1. School of Physics and Electronics, Shandong Normal University, Jinan 250014, China 2. Shandong Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou 253023, China 3. Shandong Engineering Laboratory of Swine Herd Health Big Data and Intelligent Monitoring, Dezhou University, Dezhou 253023, China
Adenosine triphosphate (ATP) is closely related to the pathogenesis of certain diseases, so the detection of trace ATP is of great significance to disease diagnosis and drug development. Graphene field-effect transistors (GFETs) have been proven to be a promising platform for the rapid and accurate detection of small molecules, while the Debye shielding limits the sensitive detection in real samples. Here, a three-dimensional wrinkled graphene field-effect transistor (3D WG-FET) biosensor for ultra-sensitive detection of ATP is demonstrated. The lowest detection limit of 3D WG-FET for analyzing ATP is down to 3.01 aM, which is much lower than the reported results. In addition, the 3D WG-FET biosensor shows a good linear electrical response to ATP concentrations in a broad range of detection from 10 aM to 10 pM. Meanwhile, we achieved ultra-sensitive (LOD: 10 aM) and quantitative (range from 10 aM to 100 fM) measurements of ATP in human serum. The 3D WG-FET also exhibits high specificity. This work may provide a novel approach to improve the sensitivity for the detection of ATP in complex biological matrix, showing a broad application value for early clinical diagnosis and food health monitoring.
Di. Virgilio F. , C. Sarti A. , Falzoni S. , De. Marchi E. , Adinolfi E. . Extracellular ATP and P2 purinergic signalling in the tumour microenvironment. Nat. Rev. Cancer, 2018, 18(10): 601 https://doi.org/10.1038/s41568-018-0037-0
2
Xu Y.Kang Q.Yang B.Chen B.He M.Hu B., A nanoprobe based on molybdenum disulfide nanosheets and silver nanoclusters for imaging and quantification of intracellular adenosine triphosphate, Anal. Chim. Acta 1134, 75 (2020)
3
Deng J.Walther A., ATP‐responsive and ATP‐fueled self‐assembling systems and materials, Adv. Mater. 32(42), 2002629 (2020)
4
H. Wang C. , Zhang Y. , Tang W. , Wang C. , K. Han Y. , Qiang L. , W. Gao J. , Liu H. , Han L. . Ultrasensitive, high-throughput and multiple cancer biomarkers simultaneous detection in serum based on graphene oxide quantum dots integrated microfluidic biosensing platform. Anal. Chim. Acta, 2021, 1178: 338791 https://doi.org/10.1016/j.aca.2021.338791
5
Xiao L.Li K.Z. Liu B.Y. Tu J.X. Li T.T. Li Y.J. Zhang G., A pH-sensitive field-effect transistor for monitoring of cancer cell external acid environment, Talanta 252, 123764 (2023)
6
N. Seyfried T. , Arismendi-Morillo G. , Mukherjee P. , Chinopoulos C. . On the origin of ATP synthesis in cancer. iScience, 2020, 23(11): 101761 https://doi.org/10.1016/j.isci.2020.101761
7
P. Sun P. , C. Chen H. , Y. Lu S. , Hai J. , T. Guo W. , H. Jing Y. , D. Wang B. . Simultaneous sensing of H2S and ATP with a two-photon fluorescent probe in Alzheimer’s disease: Toward understanding Why H2S regulates glutamate-induced ATP dysregulation. Anal. Chem., 2022, 94(33): 11573 https://doi.org/10.1021/acs.analchem.2c01850
8
M. Dwyer K. , K. Kishore B. , C. Robson S. . Conversion of extracellular ATP into adenosine: A master switch in renal health and disease. Nat. Rev. Nephrol., 2020, 16(9): 509 https://doi.org/10.1038/s41581-020-0304-7
9
Liu Y. , Q. Kong L. , Li H. , Yuan R. , Q. Chai Y. . Electrochemical aptamer biosensor based on ATP-induced 2D DNA structure switching for rapid and ultrasensitive detection of ATP. Anal. Chem., 2022, 94(18): 6819 https://doi.org/10.1021/acs.analchem.2c00613
10
Peng L.Zhou J.Liu G.Yin L.Ren S.Man S.Ma L., CRISPR-Cas12a based aptasensor for sensitive and selective ATP detection, Sensor Actuat B-Chem. 320, 128164
11
L. Yao L.J. Zhang W.X. Yin C.B. Zhang Y.J. Huo F., A tracer-type fluorescent probe for imaging adenosine triphosphate under the stresses of hydrogen sulfide and hydrogen peroxide in living cells, Analyst (Lond. ) 147(19), 4222 (2022)
12
Chen X. , Liu Y. , Fang X. , Li Z. , Pu H. , Chang J. , Chen J. , Mao S. . Ultratrace antibiotic sensing using aptamer/graphene-based field-effect transistors. Biosens. Bioelectron., 2019, 126: 664 https://doi.org/10.1016/j.bios.2018.11.034
13
Park I. , Lim J. , You S. , T. Hwang M. , Kwon J. , Koprowski K. , Kim S. , Heredia J. , A. S. Ramirez S. , Valera E. , Bashir R. . Detection of SARS-CoV-2 virus amplification using a crumpled graphene field-effect transistor biosensor. ACS Sens., 2021, 6(12): 4461 https://doi.org/10.1021/acssensors.1c01937
14
Kwon B. , Bae H. , Lee H. , Kim S. , Hwang J. , Lim H. , H. Lee J. , Cho K. , Ye J. , Lee S. , H. Lee W. . Ultrasensitive N-channel graphene gas sensors by nondestructive molecular doping. ACS Nano, 2022, 16(2): 2176 https://doi.org/10.1021/acsnano.1c08186
15
W. Gao J. , H. Wang C. , Wang C. , J. Chu Y. , Wang S. , Y. Sun M. , Ji H. , K. Gao Y. , H. Wang Y. , K. Han Y. , T. Song F. , Liu H. , Zhang Y. , Han L. . Poly-L-lysine-modified graphene field-effect transistor biosensors for ultrasensitive breast cancer miRNAs and SARS-CoV-2 RNA detection. Anal. Chem., 2022, 94(3): 1626 https://doi.org/10.1021/acs.analchem.1c03786
16
Zhang T. , Wu S. , Yang R. , Zhang G. . Graphene: Nanostructure engineering and applications. Front. Phys., 2017, 12(1): 127206 https://doi.org/10.1007/s11467-017-0648-z
17
Chen X. , Hao S. , Zong B. , Liu C. , Mao S. . Ultraselective antibiotic sensing with complementary strand DNA assisted aptamer/MoS2 field-effect transistors. Biosens. Bioelectron., 2019, 145: 111711 https://doi.org/10.1016/j.bios.2019.111711
18
Li J. , Wu D. , Yu Y. , X. Li T. , Li K. , M. Xiao M. , R. Li Y. , Y. Zhang Z. , J. Zhang G. . Rapid and unamplified identification of COVID-19 with morpholino-modified graphene field-effect transistor nanosensor. Biosens. Bioelectron., 2021, 183: 113206 https://doi.org/10.1016/j.bios.2021.113206
19
Islam S. , Shukla S. , K. Bajpai V. , K. Han Y. , S. Huh Y. , Ghosh A. , Gandhi S. . Microfluidic-based graphene field effect transistor for femtomolar detection of chlorpyrifos. Sci. Rep., 2019, 9(1): 276 https://doi.org/10.1038/s41598-018-36746-w
20
Mao S. , Chang J. , Pu H. , Lu G. , He Q. , Zhang H. , Chen J. . Two-dimensional nanomaterial-based field-effect transistors for chemical and biological sensing. Chem. Soc. Rev., 2017, 46(22): 6872 https://doi.org/10.1039/C6CS00827E
21
K. Tiwari S. , Sahoo S. , Wang N. , Huczko A. . Graphene research and their outputs: Status and prospect. Sci. Adv. Mater Dev., 2020, 5(1): 10 https://doi.org/10.1016/j.jsamd.2020.01.006
22
M. Huang X. , Z. Liu L. , Zhou S. , J. Zhao J. . Physical properties and device applications of graphene oxide. Front. Phys., 2020, 15(3): 33301 https://doi.org/10.1007/s11467-019-0937-9
23
Mukherjee S.Meshik X.Choi M.Farid S.Datta D.Lan Y.Poduri S.Sarkar K.Baterdene U.E. Huang C.Y. Wang Y.Burke P.Dutta M.A. Stroscio M., A graphene and aptamer based liquid gated FET-like electrochemical biosensor to detect adenosine triphosphate, IEEE Trans. Nanobiosci. 14(8), 967 (2015)
24
W. Yue W. , Z. Jiang S. , C. Xu S. , J. Bai C. . Fabrication of integrated field-effect transistors and detecting system based on CVD grown graphene. Sens. Actuators B Chem., 2014, 195: 467 https://doi.org/10.1016/j.snb.2014.01.071
25
Cheng M. , Yang J. , Li X. , Li H. , Du R. , Shi J. , He J. . Improving the device performances of two-dimensional semiconducting transition metal dichalcogenides: Three strategies. Front. Phys., 2022, 17(6): 63601 https://doi.org/10.1007/s11467-022-1190-1
26
Wang Z. , Hao Z. , Yu S. , G. De Moraes C. , H. Suh L. , Zhao X. , Lin Q. . An ultraflexible and stretchable aptameric graphene nanosensor for biomarker detection and monitoring. Adv. Funct. Mater., 2019, 29(44): 1905202 https://doi.org/10.1002/adfm.201905202
27
H. Bay H. , Vo R. , C. Dai X. , H. Hsu H. , M. Mo Z. , Cao S. , Y. Li W. , G. Omenetto F. , C. Jiang X. . Hydrogel gate graphene field-effect transistors as multiplexed biosensors. Nano Lett., 2019, 19(4): 2620 https://doi.org/10.1021/acs.nanolett.9b00431
28
K. Han Y. , R. Han Y. , Z. Huang Y. , Wang C. , Liu H. , Han L. , Zhang Y. . Laser‐induced graphene superhydrophobic surface transition from pinning to rolling for multiple applications. Small Methods, 2022, 6(4): 2200096 https://doi.org/10.1002/smtd.202200096
29
Wang R. , G. Ren X. , Yan Z. , J. Jiang L. , E. Sha W. , C. Shan G. . Graphene based functional devices: A short review. Front. Phys., 2019, 14(1): 13603 https://doi.org/10.1007/s11467-018-0859-y
30
Hu M. , Zhang N. , Shan G. , Gao J. , Liu J. , K. Li R. . Two-dimensional materials: Emerging toolkit for construction of ultrathin high-efficiency microwave shield and absorber. Front. Phys., 2018, 13(4): 138113 https://doi.org/10.1007/s11467-018-0809-8
31
Nakatsuka N. , A. Yang K. , Abendroth J. , Cheung K. , Xu X. , Yang H. , Z. Zhao C. , W. Zhu B. , Rim Y. , Yang Y. , Weiss P. , Stojanovic M. , Andrews A. . Aptamer–field-effect transistors overcome Debye length limitations for small-molecule sensing. Science, 2018, 362(6412): 319 https://doi.org/10.1126/science.aao6750
32
R. Wang Z. , Hao Z. , Yang C. , Wang H. , Huang C. , Zhao Z. , L. Pan Y. . Ultra-sensitive and rapid screening of acute myocardial infarction using 3D-affinity graphene biosensor. Cell Rep. Phys. Sci., 2022, 3(5): 100855 https://doi.org/10.1016/j.xcrp.2022.100855
33
W. Gao J. , K. Gao Y. , K. Han Y. , B. Pang J. , Wang C. , H. Wang Y. , Liu H. , Zhang Y. , Han L. . Ultrasensitive label-free MiRNA sensing based on a flexible graphene field-effect transistor without functionalization. ACS Appl. Electron. Mater., 2020, 2(4): 1090 https://doi.org/10.1021/acsaelm.0c00095
34
Zhang F.H. Li Y.Y. Li J.R. Tang Z.J. Xu Y., 3D graphene-based gel photocatalysts for environmental pollutants degradation, Environ. Pollut. 253, 365 (2019)
35
Deng T. , H. Zhang Z. , X. Liu Y. , X. Wang Y. , Su F. , S. Li S. , Zhang Y. , Li H. , J. Chen H. , R. Zhao Z. , Li Y. , Liu Z. . Three-dimensional graphene field-effect transistors as high-performance photodetectors. Nano Lett., 2019, 19(3): 1494 https://doi.org/10.1021/acs.nanolett.8b04099
36
Wang C. , X. Yang S. , R. Zhang H. , N. Du L. , Wang L. , Y. Yang F. , Z. Zhang X. , Liu Q. . Synthesis of atomically thin GaSe wrinkles for strain sensors. Front. Phys., 2016, 11: 116802 https://doi.org/10.1007/s11467-015-0522-9
37
Z. Huang Y. , K. Han Y. , Y. Sun J. , Zhang Y. , Han L. . Dual nanocatalysts co-decorated three-dimensional, laser-induced graphene hybrid nanomaterials integrated with a smartphone portable electrochemical system for point-of-care non-enzymatic glucose diagnosis. Mater. Today Chem., 2022, 24: 100895 https://doi.org/10.1016/j.mtchem.2022.100895
38
T. Hwang M. , Heiranian M. , Kim Y. , You S. , Leem J. , Taqieddin A. , Faramarzi V. , Jing Y. , Park I. , M. van der Zande A. , Nam S. , R. Aluru N. , Bashir R. . Ultrasensitive detection of nucleic acids using deformed graphene channel field effect biosensors. Nat. Commun., 2020, 11(1): 1543 https://doi.org/10.1038/s41467-020-15330-9
39
Wang Y. , Ni Z. , Yu T. , X. Shen Z. , Wang H. , Wu Y. , Chen W. , T. S. Wee A. . Raman studies of monolayer graphene: The substrate effect. J. Phys. Chem. C., 2008, 112(29): 10637 https://doi.org/10.1021/jp8008404
40
Itoh N. , Hanari N. . Development of a polystyrene reference material for raman spectrometer (NMIJ RM 8158-a). Anal. Sci., 2021, 37(11): 1533 https://doi.org/10.2116/analsci.21P054
41
X. Zhou X. , Liu R. , T. Hao L. , F. Liu J. . Identification of polystyrene nanoplastics using surface enhanced Raman spectroscopy. Talanta, 2021, 221: 121552 https://doi.org/10.1016/j.talanta.2020.121552
42
Qing F. , Zhang Y. , Niu Y. , Stehle R. , Chen Y. , Li X. . Towards large-scale graphene transfer. Nanoscale, 2020, 12(20): 10890 https://doi.org/10.1039/D0NR01198C
43
C. Xu S. , Zhan J. , Y. Man B. , Z. Jiang S. , W. Yue W. , B. Gao S. , G. Guo C. , P. Liu H. , H. Li Z. , H. Wang J. , Q. Zhou Y. . Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor. Nat. Commun., 2017, 8(1): 14902 https://doi.org/10.1038/ncomms14902
44
Nekrasov N. , Jaric S. , Kireev D. , V. Emelianov A. , V. Orlov A. , Gadjanski I. , I. Nikitin P. , Akinwande D. , Bobrinetskiy I. . Real-time detection of ochratoxin A in wine through insight of aptamer conformation in conjunction with graphene field-effect transistor. Biosens. Bioelectron., 2022, 200: 113890 https://doi.org/10.1016/j.bios.2021.113890
45
F. Wu G. , Tang X. , Meyyappan M. , W. C. Lai K. . Doping effects of surface functionalization on graphene with aromatic molecule and organic solvents. Appl. Surf. Sci., 2017, 425: 713 https://doi.org/10.1016/j.apsusc.2017.07.048
46
Tian M. , Qiao M. , C. Shen C. , Meng F. , A. Frank L. , V. Krasitskaya V. , J. Wang T. , M. Zhang X. , H. Song R. , X. Li Y. , J. Liu J. , C. Xu S. , H. Wang J. . Highly-sensitive graphene field effect transistor biosensor using PNA and DNA probes for RNA detection. Appl. Surf. Sci., 2020, 527: 146839 https://doi.org/10.1016/j.apsusc.2020.146839
47
N. Zhang Y. , Ding Y. , Li C. , Q. Xu H. , X. Liu C. , J. Wang J. , Ma Y. , F. Ren J. , F. Zhao Y. , W. Yue W. . An optic-fiber graphene field effect transistor biosensor for the detection of single-stranded DNA. Anal. Methods, 2021, 13(15): 1839 https://doi.org/10.1039/D1AY00101A
48
T. Lin C. , T. K. Loan P. , Y. Chen T. , K. Liu K. , H. Chen C. , H. Wei K. , J. Li L. . Label-free electrical detection of DNA hybridization on graphene using Hall effect measurements: Revisiting the sensing mechanism. Adv. Funct. Mater., 2013, 23(18): 2301 https://doi.org/10.1002/adfm.201202672
49
Sameiyan E. , Bagheri E. , Dehghani S. , Ramezani M. , Alibolandi M. , Abnous K. , M. Taghdisi S. . Aptamer-based ATP-responsive delivery systems for cancer diagnosis and treatment. Acta Biomater., 2021, 123: 110 https://doi.org/10.1016/j.actbio.2020.12.057
50
Mehringer J. , M. Do T. , Touraud D. , Hohenschutz M. , Khoshsima A. , Horinek D. , Kunz W. . Hofmeister versus Neuberg: is ATP really a biological hydrotrope. Cell Rep. Phys. Sci., 2021, 2(2): 100343 https://doi.org/10.1016/j.xcrp.2021.100343
51
C. Xu S. , Zhang C. , Z. Jiang S. , D. Hu G. , Y. Li X. , Zou Y. , P. Liu H. , Li J. , H. Li Z. , X. Wang X. , Z. Li M. , H. Wang J. . Graphene foam field-effect transistor for ultra-sensitive label-free detection of ATP. Sens. Actuators B Chem., 2019, 284: 125 https://doi.org/10.1016/j.snb.2018.12.129
52
M. Yu C. , M. Chang X. , Liu J. , P. Ding L. , X. Peng J. , Fang Y. . Creation of reduced graphene oxide based field effect transistors and their utilization in the detection and discrimination of nucleoside triphosphates. ACS Appl. Mater. Interfaces., 2015, 7(20): 10718 https://doi.org/10.1021/acsami.5b00155
53
W. Yue W.Z. Jiang S.C. Xu S.Z. Huang F.J. Bai C., Fabrication of capacitive type biosensor based on CVD grown grapheme, Proceedings 2013 International Conference on Mechatronic Sciences, Electric Engineering and Computer (MEC), Shenyang, China, 2013, pp 711–714
54
Xu S. , Man B. , Jiang S. , Yue W. , Yang C. , Liu M. , Chen C. , Zhang C. . Direct growth of graphene on quartz substrates for label-free detection of adenosine triphosphate. Nanotechnology, 2014, 25(16): 165702 https://doi.org/10.1088/0957-4484/25/16/165702
55
Snapp P. , Heiranian M. , T. Hwang M. , Bashir R. , R. Aluru N. , W. Nam S. . Current understanding and emerging applications of 3D crumpling mediated 2D material−liquid interactions. Curr. Opin. Solin. St M., 2020, 24(3): 100836 https://doi.org/10.1016/j.cossms.2020.100836
56
Shoorideh K. , O. Chui C. . On the origin of enhanced sensitivity in nanoscale FET-based biosensors. Proc. Natl. Acad. Sci. USA, 2014, 111(14): 5111 https://doi.org/10.1073/pnas.1315485111
57
Y. Qi D. , Wang C. , C. Gao Y. , W. Li H. , Q. Wu Y. . Heteroatom doping and supramolecular assembly promoted copper nanoclusters to be a stable & high fluorescence sensor for trace amounts of ATP determination. Sens. Actuators B Chem., 2022, 358: 131469 https://doi.org/10.1016/j.snb.2022.131469
58
Q. Zheng M. , F. Kang Y. , Liu D. , Y. Li C. , Zheng B. , W. Tang H. . Detection of ATP from “fluorescence” to “enhanced fluorescence” based on metal-enhanced fluorescence triggered by aptamer nanoswitch. Sens. Actuators B Chem., 2020, 319: 128263 https://doi.org/10.1016/j.snb.2020.128263
59
Peng Y.X. Li D.Yuan R.Xiang Y., A catalytic and dual recycling amplification ATP sensor based on target-driven allosteric structure switching of aptamer beacons, Biosens. Bioelectron. 105, 1 (2018)
60
Li S. , T. Zhao X. , T. Yu X. , Q. Wan Y. , Y. Yin M. , W. Zhang W. , Q. Cao B. , Wang H. . Fe3O4 nanozymes with Aptamer-Tuned catalysis for selective colorimetric analysis of ATP in blood. Anal. Chem., 2019, 91(22): 14737 https://doi.org/10.1021/acs.analchem.9b04116
61
Y. Zhao H.N. Dou L.J. Ren J.Cui M.Li N.P. Ji X.T. Liu X.Zhang C., MOF-derived porous Co3O4 coupled with AuNPs and nucleic acids as electrocatalysis signal probe for sensitive electrochemical aptasensing of adenosine triphosphate, Sens. Actuators B Chem. 362, 131753 (2022)
62
Li X. , M. Yang J. , Q. Xie J. , Y. Jiang B. , Yuan R. , Xiang Y. . Cascaded signal amplification via target-triggered formation of aptazyme for sensitive electrochemical detection of ATP. Biosens. Bioelectron., 2018, 102: 296 https://doi.org/10.1016/j.bios.2017.11.005
63
E. Fenoy G. , Piccinini E. , Knoll W. , A. Marmisolle W. , Azzaroni O. . The effect of Amino–Phosphate interactions on the biosensing performance of enzymatic graphene field-effect transistors. Anal. Chem., 2022, 94(40): 13820 https://doi.org/10.1021/acs.analchem.2c02373