A photonic glucose biosensor for chronic wound prognostics.

The ability to monitor glucose levels in chronic wound fluid of diabetic patients is a promising theranostic approach in chronic wound healing. Phenylboronic acid polymers are glucose- and pH-responsive materials. In the presence of glucose, these polymers reversibly form cyclic boronate esters, changing the properties of the polymer and forming the basis of glucose sensing. In this report, poly(4-vinylphenylboronic acid) (PVPBA) was covalently grafted to the pores of porous silicon (pSi) films (pSi-PVPBA). Polymer switching in response to changing pH and glucose concentration was monitored by means of interferometric reflectance spectroscopy (IRS). We observed that a shift of the boronic acid equilibrium between the neutral and anionic form in the polymer translated into refractive index changes that could be detected as a variation of the effective optical thickness (EOT) of the pSi-PVPBA film. The pSi/polymer composite was further investigated as a platform for the detection of glucose. Using this sensing platform, we were able to detect glucose in a buffer solution as low as 0.15 mM and also in a wound fluid sample without encountering interferences.

[1]  B. Sumerlin,et al.  Biomedical applications of boronic acid polymers , 2011 .

[2]  Ingemar Lundström,et al.  Structure of 3-aminopropyl triethoxy silane on silicon oxide , 1991 .

[3]  Y. Long,et al.  Glucose selective surface plasmon resonance-based bis-boronic acid sensor. , 2013, The Analyst.

[4]  J. Chao,et al.  Biofunctionalisation of porous silicon (PS) surfaces by using homobifunctional cross-linkers , 2006 .

[5]  Michael J Sailor,et al.  Biosensing using porous silicon double-layer interferometers: reflective interferometric Fourier transform spectroscopy. , 2005, Journal of the American Chemical Society.

[6]  J. Lai,et al.  Functional Polymers from Novel Carboxyl-Terminated Trithiocarbonates as Highly Efficient RAFT Agents , 2002 .

[7]  Nicolas H Voelcker,et al.  Porous silicon biosensors on the advance. , 2009, Trends in biotechnology.

[8]  T. Okano,et al.  Totally Synthetic Polymer Gels Responding to External Glucose Concentration: Their Preparation and Application to On−Off Regulation of Insulin Release , 1998 .

[9]  Philippe M. Fauchet,et al.  Hydrogel‐Supported Optical‐Microcavity Sensors , 2005 .

[10]  W. Goodson,et al.  Studies of wound healing in experimental diabetes mellitus. , 1977, The Journal of surgical research.

[11]  I. Rendina,et al.  Hybrid polymer-porous silicon photonic crystals for optical sensing , 2009 .

[12]  J. Castracane,et al.  Deep Infiltration of Emissive Polymers into Mesoporous Silicon Microcavities: Nanoscale Confinement and Advanced Vapor Sensing , 2013 .

[13]  Kristopher A Kilian,et al.  The importance of surface chemistry in mesoporous materials: lessons from porous silicon biosensors. , 2009, Chemical communications.

[14]  Michael J. Sailor,et al.  A Porous Silicon Optical Biosensor: Detection of Reversible Binding of IgG to a Protein A-Modified Surface , 1999 .

[15]  B. Sumerlin,et al.  Tuning the Sugar-Response of Boronic Acid Block Copolymers , 2012 .

[16]  J. Devoisselle,et al.  Confinement of Thermoresponsive Hydrogels in Nanostructured Porous Silicon Dioxide Templates , 2007 .

[17]  Tim R. Dargaville,et al.  Matrix metalloproteinase biosensor based on a porous silicon reflector , 2013 .

[18]  Katharina Gaus,et al.  Forming Antifouling Organic Multilayers on Porous Silicon Rugate Filters Towards In Vivo/Ex Vivo Biophotonic Devices , 2007 .

[19]  B. Sumerlin,et al.  Future perspectives and recent advances in stimuli-responsive materials , 2010 .

[20]  Mark D. Losego,et al.  Hydrogel-Based Glucose Sensors: Effects of Phenylboronic Acid Chemical Structure on Response , 2013 .

[21]  J. Landoulsi,et al.  Silane layers on silicon surfaces: mechanism of interaction, stability, and influence on protein adsorption. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[22]  Martin A. Cole,et al.  Stimulus-responsiveness and drug release from porous silicon films ATRP-grafted with poly(N-isopropylacrylamide). , 2011, Langmuir : the ACS journal of surfaces and colloids.

[23]  John T. Yates,et al.  FTIR Study of the Oxidation of Porous Silicon , 1997 .

[24]  E Wilkins,et al.  Glucose monitoring: state of the art and future possibilities. , 1996, Medical engineering & physics.

[25]  F. Cunin,et al.  Characterization of phospholipid bilayer formation on a thin film of porous SiO2 by reflective interferometric Fourier transform spectroscopy (RIFTS). , 2012, Langmuir : the ACS journal of surfaces and colloids.

[26]  N. Voelcker,et al.  Study of the optical properties of a thermoresponsive polymer grafted onto porous silicon scaffolds , 2013 .

[27]  Kristopher A Kilian,et al.  Peptide-modified optical filters for detecting protease activity. , 2007, ACS nano.

[28]  Vesa-Pekka Lehto,et al.  Fabrication and chemical surface modification of mesoporous silicon for biomedical applications , 2008 .

[29]  T. Okano,et al.  A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (N-vinyl-2-pyrrolidone) with a phenylboronic acid moiety , 1992 .

[30]  Igor K Lednev,et al.  High ionic strength glucose-sensing photonic crystal. , 2003, Analytical chemistry.

[31]  K. Gaus,et al.  Mesoporous silicon photonic crystal microparticles: towards single-cell optical biosensors. , 2011, Faraday discussions.

[32]  Nigel A. Surridge,et al.  The Technology Behind Glucose Meters: Test Strips , 2008 .

[33]  T. Fahey,et al.  Diabetes impairs the late inflammatory response to wound healing. , 1991, The Journal of surgical research.

[34]  Benjamin C. Tang,et al.  Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery. , 2013, ACS nano.

[35]  T. Okano,et al.  A Self-Regulated Insulin Delivery System Using Boronic Acid Gel , 1994 .

[36]  Eun-Hyung Yoo,et al.  Glucose Biosensors: An Overview of Use in Clinical Practice , 2010, Sensors.

[37]  Mher Ghulinyan,et al.  Porous silicon-based rugate filters. , 2005, Applied optics.

[38]  M. Ghadiri,et al.  A porous silicon-based optical interferometric biosensor. , 1997, Science.

[39]  Katharina Gaus,et al.  Modifying Porous Silicon with Self‐Assembled Monolayers for Biomedical Applications: The Influence of Surface Coverage on Stability and Biomolecule Coupling , 2008 .

[40]  Andreas Janshoff,et al.  Macroporous p-Type Silicon Fabry−Perot Layers. Fabrication, Characterization, and Applications in Biosensing , 1998 .

[41]  N. Voelcker,et al.  Catalyzed Oxidative Corrosion of Porous Silicon Used as an Optical Transducer for Ligand–Receptor Interactions , 2008, Chembiochem : a European journal of chemical biology.

[42]  Hongxia Chen,et al.  Formation and Characterization of Self-Assembled Phenylboronic Acid Derivative Monolayers toward Developing Monosaccharide Sensing-Interface , 2007, Sensors (Basel, Switzerland).

[43]  Philippe M. Fauchet,et al.  Macroporous Silicon Microcavities for Macromolecule Detection , 2005 .

[44]  Joseph Wang.  Electrochemical glucose biosensors. , 2008, Chemical reviews.

[45]  W. Freeman,et al.  Porous silicon in drug delivery devices and materials. , 2008, Advanced drug delivery reviews.

[46]  P. Kofinas,et al.  Color changing block copolymer films for chemical sensing of simple sugars. , 2011, Biosensors & bioelectronics.

[47]  H. F. Shurvell,et al.  Infrared spectra of phenylboronic acid (normal and deuterated) and diphenyl phenylboronate , 1968 .

[48]  H. Svensson,et al.  Impaired wound healing in an acute diabetic pig model and the effects of local hyperglycemia , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[49]  Daniel G Anderson,et al.  Injectable nano-network for glucose-mediated insulin delivery. , 2013, ACS nano.

[50]  Nicolas H Voelcker,et al.  The biocompatibility of porous silicon in tissues of the eye. , 2009, Biomaterials.

[51]  Michael J. Sailor,et al.  Chitosan Hydrogel‐Capped Porous SiO2 as a pH Responsive Nano‐Valve for Triggered Release of Insulin , 2009 .

[52]  Ying Zhu,et al.  Functionalised porous silicon as a biosensor: emphasis on monitoring cells in vivo and in vitro. , 2013, The Analyst.

[53]  B. Sumerlin,et al.  Sugar-responsive block copolymers by direct RAFT polymerization of unprotected boronic acid monomers. , 2008, Chemical communications.

[54]  R. Nolte,et al.  Polymeric monosaccharide receptors responsive at neutral pH. , 2009, Journal of the American Chemical Society.

[55]  F. Quignard,et al.  Chitosan-functionalized porous silicon optical transducer for the detection of carboxylic acid-containing drugs in water , 2011 .

[56]  G. Maglio,et al.  A nanostructured hybrid material based on polymer infiltrated porous silicon layer , 2010 .

[57]  B. T. Stokke,et al.  Glucose sensors based on a responsive gel incorporated as a Fabry-Perot cavity on a fiber-optic readout platform. , 2009, Biosensors & bioelectronics.

[58]  Martin J. Sweetman,et al.  Dual silane surface functionalization for the selective attachment of human neuronal cells to porous silicon. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[59]  J. Pfeilschifter,et al.  Large and sustained induction of chemokines during impaired wound healing in the genetically diabetic mouse: prolonged persistence of neutrophils and macrophages during the late phase of repair. , 2000, The Journal of investigative dermatology.

[60]  B. Sumerlin,et al.  Triply-responsive boronic acid block copolymers: solution self-assembly induced by changes in temperature, pH, or sugar concentration. , 2009, Chemical communications.

[61]  B. Sumerlin,et al.  Facile strategy to well-defined water-soluble boronic acid (co)polymers. , 2007, Journal of the American Chemical Society.

[62]  H Hoshino,et al.  Glucose-sensing electrode coated with polymer complex gel containing phenylboronic Acid. , 1996, Analytical chemistry.

[63]  B. Sumerlin,et al.  Glucose-Sensitivity of Boronic Acid Block Copolymers at Physiological pH. , 2012, ACS macro letters.

[64]  Linqi Shi,et al.  Phenylboronic acid-based complex micelles with enhanced glucose-responsiveness at physiological pH by complexation with glycopolymer. , 2012, Biomacromolecules.