New Medical Fluorescent Sensing Technology Based On Functional Gold-silver Nanoclusters

Noble metal nanomaterials,most well known as gold nanoclusters(AuNCs)and silver nanoclusters(AgNCs),have been increasingly applied in various areas due to their some outstanding properties such as ultra-small size,excellent luminescence,and good biocompatibility.Meanwhile,metal organic frameworks(MOFs),with porous structure,large volume-to-surface area,and adjustable pore channels,have been widely applied in the energy storage,separation,catalysis,drug carrier,and sensing detection fields.In the present thesis,three kinds of high-performance fluorescence detection platforms have been established by using gold and silver nanoclusters,in combination with solvent effects,microwell arrays,enzyme catalysis,and especially the functional encapsulation of MOFs materials.The so developed fluorimetric strategies were applied for the detection of some disease biomarkers including iodide ions in urine,microRNA(miRNA),and blood glucose.The contents of the thesis mainly include:(1)A fluorescence analysis was established for the detection of urinary iodine based on alcohol solvent-trigged AgNCs with the enhancement of its fluorescence(Chapter 2).Red fluorescent AgNCs were first prepared in aqueous medium with dihydrolipoic acid as the reducing agent.The influence of those solvents on the fluorescence properties of AgNCs was systematically investigated.It was found that alcohol solvents especially isopropanol could significantly enhance the fluorescence intensity of AgNCs.More importantly,they could trigger the highly specific recognition to iodide ions leading to the fluorescence quenching.A rapid,selective,and sensitive fluorimetric analysis method was thereby developed for probing iodide ions in urine samples based on the solvent effect of isopropanol for AgNCs with enhanced fluorescence and iodide recognition,showing the limit of detection of 7.5 nM.(2)A microwells array-based fluorimetric strategy has been developed for the detection of miRNAs in blood using AgNCs with signal amplification and sensing stability enhanced by MOFs(Chapter 3).Glass slides were first spotted with polyacrylic acid to form hydrophilic microdots and then patterned with hydrophobic hexadecyltrimethoxysilane,followed by etching the microdots to yield the microwells array.Furthermore,DNA capture probes with silver-binding sequences were covalently bound onto the amine-derivatized microwells to hybridize with targeting miRNAs.Exonuclease I-catalytic digestion was then conducted to remove any single-strand DNA probes unhybridized.Eventually,AgNCs were applied to specifically recognize the silver-binding sequences of DNA probes survived,and further coated with MOFs of ZIF-8.Unexpectedly,the red fluorescence of AgNCs probes could be dramatically enhanced due to the "electron-donor effect" of nitrogen-containing ligands of ZIF-8 coatings,together with improved sensing stability.High detection sensitivity and reproducibility could thereby be expected for detecting mi RNAs in blood with the concentrations linearly ranging from 0.25 to 500 pM,with the limit of detection of 5.0 fM.Therefore,the developed microwells array-based fluorimetric strategy should hold great promise for extensive applications for sensing miRNAs for the clinical diagnosis of various cancers and warning of potential cancer metastasis.(3)A new fluorescence analysis method has been developed for blood glucose detection based on the MOFs-encapsulated AuNCs and glucose oxidase(GOD)(Chapter 4).AuNCs with strong red fluorescence were prepared by the biomineralization process,and then covalently combined with GOD to be further encapsulated into mesoporous ZIF-8 matrix,yielding the GOD-AuNCs@ZIF-8 nanocomposites.The obtained nanocomposites were immobilized onto the inner wall of capillary tubes as the fluorescent probes for sensing glucose in blood based on the self-driven sampling and GOD catalysis,in which the catalytic production of hydrogen peroxide would induce the fluorescence quenching of AuNCs.The developed fluorimetric analysis method could allow for the rapid,sensitive,and selective detection of glucose with the limit of detection of 0.30 ?M.