Thermodynamic Analysis of the Selectivity Enhancement Obtained by Using Smart Hydrogels That Are Zwitterionic When Detecting Glucose With Boronic Acid Moieties.

Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, boronic acid-containing hydrogels are being used in a variety of implantable glucose sensors under development, including sensors based on optical, fluorescence, and swelling pressure measurements. However, some method of glucose selectivity enhancement is often necessary, because isolated boronic acid molecules have a binding constant with glucose that is some forty times smaller than their binding constant with fructose, the second most abundant sugar in the human body. In many cases, glucose selectivity enhancement is obtained by incorporating pendant tertiary amines into the hydrogel network, thereby giving rise to a hydrogel that is zwitterionic at physiological pH. However, the mechanism by which incorporation of tertiary amines confers selectivity enhancement is poorly understood. In order to clarify this mechanism, we use the osmotic deswelling technique to compare the thermodynamic interactions of glucose and fructose with a zwitterionic smart hydrogel containing boronic acid moieties. We also investigate the change in the structure of the hydrogel that occurs when it binds to glucose or to fructose using the technique of small angle neutron scattering.

[1]  F. Arnold,et al.  A membrane-moderated, conductimetric sensor for the detection and measurement of specific organic solutes in aqueous solutions , 2000 .

[2]  Bernd Hitzmann,et al.  Sensors in disposable bioreactors status and trends. , 2009, Advances in biochemical engineering/biotechnology.

[3]  Jeff Blyth,et al.  Towards the real-time monitoring of glucose in tear fluid: holographic glucose sensors with reduced interference from lactate and pH. , 2008, Biosensors & bioelectronics.

[4]  Babak Ziaie,et al.  A hydrogel-based implantable micromachined transponder for wireless glucose measurement. , 2006, Diabetes technology & therapeutics.

[5]  The Thermodynamics of a Strained Elastomer. I. General Analysis , 1948 .

[6]  B. Mattiasson,et al.  Optical responses, permeability and diol-specific reactivity of thin polyacrylamide gels containing immobilized phenylboronic acid , 2008 .

[7]  Joseph R Lakowicz,et al.  Ophthalmic glucose sensing: a novel monosaccharide sensing disposable and colorless contact lens. , 2004, The Analyst.

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

[9]  F. Horkay,et al.  Molecular simulation of the swelling of polyelectrolyte gels by monovalent and divalent counterions. , 2008, The Journal of chemical physics.

[10]  R. Rivlin.  Torsion of a Rubber Cylinder , 1947 .

[11]  Heidi E Koschwanez,et al.  In vitro, in vivo and post explantation testing of glucose-detecting biosensors: current methods and recommendations. , 2007, Biomaterials.

[12]  F. Horkay,et al.  Separation of the effects of pH and polymer concentration on the swelling pressure and elastic modulus of a pH-responsive hydrogel. , 2006, Polymer.

[13]  Xuyan Mao,et al.  Amperometric glucose biosensor based on integration of glucose oxidase with platinum nanoparticles/ordered mesoporous carbon nanocomposite , 2011 .

[14]  D. Cordes,et al.  Continuous glucose sensing with a fluorescent thin-film hydrogel. , 2003, Angewandte Chemie.

[15]  Qiao Lin,et al.  A MEMS affinity glucose sensor using a biocompatible glucose-responsive polymer. , 2009, Sensors and actuators. B, Chemical.

[16]  H. Akanuma,et al.  Increased fructose concentrations in blood and urine in patients with diabetes. , 2002, Diabetes care.

[17]  K. Dušek,et al.  Structure and elasticity of non-crystalline polymer networks , 1969 .

[18]  Timothy L. Routh,et al.  Function of an Implanted Tissue Glucose Sensor for More than 1 Year in Animals , 2010, Science Translational Medicine.

[19]  Hans-Jörg Schneider,et al.  A chemomechanical polymer that functions in blood plasma with high glucose selectivity , 2021 .

[20]  Dag Roar Hjelme,et al.  Determination of glucose levels using a functionalized hydrogel-optical fiber biosensor: toward continuous monitoring of blood glucose in vivo. , 2009, Analytical chemistry.

[21]  A. Horgan,et al.  Crosslinking of phenylboronic acid receptors as a means of glucose selective holographic detection. , 2006, Biosensors & bioelectronics.

[22]  H. Vink.  Precision measurements of osmotic pressure in concentrated polymer solutions , 1971 .

[23]  Felicity Sartain,et al.  Designed boronate ligands for glucose-selective holographic sensors. , 2006, Chemistry.

[24]  J. Pritchard,et al.  Selective holographic detection of glucose using tertiary amines. , 2006, Chemical communications.

[25]  Valdas Laurinavicius,et al.  Application of oxygen-independent biosensor for testing yeast fermentation capacity. , 2010, Biosensors & bioelectronics.

[26]  Paul V Braun,et al.  Glucose-sensitive inverse opal hydrogels: analysis of optical diffraction response. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[27]  Florian Solzbacher,et al.  Smart hydrogel based microsensing platform for continuous glucose monitoring , 2010, 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology.

[28]  Adam Heller,et al.  Direct electrical communication between chemically modified enzymes and metal electrodes. 2. Methods for bonding electron-transfer relays to glucose oxidase and D-amino-acid oxidase , 1988 .

[29]  Hiroyuki Kudo,et al.  A flexible and wearable glucose sensor based on functional polymers with soft-MEMS techniques. , 2006, Biosensors & bioelectronics.

[30]  P. Basser,et al.  Osmotic swelling of polyacrylate hydrogels in physiological salt solutions. , 2000, Biomacromolecules.

[31]  F. Horkay,et al.  Constant-volume hydrogel osmometer: a new device concept for miniature biosensors. , 2002, Biomacromolecules.

[32]  F. Horkay,et al.  Macroscopic and microscopic thermodynamic observations in swollen poly(vinyl acetate) networks , 1991 .

[33]  T. Okano,et al.  Glucose-Responsive Gel from Phenylborate Polymer and Poly (Vinyl Alcohol): Prompt Response at Physiological pH Through the Interaction of Borate with Amino Group in the Gel , 1997, Pharmaceutical Research.

[34]  F Solzbacher,et al.  Free swelling and confined smart hydrogels for applications in chemomechanical sensors for physiological monitoring. , 2009, Sensors and actuators. B, Chemical.

[35]  Roger Brown,et al.  Physical Testing of Rubber , 1987 .

[36]  P Tathireddy,et al.  Osmotic Swelling Pressure Response of Smart Hydrogels Suitable for Chronically-Implantable Glucose Sensors. , 2010, Sensors and actuators. B, Chemical.

[37]  P. Flory.  Principles of polymer chemistry , 1953 .

[38]  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.

[39]  Binghe Wang,et al.  Boronolectins and fluorescent boronolectins: An examination of the detailed chemistry issues important for the design , 2005, Medicinal research reviews.

[40]  T. Okano,et al.  Effect of the incorporation of amino groups in a glucose‐responsive polymer complex having phenylboronic acid moieties , 1991 .

[41]  J. S. Rowlinson,et al.  Molecular Thermodynamics of Fluid-Phase Equilibria , 1969 .

[42]  L. Heinemann,et al.  Sensors for glucose monitoring: technical and clinical aspects , 2001, Diabetes/metabolism research and reviews.

[43]  P. Gennes.  Scaling Concepts in Polymer Physics , 1979 .

[44]  Igor K Lednev,et al.  Photonic crystal carbohydrate sensors: low ionic strength sugar sensing. , 2003, Journal of the American Chemical Society.

[45]  P. Basser,et al.  Osmotic observations on chemically cross-linked DNA gels in physiological salt solutions. , 2004, Biomacromolecules.

[46]  F. Horkay,et al.  Neutron Scattering Properties of Randomly Cross-Linked Polyisoprene Gels , 2000 .

[47]  I. Boyaci,et al.  Thermodynamic analysis of the interaction between 3-aminophenylboronic acid and monosaccharides for development of biosensor , 2009 .

[48]  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 .

[49]  Adam Heller,et al.  Direct electrical communication between chemically modified enzymes and metal electrodes. I. Electron transfer from glucose oxidase to metal electrodes via electron relays, bound covalently to the enzyme , 1987 .