Abstract
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.
摘要
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.
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Acknowledgements
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).
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Author contributions Liu S conceived the idea. Gong X and Liu Y designed the project and performed the experiments. Gong X wrote the paper with support from Liu Y. Xiang H draw the mechanism schematic. Liu H characterized the materials. Liu S and Hu T discussed the results of the experiments. All authors contributed to the general discussion.
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Conflict of interest The authors declare no competing financial interest.
Xinxing Gong is a postgraduate student in Professor Liu’s group and will receive her master’s degree from the School of Chemistry and Chemical Engineering, Hunan University in 2019. Her current research focuses on the detection of biological target molecules by 2D nanomaterial field effect transistors.
Yeru Liu got her Master degree in applied chemistry from Zhengzhou University. Now, she is a PhD student under the supervision of Prof. Song Liu at the School of Chemistry and Chemical Engineering, Hunan University. Her research interests mainly focus on the preparation of nanodevices and the application of nanomaterials in biomedicine.
Song Liu received his PhD in 2011 from Peking University. He was a postdoctoral fellow working with Prof. Liming Dai (2011-2013) in Case Western Reserve University. After 3 years’ research in National University of Singapore (2013-2016), he is now a full professor in the Institute of Chemical Biology and Nanomedicine in Hunan University. His research interests focus on the controlled synthesis of low-dimensional materials, the application research of functional devices and nanobiological research.
Gang Yu received his PhD in 1999 from the Institute of Metal Corrosion and Protection, Chinese Academy of Sciences. He is now a full professor in the College of Chemistry and Chemical Engineering in Hunan University. His research interests focus on (1) synthesis, characterization and application of alloy nanowires, (2) nanostructured chemical sensors, biosensors and biomedical devices, (3) electroless plating and electrical plating on magnesium alloys and powders, and (4) transparent nanofunctional fluorocarbon coatings.
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Gong, X., Liu, Y., Xiang, H. et al. Membraneless reproducible MoS2 field-effect transistor biosensor for high sensitive and selective detection of FGF21. Sci. China Mater. 62, 1479–1487 (2019). https://doi.org/10.1007/s40843-019-9444-y
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DOI: https://doi.org/10.1007/s40843-019-9444-y