Facile and Compact Electrochemical Paper-Based Analytical Device for Point-of-Care Diagnostic of Dual Carcinogen Oxidative Stress Biomarkers through a Molecularly Imprinted Polymer Coated on Graphene Quantum-Dot Capped Gold.

Nanoscale imprinting significantly increases the specific surface area and recognition capabilities of a molecularly imprinted polymer by improving accessibility to analytes, binding kinetics, and template removal. Herein, we present a novel synthetic route for a dual molecularly imprinted polymer (dual-MIP) of the carcinogen oxidative stress biomarkers 3-nitrotyrosine (3-NT) and 4-nitroquinolin-N-oxide (4-NQO) as coatings on graphene quantum-dot capped gold nanoparticles (GQDs-AuNPs). The dual-MIP was successfully coated on the GQDs-AuNPs core via a (3-mercaptopropyl) trimethoxysilane (MPTMS) linkage and copolymerization with the 3-aminopropyltriethoxysilane (APTMS) functional monomer. In addition, we fabricated a facile and compact three-dimensional electrochemical paper-based analytical device (3D-ePAD) for the simultaneous determination of the dual biomarkers using a GQDs-AuNPs@dual-MIP-modified graphene electrode (GQDs-AuNPs@dual-MIP/SPGE). The developed dual-MIP device provides greatly enhanced electrochemical signal amplification due to the improved electrode-specific surface area, electrocatalytic activity, and the inclusion of large numbers of dual-imprinted sites for 3-NT and 4-NQO detection. Quantitative analysis used square wave voltammetry, with an oxidation current appearing at -0.10 V for 4-NQO and +0.78 V for 3-NT. The dual-MIP sensor revealed excellent linear dynamic ranges of 0.01 to 500 µM for 3-NT and 0.005 to 250 µM for 4-NQO, with detection limits in nanomolar levels for both biomarkers. Furthermore, the dual-MIP sensor for the simultaneous determination of 3-NT and 4-NQO provides high accuracy and precision, with no evidence of interference from urine, serum, or whole blood samples.

Smart sensor for assessment of oxidative/nitrative stress biomarkers using a dual-imprinted electrochemical paper-based analytical device.

We present a novel dual-imprinted electrochemical paper-based analytical device (Di-ePAD) to simultaneously determine 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 3-nitrotyrosine (3-NT) and assess oxidative and nitrative biomarkers in urine and plasma samples. The Di-ePAD was designed with hydrophobic barrier layers formed on filter paper to provide three-dimensional circular reservoirs and assembled electrodes. The molecularly imprinted polymer (MIP) was synthesized using a silica nanosphere decorated with silver nanoparticles (SiO2@AgNPs) as a core covered with dual-analyte imprinted sites on the polymer to recognize selectively and bind the target biomarkers. This strategy drives monodispersity and enhances the conductivity of the resulting MIP core-shell products. 3-NT-MIP and 8-OHdG-MIP were synthesized by successively coating the surface of SiO2@AgNPs with l-Cysteine via the thiol group, then terminating with MIP shells. The dual imprinted core-shell composites possess attractive properties for the target biomarkers' sensing, including catalytic activity, selectivity, and good conductivity. The Di-ePAD revealed excellent linear dynamic ranges of 0.01-500 µM for 3-NT and 0.05-500 µM for 8-OHdG, with detection limits of 0.0027 µM for 3-NT and 0.0138 µM for 8-OHdG. This newly developed method based on the synergistic effects of SiO2@AgNPs combined with promising properties of MIP offers outstanding selectivity, sensitivity, reproducibility, simplicity, and low cost for quantitative analysis of 3-NT and 8-OHdG. The proposed Di-ePAD showed good accuracy and precision when applied to actual samples, including urine and serum samples validated by a conventional HPLC method.

Novel amperometric flow-injection analysis of creatinine using a molecularly-imprinted polymer coated copper oxide nanoparticle-modified carbon-paste-electrode.

We report a novel amperometric flow-injection (FI) analysis of creatinine based on a sensor comprising copper oxide nanoparticles (CuO) coated with a molecularly-imprinted polymer (CuO@MIP) and decorating a carbon-paste electrode (CPE) to form the CuO@MIP/CPE electrode. The CuO@MIP was synthesized by using CuO as the supporting core, creatinine as the template, methacrylic acid (MAA) as monomer, N, N'-(1,2-dihydroxyethylene)bis(acrylamide) (DHEBA) as cross-linker, and 2,2'-azobis (2-methylpropionitrile) (AIBN) as initiator. Morphology and structural characterization reveal that CuO nanoparticle imprinted sites (CuO) synthesized using a precipitation method, exhibits features that are well suited to creatinine detection: high surface area, good analyte diffusion and adsorption characteristics that provide shorter response times, and large numbers of specific cavities for enhanced analyte capacity and sensitivity. Cyclic voltammetric measurements indicate that our sensor provides excellent performance toward electro-oxidation of creatinine. The amperometric FI system was used to quantitatively determine creatinine at the CuO@MIP/CPE sensor, in a phosphate buffer carrier. The imprinted sensor exhibits excellent performance for creatinine oxidation at an applied potential of +0.35 V and flow rate of 0.6 mL.min-1. The as-prepared sensor exhibits a linear dynamic range for creatinine detection from 0.5 to 200 µM (r2 = 0.995) with a limit of detection of 0.083 µM (S/N = 3). The system exhibits satisfactorily good precision (%RSD = 1.94%, n = 30) and selectivity toward creatinine. There is only approximately 20% loss from initial response after 2 weeks when stored at 4 oC. We successfully applied the FI detection system to detect creatinine in human urine samples.