Abstract
Single-stranded DNA molecules capable of molecular recognition and catalysis can now be routinely generated via the technique of in vitro selection. When coupled with adequate signal transduction modes, these synthetic functional DNA species represent a potential paradigm shift in the research and development of biosensors to meet the challenges of our rapidly changing world. Coupling functional DNA molecules with graphene materials for the design of optical biosensors has become an exciting research area in recent years, mostly because graphene materials are not only excellent quenchers of fluorescence, but they also display considerably different affinities for free and ligand-bound functional DNA molecules. We will discuss notable progress in this area in this mini-review by highlighting representative studies.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1557%2Fjmr.2017.103/MediaObjects/43578_2017_32152973_Fig1.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1557%2Fjmr.2017.103/MediaObjects/43578_2017_32152973_Fig2.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1557%2Fjmr.2017.103/MediaObjects/43578_2017_32152973_Fig3.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1557%2Fjmr.2017.103/MediaObjects/43578_2017_32152973_Fig4.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1557%2Fjmr.2017.103/MediaObjects/43578_2017_32152973_Fig5.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1557%2Fjmr.2017.103/MediaObjects/43578_2017_32152973_Fig6.jpg)
Similar content being viewed by others
References
J. Liu, Z. Cao, and Y. Lu: Functional nucleic acid sensors. Chem. Rev. 109, 1948 (2009).
N.K. Navani and Y. Li: Nucleic acid aptamers and enzymes as sensors. Curr. Opin. Chem. Biol. 10, 272 (2006).
D. Chen, H. Feng, and J.H. Li: Graphene oxide: Preparation, functionalization, and electrochemical applications. Chem. Rev. 112, 6027 (2012).
Y. Liu, X. Dong, and P. Chen: Biological and chemical sensors based on graphene materials. Chem. Soc. Rev. 41, 2283 (2012).
E. Morales-Narváez and A. Merkoci: Graphene oxide as an optical biosensing platform. Adv. Mater. 24, 3298 (2012).
K.P. Loh, Q. Bao, G. Eda, and M. Chhowalla: Graphene oxide as a chemically tunable platform for optical applications. Nat. Chem. 2, 1015 (2010).
Y. Wang, Z. Li, J. Wang, J. Li, and Y. Lin: Graphene and graphene oxide: Biofunctionalization and applications in biotechnology. Trends Biotechnol. 29, 205 (2011).
T.R. Cech: The chemistry of self-splicing RNA and RNA enzymes. Science 236, 1532 (1987).
T. Hermann and D.J. Patel: Adaptive recognition by nucleic acid aptamers. Science 287, 820 (2000).
A. Ponce-Salvatierra, K. Wawrzyniak-Turek, U. Steuerwald, C. Hobartner, and V. Pena: Crystal structure of a DNA catalyst. Nature 529, 231 (2016).
C. Tuerk and L. Gold: Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505 (1990).
A.D. Ellington and J.W. Szostak: In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818 (1990).
D.L. Robertson and G.F. Joyce: Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature 344, 467 (1990).
W. Mok and Y. Li: Recent progress in nucleic acid aptamer-based biosensors and bioassays. Sensors 8, 7050 (2008).
Y. Wang, Z. Li, T.J. Weber, D. Hu, C.T. Lin, J. Li, and Y. Lin: In situ live cell sensing of multiple nucleotides exploiting DNA/RNA aptamers and graphene oxide nanosheets. Anal. Chem. 85, 6775 (2013).
K. Ling, H. Jiang, Y. Li, X. Tao, C. Qiu, and F.R. Li: A self-assembling RNA aptamer-based graphene oxide sensor for the turn-on detection of theophylline in serum. Biosens. Bioelectron 86, 8 (2016).
L.C. Bock, L.C. Griffin, J.A. Latham, E.H. Vermaas, and J.J. Toole: Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 355, 564 (1992).
K.Y. Wang, S.H. Krawczyk, N. Bischofberger, S. Swaminathan, and P.H. Bolton: The tertiary structure of a DNA aptamer which binds to and inhibits thrombin determines activity. Biochemistry 32, 11285 (1993).
R.F. Macaya, P. Schultze, F.W. Smith, J.A. Roe, and J. Feigon: Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. Proc. Natl. Acad. Sci. U. S. A. 90, 3745 (1993).
K. Padmanabhan, K.P. Padmanabhan, J.D. Ferrara, J.E. Sadler, and A. Tulinsky: The structure of alpha-thrombin inhibited by a 15-mer single-stranded DNA aptamer. J. Biol. Chem. 268, 17651 (1993).
D.E. Huizenga and J.W. Szostak: A DNA aptamer that binds adenosine and ATP. Biochemistry 34, 656 (1995).
C.H. Lin and D.J. Patel: Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: Distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP. Chem. Biol. 4, 817 (1997).
R.R. Breaker and G.F. Joyce: A DNA enzyme that cleaves RNA. Chem. Biol. 1, 223 (1994).
S.W. Santoro and G.F. Joyce: A general purpose RNA-cleaving DNA enzyme. Proc. Natl. Acad. Sci. U. S. A. 94, 4262 (1997).
R.P. Cruz, J.B. Withers, and Y. Li: Dinucleotide junction cleavage versatility of 8-17 deoxyribozyme. Chem. Biol. 11, 57 (2004).
K. Schlosser and Y. Li: A versatile endoribonuclease mimic made of DNA: Characteristics and applications of the 8-17 RNA-cleaving DNAzyme. ChemBioChem 11, 866 (2010).
N. Carmi, S.R. Balkhi, and R.R. Breaker: Cleaving DNA with DNA. Proc. Natl. Acad. Sci. U. S. A. 95, 2233 (1998).
P.J.J. Huang, J. Lin, J. Cao, M. Vazin, and J. Liu: Ultrasensitive DNAzyme beacon for lanthanides and metal speciation. Anal. Chem. 86, 1816 (2014).
S.F. Torabi, P. Wu, C.E. McGhee, L. Chen, K. Hwang, N. Zheng, J. Cheng, and Y. Lu: In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing. Proc. Natl. Acad. Sci. U. S. A. 112, 5903 (2015).
R. Saran and J. Liu: A silver DNAzyme. Anal. Chem. 88, 4014 (2016).
K. Tram, P. Kanda, and Y. Li: Lighting up RNA-cleaving DNAzymes for biosensing. J. Nucleic Acids 2012, 958683 (2012).
M.M. Ali, S.D. Aguirre, H. Lazim, and Y. Li: Fluorogenic DNAzyme probes as bacterial indicators. Angew. Chem., Int. Ed. 50, 3751 (2011).
Z. Shen, Z. Wu, D. Chang, W. Zhang, K. Tram, C. Lee, P. Kim, B.J. Salena, and Y. Li: A catalytic DNA activated by a specific strain of bacterial pathogen. Angew. Chem., Int. Ed. 55, 2431 (2016).
B.J. Hong, Z. An, O.C. Compton, and S.T. Nguyen: Tunable biomolecular interaction and fluorescence quenching ability of graphene oxide: Application to “turn-on” DNA sensing in biological media. Small 8, 2469 (2012).
S. Gowtham, R.H. Scheicher, R. Ahuja, R. Pandey, and S.P. Karna: Physisorption of nucleobases on graphene: Density-functional calculation. Phys. Rev. B: Condens. Matter Mater. Phys. 76, 033401 (2007).
N. Varghese, U. Mogera, A. Govindaraj, A. Das, P.K. Maiti, A.K. Sood, and C.N.R. Rao: Binding of DNA nucleobases and nucleosides with graphene. Chem. Phys. Chem. 10, 206 (2009).
L.S. Green, D. Jellinek, R. Jenison, A. Östman, C.H. Heldin, and N. Janjic: Inhibitory DNA ligands to platelet-derived growth factor B-chain. Biochemistry 35, 14413 (1996).
M. Wu, R. Kempaiah, P.J. Huang, V. Maheshwari, and J. Liu: Adsorption and desorption of DNA on graphene oxide studied by fluorescently labeled oligonucleotides. Langmuir 27, 2731 (2011).
H. Lei, L. Mi, X. Zhou, J. Chen, J. Hu, S. Guo, and Y. Zhang: Adsorption of double-stranded DNA to graphene oxide preventing enzymatic digestion. Nanoscale 3, 3888 (2011).
B. Liu, Z. Sun, X. Zhang, and J. Liu: Mechanisms of DNA sensing on graphene oxide. Anal. Chem. 85, 7987 (2013).
J.S. Park, N.I. Goo, and D.E. Kim: Mechanism of DNA adsorption and desorption on graphene oxide. Langmuir 30, 12587 (2014).
Z. Liu, B. Liu, J. Ding, and J. Liu: Fluorescent sensors using DNA-functionalized graphene oxide. Anal. Bioanal. Chem. 406, 6885 (2014).
B. Liu, S. Salgado, V. Maheshwari, and J. Liu: DNA adsorbed on graphene and graphene oxide: Fundamental interactions, desorption and applications. Curr. Opin. Colloid Interface Sci. 26, 41 (2016).
M.H. Li, Y.S. Wang, J.X. Cao, S.H. Chen, X. Tang, X.F. Wang, Y.F. Zhu, and Y.Q. Huang: Ultrasensitive detection of uranyl by graphene oxide-based background reduction and RCDzyme-based enzyme strand recycling signal amplification. Biosens. Bioelectron. 72, 294 (2015).
H. Dong, W. Gao, F. Yan, H. Ji, and H. Ju: Fluorescence resonance energy transfer between quantum dots and graphene oxide for sensing biomolecules. Anal. Chem. 82, 5511 (2010).
X. Liu, F. Wang, R. Aizen, O. Yehezkeli, and I. Willner: Graphene oxide/nucleic-acid-stabilized silver nanoclusters: Functional hybrid materials for optical aptamer sensing and multiplexed analysis of pathogenic DNAs. J. Am. Chem. Soc. 135, 11832 (2013).
C. Liu, Z. Wang, H. Jia, and Z. Li: Efficient fluorescence resonance energy transfer between upconversion nanophosphors and graphene oxide: A highly sensitive biosensing platform. Chem. Commun. 47, 4661 (2011).
R.S. Swathi and K.L. Sebastian: Long range resonance energy transfer from a dye molecule to graphene has (distance)−4 dependence. J. Chem. Phys. 130, 086101 (2009).
M. Liu, H.M. Zhao, X. Quan, S. Chen, and X.F. Fan: Distance independent quenching of quantum dots by nanoscale-graphene in self-assembled sandwich immunoassay. Chem. Commun. 46, 7909 (2010).
X.H. Zhao, R.M. Kong, X.B. Zhang, H.M. Meng, W.N. Liu, W. Tan, G.L. Shen, and R.Q. Yu: Graphene–DNAzyme based biosensor for amplified fluorescence “turn-on” detection of Pb2+ with a high selectivity. Anal. Chem. 83, 5062 (2011).
M. Liu, H. Zhao, S. Chen, H. Yu, Y. Zhang, and X. Quan: Label-free fluorescent detection of Cu(II) ions based on DNA cleavage-dependent graphene-quenched DNAzymes. Chem. Commun. 47, 7749 (2011).
M. Liu, H. Zhao, S. Chen, H. Yu, Y. Zhang, and X. Quan: A “turn-on” fluorescent copper biosensor based on DNA cleavage-dependent graphene-quenched DNAzyme. Biosens. Bioelectron. 26, 4111 (2011).
Y. Wang, Z. Li, D. Hu, C.T. Lin, J. Li, and Y. Lin: Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. J. Am. Chem. Soc. 132, 9274 (2010).
L. Sheng, J. Ren, Y. Miao, J. Wang, and E. Wang: PVP-coated graphene oxide for selective determination of ochratoxin A via quenching fluorescence of free aptamer. Biosens. Bioelectron. 26, 3494 (2011).
H. Chang, L. Tang, Y. Wang, J. Jiang, and J. Li: Graphene fluorescence resonance energy transfer aptasensor for the thrombin detection. Anal. Chem. 82, 2341 (2010).
Y. Pu, Z. Zhu, D. Han, H. Liu, J. Liu, J. Liao, K. Zhang, and W. Tan: Insulin-binding aptamer-conjugated graphene oxide for insulin detection. Analyst 136, 4138 (2011).
Y. He, Y. Lin, H. Tang, and D. Pang: A graphene oxide-based fluorescent aptasensor for the turn-on detection of epithelial tumor marker mucin 1. Nanoscale 4, 2054 (2012).
H.L. Zhuang, S.J. Zhen, J. Wang, and C.Z. Huang: Sensitive detection of prion protein through long range resonance energy transfer between graphene oxide and molecular aptamer beacon. Anal. Methods 5, 208 (2013).
Y. Huang, X. Chen, Y. Xia, S. Wu, N. Duan, X. Ma, and Z. Wang: Selection, identification and application of a DNA aptamer against Staphylococcus aureus enterotoxin A. Anal. Methods 6, 690 (2014).
Y. Huang, X. Chen, N. Duan, S. Wu, Z. Wang, X. Wei, and Y. Wang: Selection and characterization of DNA aptamers against Staphylococcus aureus enterotoxin C1. Food Chem. 166, 623 (2015).
N. Duan, X. Ding, L. He, S. Wu, Y. Wei, and Z. Wang: Selection, identification and application of a DNA aptamer against Listeria monocytogenes. Food Control 33, 239 (2013).
S. Wu, N. Duan, X. Ma, Y. Xia, H. Wang, Z. Wang, and Q. Zhang: Multiplexed fluorescence resonance energy transfer aptasensor between upconversion nanoparticles and graphene oxide for the simultaneous determination of mycotoxins. Anal. Chem. 84, 6263 (2012).
H. Kurt, M. Yüce, B. Hussain, and H. Budak: Dual-excitation upconverting nanoparticle and quantum dot aptasensor for multiplexed food pathogen detection. Biosens. Bioelectron. 81, 280 (2016).
J. Liu, C. Wang, Y. Jiang, Y. Hu, J. Li, S. Yang, Y. Li, R. Yang, W. Tan, and C.Z. Huang: Graphene signal amplification for sensitive and real-time fluorescence anisotropy detection of small molecules. Anal. Chem. 85, 1424 (2013).
Q. Liu, X. Xu, L. Zhang, X. Luo, and Y. Liang: Assembly of single-stranded polydeoxyadenylic acid and β-glucan probed by the sensing platform of graphene oxide based on the fluorescence resonance energy transfer and fluorescence anisotropy. Analyst 138, 2661 (2013).
Y. Yu, Y. Liu, S.J. Zhen, and C.Z. Huang: A graphene oxide enhanced fluorescence anisotropy strategy for DNAzyme-based assay of metal ions. Chem. Commun. 49, 1942 (2013).
M. Rajendran and A.D. Ellington: Selection of fluorescent aptamer beacons that light up in the presence of zinc. Anal. Bioanal. Chem. 390, 1067 (2008).
Y. Wu, S. Zhan, L. Wang, and P. Zhou: Selection of a DNA aptamer for cadmium detection based on cationic polymer mediated aggregation of gold nanoparticles. Analyst 139, 1550 (2014).
C. Apiwat, P. Luksirikul, P. Kankla, P. Pongprayoon, K. Treerattrakoon, K. Paiboonsukwong, S. Fucharoen, T. Dharakul, and D. Japrung: Graphene based aptasensor for glycated albumin in diabetes mellitus diagnosis and monitoring. Biosens. Bioelectron. 82, 140 (2016).
Y. Wang, Z. Li, D. Hu, C.T. Lin, J. Li, and Y. Lin: Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. J. Am. Chem. Soc. 132, 9274 (2010).
X. Tan, T. Chen, X. Xiong, Y. Mao, G. Zhu, E. Yasun, C. Li, Z. Zhu, and W. Tan: Semi-quantification of ATP in live cells using nonspecific desorption of DNA from graphene oxide as internal reference. Anal. Chem. 84, 8622 (2012).
P.J. Huang and J. Liu: Molecular beacon lighting up on graphene oxide. Anal. Chem. 84, 4192 (2012).
Z. Liu, S. Chen, B. Liu, J. Wu, Y. Zhou, L. He, J. Ding, and J. Liu: Intracellular detection of ATP using an aptamer beacon covalently linked to graphene oxide resisting nonspecific probe displacement. Anal. Chem. 86, 12229 (2014).
J. Song, P.S. Lau, M. Liu, S. Shuang, C. Dong, and Y. Li: A general strategy to create RNA aptamer sensors using “regulated” graphene oxide adsorption. ACS Appl. Mater. Interfaces 6, 21806 (2014).
K. Furukawa, Y. Ueno, E. Tamechika, and H. Hibino: Protein recognition on a single graphene oxide surface fixed on a solid support. J. Mater. Chem. B 1, 1119 (2013).
Y. Ueno, K. Furukawa, K. Matsuo, S. Inoue, K. Hayashi, and H. Hibino: Molecular design for enhanced sensitivity of a FRET aptasensor built on the graphene oxide surface. Chem. Commun. 49, 10346 (2013).
Y. Ueno, K. Furukawa, K. Matsuo, S. Inoue, K. Hayashi, and H. Hibino: On-chip graphene oxide aptasensor for multiple protein detection. Anal. Chim. Acta 866, 1 (2015).
L. Liang, M. Su, L. Li, F. Lan, G. Yang, S. Ge, J. Yu, and X. Song: Aptamer-based fluorescent and visual biosensor for multiplexed monitoring of cancer cells in microfluidic paper-based analytical devices. Sens. Actuators, B 229, 347 (2016).
P. Zuo, X. Li, D.C. Dominguez, and B.C. Ye: A PDMS/paper/glass hybrid microfluidic biochip integrated with aptamer-functionalized graphene oxide nano-biosensors for one-step multiplexed pathogen detection. Lab Chip 13, 3921 (2013).
J.L. He, Z.S. Wu, H. Zhou, H.Q. Wang, J.H. Jiang, G.L. Shen, and R.Q. Yu: Fluorescence aptameric sensor for strand displacement amplification detection of cocaine. Anal. Chem. 82, 1358 (2010).
L.P. Qiu, Z.S. Wu, G.L. Shen, and R.Q. Yu: Highly sensitive and selective bifunctional oligonucleotide probe for homogeneous parallel fluorescence detection of protein and nucleotide sequence. Anal. Chem. 83, 3050 (2011).
J. Huang, Y. Chen, L. Yang, Z. Zhu, G. Zhu, X. Yang, K. Wang, and W. Tan: Amplified detection of cocaine based on strand-displacement polymerization and fluorescence resonance energy transfer. Biosens. Bioelectron. 28, 450 (2011).
K. Hu, J. Liu, J. Chen, Y. Huang, S. Zhao, J. Tian, and G. Zhang: An amplified graphene oxide-based fluorescence aptasensor based on target-triggered aptamer hairpin switch and strand-displacement polymerization recycling for bioassays. Biosens. Bioelectron. 42, 598 (2013).
C.H. Li, X. Xiao, J. Tao, D.M. Wang, C.Z. Huang, and S.J. Zhen: A graphene oxide-based strand displacement amplification platform for ricin detection using aptamer as recognition element. Biosens. Bioelectron. 91, 149 (2017).
C.H. Lu, J. Li, M.H. Lin, Y.W. Wang, H.H. Yang, X. Chen, and G.N. Chen: Amplified aptamer-based assay through catalytic recycling of the analyte. Angew. Chem., Int. Ed. 49, 8454 (2010).
C. Su, C. Liu, J. Chen, Z. Chen, and Z. He: Simultaneous determination of zeatin and systemin by coupling graphene oxide-protected aptamers with catalytic recycling of DNase I. Sens. Actuators, B 230, 442 (2016).
S. Guo, F. Yang, Y. Zhang, Y. Ning, Q. Yao, and G.J. Zhang: Amplified fluorescence sensing of miRNA by combination of graphene oxide with duplex-specific nuclease. Anal. Methods 6, 3598 (2014).
X. Liu, R. Aizen, R. Freeman, O. Yehezkeli, and I. Willner: Multiplexed aptasensors and amplified DNA sensors using functionalized graphene oxide: Application for logic gate operations. ACS Nano 6, 3553 (2012).
C. Chen and B. Li: Graphene oxide-based homogenous biosensing platform for ultrasensitive DNA detection based on chemiluminescence resonance energy transfer and exonuclease III-assisted target recycling amplification. J. Mater. Chem. B 1, 2476 (2013).
L. Cui, Z. Chen, Z. Zhu, X. Lin, X. Chen, and C.J. Yang: Stabilization of ssRNA on graphene oxide surface: An effective way to design highly robust RNA probes. Anal. Chem. 85, 2269 (2013).
C. Chen, J. Zhao, J. Jiang, and R. Yu: A novel exonuclease III-aided amplification assay for lysozyme based on graphene oxide platform. Talanta 101, 357 (2012).
S. Wu, N. Duan, X. Ma, Y. Xia, H. Wang, and Z. Wang: A highly sensitive fluorescence resonance energy transfer aptasensor for staphylococcal enterotoxin B detection based on exonuclease-catalyzed target recycling strategy. Anal. Chim. Acta 782, 59 (2013).
K. Xiao, J. Liu, H. Chen, S. Zhang, and J. Kong: A label-free and high-efficient GO-based aptasensor for cancer cells based on cyclic enzymatic signal amplification. Biosens. Bioelectron. 91, 76 (2017).
M. Liu, J. Song, S. Shuang, C. Dong, J.D. Brennan, and Y. Li: A graphene-based biosensing platform based on the release of DNA probes and rolling circle amplification. ACS Nano 8, 5564 (2014).
S. Jahanshahi-Anbuhi, K. Pennings, V. Leung, M. Liu, C. Carrasquilla, B. Kannan, Y. Li, R. Pelton, J.D. Brennan, and C.D. Filipe: Pullulan encapsulation of labile biomolecules to give stable bioassay tablets. Angew. Chem., Int. Ed. 53, 6155 (2014).
M. Liu, C.Y. Hui, Q. Zhang, J. Gu, B. Kannan, S. Jahanshahi-Anbuhi, C.D. Filipe, J.D. Brennan, and Y. Li: Target-induced and equipment-free DNA amplification with a simple paper device. Angew. Chem., Int. Ed. 55, 2709 (2016).
C. Carrasquilla, J.R. Little, Y. Li, and J.D. Brennan: Patterned paper sensors printed with long-chain DNA aptamers. Chem.–Eur. J. 21, 7369 (2015).
B. Kannan, S. Jahanshahi-Anbuhi, R.H. Pelton, Y. Li, C.D. Filipe, and J.D. Brennan: Printed paper sensors for serum lactate dehydrogenase using pullulan-based inks to immobilize reagents. Anal. Chem. 87, 9288 (2015).
P.Y. Hsieh, M. Monsur Ali, K. Tram, S. Jahanshahi-Anbuhi, C.L. Brown, J.D. Brennan, C.D. Filipe, and Y. Li: RNA protection is effectively achieved by pullulan film formation. ChemBioChem 18, 502 (2017).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Manochehry, S., Liu, M., Chang, D. et al. Optical biosensors utilizing graphene and functional DNA molecules. Journal of Materials Research 32, 2973–2983 (2017). https://doi.org/10.1557/jmr.2017.103
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1557/jmr.2017.103