Noble Metal Composite Nanomaterials-based Immunosensor For The Detection Of Tumor Markers

In recent years, with the advantages of high sensitivity, good selectivity, easy design, fast detection and inexpensive prices, electrochemical immunosensors have become hot topic in the field of life science research in electroanalytical chemistry. The application of nanomaterials are mainly used as sensor interface modification materials, biological molecules immobilized substrate and signal labels in electrochemical immunosensor. Noble metal nanomaterials have good biocompatibility, excellent electrical conductivity and high catalytic activity. The composite materials not only retain excellent properties of each component, but also have new features, which can be used for biomarkers material and good electrode-modifying materials, and also have great clinical value in the detection of tumor markers.(1) In this paper, an ultrasensitive immunosensor was designed based on Au@Pd core-shell nanoparticles for the determination of ovarian cancer marker CA125. Au@Pd core-shell nanoparticles have large specific surface area, high electric catalytic activity, good conductivity and biocompatibility, which can not only fix more biological molecules, but also can enhance the electron transfer. And the immunosensor has higher sensitivity. At the same time, Au@Pd nanoparticles were used both as electrode-modifying materials to immobilize the primary antibody (Ab1) of CA125 and as labels of secondary antibody (Ab2), which not only avoid the use of the crosslinking agent, but also reduce the influence of the activity of antibody and simplify the operation procedures. This method has high sensitivity and good specificity, good reproducibility, selectivity and stability, operating simply and quickly. The linear is in the range from 0.002 to 20 U/mL, the detection limit of 0.001 U/mL. The sensor preparation method is simple, quick response, the advantages of high sensitivity may provide potential applications for clinical diagnosis.(2) A novel and sensitive electrochemical immunosensor for the detection of pancreatic cancer biomarker carbohydrate antigen 199 (CA199) was proposed by using Au@CuxOS yolk-shell nanostructures with porous shells as labels for signal amplification. In order to build high-performance electrochemical immunosensor, we adopted a reducing oxide graphene rGO-TEPA and gold nanoparticles to modify the electrodes, which can increase the specific surface area of the electrode in order to the capture of primary antibody (Ab1), and improve the electron transfer rate. Au@CuxOS yolk-shell nanostructures with porous shells as labels, not only has large specific surface area for adsorption more antibodies, and high electrocatalytic activity toward the reduction of hydrogen peroxide (H2O2) as electrochemical signals, amplifying the immunosensor. Under optimal conditions, the immunosensor exhibited a wide linear response to CA199 ranging from 0.001 to 12 U/mL with a low detection limit of 0.0005 U/mL. This strategy can also provides a new platform for other biological molecules in clinical immune analysis.(3) We developed an immunosensor for the detection of cervical cancer biomarker Squmaous cell carcinoma antigen (SCCA) based on bimetallic PtAu hollow spheres nanoparticles. The immunosensor used the nitrogen-doped graphene (N-GS) as electrode-modifying materials to immobilize the primary antibody (Ab1) of SCCA. The preparation for bimetallic PtAu hollow spheres used TiO22 Colloidal Sphere as a Template and marked the antibodies. The N-GS having a large specific surface area can be fixed more biomolecules. Bimetallic PtAu hollow spheres nanomaterial with good electrical conductivity, high electrical catalytic activity and good biocompatibility, can be maintain biological activity of the molecule and ensure that the good response to H2O2, so as to improve the sensitivity of the sensor, the lower detection limit of the sensor. This immunosensor detection range of 0.001～15 ng/mL, the detection limit of 0.5 pg/mL, has good stability, selectivity and reproducibility.(4) In this paper, the sensitive detection of cervical cancer biomarkers was developed using rGO-TEPA as a substrate material and Au@CMK-3-Ab2-redox probe as labels. The rGO-TEPA was not only used as a substrate for the immobilization of the antibodies, but also promoted the electron transfer of the biosensors. Mesoporous carbon CMK-3 was used to immobilize Au nanoparticles, which was further utilized for the adsorption of the redox probe and secondary antibody. Using CEA and SCCA as model analytes, the sensitive detection was based on the peak current change of neutral red and thionine before and after the antigen-antibody reaction. The proposed immunoassay method showed high sensitivity, negligible cross-reactivity, good selectivity and reproducibility, and acceptable stability, providing potential applications in clinical diagnostics.