Flexible FET-type VEGF aptasensor based on nitrogen-doped graphene converted from conducting polymer.

Graphene-based field-effect transistors (FETs) have been developed rapidly and are currently considered as an alternative for postsilicon electronics. In this study, polypyrrole-converted nitrogen-doped few-layer graphene (PPy-NDFLG) was grown on Cu substrate by chemical vapor deposition combined with vapor deposition polymerization and then transferred onto a flexible substrate. Furthermore, antivascular endothelial growth factor (VEGF) RNA aptamer conjugated PPy-NDFLG was integrated into a liquid-ion gated FET geometry to fabricate a high-performance VEGF aptamer-based sensor. Field-induced high sensitivity was observed for the analyte-binding events, eventually leading to the recognition of the target molecules at an unprecedentedly low concentration (100 fM). Additionally, the aptasensor had excellent reusability, mechanical bendability, and durability in the flexible process. The developed methodology describes, for the first time, the fabrication of N-doped graphene using conducting polymers including heteroatoms in their structures as the carbonization precursor and demonstrates its use in a high-performance, flexible FET-type aptasensor to detect vascular endothelial growth factor as a cancer biomarker.

[1]  A. K. Sood,et al.  Graphene: The New Two‐Dimensional Nanomaterial , 2009 .

[2]  Jeong-O Lee,et al.  Single-walled carbon nanotube biosensors using aptamers as molecular recognition elements. , 2005, Journal of the American Chemical Society.

[3]  Oh Seok Kwon,et al.  A strategy for fabricating single layer graphene sheets based on a layer-by-layer self-assembly. , 2011, Chemical communications.

[4]  R. Mokaya,et al.  Hydrogen storage in high surface area carbons: experimental demonstration of the effects of nitrogen doping. , 2009, Journal of the American Chemical Society.

[5]  Zhihong Liu,et al.  Biosensing platform based on fluorescence resonance energy transfer from upconverting nanocrystals to graphene oxide. , 2011, Angewandte Chemie.

[6]  Jun Yan,et al.  Observation of anomalous phonon softening in bilayer graphene. , 2007, Physical review letters.

[7]  Jaesung Park,et al.  Graphene‐Encapsulated Nanoparticle‐Based Biosensor for the Selective Detection of Cancer Biomarkers , 2011, Advanced materials.

[8]  K. Novoselov,et al.  Molecular doping of graphene. , 2007, Nano letters.

[9]  Simultaneous nitrogen doping and reduction of graphene oxide. , 2009, Journal of the American Chemical Society.

[10]  T. H. van der Kwast,et al.  High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer. , 2001, Cancer research.

[11]  Lain-Jong Li,et al.  Doping single-layer graphene with aromatic molecules. , 2009, Small.

[12]  Moon-Ho Jo,et al.  Electrical detection of VEGFs for cancer diagnoses using anti-vascular endotherial growth factor aptamer-modified Si nanowire FETs. , 2009, Biosensors & bioelectronics.

[13]  Y. Ohno,et al.  Label-Free Immunosensors Based on Aptamer-Modified Graphene Field-Effect Transistors , 2010 .

[14]  H. Dai,et al.  Noncovalent sidewall functionalization of single-walled carbon nanotubes for protein immobilization. , 2001, Journal of the American Chemical Society.

[15]  Rebecca Y Lai,et al.  A folding-based electrochemical aptasensor for detection of vascular endothelial growth factor in human whole blood. , 2011, Biosensors & bioelectronics.

[16]  Jinghong Li,et al.  Electrochemical gate-controlled charge transport in graphene in ionic liquid and aqueous solution. , 2009, Journal of the American Chemical Society.

[17]  Lin Shao,et al.  Catalyst-free synthesis of nitrogen-doped graphene via thermal annealing graphite oxide with melamine and its excellent electrocatalysis. , 2011, ACS nano.

[18]  Zhenan Bao,et al.  Molecular n-type doping for air-stable electron transport in vacuum- processed n-channel organic transistors , 2010 .

[19]  J. Riu,et al.  Immediate detection of living bacteria at ultralow concentrations using a carbon nanotube based potentiometric aptasensor. , 2009, Angewandte Chemie.

[20]  G. Stucky,et al.  Fabrication of ultrafine conducting polymer and graphite nanoparticles. , 2002, Angewandte Chemie.

[21]  H. Dai,et al.  A dual platform for selective analyte enrichment and ionization in mass spectrometry using aptamer-conjugated graphene oxide. , 2010, Journal of the American Chemical Society.

[22]  Zheng Yan,et al.  Growth of graphene from solid carbon sources , 2010, Nature.

[23]  Yun Xiang,et al.  Ultrasensitive label-free aptamer-based electronic detection. , 2007, Angewandte Chemie.

[24]  Lap Man Lee,et al.  Self-aligned immobilization of proteins utilizing PEG patterns , 2006, Nanotechnology.

[25]  Jeong-O Lee,et al.  Single‐Walled Carbon Nanotube Biosensors , 2012 .

[26]  Andre K. Geim,et al.  Raman spectrum of graphene and graphene layers. , 2006, Physical review letters.

[27]  Y. Liu,et al.  Nitrogen-doped graphene as efficient metal-free electrocatalyst for oxygen reduction in fuel cells. , 2010, ACS nano.

[28]  P. Ajayan,et al.  Synthesis of nitrogen-doped graphene films for lithium battery application. , 2010, ACS nano.

[29]  Cees Dekker,et al.  Influence of electrolyte composition on liquid-gated carbon nanotube and graphene transistors. , 2010, Journal of the American Chemical Society.

[30]  R. Kaner,et al.  Honeycomb carbon: a review of graphene. , 2010, Chemical reviews.

[31]  H. Dai,et al.  N-Doping of Graphene Through Electrothermal Reactions with Ammonia , 2009, Science.

[32]  Yunqi Liu,et al.  Controllable Synthesis of Graphene and Its Applications , 2010, Advanced materials.

[33]  A. Fazzio,et al.  Electronic and transport properties of boron-doped graphene nanoribbons. , 2007, Physical review letters.

[34]  J. Jang,et al.  Micropatterning of Graphene Sheets by Inkjet Printing and Its Wideband Dipole‐Antenna Application , 2011, Advanced materials.

[35]  Lei Fu,et al.  Synthesis of Nitrogen‐Doped Graphene Using Embedded Carbon and Nitrogen Sources , 2011, Advanced materials.

[36]  Seon Joo Park,et al.  A high-performance VEGF aptamer functionalized polypyrrole nanotube biosensor. , 2010, Biomaterials.

[37]  H. R. Krishnamurthy,et al.  Monitoring dopants by Raman scattering in an electrochemically top-gated graphene transistor. , 2008, Nature nanotechnology.

[38]  Oh Seok Kwon,et al.  Polypyrrole nanotubes conjugated with human olfactory receptors: high-performance transducers for FET-type bioelectronic noses. , 2009, Angewandte Chemie.

[39]  Peng Chen,et al.  Electrical Detection of DNA Hybridization with Single‐Base Specificity Using Transistors Based on CVD‐Grown Graphene Sheets , 2010, Advanced materials.

[40]  N. Koratkar,et al.  Graphene nanoribbon composites. , 2010, ACS nano.

[41]  J. Jang,et al.  Facile fabrication of inorganic-polymer core-shell nanostructures by a one-step vapor deposition polymerization. , 2003, Angewandte Chemie.

[42]  Itamar Willner,et al.  Electronic aptamer-based sensors. , 2007, Angewandte Chemie.

[43]  Z. Bao,et al.  Use of a 1H-benzoimidazole derivative as an n-type dopant and to enable air-stable solution-processed n-channel organic thin-film transistors. , 2010, Journal of the American Chemical Society.

[44]  Yanglong Hou,et al.  Facile preparation of nitrogen-doped few-layer graphene via supercritical reaction. , 2011, ACS applied materials & interfaces.

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

[46]  Chunhai Fan,et al.  Aptamer-based biosensors , 2008 .

[47]  Kwang S. Kim,et al.  Large-scale pattern growth of graphene films for stretchable transparent electrodes , 2009, Nature.

[48]  Gui Yu,et al.  Synthesis of N-doped graphene by chemical vapor deposition and its electrical properties. , 2009, Nano letters.

[49]  Jing Kong,et al.  Role of kinetic factors in chemical vapor deposition synthesis of uniform large area graphene using copper catalyst. , 2010, Nano letters.

[50]  Robyn M. B. Loureiro,et al.  Transcriptional regulation of vascular endothelial growth factor in cancer. , 2005, Cytokine & growth factor reviews.

[51]  Yuyan Shao,et al.  Nitrogen-Doped Graphene and Its Application in Electrochemical , 2010 .

[52]  Tom T. Chen,et al.  The phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) by engineered surfaces with electrostatically or covalently immobilized VEGF. , 2009, Biomaterials.

[53]  J. Jang.  Conducting polymer nanomaterials and their applications , 2006 .

[54]  Liang Fang,et al.  Controllable N-doping of graphene. , 2010, Nano letters.

[55]  Po-Wen Chiu,et al.  Controllable graphene N-doping with ammonia plasma , 2010 .

[56]  Deep Jariwala,et al.  Atomic layers of hybridized boron nitride and graphene domains. , 2010, Nature materials.

[57]  Wojciech Pisula,et al.  Graphenes as potential material for electronics. , 2007, Chemical reviews.

[58]  Zhongfang Chen,et al.  Spin gapless semiconductor-metal-half-metal properties in nitrogen-doped zigzag graphene nanoribbons. , 2009, ACS nano.

[59]  Ursula Bilitewski,et al.  Characterization of the vascular endothelial growth factor-receptor interaction and determination of the recombinant protein by an optical receptor sensor. , 2002, Biosensors & bioelectronics.

[60]  Yi Cui,et al.  Toward N-Doped Graphene via Solvothermal Synthesis , 2011 .

[61]  C. N. R. Rao,et al.  Synthesis, Structure, and Properties of Boron‐ and Nitrogen‐Doped Graphene , 2009, 0902.3077.

[62]  Michael C. McAlpine,et al.  Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible chemical sensors. , 2007, Nature materials.

[63]  Rory Stine,et al.  Real‐Time DNA Detection Using Reduced Graphene Oxide Field Effect Transistors , 2010, Advanced materials.

[64]  J. Baek,et al.  Polyelectrolyte-functionalized graphene as metal-free electrocatalysts for oxygen reduction. , 2011, ACS nano.

[65]  Michael S Strano,et al.  Sequential delivery of dexamethasone and VEGF to control local tissue response for carbon nanotube fluorescence based micro-capillary implantable sensors. , 2008, Biomaterials.

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

[67]  J. Miyawaki,et al.  Preparation of nitrogen-doped graphene sheets by a combined chemical and hydrothermal reduction of graphene oxide. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[68]  A. Geim,et al.  Two-dimensional gas of massless Dirac fermions in graphene , 2005, Nature.

[69]  J. Baek,et al.  Formation of Large-Area Nitrogen-Doped Graphene Film Prepared from Simple Solution Casting of Edge-Selectively Functionalized Graphite and Its Electrocatalytic Activity , 2011 .

[70]  S. Banerjee,et al.  Large-Area Synthesis of High-Quality and Uniform Graphene Films on Copper Foils , 2009, Science.

[71]  Xiaohong Zheng,et al.  Dangling Bond States, Edge Magnetism, and Edge Reconstruction in Pristine and B/N-Terminated Zigzag Graphene Nanoribbons , 2010 .