Membraneless reproducible MoS2 field-effect transistor biosensor for high sensitive and selective detection of FGF21

  • Xinxing Gong (龚新星)
  • Yeru Liu (刘业茹)
  • Haiyan Xiang (向海燕)
  • Hang Liu (刘航)
  • Zhigang Liu (刘志刚)
  • Xiaorui Zhao (赵晓蕊)
  • Jishan Li (李继山)
  • Huimin Li (李惠敏)
  • Guo Hong (洪果)
  • Travis Shihao Hu
  • Hong Chen (陈洪)
  • Song Liu (刘松)Email author
  • Gang Yu (余刚)Email author


Fibroblast growth factor 21 (FGF21) serves as an essential biomarker for early detection and diagnosis of nonalcoholic fatty liver disease (NAFLD). It has received a great deal of attention recently in efforts to develop an accurate and effective method for detecting low levels of FGF21 in complex biological settings. Herein, we demonstrate a label-free, simple and high-sensitive field-effect transistor (FET) biosensor for FGF21 detection in a nonaqueous environment, directly utilizing two-dimensional molybdenum disulfide (MoS2) without additional absorption layers. By immobilizing anti-FGF21 on MoS2 surface, this biosensor can achieve the detection of trace FGF21 at less than 10 fg mL−1. High consistency and satisfactory reproducibility were demonstrated through multiple sets of parallel experiments for the MoS2 FETs. Furthermore, the biosensor has great sensitivity to detect the target FGF21 in complex serum samples, which demonstrates its great potential application in disease diagnosis of NAFLD. Overall, this study shows that thin-layered transition-metal dichalcogenides (TMDs) can be used as a potential alternative platform for developing novel electrical biosensors with high sensitivity and selectivity.


FGF21 MoS2 FET biosensor disease diagnostics 

无膜且具有重现性的MoS2场效应晶体管生物传感 器用于高灵敏度和高选择性地检测FGF21


成纤维细胞生长因子21(FGF21) 是一种用于早期检测和诊断 非酒精性脂肪肝病(NAFLD)的必需生物标志物.最近,开发在复杂 生物环境中准确有效地检测血液中低浓度FGF21的方法受到了极 大的关注.本文展示了一种无标记、简单和高灵敏度的场效应晶 体管 (FET)生物传感器,用于在非水环境中检测FGF21. 通过对二硫 化钼(MoS2)表面进行功能化将抗FGF21牢固地固定在MoS2材料上, 使该生物传感器实现检测FGF21的检测限小于10 fg mL−1.多组平 行实验证明了MoS2 FET 的高度一致性和令人满意的再现性.此外, 生物传感器对复杂血清样品中的目标FGF21具有很高的敏感度,这 表明其在NAFLD疾病诊断中具有巨大的潜在应用前景.



This work was financially supported by the National Natural Science Foundation of China (21705036, 21475036, 51271074, 21476066, and 81572500), the Natural Science Foundation of Hunan Province, China (2018JJ3035), Hunan Young Talents (2016RS3036) and the Fundamental Research Funds for the Central Universities from Hunan University. Prof. Guo Hong acknowledges the Start-up Research Grant (SRG2016-00092-IAPME), Multi-year Research Grant (MYRG2018-00079-IAPME) of the University of Macau, Science and Technology Development Fund (081/2017/A2, 0059/2018/A2, 009/2017/AMJ) and Macao SAR (FDCT).

Supplementary material

40843_2019_9444_MOESM1_ESM.pdf (549 kb)
Membraneless reproducible MoS2 field-effect transistor biosensor for high sensitive and selective detection of FGF21


  1. 1.
    Moon YA, Hammer RE, Horton JD. Deletion of ELOVL5 leads to fatty liver through activation of SREBP-1c in mice. J Lipid Res, 2009, 50: 412–423CrossRefGoogle Scholar
  2. 2.
    Estes C, Razavi H, Loomba R, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology, 2018, 67: 123–133CrossRefGoogle Scholar
  3. 3.
    Fernandes DM, Pantangi V, Azam M, et al. Pediatric nonalcoholic fatty liver disease in new york city: An autopsy study. J Pediatrics, 2018, 200: 174–180CrossRefGoogle Scholar
  4. 4.
    Kliewer SA, Mangelsdorf DJ. Fibroblast growth factor 21: From pharmacology to physiology. Am J Clinical Nutrition, 2010, 91: 254S–257SCrossRefGoogle Scholar
  5. 5.
    Cuevas-Ramos D, Almeda-Valdes P, Aguilar-Salinas C, et al. The role of fibroblast growth factor 21 (FGF21) on energy balance, glucose and lipid metabolism. Curr Diabet Rev, 2009, 5: 216–220CrossRefGoogle Scholar
  6. 6.
    Yilmaz Y, Eren F, Yonal O, et al. Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease. Eur J Clin Invest, 2010, 40: 887–892CrossRefGoogle Scholar
  7. 7.
    Li H, Fang Q, Gao F, et al. Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride. J Hepatology, 2010, 53: 934–940CrossRefGoogle Scholar
  8. 8.
    Zhang X, Yeung DCY, Karpisek M, et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes, 2008, 57: 1246–1253CrossRefGoogle Scholar
  9. 9.
    Bergveld P. Development of an ion-sensitive solid-state device for neurophysiological measurements. IEEE Trans Biomed Eng, 1970, BME-17: 70–71CrossRefGoogle Scholar
  10. 10.
    Mao S, Chang J, Pu H, et al. Two-dimensional nanomaterial-based field-effect transistors for chemical and biological sensing. Chem Soc Rev, 2017, 46: 6872–6904CrossRefGoogle Scholar
  11. 11.
    Cui Y, Wei Q, Park H, et al. Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science, 2001, 293: 1289–1292CrossRefGoogle Scholar
  12. 12.
    Patolsky F, Zheng G, Lieber CM. Nanowire-based biosensors. Anal Chem, 2006, 78: 4260–4269CrossRefGoogle Scholar
  13. 13.
    Han ZJ, Mehdipour H, Li X, et al. SWCNT networks on nanoporous silica catalyst support: Morphological and connectivity control for nanoelectronic, gas-sensing, and biosensing devices. ACS Nano, 2012, 6: 5809–5819CrossRefGoogle Scholar
  14. 14.
    Yu X, Munge B, Patel V, et al. Carbon nanotube amplification strategies for highly sensitive immunodetection of cancer biomarkers. J Am Chem Soc, 2006, 128: 11199–11205CrossRefGoogle Scholar
  15. 15.
    Kalantar-zadeh K, Ou JZ, Daeneke T, et al. Two-dimensional transition metal dichalcogenides in biosystems. Adv Funct Mater, 2015, 25: 5086–5099CrossRefGoogle Scholar
  16. 16.
    Xiao Y, Fu L. New designing for nanostructured 2D materials and 2D superlattices. Sci China Mater, 2018, 61: 761–762CrossRefGoogle Scholar
  17. 17.
    Huang X, Zeng Z, Zhang H. Metal dichalcogenide nanosheets: Preparation, properties and applications. Chem Soc Rev, 2013, 42: 1934–1946CrossRefGoogle Scholar
  18. 18.
    Liu Y, Dong X, Chen P. Biological and chemical sensors based on graphene materials. Chem Soc Rev, 2012, 41: 2283–2307CrossRefGoogle Scholar
  19. 19.
    Wei D, Liu Y. Controllable synthesis of graphene and its applications. Adv Mater, 2010, 22: 3225–3241CrossRefGoogle Scholar
  20. 20.
    Wang L, Wu B, Liu H, et al. Low temperature growth of clean single layer hexagonal boron nitride flakes and film for graphene-based field-effect transistors. Sci China Mater, 2019, 62: 1218–1225CrossRefGoogle Scholar
  21. 21.
    Perera MM, Lin MW, Chuang HJ, et al. Improved carrier mobility in few-layer MoS2 field-effect transistors with ionic-liquid gating. ACS Nano, 2013, 7: 4449–4458CrossRefGoogle Scholar
  22. 22.
    Kim S, Konar A, Hwang WS, et al. High-mobility and low-power thin-film transistors based on multilayer MoS2 crystals. Nat Commun, 2012, 3: 1011CrossRefGoogle Scholar
  23. 23.
    Kalantar-zadeh K, Ou JZ. Biosensors based on two-dimensional MoS2. ACS Sens, 2016, 1: 5–16CrossRefGoogle Scholar
  24. 24.
    Gan X, Zhao H, Quan X. Two-dimensional MoS2: A promising building block for biosensors. Biosens Bioelectron, 2017, 89: 56–71CrossRefGoogle Scholar
  25. 25.
    Liu S, Zhang X, Zhang J, et al. MoS2 with tunable surface structure directed by thiophene adsorption toward HDS and HER. Sci China Mater, 2016, 59: 1051–1061CrossRefGoogle Scholar
  26. 26.
    Sarkar D, Liu W, Xie X, et al. MoS2 field-effect transistor for next-generation label-free biosensors. ACS Nano, 2014, 8: 3992–4003CrossRefGoogle Scholar
  27. 27.
    Park H, Han G, Lee SW, et al. Label-free and recalibrated multilayer MoS2 biosensor for point-of-care diagnostics. ACS Appl Mater Interfaces, 2017, 9: 43490–43497CrossRefGoogle Scholar
  28. 28.
    Lee J, Dak P, Lee Y, et al. Two-dimensional layered MoS2 biosensors enable highly sensitive detection of biomolecules. Sci Rep, 2015, 4: 7352CrossRefGoogle Scholar
  29. 29.
    Liu J, Chen X, Wang Q, et al. Ultrasensitive monolayer MoS2 field-effect transistor based DNA sensors for screening of down syndrome. Nano Lett, 2019, 19: 1437–1444CrossRefGoogle Scholar
  30. 30.
    Li Z, Ye R, Feng R, et al. Graphene quantum dots doping of MoS2 monolayers. Adv Mater, 2015, 27: 5235–5240CrossRefGoogle Scholar
  31. 31.
    Huang Y, Zheng W, Qiu Y, et al. Effects of organic molecules with different structures and absorption bandwidth on modulating photoresponse of MoS2 photodetector. ACS Appl Mater Interfaces, 2016, 8: 23362–23370CrossRefGoogle Scholar
  32. 32.
    Benameur MM, Radisavljevic B, Héron JS, et al. Visibility of dichalcogenide nanolayers. Nanotechnology, 2011, 22: 125706CrossRefGoogle Scholar
  33. 33.
    Gong C, Colombo L, Wallace RM, et al. The unusual mechanism of partial Fermi level pinning at metal-MoS2 interfaces. Nano Lett, 2014, 14: 1714–1720CrossRefGoogle Scholar
  34. 34.
    Wang Y, Kim JC, Wu RJ, et al. Van der Waals contacts between three-dimensional metals and two-dimensional semiconductors. Nature, 2019, 568: 70–74CrossRefGoogle Scholar
  35. 35.
    Yang R, Wang Z, Feng PXL. Electrical breakdown of multilayer MoS2 field-effect transistors with thickness-dependent mobility. Nanoscale, 2014, 6: 12383–12390CrossRefGoogle Scholar
  36. 36.
    Costantino HR, Griebenow K, Langer R, et al. On the pH memory of lyophilized compounds containing protein functional groups. Biotechnol Bioeng, 1997, 53: 345–348CrossRefGoogle Scholar
  37. 37.
    Meyers RA. Molecular Biology and Biotechnology: A Comprehensive Desk Reference. Weinheim: John Wiley & Sons, 1995Google Scholar
  38. 38.
    Zhao YL, Stoddart JF. Noncovalent functionalization of singlewalled carbon nanotubes. Acc Chem Res, 2009, 42: 1161–1171CrossRefGoogle Scholar
  39. 39.
    Heller I, Janssens AM, Männik J, et al. Identifying the mechanism of biosensing with carbon nanotube transistors. Nano Lett, 2008, 8: 591–595CrossRefGoogle Scholar
  40. 40.
    Sim DM, Kim M, Yim S, et al. Controlled doping of vacancy-containing few-layer MoS2 via highly stable thiol-based molecular chemisorption. ACS Nano, 2015, 9: 12115–12123CrossRefGoogle Scholar
  41. 41.
    Kralisch S, Tönjes A, Krause K, et al. Fibroblast growth factor-21 serum concentrations are associated with metabolic and hepatic markers in humans. J Endocrinology, 2013, 216: 135–143CrossRefGoogle Scholar
  42. 42.
    Bisgaard A, Sørensen K, Johannsen TH, et al. Significant gender difference in serum levels of fibroblast growth factor 21 in danish children and adolescents. Int J Pediatr Endocrinol, 2014, 2014: 7CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Xinxing Gong (龚新星)
    • 1
  • Yeru Liu (刘业茹)
    • 1
  • Haiyan Xiang (向海燕)
    • 1
  • Hang Liu (刘航)
    • 1
  • Zhigang Liu (刘志刚)
    • 2
  • Xiaorui Zhao (赵晓蕊)
    • 1
  • Jishan Li (李继山)
    • 1
  • Huimin Li (李惠敏)
    • 1
  • Guo Hong (洪果)
    • 3
  • Travis Shihao Hu
    • 4
  • Hong Chen (陈洪)
    • 5
  • Song Liu (刘松)
    • 1
    Email author
  • Gang Yu (余刚)
    • 1
    Email author
  1. 1.Institute of Chemical Biology and Nanomedicine (ICBN), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical EngineeringHunan UniversityChangshaChina
  2. 2.Department of Head and Neck Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Phase I Clinical Trial Laboratory, The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina
  3. 3.Institute of Applied Physics and Materials EngineeringUniversity of MacauTaipa, MacauChina
  4. 4.Department of Mechanical EngineeringCalifornia State UniversityLos AngelesUSA
  5. 5.School of Materials Science and Energy EngineeringFoshan UniversityFoshanChina

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