Elaboration of a new sensor based on molecularly imprinted polymers for the detection of molecules in physiological fluids. (Elaboration de polymères à empreinte moléculaire pour la détection optique de molécule dans un fluide physiologique)

This thesis aimed at elaborating an optical sensor to detect molecules in a biological fluid. Two steroids and a xenobiotic were identified as biomarkers released in some body fluids: cyproterone acetate, cortisol and 2,4-dichlorophenoxyacetic acid respectively. On one hand, detection was performed by Molecularly Imprinted Polymers (MIPs). These tailor-made synthetic receptors display numerous qualities that foster their integration in sensors. MIPs were therefore developed against the targeted analytes. Formulation optimization was led thanks to experimental designs. On the other hand, optical transduction was made possible thanks to the structuring of a polymer into a photonic crystal. Opals were manufactured with a new process suitable for large scales and were used to mold MIPs in inverse opals. Thus, submicron structures of the polymer are responsible for the color of the sensor. A change of color is triggered by the recognition of the analyte by the polymer (upon swelling). Polymers studied displayed sufficient swelling observed by spectrophotometry. Finally, the work of this thesis consisted in elaborating polymer formulations and their integration in a sensor so as to detect an analyte with direct, rapid and unobtrusive means.

[1]  K. Mosbach,et al.  Synthesis of substrate‐selective polymers by host‐guest polymerization , 1981 .

[2]  D. Hellhammer,et al.  Self-Reported Depressive Symptoms and Stress Levels in Healthy Young Men: Associations With the Cortisol Response to Awakening , 2003, Psychosomatic medicine.

[3]  F. Navarro-Villoslada,et al.  Molecularly imprinted polymer diffraction grating as label-free optical bio(mimetic)sensor. , 2011, Biosensors & bioelectronics.

[4]  Yan Li,et al.  Direct and label-free detection of cholic acid based on molecularly imprinted photonic hydrogels , 2008 .

[5]  Shengyang Tao,et al.  Imprinted photonic polymers for chiral recognition. , 2006, Angewandte Chemie.

[6]  Karsten Haupt,et al.  Holographic Molecularly Imprinted Polymers for Label‐Free Chemical Sensing , 2013, Advanced materials.

[7]  R. H. Tredgold,et al.  Synthetic opals made by the Langmuir–Blodgett method , 2003 .

[8]  C. Lowe,et al.  Analyte-responsive holograms for (bio)chemical analysis , 2006 .

[9]  K. Sreenivasan On the application of molecularly imprinted poly(HEMA) as a template responsive release system , 1999 .

[10]  Charles F. Zukoski,et al.  Studies of the kinetics of the precipitation of uniform silica particles through the hydrolysis and condensation of silicon alkoxides , 1991 .

[11]  Yogesan Kanagasingam,et al.  Ocular biomarkers for early detection of Alzheimer's disease. , 2010, Journal of Alzheimer's disease : JAD.

[12]  Wonmok Lee,et al.  Dually tunable inverse opal hydrogel colorimetric sensor with fast and reversible color changes , 2012 .

[13]  M. Huestis,et al.  Disposition of cocaine and its metabolites in human sweat after controlled cocaine administration. , 2005, Clinical chemistry.

[14]  A. G. R. Whitehouse The dissolved constituents of human sweat. , 1935 .

[15]  Yanji Wang,et al.  Fast screening of ketamine in biological samples based on molecularly imprinted photonic hydrogels. , 2013, Analytica chimica acta.

[16]  Li‐Ping Yu,et al.  Molecularly imprinted photonic polymer based on β-cyclodextrin for amino acid sensing. , 2013, Talanta.

[17]  E. Yablonovitch,et al.  Inhibited spontaneous emission in solid-state physics and electronics. , 1987, Physical review letters.

[18]  I. Nicholls,et al.  The roles of template complexation and ligand binding conditions on recognition in bupivacaine molecularly imprinted polymers. , 2004, The Analyst.

[19]  S. Habraken,et al.  Surface plasmon resonance-based biosensors: From the development of different SPR structures to novel surface functionalization strategies , 2011 .

[20]  S. Amer,et al.  Salivary glucose concentrations in patients with diabetes mellitus--a minimally invasive technique for monitoring blood glucose levels. , 2001, Pakistan journal of pharmaceutical sciences.

[21]  K. Collins,et al.  Stimulation of adrenal glucocorticoid secretion in man by raising the body temperature , 1969, The Journal of physiology.

[22]  J. Matsui,et al.  2-(Trifluoromethyl)acrylic acid: a novel functional monomer in non-covalent molecular imprinting , 1997 .

[23]  A. Fernandez-Gutiérrez,et al.  Synthesis of a novel polyurethane-based-magnetic imprinted polymer for the selective optical detection of 1-naphthylamine in drinking water. , 2011, Biosensors & bioelectronics.

[24]  B. Sellergren,et al.  Influence of polymer morphology on the ability of imprinted network polymers to resolve enantiomers , 1993 .

[25]  J. Sturm,et al.  On-chip natural assembly of silicon photonic bandgap crystals , 2001, Nature.

[26]  P. Blankestijn,et al.  Urinary excretion of catecholamines and their metabolites in relation to circulating catecholamines. Six-hour infusion of epinephrine and norepinephrine in healthy volunteers. , 1992, Archives of general psychiatry.

[27]  Andrea Ridolfi,et al.  BIOTEX—Biosensing Textiles for Personalised Healthcare Management , 2010, IEEE Transactions on Information Technology in Biomedicine.

[28]  F. Neumann The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research. , 2009, Experimental and clinical endocrinology.

[29]  Guangtao Li,et al.  Label-free colorimetric detection of trace atrazine in aqueous solution by using molecularly imprinted photonic polymers. , 2008, Chemistry.

[30]  N. Kondo,et al.  Changes in the index of sweat ion concentration with increasing sweat during passive heat stress in humans , 2005, European Journal of Applied Physiology.

[31]  K. Nakamoto,et al.  Stretching Frequencies as a Function of Distances in Hydrogen Bonds , 1955 .

[32]  Yu Liu,et al.  Hydrogel photonic sensor for the detection of 3-pyridinecarboxamide. , 2012, Chemistry.

[33]  Combining molecular imprinted nanoparticles with surface plasmon resonance nanosensor for chloramphenicol detection in honey , 2013 .

[34]  J. Stamper,et al.  Sweat-patch test for monitoring pesticide absorption by airblast applicators , 1985, Bulletin of environmental contamination and toxicology.

[35]  Zhixian Gao,et al.  Detection of bisphenol A using an opal photonic crystal sensor , 2012 .

[36]  V. Kuban,et al.  High performance liquid chromatography/ion-trap mass spectrometry for separation and simultaneous determination of ethynylestradiol, gestodene, levonorgestrel, cyproterone acetate and desogestrel. , 2007, Analytica chimica acta.

[37]  Laura Anfossi,et al.  Molecularly imprinted polymers for corticosteroids: analysis of binding selectivity. , 2010, Biosensors & bioelectronics.

[38]  B. Sellergren,et al.  A solid-state and suspended-state magic angle spinning nuclear magnetic resonance spectroscopic investigation of a 9-ethyladenine molecularly imprinted polymer , 2007 .

[39]  K Mosbach,et al.  Assay system for the herbicide 2,4-dichlorophenoxyacetic Acid using a molecularly imprinted polymer as an artificial recognition element. , 1998, Analytical chemistry.

[40]  Nigel P. Johnson,et al.  Photonic crystal heterostructures from self-assembled opals , 2011 .

[41]  W. Y. Chen,et al.  Molecular recognition in imprinted polymers: thermodynamic investigation of analyte binding using microcalorimetry. , 2001, Journal of chromatography. A.

[42]  Lance G. Laing,et al.  Label-Free Assays on the BIND System , 2004, Journal of biomolecular screening.

[43]  Bahruddin Saad,et al.  Molecularly imprinted polymer as sorbent in micro-solid phase extraction of ochratoxin A in coffee, grape juice and urine. , 2012, Talanta.

[44]  N K Ebube,et al.  Preformulation studies and characterization of the physicochemical properties of amorphous polymers using artificial neural networks. , 2000, International journal of pharmaceutics.

[45]  E. Thomas,et al.  Broad-wavelength-range chemically tunable block-copolymer photonic gels. , 2007, Nature materials.

[46]  B. Mizaikoff,et al.  Binding site characteristics of 17beta-estradiol imprinted polymers. , 2007, Biosensors & bioelectronics.

[47]  G. P. Martin,et al.  Temperature sensitive dopamine-imprinted (N,N-methylene-bis-acrylamide cross-linked) polymer and its potential application to the selective extraction of adrenergic drugs from urine. , 2006, Journal of chromatography. A.

[48]  K. Mosbach,et al.  A Biomimetic Sensor Based on a Molecularly Imprinted Polymer as a Recognition Element Combined with Fiber-Optic Detection , 1995 .

[49]  Virapong Prachayasittikul,et al.  Molecularly imprinted polymer thin films on quartz crystal microbalance using a surface bound photo-radical initiator , 2005 .

[50]  Yanji Wang,et al.  Molecularly imprinted photonic hydrogels for fast screening of atropine in biological samples with high sensitivity. , 2013, Forensic science international.

[51]  J. Fréchet,et al.  Monolithic, “Molded”, Porous Materials with High Flow Characteristics for Separations, Catalysis, or Solid-Phase Chemistry: Control of Porous Properties during Polymerization , 1996 .

[52]  Linus Pauling,et al.  "A Theory of the Structure and Process of Formation of Antibodies" (pages 26-32) , 1940 .

[53]  F. Sondheimer,et al.  Steroids. LXXIII.1a The Direct Oppenauer Oxidation of Steroidal Formate Esters. A New Synthesis of 17α-Hydroxyprogesterone1b , 1956 .

[54]  E. Fischer Einfluss der Configuration auf die Wirkung der Enzyme , 1894 .

[55]  G. Gui,et al.  Biomarkers in the diagnosis of primary and recurrent breast cancer. , 2012, Biomarkers in medicine.

[56]  A. Kuwahara,et al.  Fluorescent molecularly imprinted polymer thin films for specific protein detection prepared with dansyl ethylenediamine-conjugated O-acryloyl L-hydroxyproline. , 2013, Biosensors & bioelectronics.

[57]  J. Smyth,et al.  STRESSORS AND MOOD MEASURED ON A MOMENTARY BASIS ARE ASSOCIATED WITH SALIVARY CORTISOL SECRETION , 1998, Psychoneuroendocrinology.

[58]  K Mosbach,et al.  Artificial antibodies to corticosteroids prepared by molecular imprinting. , 1996, Chemistry & biology.

[59]  B. Cunningham,et al.  A plastic colorimetric resonant optical biosensor for multiparallel detection of label-free biochemical interactions , 2002, Proceedings of IEEE Sensors.

[60]  X. Zhao,et al.  From planar defect in opal to planar defect in inverse opal. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[61]  U. Schedler,et al.  Molecularly imprinted polymer membranes for substance-selective solid-phase extraction from water by surface photo-grafting polymerization. , 2001, Journal of chromatography. A.

[62]  S. Ravaine,et al.  The Langmuir–Blodgett technique: A powerful tool to elaborate multilayer colloidal crystals , 2005 .

[63]  Jonathan C. Claussen,et al.  Nanostructuring Platinum Nanoparticles on Multilayered Graphene Petal Nanosheets for Electrochemical Biosensing , 2012 .

[64]  F. Trotta,et al.  Chromatographic characterization of a molecular imprinted polymer binding cortisol. , 2000, Talanta.

[65]  Nicolle S. Tulve,et al.  Review of Pesticide Urinary Biomarker Measurements from Selected US EPA Children’s Observational Exposure Studies , 2011, International journal of environmental research and public health.

[66]  R. Jacobs,et al.  Changes of natural killer cells during acute psychological stress , 1993, Journal of Clinical Immunology.

[67]  Mark E Meyerhoff,et al.  Measurement of tear glucose levels with amperometric glucose biosensor/capillary tube configuration. , 2011, Analytical chemistry.

[68]  T. Anirudhan,et al.  Silylated montmorillonite based molecularly imprinted polymer for the selective binding and controlled release of thiamine hydrochloride , 2013 .

[69]  G. Phillipou,et al.  15-Hydroxycyproterone acetate and cyproterone acetate levels in plasma and urine. , 1985, Journal of Chromatography A.

[70]  R. Walker,et al.  Adrenal status assessed by direct radioimmunoassay of cortisol in whole saliva or parotid saliva. , 1978, Clinical chemistry.

[71]  R. N. Shah,et al.  Characterization of molecularly imprinted polymers with the Langmuir-Freundlich isotherm. , 2001, Analytical chemistry.

[72]  K. Mosbach,et al.  A Simple Method for Spin‐Coating Molecularly Imprinted Polymer Films of Controlled Thickness and Porosity , 2004 .

[73]  Xuesong Li,et al.  Rational design of molecularly imprinted photonic films assisted by chemometrics , 2012 .

[74]  Huairui Guo,et al.  Design of Experiments and Data Analysis , 2012 .

[75]  J. Jensen,et al.  Photonic crystal fiber long-period gratings for biochemical sensing. , 2006, Optics express.

[76]  Feng Liu,et al.  Detection of organophosphorus compounds using a molecularly imprinted photonic crystal. , 2012, Biosensors & bioelectronics.

[77]  Á. Ríos,et al.  Selective extraction and determination of catecholamines in urine samples by using a dopamine magnetic molecularly imprinted polymer and capillary electrophoresis. , 2012, Talanta.

[78]  Jialei Bai,et al.  Molecularly imprinted photonic polymer as an optical sensor to detect chloramphenicol. , 2012, The Analyst.

[79]  Levi A. Gheber,et al.  Reading microdots of a molecularly imprinted polymer by surface-enhanced Raman spectroscopy. , 2010, Biosensors & bioelectronics.

[80]  K. Faid,et al.  Synthesis and characterization of functional methacrylate copolymers and their application in molecular imprinting , 2005 .

[81]  P Job,et al.  FORMATION AND STABILITY OF INORGANIC COMPLEXES IN SOLUTION , 1928 .

[82]  Dermot Diamond,et al.  Wearable technology for bio-chemical analysis of body fluids during exercise , 2008, 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[83]  Noriaki Hara,et al.  SPR sensor chip for detection of small molecules using molecularly imprinted polymer with embedded gold nanoparticles. , 2005, Analytical chemistry.

[84]  M. A. Kobaisi,et al.  The effect of molecular imprinting on the pore size distribution of polymers , 2007 .

[85]  M. C. Horrillo,et al.  Detection of stress through sweat analysis with an electronic nose , 2009, 2009 Spanish Conference on Electron Devices.

[86]  I. Nicholls,et al.  Spectroscopic Evaluation of Molecular Imprinting Polymerization Systems , 1997 .

[87]  T F Gallagher,et al.  Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. , 1971, The Journal of clinical endocrinology and metabolism.

[88]  G. B. West Oxidation of adrenaline in alkaline solution. , 1947, British journal of pharmacology and chemotherapy.

[89]  A. Maître,et al.  Introduction of a planar defect in a molecularly imprinted photonic crystal sensor for the detection of bisphenol A. , 2011, Journal of colloid and interface science.

[90]  P. Jandera,et al.  Molecularly imprinted polymer for solid-phase extraction of ephedrine and analogs from human plasma. , 2009, Journal of separation science.

[91]  A. Rockwood,et al.  Liquid chromatography-tandem mass spectrometry analysis of urinary free cortisol. , 2003, Clinical chemistry.

[92]  Karsten Haupt,et al.  Imprinted polymers-tailor-made mimics of antibodies and receptors. , 2003, Chemical communications.

[93]  Karsten Haupt,et al.  Molecularly Imprinted Polymers and Infrared Evanescent Wave Spectroscopy. A Chemical Sensors Approach , 1999 .

[94]  Chien-Chong Hong,et al.  A disposable microfluidic biochip with on-chip molecularly imprinted biosensors for optical detection of anesthetic propofol. , 2010, Biosensors & bioelectronics.

[95]  K. Haupt,et al.  Toward the use of a molecularly imprinted polymer in doping analysis: selective preconcentration and analysis of testosterone and epitestosterone in human urine. , 2010, Analytical chemistry.

[96]  Chen Shao,et al.  A Tool for Biomarker Discovery in the Urinary Proteome: A Manually Curated Human and Animal Urine Protein Biomarker Database* , 2011, Molecular & Cellular Proteomics.

[97]  Laura Anfossi,et al.  A connection between the binding properties of imprinted and nonimprinted polymers: a change of perspective in molecular imprinting. , 2012, Journal of the American Chemical Society.

[98]  Hua Xiong,et al.  Label-free colorimetric detection of trace cholesterol based on molecularly imprinted photonic hydrogels , 2011 .

[99]  John,et al.  Strong localization of photons in certain disordered dielectric superlattices. , 1987, Physical review letters.

[100]  C. Barrios,et al.  Molecularly imprinted polymer for label-free integrated optical waveguide bio(mimetic)sensors , 2012 .

[101]  M. Trumper Bodily Changes in Pain, Hunger, Fear and Rage: An Account of Recent Researches into the Function of Emotional Excitement , 1930, The Psychological Clinic.

[102]  M. R. Gagné,et al.  Porogen and Cross-Linking Effects on the Surface Area, Pore Volume Distribution, and Morphology of Macroporous Polymers Obtained by Bulk Polymerization§ , 2001 .

[103]  Karsten Haupt,et al.  Molecularly imprinted microgels as enzyme inhibitors. , 2009, Journal of the American Chemical Society.

[104]  Georg von Freymann,et al.  Mesoporous bragg stack color tunable sensors. , 2006, Nano letters.

[105]  B. Sellergren,et al.  Method for synthesis and screening of large groups of molecularly imprinted polymers. , 1999, Analytical chemistry.

[106]  Karsten Haupt,et al.  Writing droplets of molecularly imprinted polymers by nano fountain pen and detecting their molecular interactions by surface-enhanced Raman scattering. , 2009, Analytical chemistry.

[107]  Yan Li,et al.  Ultrasensitive Specific Stimulant Assay Based on Molecularly Imprinted Photonic Hydrogels , 2008 .

[108]  Sergey A. Piletsky,et al.  Rational design of a polymer specific for microcystin-LR using a computational approach. , 2002, Analytical chemistry.

[109]  R. Potts,et al.  Correlation between sweat glucose and blood glucose in subjects with diabetes. , 2012, Diabetes technology & therapeutics.

[110]  Zi-hui Meng,et al.  A covalently imprinted photonic crystal for glucose sensing , 2013 .

[111]  F. Braceland THE STRESS OF LIFE , 1976 .

[112]  Hierarchically Nanostructured Polymer Films Based on Molecularly Imprinted Surface‐Bound Nanofilaments , 2007 .

[113]  Yin-Xia Zhang,et al.  Highly-sensitive and selective colorimetric sensor for amino acids chiral recognition based on molecularly imprinted photonic polymers , 2013 .

[114]  A. Maître,et al.  Inverse opals of molecularly imprinted hydrogels for the detection of bisphenol A and pH sensing. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[115]  I Tothill,et al.  Surface plasmon resonance sensor for domoic acid based on grafted imprinted polymer. , 2004, Biosensors & bioelectronics.

[116]  I. Lamster,et al.  The diagnostic applications of saliva--a review. , 2002, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[117]  A. Molinelli,et al.  Towards the rational development of molecularly imprinted polymers: 1H NMR studies on hydrophobicity and ion-pair interactions as driving forces for selectivity. , 2005, Biosensors & bioelectronics.

[118]  Å. Hansen,et al.  Analytical methods for determining urinary catecholamines in healthy subjects , 2001 .

[119]  F. Borrull,et al.  Synthesis by precipitation polymerisation of molecularly imprinted polymer microspheres for the selective extraction of carbamazepine and oxcarbazepine from human urine. , 2009, Journal of chromatography. A.

[120]  D. N. Rao,et al.  Spectral and morphological changes of 3D polystyrene photonic crystals with the incorporation of alcohols , 2012 .

[121]  H. Al‐Lohedan,et al.  Kinetics of the autoxidation of adrenaline and [copper(II)(adrenaline)]2+ in alkaline aqueous and micellar media , 2013, Transition Metal Chemistry.

[122]  C. Muller,et al.  The use of saliva for assessment of cortisol pulsatile secretion by deconvolution analysis , 2013, Psychoneuroendocrinology.

[123]  Shouzhuo Yao,et al.  Molecular imprinting polymer coated BAW bio-mimic sensor for direct determination of epinephrine , 2000 .

[124]  M. Hümpel,et al.  Transfer of cyproterone acetate to the milk of lactating women. , 1980, Contraception.

[125]  Li‐Ping Yu,et al.  A molecularly imprinted photonic polymer sensor with high selectivity for tetracyclines analysis in food. , 2012, The Analyst.

[126]  R. Vijaya,et al.  Photonic crystal sensors: An overview , 2010 .

[127]  Sae Lynne Schatz,et al.  Measuring the Effectiveness of Stress Prevention Programs in Military Personnel , 2011, HCI.

[128]  Lingxin Chen,et al.  Molecularly imprinted photonic hydrogels as colorimetric sensors for rapid and label-free detection of vanillin. , 2012, Journal of agricultural and food chemistry.

[129]  Jun Kimura,et al.  Development of urine glucose meter based on micro-planer amperometric biosensor and its clinical application for self-monitoring of urine glucose. , 2009, Biosensors & bioelectronics.

[130]  Di Zhang,et al.  Construction of Self‐Reporting Specific Chemical Sensors with High Sensitivity , 2007 .

[131]  N. Sugimoto,et al.  Composite of Au nanoparticles and molecularly imprinted polymer as a sensing material. , 2004, Analytical chemistry.

[132]  R. Aebersold,et al.  Mass spectrometry-based proteomics , 2003, Nature.