Application Of Core-shell Nanomaterial-mediated Signal Amplification Strategies In Biosensors

Cancer is one of the leading causes of human death,and the accurate detection of tumour markers is of great importance in the early diagnosis of cancer.Electrochemical immunosensors are a new class of biosensors constructed by combining the specificity of antigen-antibody recognition with the sensitivity of electrical analysis,and have good prospects for application in clinical diagnosis.As scientific research continues,the development of electrochemical biosensors with better stability and higher sensitivity faces new challenges.In this study,a series of electrochemical immunosensors were constructed for the determination of various tumour markers by combining high performance core-shell nanomaterials with signal amplification techniques such as composite nanomaterials synergistic catalytic amplification,nanoenzyme catalytic amplification,redox cyclic amplification and dual signal ratiometric amplification.The research work is as follows:1.Enzyme-free electrochemical immunosensor based on Au@Si O₂/Cu₂O:In this work,silver nanoparticles/aminated two-dimensional nitrogen carbide nanosheets（Ag/g-C₃N₄）is the modification platform of the electrode;the gold@silica/cuprous oxide nanocomposite（Au@Si O₂/Cu₂O）is used as the signal label,and the chronoamperometry（i-t）is used to monitor the hydrogen peroxide（H₂O₂）Respond to the current value,so as to realize the sensitive measurement of carcinoembryonic antigen（CEA）.The immunosensor has a simple construction process,fast detection speed and good sensitivity.There is a good linear range between 0.01 pg/m L-80 ng/m L,and the detection limit is as low as 0.0038 pg/m L（S/N=3）.2.Electrochemical immunosensor based on nanozyme-induced metallization strategy:In the long incubation process,the shedding of the signal label seriously affects the sensitivity of the electrochemical immunosensor.In this work,egg-yolk structured gold@cerium dioxide（Au@Ce O₂ YSNs）nanoenzymes hydrolyse sodium ascorbyl phosphate（SAP）in the test solution to ascorbic acid（AA）,thereby reducing the silver ions（Ag⁺）in solution to silver monomers（Ag）that aggregate on the electrode surface.The electrical signal of Ag is proportional to the logarithm of the concentration of alpha-fetoprotein（AFP）.The linear range of the immunosensor is 0.1 pg/m L-200 ng/m L,and the detection limit is 0.035 pg/m L（S/N=3）.3.Electrochemical immunosensors based on the electrochemical-chemical-chemical（ECC）cyclic amplification signal strategy:here a ferrocenecarboxylic acid（Ce O₂/Au NPs@Si O₂-Fc A）connected to a cerium dioxide/gold nanoparticle@silica composite is used as the signal probe,while the detection solution contains both the reducing agent hydroquinone（HQ）and tris（2-carboxyethyl）phosphine（TCEP）.First,Fc A is oxidised to Fc A⁺at the electrode,while HQ reduces Fc A⁺to Fc A to trigger a cyclic reaction in the inner ring.Subsequently,TCEP reduces the oxidation product of HQ,para-phenylenediquinone（BQ）,to HQ again,completing the cyclic reaction in the outer ring.This system enables the efficient regeneration of the electroactive substance Fc A,thus ensuring adequate amplification of the electrical signal.Under optimal experimental conditions,the method achieves a linear range of 0.01 pg/m L to 80 ng/m L for the detection of CEA with a detection limit of 0.0037 pg/m L（S/N=3）.4.Research on a ratiometric electrochemical immunosensor triggered by Advanced Oxidation Technique（AOP）:the sensor uses sodium alginate（SA）adsorbed gold nanoparticles/reduced graphene oxide-methylene blue（Au/r GO-MB/SA）as the substrate,cobalt tetroxide@silica functionalized with silver nanoparticles（Co₃O₄-Ag@Si O₂）is used as the signal label.When the detection solution contains persulfate（PMS）,the signal probe Co₃O₄-Ag@Si O₂ will activate PMS to generate SO₄^·-/·OH and other free radicals to degrade MB.Square wave voltammetry（SWV）analysis shows that with the increase of CEA concentration,the oxidation peak current（+0.10 V）of Ag gradually increases,while the oxidation peak current（-0.25 V）of MB gradually decreases.The results show that the dual signal ratio(I=I_Ag/I_MB)has a linear relationship with the logarithm of the CEA concentration in the range of 0.01 pg/m L-40 ng/m L,and the detection limit is as low as 3.42 fg/m L（S/N=3）.