRISPR-Cas13a system: a novel tool for molecular diagnostics[J/OL]. Front. Microbiol., 2022, 13: 1060947[2025-03-25]. .
[37]	FORSYTH R, DEVADOSS A, GUY O J. Graphene field effect transistors for biomedical applications: current status and future prospects[J/OL]. Diagnostics, 2017, 7(3): 45[2025-03-25]. .
[38]	HWANG M T, WANG Z, PING J, et al.. DNA nanotweezers and graphene transistor enable label-free genotyping[J/OL]. Adv. Mater., 2018: e1802440[2025-03-25]. .
[39]	SUN Y, YANG C, JIANG X, et al.. High-intensity vector signals for detecting SARS-CoV-2 RNA using CRISPR/Cas13a couple with stabilized graphene field-effect transistor[J/OL]. Biosens. Bioelectron., 2023, 222: 114979[2025-03-25]. .
[40]	WANG Q, BAO L, WANG L, et al.. Duplex-specific-nuclease-assisted graphene field-effect transistor biosensor: a novel platform for preamplification-free detection of cancer related miRNA[J/OL]. Carbon, 2024, 230: 119670[2025-03-25]. .
[41]	FU W, FENG L, MAYER D, et al.. Electrolyte-gated graphene ambipolar frequency multipliers for biochemical sensing[J]. Nano Lett., 2016, 16(4): 2295-2300.
[42]	陈硕,高佳奇,王迪,等.DNA四面体纳米结构及其在生物技术领域的应用进展[J].生物技术进展,2020,10(6):661-667.
	CHEN S, GAO J Q, WANG D, et al.. DNA tetrahedral nanostructure and its application progress in biotechnology[J]. Curr. Biotechnol., 2020, 10(6): 661-667.
[43]	JEONG S, SON S U, KIM J, et al.. Rapid and simultaneous multiple detection of a tripledemic using a dual-gate oxide semiconductor thin-film transistor-based immunosensor[J/OL]. Biosens. Bioelectron., 2023, 241: 115700[2025-03-25]. .
[44]	TU J, MIN J, SONG Y, et al.. A wireless patch for the monitoring of C-reactive protein in sweat[J]. Nat. Biomed. Eng., 2023, 7(10): 1293-1306.

FET传感器探针类型		靶标类型	样本前处理	检测时间	检测限	参考文献
DNA	y形DNA双探针	SARS-CoV-2 RNA	模拟唾液样本	1 min	0.03 copy·μL^-1	[12]
	三茎结构DNA探针	SARS-CoV-2变异株RNA	模拟咽拭子样本	15 min	0.03 copy·μL^-1	[13]
	四面体DNA纳米结构探针	SARS-CoV-2 RNA	加热释放核酸	80 s	0.02 copy·μL^-1	[14]
	四面体 DNA结构三探针	SARS-CoV-2 RNA	50℃加热20 min	5 min	0.025 copy·μL^-1	[15]
核酸适配体	核酸适配体+ssDNA	SARS-CoV-2 RNA	15 min快速提取咽拭子样本核酸	1 min	C_t >35	[16]
核酸适配体	核酸适配体	SARS-CoV-2 RNA	加热释放核酸	4 min	0.02 copy·μL^-1	[17]
核酸类似物	PMO	SARS-CoV-2 RNA	呼吸道样本 RNA提取试剂盒	2 min	2.29 fmol·L^-1	[18]
	PMO	DNA	/	5 min	6 fmol·L^-1	[19]
	PNA	microRNA	模拟血清样本	30 min	10 fmol·L^-1	[20]
报告RNA	报告RNA+crRNA	CoV ORF1ab、 CoV N、 HCV RNA	模拟唾液样本	30 min	25 amol·L^-1	[21]
	报告RNA+双crRNA	CoV ORF1ab、 CoV N RNA	模拟咽拭子样本	30 min	1.56 amol·L^-1	[22]
	报告RNA+crRNA	SARS-CoV-2 N RNA	95℃加热5 min	30 min	1 amol·L^-1	[23]

FET传感器探针类型		靶标类型	样本前处理	检测时间	检测限	参考文献
DNA	y形DNA双探针	SARS-CoV-2 RNA	模拟唾液样本	1 min	0.03 copy·μL^-1	[12]
	三茎结构DNA探针	SARS-CoV-2变异株RNA	模拟咽拭子样本	15 min	0.03 copy·μL^-1	[13]
	四面体DNA纳米结构探针	SARS-CoV-2 RNA	加热释放核酸	80 s	0.02 copy·μL^-1	[14]
	四面体 DNA结构三探针	SARS-CoV-2 RNA	50℃加热20 min	5 min	0.025 copy·μL^-1	[15]
核酸适配体	核酸适配体+ssDNA	SARS-CoV-2 RNA	15 min快速提取咽拭子样本核酸	1 min	C_t >35	[16]
核酸适配体	核酸适配体	SARS-CoV-2 RNA	加热释放核酸	4 min	0.02 copy·μL^-1	[17]
核酸类似物	PMO	SARS-CoV-2 RNA	呼吸道样本 RNA提取试剂盒	2 min	2.29 fmol·L^-1	[18]
	PMO	DNA	/	5 min	6 fmol·L^-1	[19]
	PNA	microRNA	模拟血清样本	30 min	10 fmol·L^-1	[20]
报告RNA	报告RNA+crRNA	CoV ORF1ab、 CoV N、 HCV RNA	模拟唾液样本	30 min	25 amol·L^-1	[21]
	报告RNA+双crRNA	CoV ORF1ab、 CoV N RNA	模拟咽拭子样本	30 min	1.56 amol·L^-1	[22]
	报告RNA+crRNA	SARS-CoV-2 N RNA	95℃加热5 min	30 min	1 amol·L^-1	[23]

场效应晶体管生物传感器在核酸检测中的应用进展

Application Progress of Biosensors Based on Field-effect Transistors in Nucleic Acid Detection

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 44

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张春雷. 病原微生物检测技术研究进展[J]. 生物技术进展, 2024, 14(2): 189-195.
[2]	杨玉琦, 何秀霞. 滚环扩增技术在电化学生物传感器中的应用[J]. 生物技术进展, 2023, 13(6): 863-867.
[3]	康帅帅, 王瑞安, 许文涛, 朱龙佼. 磁适配体生物传感器[J]. 生物技术进展, 2023, 13(3): 339-344.
[4]	雷豆豆, 马润然, 王伽伯, 孔维军. 食品中农药残留的新型生物检测技术研究进展[J]. 生物技术进展, 2023, 13(1): 1-10.
[5]	赵文卓, 李成勋, 胡作建, 余红秀. 功能核酸用于致病菌检测的研究进展[J]. 生物技术进展, 2023, 13(1): 30-38.
[6]	吴一凡, 林晟豪, 许文涛. 小分子靶标的核糖开关生物传感器研究进展[J]. 生物技术进展, 2022, 12(2): 168-175.
[7]	胡妍, 陈玲. 基于生物膜干涉技术检测PDL1抗体与PDL1抗原的亲和力[J]. 生物技术进展, 2021, 11(6): 795-801.
[8]	格日乐其木格, 牛振峰, 董丹, 张涛涛, 峥嵘. CRISPR-Cas系统在微生物研究中的应用进展[J]. 生物技术进展, 2021, 11(3): 253-259.
[9]	白小莲,爱军. 生物传感器在食源性致病菌大肠杆菌O157∶H7检测中的应用进展[J]. 生物技术进展, 2021, 11(3): 269-278.
[10]	杨佳怡,陈桂芳,高运华,王志栋,吴枭. HPV核酸检测标准物质研究进展[J]. 生物技术进展, 2020, 10(6): 590-596.
[11]	陈硕,高佳奇,王迪,龙艳,李亮,张晓. DNA四面体纳米结构及其在生物技术领域的应用进展[J]. 生物技术进展, 2020, 10(6): 661-667.
[12]	胡思宏,游国叶. 数字PCR在新型冠状病毒检测中的应用前景[J]. 生物技术进展, 2020, 10(6): 674-679.
[13]	高先娟,汲霞,王清路,杜青青,王凤丹,王怀生. 羧基化石墨烯/半胱胺修饰金电极对多巴胺的电化学行为研究[J]. 生物技术进展, 2020, 10(3): 292-298.
[14]	徐蕾，肖桂清，盛晓菁，戚智青，刁勇. PCR增强剂在核酸体外扩增检测技术的研究进展[J]. 生物技术进展, 2020, 10(2): 137-143.
[15]	马翾，高思悦，李可馨，梁志宏，姚志轶. 硫酸软骨素荧光传感器的构建新策略[J]. 生物技术进展, 2020, 10(2): 164-169.