Novel Graphene Biosensor Based on the Functionalization of Multifunctional Nano-bovine Serum Albumin for the Highly Sensitive Detection of Cancer Biomarkers
Corresponding Author: Jianlong Zhao
Nano-Micro Letters,
Vol. 11 (2019), Article Number: 20
Abstract
A simple, convenient, and highly sensitive bio-interface for graphene field-effect transistors (GFETs) based on multifunctional nano-denatured bovine serum albumin (nano-dBSA) functionalization was developed to target cancer biomarkers. The novel graphene–protein bioelectronic interface was constructed by heating to denature native BSA on the graphene substrate surface. The formed nano-dBSA film served as the cross-linker to immobilize monoclonal antibody against carcinoembryonic antigen (anti-CEA mAb) on the graphene channel activated by EDC and Sulfo-NHS. The nano-dBSA film worked as a self-protecting layer of graphene to prevent surface contamination by lithographic processing. The improved GFET biosensor exhibited good specificity and high sensitivity toward the target at an ultralow concentration of 337.58 fg mL−1. The electrical detection of the binding of CEA followed the Hill model for ligand–receptor interaction, indicating the negative binding cooperativity between CEA and anti-CEA mAb with a dissociation constant of 6.82 × 10−10 M. The multifunctional nano-dBSA functionalization can confer a new function to graphene-like 2D nanomaterials and provide a promising bio-functionalization method for clinical application in biosensing, nanomedicine, and drug delivery.
Highlights:
1 A simple and convenient graphene bio-interface was designed by using multifunctional nano-denatured bovine serum albumin (nano-dBSA) film.
2 Highly sensitive cancer biomarker detection in diluted serum at the femtogram per milliliter level was achieved using the nano-dBSA functionalized graphene field-effect transistor.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- J.D. Cohen, L. Li, Y. Wang, C. Thoburn, B. Afsari et al., Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359, 926–930 (2018). https://doi.org/10.1126/science.aar3247
- R.L. Siegel, A. Jemal, R.C. Wender, T. Gansler, J. Ma et al., An assessment of progress in cancer control. CA-Cancer J. Clin. 68(5), 329–339 (2018). https://doi.org/10.3322/caac.21460
- Y. Cao, G. Mo, J. Feng, X. He, L. Tang et al., Based on ZnSe quantum dots labeling and single particle mode ICP-MS coupled with sandwich magnetic immunoassay for the detection of carcinoembryonic antigen in human serum. Anal. Chim. Acta 1028, 22e31 (2018). https://doi.org/10.1016/j.aca.2018.04.039
- J.A. Baron, Screening for cancer with molecular markers: progress comes with potential problems. Nat. Rev. Cancer 12(5), 368–371 (2012). https://doi.org/10.1038/nrc3260
- D. Xie, Y. Wang, J. Shen, J. Hu, P. Yin et al., Detection of carcinoembryonic antigen in peritoneal fluid of patients undergoing laparoscopic distal gastrectomy with complete mesogastric excision. Br. J. Surg. 105, 1471–1479 (2018). https://doi.org/10.1002/bjs.10881
- R. Elisei, A. Pinchera, Advances in the follow-up of differentiated or medullary thyroid cancer. Nat. Rev. Endocrinol. 8(8), 466–475 (2012). https://doi.org/10.1038/nrendo.2012.38
- N. Laboria, A. Fragoso, W. Kemmner, D. Latta, O. Nilsson et al., Amperometric immunosensor for carcinoembryonic antigen in colon cancer samples based on monolayers of dendritic bipodal scaffolds. Anal. Chem. 82, 1712–1719 (2010). https://doi.org/10.1021/ac902162e
- F. Yea, Y. Zhao, R. El-Sayed, M. Muhammed, M. Hassan, Advances in nanotechnology for cancer biomarkers. Nano Today 18, 103–123 (2018). https://doi.org/10.1016/j.nantod.2017.12.008
- G. Nie, Y. Tang, B. Zhang, Y. Wang, Q. Guo, Label-free photoelectrochemical immunosensing platform for detection of carcinoembryonic antigen through photoactive conducting poly(5-formylindole) nanocomposite. Biosens. Bioelectron. 116, 60–66 (2018). https://doi.org/10.1016/j.bios.2018.05.041
- B. Liu, Y. Li, H. Wan, L. Wang, W. Xu et al., High performance, multiplexed lung cancer biomarker detection on a plasmonic gold chip. Adv. Funct. Mater. 26(44), 7994–8002 (2016). https://doi.org/10.1002/adfm.201603547
- J. Peng, Y.Q. Lai, Y.Y. Chen, J. Xu, L.P. Sun et al., Sensitive detection of carcinoembryonic antigen using stability-limited few-layer black phosphorus as an electron donor and a reservoir. Small 13(15), 1603589 (2017). https://doi.org/10.1002/smll.201603589
- T. Wang, D. Qi, H. Yang, Z. Liu, M. Wang et al., Tactile chemomechanical transduction based on an elastic microstructured array to enhance the sensitivity of portable biosensors. Adv. Mater. 31, 1803883 (2018). https://doi.org/10.1002/adma.201803883
- L. Duan, L. Yobas, Label-free multiplexed electrical detection of cancer markers on a microchip featuring an integrated fluidic diode nanopore array. ACS Nano 12, 7892–7900 (2018). https://doi.org/10.1021/acsnano.8b02260
- G. Jie, J. Ge, X. Gao, C. Li, Amplified electrochemiluminescence detection of CEA based on magnetic Fe3O4@Au nanoparticles-assembled Ru@SiO2 nanocomposites combined with multiple cycling amplification strategy. Biosens. Bioelectron. 118, 115–121 (2018). https://doi.org/10.1016/j.bios.2018.07.046
- Y. Zhou, S.H. Chen, X.L. Luo, Y.Q. Chai, R. Yuan, Ternary electrochemiluminescence nanostructure of Au nanoclusters as a highly efficient signal label for ultrasensitive detection of cancer biomarkers. Anal. Chem. 90(16), 10024–10030 (2018). https://doi.org/10.1021/acs.analchem.8b02642
- G. Xu, J. Abbott, L. Qin, K.Y. Yeung, Y. Song et al., Electrophoretic and field-effect graphene for all-electrical DNA array technology. Nat. Commun. 5, 4866 (2014). https://doi.org/10.1038/ncomms5866
- J.E. Kim, Y.H. No, J.N. Kim, Y.S. Shin, W.T. Kang et al., Highly sensitive graphene biosensor by monomolecular self-assembly of receptors on graphene surface. Appl. Phys. Lett. 110, 203702 (2017). https://doi.org/10.1063/1.4983084
- Y. Cui, Q. Wei, H. Park, C.M. Lieber, Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293, 1289–1292 (2001). https://doi.org/10.1126/science.1062711
- W.U. Wang, C. Chen, K.H. Lin, Y. Fang, C.M. Lieber, Label-free detection of small-molecule–protein interactions by using nanowire nanosensors. Proc. Natl. Acad. Sci. USA 102, 3208 (2005). https://doi.org/10.1073/pnas.0406368102
- R.J. Chen, S. Bangsaruntip, K.A. Drouvalakis, N.W. Kam, M. Shim et al., Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors. Proc. Natl. Acad. Sci. USA 100, 4984 (2003). https://doi.org/10.1073/pnas.0837064100
- G. Xu, J. Abbott, D.H. Ham, Optimization of CMOS-ISFET-based biomolecular sensing: analysis and demonstration in DNA detection. IEEE Trans. Electron Devices 63, 3249–3256 (2016). https://doi.org/10.1109/TED.2016.2582845
- M. Medina-Sanchez, S. Miserere, A. Merkoci, Nanomaterials and lab-on-a-chip technologies. Lab Chip 12, 1932 (2012). https://doi.org/10.1039/c2lc40063d
- J.A. Mann, T. Alava, H.G. Craighead, W.R. Dichtel, Preservation of antibody selectivity on graphene by conjugation to a tripod monolayer. Angew. Chem. Int. Ed. 52, 3177–3180 (2013). https://doi.org/10.1002/anie.201209149
- Y. Liu, X. Dong, P. Chen, Biological and chemical sensors based on graphene materials. Chem. Soc. Rev. 41, 2283–2307 (2012). https://doi.org/10.1039/C1CS15270J
- T.P.D. Shareena, D. McShan, A.K. Dasmahapatra, P.B. Tchounwou, A review on graphene-based nanomaterials in biomedical applications and risks in environment and health. Nano-Micro Lett. 10, 53 (2018). https://doi.org/10.1007/s40820-018-0206-4
- C. Wang, Y. Li, Y. Zhu, X. Zhou, Q. Lin, M. He, High-κ-solid-gate transistor configured graphene biosensor with fully integrated structure and enhanced sensitivity. Adv. Funct. Mater. 26, 7668–7678 (2016). https://doi.org/10.1002/adfm.201602960
- V. Yadav, S. Roy, P. Singh, Z. Khan, A. Jaiswal, 2D MoS2-based nanomaterials for therapeutic, bioimaging, and biosensing applications. Small 15, 1803706 (2018). https://doi.org/10.1002/smll.201803706
- C.H. Naylor, N.J. Kybert, C. Schneier, J. Xi, G. Romero et al., Scalable production of molybdenum disulfide based biosensors. ACS Nano 10, 6173–6179 (2016). https://doi.org/10.1021/acsnano.6b02137
- Y. Chen, R. Ren, H. Pu, J. Chang, S. Mao et al., Field-effect transistor biosensors with two-dimensional black phosphorus nanosheets. Biosens. Bioelectron. 89, 505–510 (2017). https://doi.org/10.1016/j.bios.2016.03.059
- E.N. Primo, M.J. Kogan, H.E. Verdejo, S. Bollo, M.D. Rubianes et al., Label-free graphene oxide-based surface plasmon resonance immunosensor for the quantification of galectin-3, a novel cardiac biomarker. ACS Appl. Mater. Interfaces 10, 23501–23508 (2018). https://doi.org/10.1021/acsami.8b03039
- E. Morales-Narváez, L. Baptista-Pires, A. Zamora-Gálvez, A. Merkoçi, Graphene-based biosensors: going simple. Adv. Mater. 29, 1604905 (2017). https://doi.org/10.1002/adma.201604905
- J. Peña-Bahamonde, H.N. Nguyen, S.K. Fanourakis, D.F. Rodrigues, Recent advances in graphene based biosensor technology with applications in life sciences. J. Nanobiotechnol. 16, 75 (2018). https://doi.org/10.1186/s12951-018-0400-z
- P. Bollella, G. Fusco, C. Tortolini, G. Sanzò, G. Favero et al., Beyond graphene: electrochemical sensors and biosensors for biomarkers detection. Biosens. Bioelectron. 89, 152–166 (2017). https://doi.org/10.1016/j.bios.2016.03.068
- Z. Zhu, An overview of carbon nanotubes and graphene for biosensing applications. Nano-Micro Lett. 9, 25 (2017). https://doi.org/10.1007/s40820-017-0128-6
- K.S. Novoselov, A.K. Geim, S.V. Morozov, D. Jiang, Y. Zhang et al., Electric field effect in atomically thin carbon films. Science 306, 666–669 (2004). https://doi.org/10.1126/science.1102896
- V. Georgakilas, M. Otyepka, A.B. Bourlinos, V. Chandra, N. Kim et al., Functionalization of graphene: covalent and non-covalent approaches, derivatives and applications. Chem. Rev. 112, 6156–6214 (2012). https://doi.org/10.1021/cr3000412
- S. Viswanathan, T.N. Narayanan, K. Aran, K.D. Fink, J. Paredes et al., Graphene–protein field effect biosensors: glucose sensing. Mater. Today 18, 513–522 (2015). https://doi.org/10.1016/j.mattod.2015.04.003
- M.T. Hwang, P.B. Landon, J. Lee, D. Choi, A.H. Mo et al., Highly specific SNP detection using 2D graphene electronics and DNA strand displacement. Proc. Natl. Acad. Sci. USA 113, 7088–7093 (2016). https://doi.org/10.1073/pnas.1603753113
- S.K. Jang, J. Jang, W.S. Choe, S. Lee, Harnessing denatured protein for controllable bipolar doping of a monolayer graphene. ACS Appl. Mater. Interfaces 7, 1250–1256 (2015). https://doi.org/10.1021/am507246v
- N. Gao, T. Gao, X. Yang, X. Dai, W. Zhou et al., Specific detection of biomolecules in physiological solutions using graphene transistor biosensors. Proc. Natl. Acad. Sci. USA 113, 14633–14638 (2016). https://doi.org/10.1073/pnas.1625010114
- W.Y. Fu, L. Jiang, E.P. van Geest, M.C. LimaL, G.F. Schneider, Sensing at the surface of graphene field-effect transistors. Adv. Mater. 29, 1603610 (2017). https://doi.org/10.1002/adma.201603610
- S. Liu, Y. Fu, C. Xiong, Z. Liu, L. Zheng et al., Detection of bisphenol a using DNA-functionalized graphene field effect transistors integrated in microfluidic systems. ACS Appl. Mater. Interfaces 10, 23522–23528 (2018). https://doi.org/10.1021/acsami.8b04260
- S.K. Tuteja, C. Ormsby, S. Neethirajan, Noninvasive label-free detection of cortisol and lactate using graphene embedded screen-printed electrode. Nano-Micro Lett. 10, 41 (2018). https://doi.org/10.1007/s40820-018-0193-5
- L. Zhou, K. Wang, Z. Wu, H. Dong, H. Sun et al., Investigation of controllable nanoscale heat-denatured bovine serum albumin films on graphene. Langmuir 32, 12623 (2016). https://doi.org/10.1021/acs.langmuir.6b03296
- M. Hu, J. Yan, Y. He, H.T. Lu, L.X. Weng et al., Ultrasensitive, multiplexed detection of cancer biomarkers directly in serum by using a quantum dot-based microfluidic protein chip. ACS Nano 4, 488–494 (2010). https://doi.org/10.1021/nn901404h
- E. Stern, R. Wagner, F.J. Sigworth, R. Breaker, T.M. Fahmy et al., Importance of the Debye screening length on nanowire field effect transistor sensors. Nano Lett. 7, 3405–3409 (2007). https://doi.org/10.1021/nl071792z
- Y. Ohno, K. Maehashi, K. Matsumoto, Chemical and biological sensing applications based on graphene field-effect transistors. Biosens. Bioelectron. 26, 1727–1730 (2010). https://doi.org/10.1016/j.bios.2010.08.001
- F. Schwierz, Graphene transistors. Nat. Nanotechnol. 5, 487–496 (2010). https://doi.org/10.1038/nnano.2010.89
- L.H. Hess, M.V. Hauf, M. Seifert, F. Speck, T. Seyller et al., High-transconductance graphene solution-gated field effect transistors. Appl. Phys. Lett. 99, 033503 (2011). https://doi.org/10.1063/1.3614445
- L.H. Hess, M. Jansen, V. Maybeck, M.V. Hauf, M. Seifert et al., Graphene transistor arrays for recording action potentials from electrogenic cells. Adv. Mater. 23, 5045–5049 (2011). https://doi.org/10.1002/adma.201102990
- D.B. Farmer, H.Y. Chiu, Y.M. Lin, K.A. Jenkins, F.N. Xia et al., Utilization of a buffered dielectric to achieve high field-effect carrier mobility in graphene transistors. Nano Lett. 9, 4474 (2009). https://doi.org/10.1021/nl902788u
- H.L. Xu, Z.Y. Zhang, L.M. Peng, Measurements and microscopic model of quantum capacitance in graphene. Appl. Phys. Lett. 98, 133122 (2011). https://doi.org/10.1063/1.3574011
- H.L. Xu, Z.Y. Zhang, S. Wang, X.L. Liang, L.M. Peng, Quantum capacitance limited vertical scaling of graphene field-effect transistor. ACS Nano 5, 2340–2347 (2011). https://doi.org/10.1021/nn200026e
- B.J. Casey, P. Kofinas, Selective binding of carcinoembryonic antigen using imprinted polymeric hydrogels. J. Biomed. Mater. Res. A 87, 359–363 (2008). https://doi.org/10.1002/jbm.a.31757
- L.K. Koopal, W.H. Riemsdijk, J.D. Wit, M.F. Benedetti, Analytical isotherm equations for multicomponent adsorption to heterogeneous surfaces. J. Colloid Interface Sci. 166, 51–60 (1994). https://doi.org/10.1006/jcis.1994.1270
- D. Ringot, B. Lerzy, K. Chaplain, J.P. Bonhoure, E. Auclair et al., In vitro biosorption of ochratoxin A on the yeast industry by-products: comparison of isotherm models. Bioresour. Technol. 98, 1812–1821 (2007). https://doi.org/10.1016/j.biortech.2006.06.015
- A. Haggarty, C. Legler, M.J. Krantz, A. Fuks, Epitopes of carcinoembryonic antigen defined by monoclonal antibodies prepared from mice immunized with purified carcinoembryonic antigen or HCT-8R cells. Cancer Res. 46, 300–309 (1986)
- J.E. Morris, M.L. Egan, C.W. Todd, The binding of carcinoembryonic antigen by antibody and its fragments. Cancer Res. 35, 1804–1808 (1975)
- M. Nap, M.L. Hammarstrom, O. Bormer, S. Hammarstrom, C. Wagener et al., Specificity and affinity of monoclonal antibodies against carcinoembryonic antigen. Cancer Res. 52, 2329–2339 (1992)
- H. Bjorkelund, L. Gedda, K. Andersson, Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply dependency of cellular context. PLoS ONE 6(1), e16536 (2011). https://doi.org/10.1371/journal.pone.0016536
- Y.M. Lei, M.M. Xiao, Y.T. Li, L. Xu, H. Zhang et al., Detection of heart failure-related biomarker in whole blood with graphene field effect transistor biosensor. Biosens. Bioelectron. 91, 1–7 (2017). https://doi.org/10.1016/j.bios.2016.12.018
- T. Berninger, C. Bliem, E. Piccinini, O. Azzaroni, W. Knoll, Cascading reaction of arginase and urease on a graphene-based FET for ultrasensitive, real-time detection of arginine. Biosens. Bioelectron. 115, 104–110 (2018). https://doi.org/10.1016/j.bios.2018.05.027
References
J.D. Cohen, L. Li, Y. Wang, C. Thoburn, B. Afsari et al., Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359, 926–930 (2018). https://doi.org/10.1126/science.aar3247
R.L. Siegel, A. Jemal, R.C. Wender, T. Gansler, J. Ma et al., An assessment of progress in cancer control. CA-Cancer J. Clin. 68(5), 329–339 (2018). https://doi.org/10.3322/caac.21460
Y. Cao, G. Mo, J. Feng, X. He, L. Tang et al., Based on ZnSe quantum dots labeling and single particle mode ICP-MS coupled with sandwich magnetic immunoassay for the detection of carcinoembryonic antigen in human serum. Anal. Chim. Acta 1028, 22e31 (2018). https://doi.org/10.1016/j.aca.2018.04.039
J.A. Baron, Screening for cancer with molecular markers: progress comes with potential problems. Nat. Rev. Cancer 12(5), 368–371 (2012). https://doi.org/10.1038/nrc3260
D. Xie, Y. Wang, J. Shen, J. Hu, P. Yin et al., Detection of carcinoembryonic antigen in peritoneal fluid of patients undergoing laparoscopic distal gastrectomy with complete mesogastric excision. Br. J. Surg. 105, 1471–1479 (2018). https://doi.org/10.1002/bjs.10881
R. Elisei, A. Pinchera, Advances in the follow-up of differentiated or medullary thyroid cancer. Nat. Rev. Endocrinol. 8(8), 466–475 (2012). https://doi.org/10.1038/nrendo.2012.38
N. Laboria, A. Fragoso, W. Kemmner, D. Latta, O. Nilsson et al., Amperometric immunosensor for carcinoembryonic antigen in colon cancer samples based on monolayers of dendritic bipodal scaffolds. Anal. Chem. 82, 1712–1719 (2010). https://doi.org/10.1021/ac902162e
F. Yea, Y. Zhao, R. El-Sayed, M. Muhammed, M. Hassan, Advances in nanotechnology for cancer biomarkers. Nano Today 18, 103–123 (2018). https://doi.org/10.1016/j.nantod.2017.12.008
G. Nie, Y. Tang, B. Zhang, Y. Wang, Q. Guo, Label-free photoelectrochemical immunosensing platform for detection of carcinoembryonic antigen through photoactive conducting poly(5-formylindole) nanocomposite. Biosens. Bioelectron. 116, 60–66 (2018). https://doi.org/10.1016/j.bios.2018.05.041
B. Liu, Y. Li, H. Wan, L. Wang, W. Xu et al., High performance, multiplexed lung cancer biomarker detection on a plasmonic gold chip. Adv. Funct. Mater. 26(44), 7994–8002 (2016). https://doi.org/10.1002/adfm.201603547
J. Peng, Y.Q. Lai, Y.Y. Chen, J. Xu, L.P. Sun et al., Sensitive detection of carcinoembryonic antigen using stability-limited few-layer black phosphorus as an electron donor and a reservoir. Small 13(15), 1603589 (2017). https://doi.org/10.1002/smll.201603589
T. Wang, D. Qi, H. Yang, Z. Liu, M. Wang et al., Tactile chemomechanical transduction based on an elastic microstructured array to enhance the sensitivity of portable biosensors. Adv. Mater. 31, 1803883 (2018). https://doi.org/10.1002/adma.201803883
L. Duan, L. Yobas, Label-free multiplexed electrical detection of cancer markers on a microchip featuring an integrated fluidic diode nanopore array. ACS Nano 12, 7892–7900 (2018). https://doi.org/10.1021/acsnano.8b02260
G. Jie, J. Ge, X. Gao, C. Li, Amplified electrochemiluminescence detection of CEA based on magnetic Fe3O4@Au nanoparticles-assembled Ru@SiO2 nanocomposites combined with multiple cycling amplification strategy. Biosens. Bioelectron. 118, 115–121 (2018). https://doi.org/10.1016/j.bios.2018.07.046
Y. Zhou, S.H. Chen, X.L. Luo, Y.Q. Chai, R. Yuan, Ternary electrochemiluminescence nanostructure of Au nanoclusters as a highly efficient signal label for ultrasensitive detection of cancer biomarkers. Anal. Chem. 90(16), 10024–10030 (2018). https://doi.org/10.1021/acs.analchem.8b02642
G. Xu, J. Abbott, L. Qin, K.Y. Yeung, Y. Song et al., Electrophoretic and field-effect graphene for all-electrical DNA array technology. Nat. Commun. 5, 4866 (2014). https://doi.org/10.1038/ncomms5866
J.E. Kim, Y.H. No, J.N. Kim, Y.S. Shin, W.T. Kang et al., Highly sensitive graphene biosensor by monomolecular self-assembly of receptors on graphene surface. Appl. Phys. Lett. 110, 203702 (2017). https://doi.org/10.1063/1.4983084
Y. Cui, Q. Wei, H. Park, C.M. Lieber, Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293, 1289–1292 (2001). https://doi.org/10.1126/science.1062711
W.U. Wang, C. Chen, K.H. Lin, Y. Fang, C.M. Lieber, Label-free detection of small-molecule–protein interactions by using nanowire nanosensors. Proc. Natl. Acad. Sci. USA 102, 3208 (2005). https://doi.org/10.1073/pnas.0406368102
R.J. Chen, S. Bangsaruntip, K.A. Drouvalakis, N.W. Kam, M. Shim et al., Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors. Proc. Natl. Acad. Sci. USA 100, 4984 (2003). https://doi.org/10.1073/pnas.0837064100
G. Xu, J. Abbott, D.H. Ham, Optimization of CMOS-ISFET-based biomolecular sensing: analysis and demonstration in DNA detection. IEEE Trans. Electron Devices 63, 3249–3256 (2016). https://doi.org/10.1109/TED.2016.2582845
M. Medina-Sanchez, S. Miserere, A. Merkoci, Nanomaterials and lab-on-a-chip technologies. Lab Chip 12, 1932 (2012). https://doi.org/10.1039/c2lc40063d
J.A. Mann, T. Alava, H.G. Craighead, W.R. Dichtel, Preservation of antibody selectivity on graphene by conjugation to a tripod monolayer. Angew. Chem. Int. Ed. 52, 3177–3180 (2013). https://doi.org/10.1002/anie.201209149
Y. Liu, X. Dong, P. Chen, Biological and chemical sensors based on graphene materials. Chem. Soc. Rev. 41, 2283–2307 (2012). https://doi.org/10.1039/C1CS15270J
T.P.D. Shareena, D. McShan, A.K. Dasmahapatra, P.B. Tchounwou, A review on graphene-based nanomaterials in biomedical applications and risks in environment and health. Nano-Micro Lett. 10, 53 (2018). https://doi.org/10.1007/s40820-018-0206-4
C. Wang, Y. Li, Y. Zhu, X. Zhou, Q. Lin, M. He, High-κ-solid-gate transistor configured graphene biosensor with fully integrated structure and enhanced sensitivity. Adv. Funct. Mater. 26, 7668–7678 (2016). https://doi.org/10.1002/adfm.201602960
V. Yadav, S. Roy, P. Singh, Z. Khan, A. Jaiswal, 2D MoS2-based nanomaterials for therapeutic, bioimaging, and biosensing applications. Small 15, 1803706 (2018). https://doi.org/10.1002/smll.201803706
C.H. Naylor, N.J. Kybert, C. Schneier, J. Xi, G. Romero et al., Scalable production of molybdenum disulfide based biosensors. ACS Nano 10, 6173–6179 (2016). https://doi.org/10.1021/acsnano.6b02137
Y. Chen, R. Ren, H. Pu, J. Chang, S. Mao et al., Field-effect transistor biosensors with two-dimensional black phosphorus nanosheets. Biosens. Bioelectron. 89, 505–510 (2017). https://doi.org/10.1016/j.bios.2016.03.059
E.N. Primo, M.J. Kogan, H.E. Verdejo, S. Bollo, M.D. Rubianes et al., Label-free graphene oxide-based surface plasmon resonance immunosensor for the quantification of galectin-3, a novel cardiac biomarker. ACS Appl. Mater. Interfaces 10, 23501–23508 (2018). https://doi.org/10.1021/acsami.8b03039
E. Morales-Narváez, L. Baptista-Pires, A. Zamora-Gálvez, A. Merkoçi, Graphene-based biosensors: going simple. Adv. Mater. 29, 1604905 (2017). https://doi.org/10.1002/adma.201604905
J. Peña-Bahamonde, H.N. Nguyen, S.K. Fanourakis, D.F. Rodrigues, Recent advances in graphene based biosensor technology with applications in life sciences. J. Nanobiotechnol. 16, 75 (2018). https://doi.org/10.1186/s12951-018-0400-z
P. Bollella, G. Fusco, C. Tortolini, G. Sanzò, G. Favero et al., Beyond graphene: electrochemical sensors and biosensors for biomarkers detection. Biosens. Bioelectron. 89, 152–166 (2017). https://doi.org/10.1016/j.bios.2016.03.068
Z. Zhu, An overview of carbon nanotubes and graphene for biosensing applications. Nano-Micro Lett. 9, 25 (2017). https://doi.org/10.1007/s40820-017-0128-6
K.S. Novoselov, A.K. Geim, S.V. Morozov, D. Jiang, Y. Zhang et al., Electric field effect in atomically thin carbon films. Science 306, 666–669 (2004). https://doi.org/10.1126/science.1102896
V. Georgakilas, M. Otyepka, A.B. Bourlinos, V. Chandra, N. Kim et al., Functionalization of graphene: covalent and non-covalent approaches, derivatives and applications. Chem. Rev. 112, 6156–6214 (2012). https://doi.org/10.1021/cr3000412
S. Viswanathan, T.N. Narayanan, K. Aran, K.D. Fink, J. Paredes et al., Graphene–protein field effect biosensors: glucose sensing. Mater. Today 18, 513–522 (2015). https://doi.org/10.1016/j.mattod.2015.04.003
M.T. Hwang, P.B. Landon, J. Lee, D. Choi, A.H. Mo et al., Highly specific SNP detection using 2D graphene electronics and DNA strand displacement. Proc. Natl. Acad. Sci. USA 113, 7088–7093 (2016). https://doi.org/10.1073/pnas.1603753113
S.K. Jang, J. Jang, W.S. Choe, S. Lee, Harnessing denatured protein for controllable bipolar doping of a monolayer graphene. ACS Appl. Mater. Interfaces 7, 1250–1256 (2015). https://doi.org/10.1021/am507246v
N. Gao, T. Gao, X. Yang, X. Dai, W. Zhou et al., Specific detection of biomolecules in physiological solutions using graphene transistor biosensors. Proc. Natl. Acad. Sci. USA 113, 14633–14638 (2016). https://doi.org/10.1073/pnas.1625010114
W.Y. Fu, L. Jiang, E.P. van Geest, M.C. LimaL, G.F. Schneider, Sensing at the surface of graphene field-effect transistors. Adv. Mater. 29, 1603610 (2017). https://doi.org/10.1002/adma.201603610
S. Liu, Y. Fu, C. Xiong, Z. Liu, L. Zheng et al., Detection of bisphenol a using DNA-functionalized graphene field effect transistors integrated in microfluidic systems. ACS Appl. Mater. Interfaces 10, 23522–23528 (2018). https://doi.org/10.1021/acsami.8b04260
S.K. Tuteja, C. Ormsby, S. Neethirajan, Noninvasive label-free detection of cortisol and lactate using graphene embedded screen-printed electrode. Nano-Micro Lett. 10, 41 (2018). https://doi.org/10.1007/s40820-018-0193-5
L. Zhou, K. Wang, Z. Wu, H. Dong, H. Sun et al., Investigation of controllable nanoscale heat-denatured bovine serum albumin films on graphene. Langmuir 32, 12623 (2016). https://doi.org/10.1021/acs.langmuir.6b03296
M. Hu, J. Yan, Y. He, H.T. Lu, L.X. Weng et al., Ultrasensitive, multiplexed detection of cancer biomarkers directly in serum by using a quantum dot-based microfluidic protein chip. ACS Nano 4, 488–494 (2010). https://doi.org/10.1021/nn901404h
E. Stern, R. Wagner, F.J. Sigworth, R. Breaker, T.M. Fahmy et al., Importance of the Debye screening length on nanowire field effect transistor sensors. Nano Lett. 7, 3405–3409 (2007). https://doi.org/10.1021/nl071792z
Y. Ohno, K. Maehashi, K. Matsumoto, Chemical and biological sensing applications based on graphene field-effect transistors. Biosens. Bioelectron. 26, 1727–1730 (2010). https://doi.org/10.1016/j.bios.2010.08.001
F. Schwierz, Graphene transistors. Nat. Nanotechnol. 5, 487–496 (2010). https://doi.org/10.1038/nnano.2010.89
L.H. Hess, M.V. Hauf, M. Seifert, F. Speck, T. Seyller et al., High-transconductance graphene solution-gated field effect transistors. Appl. Phys. Lett. 99, 033503 (2011). https://doi.org/10.1063/1.3614445
L.H. Hess, M. Jansen, V. Maybeck, M.V. Hauf, M. Seifert et al., Graphene transistor arrays for recording action potentials from electrogenic cells. Adv. Mater. 23, 5045–5049 (2011). https://doi.org/10.1002/adma.201102990
D.B. Farmer, H.Y. Chiu, Y.M. Lin, K.A. Jenkins, F.N. Xia et al., Utilization of a buffered dielectric to achieve high field-effect carrier mobility in graphene transistors. Nano Lett. 9, 4474 (2009). https://doi.org/10.1021/nl902788u
H.L. Xu, Z.Y. Zhang, L.M. Peng, Measurements and microscopic model of quantum capacitance in graphene. Appl. Phys. Lett. 98, 133122 (2011). https://doi.org/10.1063/1.3574011
H.L. Xu, Z.Y. Zhang, S. Wang, X.L. Liang, L.M. Peng, Quantum capacitance limited vertical scaling of graphene field-effect transistor. ACS Nano 5, 2340–2347 (2011). https://doi.org/10.1021/nn200026e
B.J. Casey, P. Kofinas, Selective binding of carcinoembryonic antigen using imprinted polymeric hydrogels. J. Biomed. Mater. Res. A 87, 359–363 (2008). https://doi.org/10.1002/jbm.a.31757
L.K. Koopal, W.H. Riemsdijk, J.D. Wit, M.F. Benedetti, Analytical isotherm equations for multicomponent adsorption to heterogeneous surfaces. J. Colloid Interface Sci. 166, 51–60 (1994). https://doi.org/10.1006/jcis.1994.1270
D. Ringot, B. Lerzy, K. Chaplain, J.P. Bonhoure, E. Auclair et al., In vitro biosorption of ochratoxin A on the yeast industry by-products: comparison of isotherm models. Bioresour. Technol. 98, 1812–1821 (2007). https://doi.org/10.1016/j.biortech.2006.06.015
A. Haggarty, C. Legler, M.J. Krantz, A. Fuks, Epitopes of carcinoembryonic antigen defined by monoclonal antibodies prepared from mice immunized with purified carcinoembryonic antigen or HCT-8R cells. Cancer Res. 46, 300–309 (1986)
J.E. Morris, M.L. Egan, C.W. Todd, The binding of carcinoembryonic antigen by antibody and its fragments. Cancer Res. 35, 1804–1808 (1975)
M. Nap, M.L. Hammarstrom, O. Bormer, S. Hammarstrom, C. Wagener et al., Specificity and affinity of monoclonal antibodies against carcinoembryonic antigen. Cancer Res. 52, 2329–2339 (1992)
H. Bjorkelund, L. Gedda, K. Andersson, Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply dependency of cellular context. PLoS ONE 6(1), e16536 (2011). https://doi.org/10.1371/journal.pone.0016536
Y.M. Lei, M.M. Xiao, Y.T. Li, L. Xu, H. Zhang et al., Detection of heart failure-related biomarker in whole blood with graphene field effect transistor biosensor. Biosens. Bioelectron. 91, 1–7 (2017). https://doi.org/10.1016/j.bios.2016.12.018
T. Berninger, C. Bliem, E. Piccinini, O. Azzaroni, W. Knoll, Cascading reaction of arginase and urease on a graphene-based FET for ultrasensitive, real-time detection of arginine. Biosens. Bioelectron. 115, 104–110 (2018). https://doi.org/10.1016/j.bios.2018.05.027