Descripción del proyecto
THE MAIN PROJECT OBJECTIVE IS THE DEVELOPMENT OF A COMMON AND INTEGRAL ELECTROCHEMICAL IMMUNOSENSOR PLATFORM THAT COULD BE EQUALLY USED FOR BIOMEDICAL FUNDAMENTAL RESEARCH (ALSO FOR THE SEARCH AND ASSESSMENT OF NEW BIOMARKERS), POINT OF CARE CLINICAL DIAGNOSE SYSTEMS, NEW THERAPIES DEVELOPMENT AND THERAPEUTIC DRUG MONITORING SYSTEMS FOR PERSONALIZED MEDICINE. IN THIS PROJECT THE PLATFORM WILL BE ADDRESSED TO THE DETECTION AND PROFILE CHARACTERIZATION OF THE NEUROACTIVE TRYPTOPHAN METABOLITES RELATED WITH THE SEROTONIN-MELATONIN AND THE KYNURENINE-QUINOLINIC PATHWAYS THAT ACTUALLY ARE TENTATIVELY RELATED WITH SEVERAL NEURODEGENERATIVE DISEASES SUCH AS ALZHEIMER AND HUNTINGTON DISEASE AND SEVERAL MENTAL (NEUROLOGICAL) DISORDERS SUCH AS THE MAJOR DEPRESSIVE DISORDER, SLEEP DISORDERS OR SCHIZOPHRENIA. THE CHANGES IN THE PROFILE OF THESE NEUROACTIVE SUBSTANCES COULD BE IN THE ORIGIN OF SOME OF THESE DISEASES OR COULD BE ONLY A CONSEQUENCE OF THE NEUROLOGICAL-METABOLIC ALTERATION, BUT, IN ANY CASE, IT WOULD BE A GOOD BIOMARKER FOR SEVERAL NEUROLOGICAL DISEASES THAT ARE RELATED WITH THE POPULATION AGING AND WITH THE MODERN WAY OF LIFE.THE NEW TECHNOLOGICAL APPROACH FOR THIS ELECTROCHEMICAL IMMUNOSENSOR PLATFORM IS BASED ON THE MODIFICATION OF THE SYSTEM CONDUCTANCE THAT IS GENERATED BY THE FORMATION OF THE ANTIGEN-ANTIBODY COMPLEXES AND THE MODIFICATION OF THE LOCAL ELECTRICAL FIELD AND THE ION MOBILITY ON THE SENSOR SURFACE. IMPEDIMETRIC SIGNAL DETECTION DOESNT REQUIRE ANY LABELING AND COULD DETECT WITH HIGH SENSITIVITY THE FORMATION OF THE ANTIGEN-ANTIBODY COMPLEXES.THE CHEMICAL SIGNAL WILL BE RAISED FROM THE MOLECULAR RECOGNITION EVENTS IN THE FORMATION OF ANALYTE-ANTIBODY COMPLEXES. THE CAREFUL SELECTION OF IMMUNIZING HAPTENS AND COMPETITOR STRUCTURES LET TO CONTROL THE RELATIVE SENSITIVITY-SELECTIVITY OF THE IMMUNOASSAYS. THE MIDRANGE DETECTION LEVELS FOR THESE COMPOUNDS MUST BE IN THE SUBMICROMOLAR TO 100 MICROMOLAR RANGE IN PLASMA. THIS MEANS THAT THE RELATIVE SENSITIVITY WILL MOVE ONLY IN THREE ORDERS OF MAGNITUDE FOR THE DIFFERENT TARGET COMPOUNDS. INITIALLY A TOTAL OF 8 TARGET ANALYTES WILL BE DETERMINED FOR PROFILING: TRYPTAMINE, SEROTONIN, MELATONIN, KYNURENINE, 3-HYDROXYKYNURENINE, KYNURENIC ACID, QUINOLINIC ACID AND TRYPTOPHAN.TO DEVELOP AN IMMUNOASSAY TO MEASURE CONCENTRATION OF SMALL MOLECULES IT IS REQUIRED THE PREPARATION OF THE APPROPRIATE IMMUNOGENIC DERIVATIVE BECAUSE THE ANALYTE IT IS NOT IMMUNOGENIC BY ITSELF. IT HAS BEEN DEMONSTRATED THAT THE COMPETITOR NATURE PLAY A CRITICAL ROLE ON THE IMMUNOASSAY PERFORMANCE IN TERMS OF ASSAY SENSITIVITY AND SELECTIVITY. TO OBTAIN A GOOD IMMUNOASSAY FOR QUANTIFICATION OF LOW MOLECULAR WEIGHT COMPOUNDS, THAT ARE DIFFERENT STEPS OF A COMMON METABOLIC PATHWAY, IT IS MANDATORY DEVELOP A SELECTIVE (WITH NO OR MINIMUM CROSS-REACTIVITY AGAINST THE OTHER COMPOUNDS IN THAT PATHWAY) AND HIGHLY SENSITIVE IMMUNOASSAY. TO ACHIEVE THESE TWO GOALS, THE STRATEGY THAT MAKES USE OF THE PROPER TARGET ANALYTE TO LINK IT DIRECTLY TO THE CARRIER MOLECULE IS NOT A GOOD IDEA. THIS SUBPROJECT WILL PREPARE A FULL SET OF NEW HAPTENS FOR THE TARGET COMPOUNDS, THEIR CONJUGATES AND DEVELOP THE REFERENCE IMMUNOASSAY WITH THE NEW REAGENTS. FINALLY WE STUDY THE BASIC IMMOBILIZATION CHEMISTRY ON THE SENSOR SURFACE AND THE PERFORMANCE OF IMPEDIMETRIC TRANSDUCTION WITH 3D-IDS ELECTRODES. RIPTOFANO\NANOESTRUTURAS\MATERIALES BIOHIBRIDOS\IMPEDANCIA\INMONOSENSORES\INMUNOREACTIVOS\KYNURENINA\SEROTONINA