The Application Of Nanocomposite Materials In The Immunosensors For The Detection Of Disease Markers

With the features of easy operating condition, high sensitivity, good selectivity and fast detection speed, electrochemical immunosensors have been widely studied. Recently, nanocomposite materials with the properties of the controllable performance have been gradually applied to the field of electrochemical immunosensors which, gotten a breakthrough.(1) A novel and effective nonenzymatic immunosensor for the sensitive detection of squamous cell carcinoma antigen (SCC-Ag) was described based on triple-layered core-shell Au@Pd@Pt nanoparticles (Au@Pd@Pt NPs). To prepare the immunosensor, primary anti-SCC antibodies (Ab1) were immobilized onto nanoporous gold films (NPGF) of a modified glassy carbon electrode. Au@Pd@Pt NPs possessing strong catalytic activity for the reduction of H2O2 were used as catalytic labels of secondary anti-SCC antibodies (Ab2). Because of the catalytic activities of Au@Pd@Pt NPs and the large surface area of the NPGF, high sensitivity was achieved for the detection of SCC-Ag. The prepared immunosensor showed remarkable results, such as low detection limits (0.6 pg/mL), a wide linear range (0.001～10.0 ng/mL) and high stability and selectivity in the detection of SCC-Ag. Furthermore, the prepared immunosensor exhibited promising properties, which might be useful for real serum sample tests.(2) A simple nonenzymatic immunosensor was developed for sensitive and selective determination of squamous cell carcinoma antigen (SCC-Ag) based on bimetallic gold-silver nanoclusters (AuAg NCs) and reduced graphene oxide-tetraethylene pentamine (rGO-TEPA). rGO-TEPA was used as substrate material to immobilize antibodies, which had the advantages of large surface area and excellent conductivity to enhance the electrochemical response signal. AuAg NCs which was synthetized through simple mortar grinding route was used as catalytic labels of secondary antibodies; meanwhile, AuAg NCs could efficiently enhance the electron transfer. Under the optimal condition, the electrochemical immunoassay exhibited a wide linear range of 0.005～20 ng/mL with a low detection limit of 1.3 pg/mL for SCC-Ag detection. The proposed sensing strategy enriches the electrochemical immunoassays and has a promising application in bioassay analysis.(3) In this paper, a novel, sensitive electrochemical immunosensor for simultaneous determination of sguamous cell carcinoma associated antigen (SCC-Ag) and carcinoembryonic antigen (CEA) for the combined diagnosis of cervical cancer was designed. The amplification strategy for electrochemical immunoassay was based on poly [3-(1,1’-dimethyl-4-piperidine-methylene) thiophene-2,5-diylchloride] (PDPMT-C1) and functionalized mesoporous ferroferric oxide nanoparticles (Fe3O4 NPs). PDPMT-C1 dispersed in chitosan solution with enhanced electrical conductivity and solubility was used as matrices to immobilize the first antibodies. Different redox probes (thionine and ferrocenecarboxylic acid) functionalized Fe3O4 NPs were incubated with two kinds of secondary antibodies to fabricate the labels. Using an electrochemical analysis technique, two well-separated peaks were generated by Th and Fca, making the simultaneous detection of two analytes on the electrode possible. Under optimized conditions, this method showed wide linear ranges of 3 orders of magnitude with the detection limits of 4 pg/mL and 5 pg/mL, respectively. The disposable immunosensor possessed excellent clinical value in cervical cancer diagnostics.(4) A highly sensitive electrochemical immunosensor for the detection of typical bladder cancer biomarker-nuclear matrix protein 22 (NMP22) was developed by using reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) and trimetallic nanoparticles. To construct a high-performance electrochemical immunosensor, rGO-TEPA was used as the ideal material for signal amplification and immobilization of trimetallic nanoparticles. Antibody of NMP22 (Ab) was loaded onto the surface of trimetallic nanoparticles. Trimetallic nanoparticles constructed an effective platform for anchoring larger amounts of antibody and keeping their high stability and bioactivity. Moreover, trimetallic nanoparticles accelerated electron transfer for signal enhancement by the synergistic effect of three different metals. Through an immunoassay protocol, the immunosensor was built successfully, which showed satisfactory performance for the detection of NMP22, such as simple fabrication, low detection limits (0.01 U/mL), wide linear range (from 0.040 to 20 U/mL), short analysis time (2 min), high stability and selectivity. (5) An advanced immunosensor was reported for the sensitive detection of human immunoglobulin (IgG) by using Ag-CeO2 nanocomposite materials. The Ag-CeO2 nanocomposite materials with good electronic conductivity, fast response have good catalytic effect towards H2O2. Therefore, Ag-CeO2 nanocomposite materials were used as the electrode modified materials to improve immunesensor’sensitivity and stability. The immunosensor had an extremely sensitive response to IgG in a linear range of 0.500～100 pg/mL with a detection limit of 0.2 pg/mL. The proposed immunesensor exhibited good reproducibility, long time stability and high specificity, and great potential for application for IgG detection.