Silicon Nanowire Field-Effect Transistor as Label-Free Detection of Hepatitis B Virus Proteins with Opposite Net Charges
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Device Fabrication
2.3. Device Cleaning, Surface Modification, and Antibody Immobilization
2.4. Surface Modification and Probe Immobilization Verification
2.5. Electrical Property of pSiNWFET Measurement
2.6. Extraction of Threshold Voltage Shift in pSiNWFET
2.7. Extraction of the Equilibrium Dissociation Constant (KD) in pSiNWFET
2.8. Protein Zeta Potential Measurement
3. Results and Discussion
3.1. Device Structure
3.2. Surface Modification and Probe Immobilization Verification
3.3. Electrical Properties Measurement of Surface Modification and Probe Immobilization
3.4. Biosensing of Various Concentrations of HBsAg and HBx
3.5. Equilibrium Dissociation Constant (KD) of Protein–Protein Interaction on pSiNWFET
3.6. Prospective of pSiNWFET Sensor as Multiplexing Biochip for HBV Detection in Monitoring Patients’ Status
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
- Iannacone, M.; Guidotti, L.G. Immunobiology and pathogenesis of hepatitis B virus infection. Nat. Rev. Immunol. 2021, 1–14. [Google Scholar] [CrossRef]
- Yuen, M.F.; Chen, D.S.; Dusheiko, G.M.; Janssen, H.L.A.; Lau, D.T.Y.; Locarnini, S.A.; Peters, M.G.; Lai, C.L. Hepatitis B virus infection. Nat. Rev. Dis. Primers 2018, 4, 1–20. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Global Hepatitis Report 2017. World Health Organization, 2017. Available online: https://apps.who.int/iris/handle/10665/255016 (accessed on 9 October 2021).
- World Health Organization. Global Health Sector Strategy on Viral Hepatitis 2016–2021. Towards Ending Viral Hepatitis. World Health Organization, 2016. Available online: https://apps.who.int/iris/handle/10665/246177 (accessed on 9 October 2021).
- Chan, H.L.; Thompson, A.; Martinot-Peignoux, M.; Piratvisuth, T.; Cornberg, M.; Brunetto, M.R.; Tillmann, H.L.; Kao, J.H.; Jia, J.D.; Wedemeyer, H.; et al. Hepatitis B surface antigen quantification: Why and how to use it in 2011—A core group report. J. Hepatol. 2011, 55, 1121–1131. [Google Scholar] [CrossRef] [PubMed]
- Kim, S.-H. ELISA for Quantitative Determination of Hepatitis B Virus Surface Antigen. Immune Netw. 2017, 17, 451–459. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Höner Zu Siederdissen, C.; Cornberg, M. The role of HBsAg levels in the current management of chronic HBV infection. Ann. Gastroenterol. 2014, 27, 105–112. [Google Scholar] [PubMed]
- Tang, K.F.; Xie, J.; Chen, M.; Liu, Q.; Zhou, X.Y.; Zeng, W.; Huang, A.L.; Zuo, G.Q.; Wang, Y.; Xiang, R.; et al. Knockdown of damage-specific DNA binding protein 1 (DDB1) enhances the HBx-siRNA-mediated inhibition of HBV replication. Biologicals 2008, 36, 177–183. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yen, C.-J.; Yang, S.-T.; Chen, R.-Y.; Huang, W.; Chayama, K.; Lee, M.-H.; Yang, S.-J.; Lai, H.-S.; Yen, H.-Y.; Hsiao, Y.-W.; et al. Hepatitis B virus X protein (HBx) enhances centrosomal P4.1-associated protein (CPAP) expression to promote hepatocarcinogenesis. J. Biomed. Sci. 2019, 26, 44. [Google Scholar]
- Yue, D.; Zhang, Y.; Cheng, L.; Ma, J.; Xi, Y.; Yang, L.; Su, C.; Shao, B.; Huang, A.; Xiang, R.; et al. Hepatitis B virus X protein (HBx)-induced abnormalities of nucleic acid metabolism revealed by 1H-NMR-based metabonomics. Sci. Rep. 2016, 6, 24430. [Google Scholar]
- Salerno, D.; Chiodo, L.; Alfano, V.; Floriot, O.; Cottone, G.; Paturel, A.; Pallocca, M.; Plissonnier, M.L.; Jeddari, S.; Belloni, L.; et al. Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription. Gut 2020, 69, 2016–2024. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zampino, R.; Boemio, A.; Sagnelli, C.; Alessio, L.; Adinolfi, L.E.; Sagnelli, E.; Coppola, N. Hepatitis B virus burden in developing countries. World J. Gastroenterol. 2015, 21, 11941–11953. [Google Scholar] [CrossRef]
- Abbas, Z.; Siddiqui, A.R. Management of hepatitis B in developing countries. World J. Hepatol. 2011, 3, 292–299. [Google Scholar] [CrossRef] [PubMed]
- Wait, S.; Chen, D.S. Towards the eradication of hepatitis B in Taiwan. Kaohsiung J. Med. Sci. 2012, 28, 1–9. [Google Scholar] [CrossRef] [Green Version]
- Kaisti, M. Detection principles of biological and chemical FET sensors. Biosens. Bioelectron. 2017, 98, 437–448. [Google Scholar] [CrossRef] [PubMed]
- Chen, K.-I.; Li, B.-R.; Chen, Y.-T. Silicon nanowire field-effect transistor-based biosensors for biomedical diagnosis and cellular recording investigation. Nano Today 2011, 6, 131–154. [Google Scholar] [CrossRef]
- Lin, C.H.; Hung, C.H.; Hsiao, C.Y.; Lin, H.C.; Ko, F.H.; Yang, Y.S. Poly-silicon nanowire field-effect transistor for ultrasensitive and label-free detection of pathogenic avian influenza DNA. Biosens. Bioelectron. 2009, 24, 3019–3024. [Google Scholar] [CrossRef] [PubMed]
- Huang, Y.-W.; Wu, C.-S.; Chuang, C.-K.; Pang, S.-T.; Pan, T.-M.; Yang, Y.-S.; Ko, F.-H. Real-Time and Label-Free Detection of the Prostate-Specific Antigen in Human Serum by a Polycrystalline Silicon Nanowire Field-Effect Transistor Biosensor. Anal. Chem. 2013, 85, 7912–7918. [Google Scholar] [CrossRef]
- Su, P.C.; Chen, B.H.; Lee, Y.C.; Yang, Y.S. Silicon Nanowire Field-Effect Transistor as Biosensing Platforms for Post-Translational Modification. Biosensors 2020, 10, 213. [Google Scholar] [CrossRef]
- Zafar, S.; D’Emic, C.; Jagtiani, A.; Kratschmer, E.; Miao, X.; Zhu, Y.; Mo, R.; Sosa, N.; Hamann, H.; Shahidi, G.; et al. Silicon Nanowire Field Effect Transistor Sensors with Minimal Sensor-to-Sensor Variations and Enhanced Sensing Characteristics. ACS Nano 2018, 12, 6577–6587. [Google Scholar] [CrossRef]
- Shen, M.-Y.; Li, B.-R.; Li, Y.-K. Silicon nanowire field-effect-transistor based biosensors: From sensitive to ultra-sensitive. Biosens. Bioelectron. 2014, 60, 101–111. [Google Scholar] [CrossRef]
- Sheikh, N.J.; Sheikh, O. Forecasting of biosensor technologies for emerging point of care and medical IoT applications using bibliometrics and patent analysis. In Proceedings of the 2016 Portland International Conference on Management of Engineering and Technology (PICMET), Honolulu, HI, USA, 4–8 September 2016. [Google Scholar] [CrossRef]
- Syu, Y.-C.; Hsu, W.-E.; Lin, C.-T. Review—Field-Effect Transistor Biosensing: Devices and Clinical Applications. ECS J. Solid State Sci. Technol. 2018, 7, Q3196–Q3207. [Google Scholar] [CrossRef]
- Pateraki, M.; Fysarakis, K.; Sakkalis, V.; Spanoudakis, G.; Varlamis, I.; Maniadakis, M.; Lourakis, M.; Ioannidis, S.; Cummins, N.; Schuller, B.; et al. Biosensors and Internet of Things in smart healthcare applications: Challenges and opportunities. In Wearable and Implantable Medical Devices; Academic Press: Cambridge, MA, USA, 2020; pp. 25–53. [Google Scholar]
- Lin, H.-C.; Lee, M.-H.; Su, C.-J.; Huang, T.-Y.; Lee, C.C.; Yang, Y.-S. A simple and low-cost method to fabricate TFTs with poly-Si nanowire channel. IEEE Electron Device Lett. 2005, 26, 643–645. [Google Scholar] [CrossRef]
- Lu, M.P.; Hsiao, C.Y.; Lai, W.T.; Yang, Y.S. Probing the sensitivity of nanowire-based biosensors using liquid-gating. Nanotechnology 2010, 21, 425505. [Google Scholar] [CrossRef] [PubMed]
- Lin, C.H.; Feng, M.H.; Hwang, C.H.; Wu, J.Y.S.; Su, P.C.; Lin, M.Y.; Chen, C.H.; Chen, B.H.; Huang, B.Y.; Lu, M.P.; et al. Surface composition and interactions of mobile charges with immobilized molecules on polycrystalline silicon nanowires. Sens. Actuators B Chem. 2015, 211, 7–16. [Google Scholar] [CrossRef]
- Hsiao, C.Y.; Lin, C.H.; Hung, C.H.; Su, C.J.; Lo, Y.R.; Lee, C.C.; Lin, H.C.; Ko, F.H.; Huang, T.Y.; Yang, Y.S. Novel poly-silicon nanowire field effect transistor for biosensing application. Biosens. Bioelectron. 2009, 24, 1223–1229. [Google Scholar] [CrossRef] [PubMed]
- Lee, I.-K.; Jeun, M.; Jang, H.-J.; Cho, W.-J.; Lee, K.H. A self-amplified transistor immunosensor under dual gate operation: Highly sensitive detection of hepatitis B surface antigen. Nanoscale 2015, 7, 16789–16797. [Google Scholar] [CrossRef]
- Basu, J.; Baral, A.; Samanta, N.; Mukherjee, N.; Roychaudhuri, C. Low Noise Field Effect Biosensor with Electrochemically Reduced Graphene Oxide. J. Electrochem. Soc. 2018, 165, B3201–B3207. [Google Scholar] [CrossRef] [Green Version]
- Ortiz-Conde, A.; Sánchez, F.G.; Liou, J.J.; Cerdeira, A.; Estrada, M.; Yue, Y. A review of recent MOSFET threshold voltage extraction methods. Microelectron. Reliab. 2002, 42, 583–596. [Google Scholar] [CrossRef]
- Duan, X.; Li, Y.; Rajan, N.K.; Routenberg, D.A.; Modis, Y.; Reed, M.A. Quantification of the affinities and kinetics of protein interactions using silicon nanowire biosensors. Nat. Nanotech. 2012, 7, 401–407. [Google Scholar] [CrossRef]
- Hobbs, R.G.; Petkov, N.; Holmes, J.D. Semiconductor Nanowire Fabrication by Bottom-Up and Top-Down Paradigms. Chem. Mater. 2012, 24, 1975–1991. [Google Scholar] [CrossRef] [Green Version]
- Noor, M.O.; Krull, U.J. Silicon nanowires as field-effect transducers for biosensor development: A review. Anal. Chim. Acta 2014, 825, 1–25. [Google Scholar] [CrossRef]
- Wu, J.Y.; Lin, C.H.; Feng, M.H.; Chen, C.H.; Su, P.C.; Yang, P.W.; Zheng, J.M.; Fu, C.W.; Yang, Y.S. Preparation of Silicon Nanowire Field-effect Transistor for Chemical and Biosensing Applications. J. Vis. Exp. 2016, 110, 53660. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McArthur, S.L.; Mishra, G.; Easton, C.D. Applications of XPS in Biology and Biointerface Analysis. In Surface Analysis and Techniques in Biology; Smentkowski, V., Ed.; Springer International: Berlin, Germany, 2014. [Google Scholar]
- Yan, X.; Xu, T.; Chen, G.; Yang, S.; Liu, H.; Xue, Q. Preparation and characterization of electrochemically deposited carbon nitride films on silicon substrate. J. Phys. D Appl. Phys. 2004, 37, 907–913. [Google Scholar] [CrossRef]
- Miranda, A.; Martínez, L.; De Beule, P.A.A. Facile synthesis of an aminopropylsilane layer on Si/SiO2 substrates using ethanol as APTES solvent. MethodsX 2020, 7, 100931. [Google Scholar] [CrossRef]
- Lee, Y.S.; Kim, B.K.; Choi, E.C. Physicochemical properties of recombinant hepatitis B surface antigen expressed in mammalian cell (C127). Arch. Pharm. Res. 1998, 21, 521–526. [Google Scholar] [CrossRef] [PubMed]
- Jameel, S.; Siddiqui, A.; Maguire, H.F.; Rao, K.V. Hepatitis B virus X protein produced in Escherichia coli is biologically functional. J. Virol. 1990, 64, 3963–3966. [Google Scholar] [CrossRef] [Green Version]
- Cleaves, H.J. Isoelectric Point. In Encyclopedia of Astrobiology; Gargaud, M., Amils, R., Cernichicaro Quintanilla, J., Cleaves, H.J., Irvine, W.M., Pinti, D., Viso, M., Eds.; Springer: Berlin/Heidelberg, Germany, 2011; p. 858. [Google Scholar]
- Zhang, S.; Garcia-D’Angeli, A.; Brennand, J.P.; Huo, Q. Predicting detection limits of enzyme-linked immunosorbent assay (ELISA) and bioanalytical techniques in general. Analyst 2014, 139, 439–445. [Google Scholar] [CrossRef]
- Fritz, J.; Cooper, E.B.; Gaudet, S.; Sorger, P.K.; Manalis, S.R. Electronic detection of DNA by its intrinsic molecular charge. Proc. Natl. Acad. Sci. USA 2002, 99, 14142–14146. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tulzer, G.; Heitzinger, C. Fluctuations due to association and dissociation processes at nanowire-biosensor surfaces and their optimal design. Nanotechnology 2015, 26, 025502. [Google Scholar] [CrossRef]
- Tyas, A.A.; Raeni, S.F.; Sakti, S.P.; Sabarudin, A. Recent Advances of Hepatitis B Detection towards Paper-Based Analytical Devices. Sci. World J. 2021, 2021, 6643573. [Google Scholar] [CrossRef]
- Wu, C.-Y.; Cheng, H.-Y.; Ou, K.-L.; Wu, C.-C. Real-time sensing of hepatitis B virus X gene using an ultrasensitive nanowire field effect transistor. J. Polym. Eng. 2014, 34, 273–277. [Google Scholar] [CrossRef]
- Poghossian, A.; Schöning, M.J. Label-Free Sensing of Biomolecules with Field-Effect Devices for Clinical Applications. Electroanalysis 2014, 26, 1197–1213. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Yong, S.K.; Shen, S.-K.; Chiang, C.-W.; Weng, Y.-Y.; Lu, M.-P.; Yang, Y.-S. Silicon Nanowire Field-Effect Transistor as Label-Free Detection of Hepatitis B Virus Proteins with Opposite Net Charges. Biosensors 2021, 11, 442. https://0-doi-org.brum.beds.ac.uk/10.3390/bios11110442
Yong SK, Shen S-K, Chiang C-W, Weng Y-Y, Lu M-P, Yang Y-S. Silicon Nanowire Field-Effect Transistor as Label-Free Detection of Hepatitis B Virus Proteins with Opposite Net Charges. Biosensors. 2021; 11(11):442. https://0-doi-org.brum.beds.ac.uk/10.3390/bios11110442
Chicago/Turabian StyleYong, Suh Kuan, Shang-Kai Shen, Chia-Wei Chiang, Ying-Ya Weng, Ming-Pei Lu, and Yuh-Shyong Yang. 2021. "Silicon Nanowire Field-Effect Transistor as Label-Free Detection of Hepatitis B Virus Proteins with Opposite Net Charges" Biosensors 11, no. 11: 442. https://0-doi-org.brum.beds.ac.uk/10.3390/bios11110442