Sensitive SERS glucose sensing in biological media using alkyne functionalized boronic acid on planar substrates.

In this work, we propose a novel glucose binding mechanism on a highly sensitive SERS substrate, in order to overcome challenges in specific glucose detection in bio-fluids. We make use of phenylboronic acid as a receptor for saccharide capture onto the substrate and the ability of the captured glucose molecule to undergo secondary binding with an alkyne-functionalized boronic acid to form a glucose-alkyne-boronic acid complex. The formation of this complex shows high selectivity for glucose, over other saccharides. In addition, the alkyne group of the alkyne-functionalized boronic acid exhibits a distinct Raman peak at 1996 cm(-1) in a biological silent region (1800-2800 cm(-1)) where most endogenous molecules, including glucose, show no Raman scattering, thus offering a high sensitivity over other SERS glucose sensing. The substrate offers long-term stability, as well as high SERS enhancement to the glucose-alkyne boronic acid complex on substrate. In addition, the reversibility of SERS signals at various incubation stages also shows reusability capabilities, whereas positive results in clinical urine samples demonstrate clinical feasibility. All these strongly suggest that this newly developed SERS-based assay offers great potential in glucose sensing.

[1]  Ajay Agarwal,et al.  Development of highly reproducible nanogap SERS substrates: comparative performance analysis and its application for glucose sensing. , 2011, Biosensors & bioelectronics.

[2]  Satoshi Kawata,et al.  Alkyne-tag Raman imaging for visualization of mobile small molecules in live cells. , 2012, Journal of the American Chemical Society.

[3]  Richard P Van Duyne,et al.  Transcutaneous glucose sensing by surface-enhanced spatially offset Raman spectroscopy in a rat model. , 2010, Analytical chemistry.

[4]  Zaiping Guo,et al.  Preparation and characterization of spinel Li4Ti5O12 nanoparticles anode materials for lithium ion battery , 2012, Journal of Nanoparticle Research.

[5]  J. C. Norrild,et al.  A fluorescent glucose sensor binding covalently to all five hydroxy groups of α-D-glucofuranose. A reinvestigation , 1999 .

[6]  D. A. Stuart,et al.  Surface Enhanced Raman Spectroscopy: New Materials, Concepts, Characterization Tools, and Applications , 2005 .

[7]  Naomi J. Halas,et al.  Label-free detection of DNA hybridization using surface enhanced Raman spectroscopy. , 2010, Journal of the American Chemical Society.

[8]  M. Albrecht,et al.  Anomalously intense Raman spectra of pyridine at a silver electrode , 1977 .

[9]  D. A. Stuart,et al.  In vivo glucose measurement by surface-enhanced Raman spectroscopy. , 2006, Analytical chemistry.

[10]  Ricardo Aroca,et al.  New Approaches in Biomedical Spectroscopy , 2007 .

[11]  T. James.  Saccharide-selective boronic acid based photoinduced electron transfer (PET) fluorescent sensors , 2007 .

[12]  Remy Cromer,et al.  SERS nanoparticles: a new optical detection modality for cancer diagnosis. , 2007, Nanomedicine.

[13]  Olga Lyandres,et al.  Real-time glucose sensing by surface-enhanced Raman spectroscopy in bovine plasma facilitated by a mixed decanethiol/mercaptohexanol partition layer. , 2005, Analytical chemistry.

[14]  Naomi J Halas,et al.  Gold nanoparticles can induce the formation of protein-based aggregates at physiological pH. , 2009, Nano letters.

[15]  Michael S. Feld,et al.  Surface-Enhanced Raman Spectroscopy in Single Living Cells Using Gold Nanoparticles , 2002 .

[16]  A. C. Jamison,et al.  4-Mercaptophenylboronic acid SAMs on gold: comparison with SAMs derived from thiophenol, 4-mercaptophenol, and 4-mercaptobenzoic acid. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[17]  Chit Yaw Fu,et al.  Enhancement in SERS intensity with hierarchical nanostructures by bimetallic deposition approach , 2012 .

[18]  A. J. Nijdam,et al.  Small molecule- and amino acid-induced aggregation of gold nanoparticles. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[19]  N. Shah,et al.  Sensitive and selective chem/bio sensing based on surface-enhanced Raman spectroscopy (SERS) , 2006 .

[20]  Satoshi Kawata,et al.  Raman and SERS microscopy for molecular imaging of live cells , 2013, Nature Protocols.

[21]  R. V. Duyne,et al.  Glucose Sensing with Surface-Enhanced Raman Spectroscopy , 2006 .

[22]  J. Frederiksen,et al.  A New Glucose-Selective Fluorescent Bisboronic Acid. First Report of Strong α-Furanose Complexation in Aqueous Solution at Physiological pH1 , 1999 .

[23]  Y. Ozaki,et al.  Influence of substituent type and position on the adsorption mechanism of phenylboronic acids: infrared, Raman, and surface-enhanced Raman spectroscopy studies. , 2013, The journal of physical chemistry. A.

[24]  Gregory S. Tschumper,et al.  Vibrational spectroscopy of N-methyliminodiacetic acid (MIDA)-protected boronate ester: examination of the B-N dative bond. , 2011, The journal of physical chemistry. A.

[25]  Richard P Van Duyne,et al.  In vivo, transcutaneous glucose sensing using surface-enhanced spatially offset Raman spectroscopy: multiple rats, improved hypoglycemic accuracy, low incident power, and continuous monitoring for greater than 17 days. , 2011, Analytical chemistry.

[26]  D. A. Stuart,et al.  Glucose sensing using near-infrared surface-enhanced Raman spectroscopy: gold surfaces, 10-day stability, and improved accuracy. , 2005, Analytical chemistry.

[27]  S. Zou,et al.  Sensitive carbohydrate detection using surface enhanced Raman tagging. , 2010, Analytical chemistry.

[28]  Steven R. Emory,et al.  Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering , 1997, Science.

[29]  J. Zhao,et al.  Controlled plasmonic nanostructures for surface-enhanced spectroscopy and sensing. , 2008, Accounts of chemical research.

[30]  T. James,et al.  Glucose sensing via aggregation and the use of "knock-out" binding to improve selectivity. , 2013, Journal of the American Chemical Society.

[31]  Sanjay Mehrotra,et al.  Prediction range estimation from noisy Raman spectra with robust optimization. , 2010, The Analyst.

[32]  R. V. Van Duyne,et al.  A glucose biosensor based on surface-enhanced Raman scattering: improved partition layer, temporal stability, reversibility, and resistance to serum protein interference. , 2004, Analytical chemistry.

[33]  H. Kitano,et al.  Interfacial Recognition of Sugars by Boronic Acid-Carrying Self-Assembled Monolayer† , 2000 .

[34]  Christy L. Haynes,et al.  Surface‐enhanced Raman sensors: early history and the development of sensors for quantitative biowarfare agent and glucose detection , 2005 .

[35]  E. Anslyn,et al.  Creative Chemical Sensor Systems , 2007 .

[36]  R. V. Van Duyne,et al.  Toward a glucose biosensor based on surface-enhanced Raman scattering. , 2003, Journal of the American Chemical Society.

[37]  P. Paul,et al.  Structures of carbohydrate-boronic acid complexes determined by NMR and molecular modelling in aqueous alkaline media. , 2004, Organic & biomolecular chemistry.

[38]  D. A. Stuart,et al.  Towards advanced chemical and biological nanosensors-An overview. , 2005, Talanta.

[39]  K. Kendall,et al.  Aggregation and adhesion of gold nanoparticles in phosphate buffered saline , 2012, Journal of Nanoparticle Research.

[40]  Satoshi Kawata,et al.  Imaging of EdU, an alkyne-tagged cell proliferation probe, by Raman microscopy. , 2011, Journal of the American Chemical Society.