Fabrication Of The Novel Chemical Sensors And Their Applications In Monitoring Disease Markers And Metal Ions

With the development of medicine, different disease markers have appeared, such as sialic acid(SA) of cell surface, the glycated hemoglobin(Hb A1c) in the blood and amyloid beta(Aβ) in the cerebrospinal fluid. The concentration change of biomarkers will reflect the severity of the disease. Therefore, highly sensitive and selective assays are essential for physiology, disease diagnostics, drug screening and control.Since the emergence of nanomaterials, many studies have been reported on preparation, characterization and application of nanomaterials. At present, nanomaterials have been widely used in the preparation of photochemical and electrochemical biosensors, due to its good water solubility, non-toxic and absorbability. Colorimetric sensors have been widely used in the environmental monitoring, drug analyses, food testing and clinical diagnostics, because of their merits such as simple design, conveniently operation, fast and cost-effective. At the same time, combined with electrochemical biosensors, the preparation of chemically modified electrodes(CMEs) can improve the sensitivity and selectivity of the detection. So, CMEs also have been widely used for biological molecules.This paper summarizes the research progress of gold nanoparticles-based colorimetric sensors, graphene-electrochemical sensors and the boric acid recognition, and a series of detailed studies are conducted, as summarized below.(1) A novel potentiometric approach was described for probing SA using a poly(anilineboronic acid)/graphene modified glassy carbon(GC) electrode. The proposed electrode was prepared by electrodeposition of reduced graphene oxide(ERGO) at a GC electrode and then coated with a poly(anilineboronic acid)(PABA)film by electropolymerization of its monomer. Principle of SA detection at the PABA/ERGO/GC electrode was ascribed to a reversible and covalent boronic acid-diol binding which was sensitive to the electrochemical potential of the prepared sensor. The graphene layer introduced on the electrode surface was shown to dramatically improve the sensitivity of the sensor response. Under optimum conditions, the change of open circuit potential showed good linear relation with the concentration of SA, with wide linear range of 2 μM~1.38 m M, correlation coefficient of 0.998, and a low detection limit of 0.8 μM(S/N=3). In addition, the proposed sensor exhibited good reproducibility, high stability, good regeneration, and remarkable selectivity. For the analysis of SA in human blood serum, the high accuracy and good recoveries revealed the great potential in the practical applications.(2) A voltammetric sensor for determination of Hb A1 c was developed based on the composite of phenylboronic acid-modified pyrroloquinoline quinine(PBA-PQQ) and graphene. After the electrodeposition of reduced graphene oxide(ERGO) on the GC electrode, PQQ formed multilayer adsorption on the electrode by potential cycling and further was modified with PBA. The binding of boronic acid groups with Hb A1 c by boronic acid-diol complexation could cause the change of the oxidation peak current of PQQ on the electrode, which was utilized for Hb A1 c detection. Under the optimized conditions, the PBA-PQQ/ERGO/GC electrode provided high selectivity and high sensitivity for Hb A1 c detection with a linear range of 9.4~65.8 μg·m L-1, correlation coefficient of 0.998, a low detection limit of 1.25 μg m L-1(S/N=3). Additionally, the fabricated sensor was also successfully applied in the determination of percent Hb A1 c in whole blood of healthy individuals.(3) A simple, rapid colorimetric sensor for Hg2+ based on anti-aggregation of gold nanoparticles(Au NPs) in the presence of 4-mercaptophenylboronic acid(MPBA) was presented. MPBA can bind to the Au NPs via Au-S bonds and induces the aggregation of Au NPs by self-dehydration condensation, resulting in a visible color change of Au NPs from red to blue. In the presence of Hg2+, the thiol group of MPBA combines Hg2+ preferentially and thus MPBA loses the ability of aggregating Au NPs, which is responsible for the color change from blue to red. Results indicated that the absorbance ratio(A520/A690) was linear for the Hg2+ concentration in the range of 0.01~5 μM. The limit of detection of the colorimetric sensor was 8 n M(S/N=3). The colorimetric changes of the sensor were extremely specific for Hg2+ and no obvious color change was observed towards other competitive metal ions. The analysis of Hg2+ in water samples showed a satisfactory result, revealing that the assay might open a new avenue for the Hg2+ determination.(4) A simple method for specific colorimetric sensing of Alzheimer’s disease related Aβ was developed based on the aggregation of gold nanoparticles in the presence of copper ion(Cu2+). Without Cu2+, Aβ was absorbed on gold colloidal surface that must be dominated by an electrostatic interaction, Au NPs were in dispersion status and the solution still remained red. In the presence of Cu2+, Aβ bound to Cu2+, aggregating Au NPs, which was responsible for the color change from red to blue. Results indicated that the absorbance ration(A609/A520) was linear for the Aβ concentration in the range of 10.5~313.5 n M and correlation coefficient of 0.998, The limit of detection of the colorimetric sensor was 0.6 n M(S/N=3). Our newly developed assay was used to detect other Aβ molecules including Aβ fragment, Aβ(1–42), and Aβ aggregates, the colorimetric changes of the sensor were extremely specific for Aβ. This system is simple, rapid and sensitive, and the promising results from practical samples(human serum) indicates the great potential for the routine detection.