Fluorescent sensors using DNA-functionalized graphene oxide

In the past few years, graphene oxide (GO) has emerged as a unique platform for developing DNA-based biosensors, given the DNA adsorption and fluorescence-quenching properties of GO. Adsorbed DNA probes can be desorbed from the GO surface in the presence of target analytes, producing a fluorescence signal. In addition to this initial design, many other strategies have been reported, including the use of aptamers, molecular beacons, and DNAzymes as probes, label-free detection, utilization of the intrinsic fluorescence of GO, and the application of covalently linked DNA probes. The potential applications of DNA-functionalized GO range from environmental monitoring and cell imaging to biomedical diagnosis. In this review, we first summarize the fundamental surface interactions between DNA and GO and the related fluorescence-quenching mechanism. Following that, the various sensor design strategies are critically compared. Problems that must be overcome before this technology can reach its full potential are described, and a few future directions are also discussed.

[1]  G. F. Joyce,et al.  A general purpose RNA-cleaving DNA enzyme. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Ying Wang,et al.  In situ live cell sensing of multiple nucleotides exploiting DNA/RNA aptamers and graphene oxide nanosheets. , 2013, Analytical chemistry.

[3]  Chunhai Fan,et al.  A graphene-enhanced molecular beacon for homogeneous DNA detection. , 2010, Nanoscale.

[4]  Michael A. Brook,et al.  Design of Gold Nanoparticle-Based Colorimetric Biosensing Assays , 2008 .

[5]  Chung-Yuen Hui,et al.  Peeling single-stranded DNA from graphite surface to determine oligonucleotide binding energy by force spectroscopy. , 2008, Nano letters.

[6]  Ru-Qin Yu,et al.  Highly sensitive and selective strategy for microRNA detection based on WS2 nanosheet mediated fluorescence quenching and duplex-specific nuclease signal amplification. , 2014, Analytical chemistry.

[7]  Longhua Tang,et al.  DNA-directed self-assembly of graphene oxide with applications to ultrasensitive oligonucleotide assay. , 2011, ACS nano.

[8]  Juewen Liu,et al.  Functional DNA nanotechnology: emerging applications of DNAzymes and aptamers. , 2006, Current opinion in biotechnology.

[9]  Dong-Eun Kim,et al.  A graphene oxide-based platform for the assay of RNA synthesis by RNA polymerase using a fluorescent peptide nucleic acid probe. , 2013, Chemical communications.

[10]  Itamar Willner,et al.  Integrated Nanoparticle—Biomolecule Hybrid Systems: Synthesis, Properties, and Applications , 2005 .

[11]  M. Mascini,et al.  Analytical applications of aptamers. , 2005, Biosensors & bioelectronics.

[12]  Eun Jeong Cho,et al.  Applications of aptamers as sensors. , 2009, Annual review of analytical chemistry.

[13]  S. Grimme,et al.  Structures and interaction energies of stacked graphene-nucleobase complexes. , 2008, Physical chemistry chemical physics : PCCP.

[14]  M. Liu,et al.  A "turn-on" fluorescent copper biosensor based on DNA cleavage-dependent graphene-quenched DNAzyme. , 2011, Biosensors & bioelectronics.

[15]  Da Chen,et al.  Graphene oxide: preparation, functionalization, and electrochemical applications. , 2012, Chemical reviews.

[16]  Martin Pumera,et al.  Graphene in biosensing , 2011 .

[17]  Xiaoning Yang,et al.  Molecular dynamics simulation of adsorption of pyrene-polyethylene glycol onto graphene. , 2014, Journal of colloid and interface science.

[18]  Cheng Sun,et al.  Tunable assembly of graphene oxide surfactant sheets: wrinkles, overlaps and impacts on thin film properties , 2010 .

[19]  Juewen Liu,et al.  Adsorption of DNA onto gold nanoparticles and graphene oxide: surface science and applications. , 2012, Physical chemistry chemical physics : PCCP.

[20]  Klaus Kern,et al.  Atomic structure of reduced graphene oxide. , 2010, Nano letters.

[21]  T. Seo,et al.  The photoluminescent graphene oxide serves as an acceptor rather than a donor in the fluorescence resonance energy transfer pair of Cy3.5-graphene oxide. , 2011, Chemical communications.

[22]  H. Pei,et al.  Nanomaterial‐Based Fluorescent DNA Analysis: A Comparative Study of the Quenching Effects of Graphene Oxide, Carbon Nanotubes, and Gold Nanoparticles , 2013 .

[23]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[24]  H. Ju,et al.  Fluorescence resonance energy transfer between quantum dots and graphene oxide for sensing biomolecules. , 2010, Analytical chemistry.

[25]  Qing-Ying Luo,et al.  Graphene oxide based fluorescent aptasensor for adenosine deaminase detection using adenosine as the substrate. , 2012, Biosensors & bioelectronics.

[26]  Juewen Liu,et al.  Mechanisms of DNA sensing on graphene oxide. , 2013, Analytical chemistry.

[27]  M. Servos,et al.  Adsorption of DNA oligonucleotides by titanium dioxide nanoparticles. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[28]  Dan Wu,et al.  Graphene-Based Optical and Electrochemical Biosensors: A Review , 2013 .

[29]  Mayra S. Artiles,et al.  Graphene-based hybrid materials and devices for biosensing. , 2011, Advanced drug delivery reviews.

[30]  K. L. Sebastian,et al.  Long range resonance energy transfer from a dye molecule to graphene has (distance)(-4) dependence. , 2009, The Journal of chemical physics.

[31]  P. J. Huang,et al.  Rationally designed nucleobase and nucleotide coordinated nanoparticles for selective DNA adsorption and detection. , 2013, Analytical chemistry.

[32]  Xi Chen,et al.  Graphene oxide-protected DNA probes for multiplex microRNA analysis in complex biological samples based on a cyclic enzymatic amplification method. , 2012, Chemical communications.

[33]  Hongje Jang,et al.  A Graphene‐Based Platform for the Assay of Duplex‐DNA Unwinding by Helicase† , 2010, Angewandte Chemie.

[34]  R. Yu,et al.  A novel biosensing strategy for screening G-quadruplex ligands based on graphene oxide sheets. , 2012, Biosensors & bioelectronics.

[35]  Xuping Sun,et al.  Nano-C(60) : a novel, effective, fluorescent sensing platform for biomolecular detection. , 2011, Small.

[36]  Label-free detection of microRNA: two-step signal enhancement with a hairpin-probe-based graphene fluorescence switch and isothermal amplification. , 2013, Chemistry.

[37]  Kwang S. Kim,et al.  Quencher-free molecular beacon: Enhancement of the signal-to-background ratio with graphene oxide. , 2011, Bioorganic & medicinal chemistry letters.

[38]  Wei Wei,et al.  Detection of DNA damage by using hairpin molecular beacon probes and graphene oxide. , 2012, Talanta.

[39]  V. Maheshwari,et al.  Adsorption and desorption of DNA on graphene oxide studied by fluorescently labeled oligonucleotides. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[40]  M. Yigit,et al.  Nano-graphene oxide as a novel platform for monitoring the effect of LNA modification on nucleic acid interactions. , 2014, The Analyst.

[41]  J. Szostak,et al.  A DNA aptamer that binds adenosine and ATP. , 1995, Biochemistry.

[42]  C. Huang,et al.  A graphene oxide enhanced fluorescence anisotropy strategy for DNAzyme-based assay of metal ions. , 2013, Chemical communications.

[43]  I. Willner,et al.  Multiplexed aptasensors and amplified DNA sensors using functionalized graphene oxide: application for logic gate operations. , 2012, ACS nano.

[44]  N O Reich,et al.  Nanometal surface energy transfer in optical rulers, breaking the FRET barrier. , 2005, Journal of the American Chemical Society.

[45]  Longhua Tang,et al.  Duplex DNA/Graphene Oxide Biointerface: From Fundamental Understanding to Specific Enzymatic Effects , 2012 .

[46]  C. Fan,et al.  A graphene-based fluorescent nanoprobe for silver(I) ions detection by using graphene oxide and a silver-specific oligonucleotide. , 2010, Chemical communications.

[47]  Roberto Car,et al.  Functionalized single graphene sheets derived from splitting graphite oxide. , 2006, The journal of physical chemistry. B.

[48]  Andre K. Geim,et al.  Electric Field Effect in Atomically Thin Carbon Films , 2004, Science.

[49]  Nianqiang Wu,et al.  Fluorescent aptamer-functionalized graphene oxide biosensor for label-free detection of mercury(II). , 2013, Biosensors & bioelectronics.

[50]  Y. Huang,et al.  A power-free microfluidic chip for SNP genotyping using graphene oxide and a DNA intercalating dye. , 2013, Chemical communications.

[51]  H. Hibino,et al.  Molecular design for enhanced sensitivity of a FRET aptasensor built on the graphene oxide surface. , 2013, Chemical communications.

[52]  Young Jun Seo,et al.  A highly discriminating quencher-free molecular beacon for probing DNA. , 2004, Journal of the American Chemical Society.

[53]  Yuyan Shao,et al.  Graphene Based Electrochemical Sensors and Biosensors: A Review , 2010 .

[54]  Guo-Jun Zhang,et al.  PNA-assembled graphene oxide for sensitive and selective detection of DNA. , 2013, The Analyst.

[55]  Juewen Liu,et al.  Platinated DNA oligonucleotides: new probes forming ultrastable conjugates with graphene oxide. , 2014, Nanoscale.

[56]  Ronghua Yang,et al.  Carbon nanotube-quenched fluorescent oligonucleotides: probes that fluoresce upon hybridization. , 2008, Journal of the American Chemical Society.

[57]  Po-Jung Jimmy Huang,et al.  Molecular beacon lighting up on graphene oxide. , 2012, Analytical chemistry.

[58]  Xuping Sun,et al.  A novel application of porphyrin nanoparticles as an effective fluorescent assay platform for nucleic acid detection , 2011 .

[59]  Visualizing graphene based sheets by fluorescence quenching microscopy. , 2009, Journal of the American Chemical Society.

[60]  Chi‐Man Lawrence Wu,et al.  Adsorption of nucleobase pairs on hexagonal boron nitride sheet: hydrogen bonding versus stacking. , 2013, Physical chemistry chemical physics : PCCP.

[61]  Jang‐Kyo Kim,et al.  A molecular beacon and graphene oxide-based fluorescent biosensor for Cu(2+) detection. , 2013, Biosensors & bioelectronics.

[62]  P. Asbeck,et al.  Graphene: Status and prospects as a microwave material , 2011, WAMICON 2011 Conference Proceedings.

[63]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[64]  Jian-hui Jiang,et al.  Graphene fluorescence resonance energy transfer aptasensor for the thrombin detection. , 2010, Analytical chemistry.

[65]  Shubin Yang,et al.  Adsorption of polycyclic aromatic hydrocarbons on graphene oxides and reduced graphene oxides. , 2013, Chemistry, an Asian journal.

[66]  Itamar Willner,et al.  Integrated nanoparticle-biomolecule hybrid systems: synthesis, properties, and applications. , 2004, Angewandte Chemie.

[67]  Xiangxiang Wu,et al.  Graphene oxide-based biosensor for sensitive fluorescence detection of DNA based on exonuclease III-aided signal amplification. , 2012, Analytica chimica acta.

[68]  Yingfu Li,et al.  Nucleic acid aptamers and enzymes as sensors. , 2006, Current opinion in chemical biology.

[69]  Sunil Kumar Singh,et al.  Size distribution analysis and physical/fluorescence characterization of graphene oxide sheets by flow cytometry , 2011 .

[70]  Arben Merkoçi,et al.  Graphene Oxide as an Optical Biosensing Platform , 2012, Advanced materials.

[71]  Po-Jung Jimmy Huang,et al.  Separation of Short Single- and Double-Stranded DNA Based on Their Adsorption Kinetics Difference on Graphene Oxide , 2013, Nanomaterials.

[72]  M. Famulok,et al.  Functional Nucleic Acid Sensors as Screening Tools , 2009 .

[73]  Wei Ren,et al.  Graphene surface-anchored fluorescence sensor for sensitive detection of microRNA coupled with enzyme-free signal amplification of hybridization chain reaction. , 2012, ACS applied materials & interfaces.

[74]  Ronghua Yang,et al.  Nucleic acid conjugated nanomaterials for enhanced molecular recognition. , 2009, ACS nano.

[75]  Huang-Hao Yang,et al.  Increasing the sensitivity and single-base mismatch selectivity of the molecular beacon using graphene oxide as the "nanoquencher". , 2010, Chemistry.

[76]  F. Bechstedt,et al.  Attracted by long-range electron correlation: adenine on graphite. , 2005, Physical review letters.

[77]  R. Ruoff,et al.  Chemical methods for the production of graphenes. , 2009, Nature nanotechnology.

[78]  A. Govindaraj,et al.  Binding of DNA nucleobases and nucleosides with graphene. , 2009, Chemphyschem : a European journal of chemical physics and physical chemistry.

[79]  Yingwei Zhang,et al.  Carbon nanospheres for fluorescent biomolecular detection , 2011 .

[80]  M. Estévez,et al.  A surface energy transfer nanoruler for measuring binding site distances on live cell surfaces. , 2010, Journal of the American Chemical Society.

[81]  M. Singh,et al.  Fluorescent lifetime quenching near d = 1.5 nm gold nanoparticles: probing NSET validity. , 2006, Journal of the American Chemical Society.

[82]  M. Fernandes,et al.  Comparing the interactions of DNA, polyamide (PNA) and polycarbamate nucleic acid (PCNA) oligomers with graphene oxide (GO). , 2012, Physical chemistry chemical physics : PCCP.

[83]  Juewen Liu,et al.  Functional nucleic acid sensors. , 2009, Chemical reviews.

[84]  Weihong Tan,et al.  Semiquantification of ATP in live cells using nonspecific desorption of DNA from graphene oxide as the internal reference. , 2012, Analytical chemistry.

[85]  K. Novoselov,et al.  A roadmap for graphene , 2012, Nature.

[86]  R. Ahuja,et al.  Physisorption of nucleobases on graphene : Density-functional calculations , 2007, 0704.1316.

[87]  K. L. Sebastian,et al.  Resonance energy transfer from a dye molecule to graphene. , 2008, The Journal of chemical physics.

[88]  Xiongce Zhao Self-Assembly of DNA Segments on Graphene and Carbon Nanotube Arrays in Aqueous Solution: A Molecular Simulation Study , 2011 .

[89]  N. Mohanty,et al.  Graphene-based single-bacterium resolution biodevice and DNA transistor: interfacing graphene derivatives with nanoscale and microscale biocomponents. , 2008, Nano letters.

[90]  Weihong Tan Molecular Engineering of DNA: Molecular Beacons , 2009 .

[91]  E. Tamechika,et al.  Protein recognition on a single graphene oxide surface fixed on a solid support. , 2013, Journal of materials chemistry. B.

[92]  Huafeng Yang,et al.  Direct electrochemistry of glucose oxidase and biosensing for glucose based on graphene. , 2009, Analytical chemistry.

[93]  W. Tan,et al.  Insulin-binding aptamer-conjugated graphene oxide for insulin detection. , 2011, The Analyst.

[94]  Chunhai Fan,et al.  A Graphene Nanoprobe for Rapid, Sensitive, and Multicolor Fluorescent DNA Analysis , 2010 .

[95]  Kai Yang,et al.  Nano-Graphene in Biomedicine: Theranostic Applications , 2013 .

[96]  J. Szostak,et al.  In vitro selection of functional nucleic acids. , 1999, Annual review of biochemistry.

[97]  Jian-hui Jiang,et al.  A novel exonuclease III-aided amplification assay for lysozyme based on graphene oxide platform. , 2012, Talanta.

[98]  Yaping Hu,et al.  Graphene signal amplification for sensitive and real-time fluorescence anisotropy detection of small molecules. , 2013, Analytical chemistry.

[99]  Po-Jung Jimmy Huang,et al.  DNA-length-dependent fluorescence signaling on graphene oxide surface. , 2012, Small.

[100]  Po-Jung Jimmy Huang,et al.  Attaching DNA to nanoceria: regulating oxidase activity and fluorescence quenching. , 2013, ACS applied materials & interfaces.

[101]  Huang-Hao Yang,et al.  Using graphene to protect DNA from cleavage during cellular delivery. , 2010, Chemical communications.

[102]  Sanjay Tyagi,et al.  Molecular Beacons: Probes that Fluoresce upon Hybridization , 1996, Nature Biotechnology.

[103]  Huang-Hao Yang,et al.  Amplified aptamer-based assay through catalytic recycling of the analyte. , 2010, Angewandte Chemie.

[104]  Yi Lu,et al.  Metal ion sensors based on DNAzymes and related DNA molecules. , 2011, Annual review of analytical chemistry.

[105]  S. Dong,et al.  Electrochemical sensing and biosensing platform based on chemically reduced graphene oxide. , 2009, Analytical chemistry.

[106]  Xue-mei Li,et al.  A duplex–triplex nucleic acid nanomachine that probes pH changes inside living cells during apoptosis , 2013, Analytical and Bioanalytical Chemistry.

[107]  Dong-Eun Kim,et al.  Desorption of single-stranded nucleic acids from graphene oxide by disruption of hydrogen bonding. , 2013, The Analyst.

[108]  Huang-Hao Yang,et al.  A graphene platform for sensing biomolecules. , 2009, Angewandte Chemie.

[109]  Filip Braet,et al.  Carbon nanomaterials in biosensors: should you use nanotubes or graphene? , 2010, Angewandte Chemie.

[110]  Chad A. Mirkin,et al.  Nanostructures in Biodiagnostics , 2005 .

[111]  Weihong Tan,et al.  Aptamers from cell-based selection for bioanalytical applications. , 2013, Chemical reviews.

[112]  Yanchun Zhao,et al.  A Graphene Oxide–Based Sensing Platform for The Label-free Assay of DNA Sequence and Exonuclease Activity via Long Range Resonance Energy Transfer , 2013, Journal of Fluorescence.

[113]  Xiangmin Miao,et al.  A novel fluorescent biosensor for sequence-specific recognition of double-stranded DNA with the platform of graphene oxide. , 2011, The Analyst.

[114]  Tae Seok Seo,et al.  Graphene oxide arrays for detecting specific DNA hybridization by fluorescence resonance energy transfer. , 2010, Biosensors & bioelectronics.

[115]  M. Famulok,et al.  Functional Aptamers and Aptazymes in Biotechnology, Diagnostics, and Therapy , 2007 .

[116]  Arben Merkoçi,et al.  Carbon nanotubes and graphene in analytical sciences , 2012, Microchimica Acta.

[117]  W. Duan,et al.  Adsorption of DNA/RNA nucleobases on hexagonal boron nitride sheet: an ab initio study. , 2011, Physical chemistry chemical physics : PCCP.

[118]  Chunhai Fan,et al.  A graphene-based sensor array for high-precision and adaptive target identification with ensemble aptamers. , 2012, Journal of the American Chemical Society.

[119]  Jacek Klinowski,et al.  Structure of Graphite Oxide Revisited , 1998 .

[120]  O. P. Repnytska,et al.  DNA interaction with single-walled carbon nanotubes: a SEIRA study , 2003 .

[121]  R R Breaker,et al.  A DNA enzyme that cleaves RNA. , 1994, Chemistry & biology.

[122]  F. Braet,et al.  Carbon Nanomaterials in Biosensors: Should You Use Nanotubes or Graphene? , 2010 .

[123]  Chunhai Fan,et al.  Target-responsive structural switching for nucleic acid-based sensors. , 2010, Accounts of chemical research.

[124]  P. J. Huang,et al.  Synergistic pH effect for reversible shuttling aptamer-based biosensors between graphene oxide and target molecules , 2011 .

[125]  Michael A. Brook,et al.  Design of Gold Nanoparticle‐Based Colorimetric Biosensing Assays , 2008, Chembiochem : a European journal of chemical biology.

[126]  Andre K. Geim,et al.  The rise of graphene. , 2007, Nature materials.

[127]  Lei Wang,et al.  Nucleic acid detection using carbon nanoparticles as a fluorescent sensing platform. , 2011, Chemical communications.

[128]  Peng Chen,et al.  Biological and chemical sensors based on graphene materials. , 2012, Chemical Society reviews.

[129]  S. Bose,et al.  Recent advances in graphene-based biosensors. , 2011, Biosensors & bioelectronics.

[130]  Zhe Wang,et al.  Efficient fluorescence resonance energy transfer between upconversion nanophosphors and graphene oxide: a highly sensitive biosensing platform. , 2011, Chemical communications.

[131]  Nianqiang Wu,et al.  Detection of lead (II) with a "turn-on" fluorescent biosensor based on energy transfer from CdSe/ZnS quantum dots to graphene oxide. , 2013, Biosensors & bioelectronics.

[132]  T. Seo,et al.  A novel molecular beacon bearing a graphite nanoparticle as a nanoquencher for in situ mRNA detection in cancer cells. , 2012, ACS applied materials & interfaces.

[133]  Yuehe Lin,et al.  Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. , 2010, Journal of the American Chemical Society.

[134]  A. Ono,et al.  Specific interactions between silver(I) ions and cytosine-cytosine pairs in DNA duplexes. , 2008, Chemical communications.

[135]  Chunhai Fan,et al.  Single-layer MoS2-based nanoprobes for homogeneous detection of biomolecules. , 2013, Journal of the American Chemical Society.

[136]  Yi Lin,et al.  A graphene oxide-based fluorescent aptasensor for the turn-on detection of epithelial tumor marker mucin 1. , 2012, Nanoscale.

[137]  Michael S Strano,et al.  Detection of DNA hybridization using the near-infrared band-gap fluorescence of single-walled carbon nanotubes. , 2006, Nano letters.

[138]  E. Wang,et al.  PVP-coated graphene oxide for selective determination of ochratoxin A via quenching fluorescence of free aptamer. , 2011, Biosensors & bioelectronics.

[139]  Weihong Tan,et al.  A versatile graphene-based fluorescence "on/off" switch for multiplex detection of various targets. , 2011, Biosensors & bioelectronics.

[140]  Tao Li,et al.  A lead(II)-driven DNA molecular device for turn-on fluorescence detection of lead(II) ion with high selectivity and sensitivity. , 2010, Journal of the American Chemical Society.

[141]  Juewen Liu,et al.  Aptamer-based biosensors for biomedical diagnostics. , 2014, The Analyst.

[142]  Shouwu Guo,et al.  Adsorption of double-stranded DNA to graphene oxide preventing enzymatic digestion. , 2011, Nanoscale.

[143]  Courtney R. Thomas,et al.  Mechanized silica nanoparticles: a new frontier in theranostic nanomedicine. , 2011, Accounts of chemical research.

[144]  Yuehe Lin,et al.  Graphene and graphene oxide: biofunctionalization and applications in biotechnology , 2011, Trends in Biotechnology.

[145]  Jing Li,et al.  A highly sensitive and selective catalytic DNA biosensor for lead ions [9] , 2000 .

[146]  Jing‐Juan Xu,et al.  On-chip selective capture of cancer cells and ultrasensitive fluorescence detection of survivin mRNA in a single living cell. , 2013, Lab on a chip.

[147]  Shulin Zhao,et al.  Aptasensor for amplified IgE sensing based on fluorescence quenching by graphene oxide. , 2013, Luminescence : the journal of biological and chemical luminescence.

[148]  F. Guinea,et al.  The electronic properties of graphene , 2007, Reviews of Modern Physics.

[149]  K. Geckeler,et al.  Graphene–DNA hybrid materials: Assembly, applications, and prospects , 2012 .