Fabrication Of Transition Metal Nanomaterials And Application In Immunosensing

Cancer,fundamentally a complex and highly heterogeneous disease characterized by uncontrolled cellular proliferation and division,remains a prominent and devastating illness responsible for over six million deaths annually worldwide.For years,cancer research has focused on uncovering the molecular differences between healthy and cancerous cells.Early detection and successful treatment of cancer are critical in significantly reducing human mortality rates.Amongst all types of biomedical instruments,immunosensors are considered highly effective diagnostic tools due to their robust durability,compact size,and ease of use.Immunosensors typically involve the conversion process of target analytes encountering biological receptor elements,which may transform biochemical information and enable quantitative analysis of the target analyte by measuring changes in antigen concentration.Transition metal nanomaterials have gained increasing attention in the field of immunosensing due to their high surface area-to-volume ratio,abundant binding sites,high porosity,excellent thermal stability,and rich surface structure features.They can serve as both electrical/optical/thermal signal tags to enhance sensor sensitivity through multiple signal amplification methods,and as catalytic materials to catalyze the dissociation of reactants into active free radicals,thereby improving the emission of luminophores.In this paper,we aim to improve immunosensor sensitivity by using transition metal nanomaterials as signal amplification tags,and construct highly efficient electrochemical/photothermal/electrochemiluminescence biosensors for the sensitive detection of tumor biomarkers.The research in this thesis focuses on the following five areas:1.Template-free preparation of CoS₂@C hollow nanotubes for electrochemical immunosensorEffective treatment of cancer relies on the early detection of tumor markers.In this chapter,CoS₂@C three-dimensional hollow nanotubes are prepared using an efficient template-free method,and the unique structure provide a larger reaction area and better catalytic ability.Furthermore,the covalently bonded horseradish peroxidase（HRP）can further catalyze H₂O₂ reduction and amplify the electrical signal.Carcinoembryonic antigen（CEA）is quantified by immediate current response（i-t）,and the prepared immunosensor has excellent analytical performance under optimized conditions.2.Construction of Fenton electrochemical immunosensor based on Cu₂Mo S₄ photothermal classNanoprobes play an important role in electrochemical immunosensors,and their activity and stability remain controversial topics.In this chapter,a novel nanoprobe is designed and developed and use for the sensitive detection of CEA.First,Cu₂Mo S₄ with peroxidase activity is prepared using Cu₂O as a self-sacrificing template,which can be efficiently mass transferred in a Fenton-like reaction.Interestingly,the Cu²⁺produced by this reaction can be trapped by ethylenediaminetetraacetic acid（EDTA）to stabilize the signal.More importantly,near infrared（NIR）irradiation can significantly increase the efficiency of the Fenton reaction,thus achieving"signal on".The peak current response is increased by 265%within 5 min.3.Temperature sensing platform constructed based on Cu₂O-Cu₃₁S₁₆ photothermal conversion systemCEA is closely associated with the development of cancer,and its quantification is a key step in the early clinical diagnosis of cancer.However,the most commonly used CEA detection methods mainly compare or measure the depth of color of colored substance solution to determine its content,but the accuracy is not high when a second colored substance is present in the solution to be measured.Here,this chapter rationalizes the design of a photothermal probe（Cu₂O@Ca CO₃@HA）in which Ca CO₃ acts as a protective shell（Cu₂O@Ca CO₃）for Cu₂O nanoparticles to prevent Cu₂O oxidation and hyaluronic acid（HA）confers biocompatibility to the material.Cu₂O can be specifically activated by hydrogen sulfide（H₂S）to convert into Cu₃₁S₁₆ nanoparticles and shows remarkable photothermal properties that can be used for bioanalysis by simply recording the temperature signal with a thermal imager.In particular,the presence of redox pairs provides further electrochemical-assisted validation of the temperature identification system,enabling multi-modal analysis.4.Co₃O₄/NiCo₂O₄ catalyst for efficient electrochemiluminescence of luminolLuminol has received a lot of attention from analysts as one of the most efficient and commonly used electrochemiluminescence（ECL）reagents.However,efficient luminol anodic luminescence systems are limited by the generation of reactive oxygen species（ROS）.Usually,ROS are generated by reaction reagents and dissolved oxygen.Unfortunately,the former has the disadvantages of biotoxicity and instability,while the latter usually does not generate sufficient ROS due to its limited solubility in aqueous solutions and low decomposition rate.Therefore,there is an urgent need to develop efficient luminol anode systems.In this chapter,Co₃O₄/NiCo₂O₄ bilayer nanoboxes（DSNBs）heterojunctions with different nuclear compositions were synthesized to promote the formation of superoxide/peroxia-like species by modulating the three-dimensional electronic structure between different metals.An efficient oxygen precipitation reaction（OER）was achieved and directly involved in the luminescence process of luminol,with a 700-fold increase in ECL signal（compared to the same concentration of luminol solution）.This work not only establishes the OER-mediated ECL system,but also deepens the understanding of the relationship between ROS and luminol,and provides a new way to study the luminol-anodic ECL luminescence system.5.Efficient two-electron oxygen reduction reaction of two-dimensional metal-organic skeleton nanosheets for cathodic luminol electrochemiluminescenceThe exploration of electrocatalytic-luminol systems is still in the developmental stage due to the weak ECL phenomenon of cathodic luminol,and it is still a challenge to establish the conformational relationship between electrocatalytic materials and ECL performance.In this chapter,functionalized two-dimensional NiZn MOF nanosheets are synthesized using metal-organic frameworks（MOF）with controlled heat treatment and successfully applied to the two-electron（2e^-）oxygen reduction reaction（ORR）.Interestingly,both intermediates and products of the ORR reaction are found to significantly affect the luminol ECL emission.Notably,the extension of NiM MOF（M=Fe,Co,Zn）to the 2e^-ORR and the achievement of efficient luminol emission are certainly beneficial for the construction of cathodic luminol systems.This work demonstrates the relationship between electrocatalytic materials and luminol ECL performance and broadens the application of ECL reactions.Finally,the proposed sensor is successfully used for the sensitive detection of alpha-fetoprotein（AFP）.