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Development of sensors for the detection of clinically relevant substances using molecular imprinting

By Steven A. Fowler

Abstract

This thesis investigates the development of sensing devices based on molecularly imprinted polymers for the detection of clinically relevant analytes. Three analytes were considered, metronidazole, creatinine and propofol. A molecularly imprinted polymer (MIP) was computationally designed for metronidazole and tested using SPE techniques. This polymer was then grafted onto a transducer surface using an immobilised initiator. Amperometric and impedance detection of metronidazole were investigated. The capacitive detection of creatinine was reproduced from the literature (Panasyuk- Delaney et al., 2002) as this approach could be applied to other MIPs to form a universal platform for sensor development. However, the sensors produced using this methodology were difficult to reproduce and attempts to improve them were unsuccessful. A model for capacitive electrodes was developed to explain the obtained results. To address the key challenges found in the aforementioned work, a dual polymerisable monomer was used as a conductive anchor for the amperometric and impedance detection of propofol. The developed amperometric sensors demonstrated very high sensitivity (limit of detection was below 5 µM), although the electrodes lacked in selectivity. In conclusion, this thesis illustrates some of the key areas which need to be considered in the development of MIP-based devices and investigates some innovative solutions to these problems

Publisher: Cranfield University
Year: 2009
OAI identifier: oai:dspace.lib.cranfield.ac.uk:1826/5665
Provided by: Cranfield CERES

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Citations

  1. (1996). A 'mixed' selfassembled monolayer for an impedimetric immunosensor. doi
  2. (2005). A computational and experimental investigation of the interaction between the template molecule and the functional monomer used in the molecularly imprinted polymer. doi
  3. (1999). A disposable biosensor for urea determination in blood based on an ammonium-sensitive transducer. doi
  4. (2000). A ISFET cartridge for electrolyte measurement by micromachinery. doi
  5. (2000). A miniaturized pH and pCO2 intravascular catheter using optical monitoring and a dual concentric-flow microdialysis approach. doi
  6. (2003). A new electrocatalytic mechanism for the oxidation of phenols at platinum electrodes. doi
  7. (2004). A new method for the quantitation of propofol in human plasma: efficient solid-phase extraction and liquid chromatography/APCI-triple quadrupole mass spectrometry detection. Molecularly Imprinted Polymers in Separation Science, doi
  8. (2007). A new methodology for the rational design of molecularly imprinted polymers. doi
  9. (2004). A Novel Capacitive Immunosensor Using Electropolymerized Insulating Poly (o-phenylenediamine) Film on a Glass Carbon Electrode for Probing Transferrin. doi
  10. (2006). A novel method for glucose determination based on electrochemical impedance spectroscopy using glucose oxidase self-assembled biosensor. doi
  11. (2001). A solid binding matrix/molecularly imprinted polymer-based sensor system for the determination of clenbuterol in bovine liver using differential-pulse voltammetry. Sensors and Actuators, doi
  12. (2005). A stable three-enzyme creatinine biosensor. 3. Immobilization of creatinine amidohydrolase and sensor development. doi
  13. (2001). A versatile biosensor device for continuous biomedical monitoring. doi
  14. (2004). Accuracy and performance of a modified continuous intravascular blood gas monitoring device during thoracoscopic surgery. doi
  15. (2004). Accurate pKa Determination for a Heterogeneous Group of Organic Molecules. doi
  16. (1991). Adsorptive stripping voltammetry of selected cephalosporin antibiotics and their direct determination in urine. doi
  17. (2008). AFM Forces Measured between Gold Surfaces Coated with Self-Assembled Monolayers of 1-Hexadecanethiol. doi
  18. (2003). Albumin adsorption on alkanethiols self-assembled monolayers on gold electrodes studied by chronopotentiometry. doi
  19. (1994). Alkanethiol Monolayers on Preoxidized Gold. Encapsulation of Gold Oxide under an Organic Monolayer. doi
  20. (1999). Amperometric biosensors for clinical and therapeutic drug monitoring: a review. doi
  21. (1996). Amperometric enzyme biosensors for the analysis of drugs and metabolites. doi
  22. (1998). Amperometric immunosensor for lactate dehydrogenase LD-1. doi
  23. (1997). Amperometric lactate oxidase catheter for real-time lactate monitoring based on thin film technology. doi
  24. (2003). Amperometric metronidazole sensor based on the supermolecular recognition by metalloporphyrin incorporated in carbon paste electrode. doi
  25. (2002). Amperometric urea biosensor based on urease and electropolymerized toluidine blue dye as a pHsensitive redox probe. doi
  26. (1998). An Amperometric Immunosensor for Cocaine. doi
  27. (1998). Analysis of gentamicin by liquid chromatography with pulsed electrochemical detection. doi
  28. (2000). Analytical doi
  29. (2000). Analytical chemistry: an introduction, doi
  30. (2006). Analytical electrochemistry, doi
  31. (2006). Anatomy of a successful imprint: Analysing the recognition mechanisms of a molecularly imprinted polymer for quercetin. doi
  32. (2006). Application of a novel electrosynthesized polydopamine-imprinted film to the capacitive sensing of nicotine. doi
  33. (2004). Approaches to the rational design of molecularly imprinted polymers. doi
  34. (2004). Artificial Receptor Layer for Herbicide Detection Based on Electrosynthesized Molecular Imprinting Technique and Capacitive Transduction. doi
  35. (2006). Assay of glucose in urine and drinking water with voltammetric working sensors of infrared photo diode electrode. Sensors and Actuators A: Physical, doi
  36. (2001). Assessing a photocured self-plasticised acrylic membrane recipe for Na+ and K+ ion selective electrodes. doi
  37. (2007). Biomedical sensor using thick film technology for transcutaneous oxygen measurement. doi
  38. (2001). Bite-and-Switch' approach using computationally designed molecularly imprinted polymers for sensing of creatinine. doi
  39. (1997). Blocking behavior of self-assembled monolayers on gold electrodes. doi
  40. (1999). Building fluorescent sensors by template polymerization: The preparation of a fluorescent sensor for d-Fructose. doi
  41. (1998). Capacitive Approach to Determine Phospholipase A2 Activity toward Artificial and Natural Substrates. doi
  42. (2005). Capacitive Biosensor for Glutathione Detection Based on Electropolymerized Molecularly Imprinted Polymer and Kinetic Investigation of the Recognition Process. doi
  43. (2004). Capacitive chemical sensor for fenvalerate assay based on electropolymerized molecularly imprinted polymer as the sensitive layer. doi
  44. (2002). Capacitive creatinine sensor based on a photografted molecularly imprinted polymer. doi
  45. (2007). Capacitive Detection in Ultrathin Chemosensors Prepared by Molecularly Imprinted Grafting Photopolymerization. doi
  46. (2001). Capacitive detection of glucose using molecularly imprinted polymers. doi
  47. (1996). Capacitive detection of surfactant adsorption on hydrophobized gold electrodes. doi
  48. (2002). Capacitive immunosensor for transferrin based on an o-aminobenzenthiol oligomer layer. doi
  49. (1996). Capacitive sensor for lipolytic enzymes. Thin Solid Films, doi
  50. (2004). Capacitive sensors using electropolymerized o-phenylenediamine film doped with ion-pair complex as selective elements for the determination of pentoxyverine. doi
  51. (2006). Capturing molecules with templated materials-Analysis and rational design of molecularly imprinted polymers. doi
  52. (2005). Carbon-paste electrode modified with cobalt-5-nitrolsalophen as a sensitive voltammetric sensor for detection of captopril. doi
  53. (1997). Cathodic Stripping Voltammetric Determination of Ceftazidime in Urine at a Hanging Mercury Drop Electrode. doi
  54. (2004). Characteristics of a label-free piezoelectric immunosensor detecting Pseudomonas aeruginosa. doi
  55. (2000). Chemical grafting of molecularly imprinted homopolymers to the surface of microplates. Application of artificial adrenergic receptor in enzyme-linked assay for β-agonists determination. doi
  56. (2002). Chemically Mediated Grain Growth in Nanotextured Au, Au/Cu Thin Films:  Novel Substrates for the Formation of Self-Assembled Monolayers. doi
  57. (2009). Chimeric Polymers Formed from a Monomer Capable of FreeRadical, Oxidative and Electrochemical Polymerisation. Chemical Communications, doi
  58. (2003). Combinatorial methods in molecular imprinting. doi
  59. (1997). Comparison of the Voltammetric Behavior of Metronidazole at a DNAModified Glassy Carbon Electrode, a Mercury Thin Film Electrode and a Glassy Carbon Electrode. doi
  60. (1995). Competitive amperometric morphine sensor based on an agarose immobilised molecularly imprinted polymer. doi
  61. (2008). Computational design and synthesis of molecular imprinted polymers with high selectivity for removal of aniline from contaminated water. doi
  62. (2006). Computational design and synthesis of molecularly imprinted polymers with high binding capacity for pharmaceutical applications-model case: Adsorbent for abacavir. doi
  63. (1992). Consequences of microscopic surface roughness for molecular self-assembly. doi
  64. (2004). Construction and Analytical Application of a Novel IonSelective Capacitive Sensor for Determination of Cinchonine. doi
  65. (2005). Construction of a novel molecularly imprinted sensor for the determination of O,O-dimethyl-(2,4-dichlorophenoxyacetoxyl)(3'-nitrophenyl)methinephosphonate. doi
  66. (1999). Continuous arterial blood gas monitoring during bilateral sequential lung transplantation. doi
  67. (2007). Continuous glucose monitoring in interstitial fluid using glucose oxidase-based sensor compared to established blood glucose measurement in rats. doi
  68. (1998). Continuous measurement of subcutaneous lactate concentration during exercise by combining open-flow microperfusion and thin-film lactate sensors. doi
  69. (1994). Covalent immobilization of protein monolayers for biosensor applications. doi
  70. (2001). Detection of gentamicin in milk by immunoassay and flow injection analysis with electrochemical measurement. doi
  71. (1999). Detection of uric acid with a new type of conducting polymer-based enzymatic sensor by bipotentiostatic technique. doi
  72. (2003). Determination of the antibiotic drug pefloxacin in bulk form, tablets and human serum using square wave cathodic adsorptive stripping voltammetry. doi
  73. (1995). Determination of urea in blood serum by a urease biosensor based on an ion-sensitive field-effect transistor. doi
  74. (2004). Development of a creatinine-sensitive sensor for medical analysis. doi
  75. (2007). Development of silicon-based potentiometric sensors: Towards a miniaturized electronic tongue. doi
  76. (1992). Differential pulse polarographic determination of cefoxitin.
  77. (2003). Disposable amperometric immunosensor system for rabbit IgG using a conducting polymer modified screen-printed electrode. doi
  78. (1994). Effect of Gold Topography and Surface Pretreatment on the Self-Assembly of Alkanethiol Monolayers. doi
  79. (1999). Electrical control of alkanethiols self-assembly on a gold surface as an approach for preparation of microelectrode arrays. doi
  80. (1998). Electro-oxidation of ethanol on gold: analysis of the reaction products and mechanism. doi
  81. (1991). Electrochemical analysis of cephalosporin antibiotics. doi
  82. (2006). Electrochemical and spectroelectrochemical studies on aniline in organic medium and its antiknock mechanism. doi
  83. (2007). Electrochemical detection of 2,6-diisopropylphenol (propofol) in reversed phase HPLC at high pH. doi
  84. (2007). Electrochemical detection of tobramycin or gentamicin according to the European Pharmacopoeia analytical method. doi
  85. (1990). Electrochemical determination of 2,6-diisopropylphenol after high-performance liquid chromatography of extracts from serum. doi
  86. (2004). Electrochemical determination of Cephalothin antibiotic by adsorptive stripping voltammetric technique. doi
  87. (2004). Electrochemical reduction and voltammetric determination of metronidazole at a nanomaterial thin film coated glassy carbon electrode. doi
  88. (1997). Electrochemical reduction of metronidazole at a DNA-modified glassy carbon electrode. doi
  89. (1998). Electrochemical reduction of metronidazole at activated glassy carbon electrode and its determination in pharmaceutical dosage forms. doi
  90. (2001). Electrochemical sensors using screen-printed carbon electrode assemblies modified with the [beta]-cyclodextrin or carboxymethylated [beta]-cyclodextrin polymer films for determination of tricyclic antidepressive drugs. doi
  91. (2008). Electrochemical synthesis of polyaniline nanonetworks on p-aminobenzene sulfonic acid functionalized glassy carbon electrode. Its use for the simultaneous determination of ascorbic acid and uric acid. doi
  92. (1999). Electropolymerized Molecularly Imprinted Polymers as Receptor Layers in Capacitive Chemical Sensors. doi
  93. (1994). Enzymatic flowinjection determination of urea in blood serum using potentiometric gas sensor with internal nonactin based ISE. doi
  94. (2001). Evaluation of creatine transport using Caco-2 monolayers as an in vitro model for intestinal absorption. doi
  95. (2001). Fabrication of a sensing module using micromachined biosensors. doi
  96. (1998). Fast Amperometric Assay for E. coli O157:H7 Using Partially Immersed Immunoelectrodes. doi
  97. (1997). Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, doi
  98. (2001). Fiber-Optic Luminescent Sensors with Composite Oxygen-Sensitive Layers and Anti-Biofouling Coatings. doi
  99. (2003). First human experiments with a novel non-invasive, non-optical continuous glucose monitoring system. doi
  100. (2007). Flow injection analysis of blood l-lactate by using a Prussian Blue-based biosensor as amperometric detector. doi
  101. (1998). Flow Injection Immunoanalysis Based on a Magnetoimmunosensor System. doi
  102. (1998). Fluorescent Functional Recognition Sites through Molecular Imprinting. A Polymer-Based Fluorescent Chemosensor for Aqueous cAMP. doi
  103. (1994). Forensic investigation of gentamicin sulfates by anion-exchange ion chromatography with pulsed electrochemical detection. doi
  104. (2000). Glucose sensor with improved haemocompatibilty.
  105. (1996). Highperformance liquid chromatographic assay of propofol in human and rat plasma and fourteen rat tissues using electrochemical detection. doi
  106. (1999). Immunosensors based on supported lipid membranes, protein films and liposomes modified by antibodies. Sensors and Actuators, doi
  107. (2001). Impedometric herbicide chemosensors based on molecularly imprinted polymers. doi
  108. (2002). Implantable chemical sensors for real-time clinical monitoring: progress and challenges. doi
  109. (1998). Imprinted membranes for sensor technology: opposite behavior of covalently and noncovalently imprinted membranes. doi
  110. (2008). Improved liquid chromatographic method with pulsed electrochemical detection for the analysis of gentamicin. doi
  111. (2007). Improving blood compatibility of intravascular oxygen sensors via catalytic decomposition of S-nitrosothiols to generate nitric oxide in situ. doi
  112. (1993). In vivo blood-gas and electrolyte sensors: Progress and challenges. doi
  113. (2002). In-situ spectroelectrochemical evidences for the copolymerization of o-toluidine with diphenylamine-4-sulphonic acid by UV-visible spectroscopy. Spectrochimica Acta - doi
  114. (1997). Intravascular carbon dioxide monitoring using micro-flow colorimetry. doi
  115. (2004). Ionometric determination of gentamicin and kanamycin in biological fluids and ready-to-use medicinal forms. doi
  116. (1996). Kinetic and Mechanistic Studies of Iniferter Photopolymerizations. doi
  117. (2000). Living" Free Radical Photopolymerization Initiated from SurfaceGrafted Iniferter Monolayers. doi
  118. (2007). Macroporous molecularly imprinted polymer/cryogel composite systems for the removal of endocrine disrupting trace contaminants. doi
  119. (1988). Measurement of nanomolar levels of psychoactive drugs in urine by adsorptive stripping voltammetry. doi
  120. (2006). Metabolic alkalosis. doi
  121. (2000). Methods for reducing biosensor membrane biofouling. doi
  122. (2000). Microdialysis measurement of glucose in subcutaneous adipose tissue up to three weeks in Type 1 diabetic patients. doi
  123. (1998). Microdialysis of glucose in subcutaneous adipose tissue up to 3 weeks in healthy volunteers. doi
  124. (1996). Model of an immobilized enzyme conductimetric urea biosensor. doi
  125. (2005). Molecular imprinted polymer sensors: Implications for therapeutics. Molecularly Imprinted Polymers: doi
  126. (2002). Molecularly imprinted composite materials via iniferter-modified supports. doi
  127. (2000). Molecularly Imprinted Polymers and Their Use in Biomimetic Sensors. doi
  128. (2006). Molecularly imprinted polymers in clinical diagnostics-Future potential and existing problems. doi
  129. (2005). Molecularly imprinted polymers--potential and challenges in analytical chemistry. doi
  130. (1999). Molecularly imprinted self-assembled films with specificity to cholesterol. Sensors and Actuators, doi
  131. (2001). Neurotrend: Cerebral tissue monitoring system.
  132. (2006). New electrodes for old: From carbon nanotubes to edge plane pyrolytic graphite. doi
  133. (2009). New reactive polymer for protein immobilisation on sensor surfaces. doi
  134. (2002). Nitric oxide releasing silicone rubbers with improved blood compatibility: preparation, characterization, and in vivo evaluation. doi
  135. (1996). Novel potentiometric silicon sensor for medical devices. Sensors and Actuators doi
  136. (1998). Novel system for real-time ex vivo lactate monitoring in human whole blood. doi
  137. (1990). Online blood electrolyte monitoring with a ChemFET microcell system. doi
  138. (1999). Optimization of capacitive affinity sensors: Drift suppression and signal amplification. doi
  139. (2005). Paratrend Sensor Evaluation. doi
  140. (1999). Performance of subcutaneously implanted glucose sensors for continuous monitoring. doi
  141. (1990). Pharmacokinetics of propofol: influence of fentanyl administration. doi
  142. (2005). Photoiniferter-Based Thermoresponsive Graft Architecture with Albumin Covalently Fixed at Growing Graft Chain End. doi
  143. (1991). Potentiometric enzyme channeling immunosensor for proteins. doi
  144. (2001). Potentiometric ion-selective silicon sensors for the on-line monitoring of blood electrolytes. doi
  145. (2004). Preparation of the molecularly imprinted polymers-based capacitive sensor specific for tegafur and its characterization by electrochemical impedance and piezoelectric quartz crystal microbalance. doi
  146. (1994). Propofol: An update on its clinical use. doi
  147. (2004). Reactions of the nitro radical anion of metronidazole in aqueous and mixed solvent: a cyclic voltammetric study. doi
  148. (2000). Recent developments in electroanalytical chemistry of cephalosporins and cefamycins. doi
  149. (2001). Recognition of ephedrine enantiomers by molecularly imprinted polymers designed using a computational approach. doi
  150. (2004). Reliability of the NeuroTrend sensor system under hyperbaric conditions. doi
  151. (2005). Removal of self-assembled monolayers of alkanethiolates on gold by plasma cleaning. doi
  152. (1988). Review of chemical sensors for physiological measurement. doi
  153. (1996). Selectivity and sensitivity of ultrathin purine-templated overoxidized polypyrrole film electrodes. doi
  154. (1998). Self-Assembled Monolayers on Oxidized Metals. 2. Gold Surface Oxidative Pretreatment, Monolayer Properties, and Depression Formation. doi
  155. (2000). Solid-state ion sensors with a liquid junction-free polymer membranebased reference electrode for blood analysis. doi
  156. (2006). Structural development of a minimally invasive sensor chip for blood glucose monitoring. Analytica Chimica Acta, doi
  157. (2000). Structure and growth of self-assembling monolayers. doi
  158. (1988). Study of ECE reactions with multiple parallel chemical steps using linear scan voltammetry. doi
  159. (2007). Study of the properties of molecularly imprinted polymers by computational and conformational analysis. doi
  160. (1993). Study on the determination of metronidazole in human serum by adsorptive stripping voltammetry. doi
  161. (2004). Study on the recognition of templates and their analogues on molecularly imprinted polymer using computational and conformational analysis approaches. doi
  162. (1998). Study on the voltammetric behavior of metronidazole and its determination at a Co/GC modified electrode. doi
  163. (2002). Synthesis of a novel methacrylic monomer iniferter and its application in surface photografting on crosslinked polymer substrates. doi
  164. (2005). Synthesis, electrochemistry, absorption and electro-polymerization of aniline-ethynyl metalloporphyrins. doi
  165. (1995). The Chemistry of Self-Assembled Long-Chain Alkanethiol Monolayers on Gold. doi
  166. (2007). The role of independently variable grafting density and layer thickness of polymer nanolayers on peptide adsorption and cell adhesion. doi
  167. (1997). Thromboresistant Chemical Sensors Using Combined Nitric Oxide Release/Ion Sensing Polymeric Films. doi
  168. (1998). Towards the rational design of molecularly imprinted polymers. doi
  169. (2005). Towards the rational development of molecularly imprinted polymers: 1H NMR studies on hydrophobicity and ion-pair interactions as driving forces for selectivity. doi
  170. (1993). Ultramicroelectrodes in electrochemistry. doi
  171. (2006). Urea impedimetric biosensor based on polymer degradation onto interdigitated electrodes. doi
  172. (1991). Urea sensor based on an ammonium-ion-sensitive field-effect transistor. doi
  173. (2008). Use of molecularly imprinted solid-phase extraction sorbent for the determination of four 5-nitroimidazoles and three of their metabolites from egg-based samples before tandem LC-ESIMS/MS analysis. doi
  174. (2006). Usefulness of Transcutaneous Carbon Dioxide Pressure Monitoring to Measure Blood Gases in Adults Hospitalized for Respiratory Disease. Archivos de doi
  175. (1995). Utilization of a self-assembled peptide monolayer for an impedimetric immunosensor. Sensors and Actuators, doi
  176. (1999). Voltammetric Behaviour of Metronidazole at Mercury Electrodes. doi
  177. (2005). Voltammetry and determination of metronidazole at a carbon fiber microdisk electrode. doi

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