Novel Electrochemical Biosensors Based On Metal-Organic Frameworks Composites

As more and more people pay attention to the sustainable development of society and economy,improving the analysis performance of biosensors in the fields of environmental monitoring,social security,quality control and clinical diagnosis has become one of the most active fields in current analytical research.The electrochemical biosensor,an important branch of biosensors,has widely used in clinical detection,biotechnology,pharmaceutical industry,environmental analysis and other fields.Therefore,a large number of researchers are committed to searching for suitable electrode modification materials for specific biosensors.Metal-organic frameworks(MOFs)are a surprisingly porous class of crystalline materials that are consisted of metal ions(metal clusters)and organic linkers.Due to their intrinsic merits,such as large surface areas,high porosity,and modifiable surface properties,et.al.,MOFs have been widely applied in the fields of gas adsorption and separation,catalysis,energy,biomedical imaging and drug delivery.Also,they are promising electrochemical sensing platforms because of their unique structure.What's more,the integration MOFs and other functional materials can give MOFs various new properties and functions,making it possible to develop novel electrochemical biosensors and enhance their sensing performances.Therefore,a series of modified MOFs-based electrochemical biosensors with excellent performance were fabricated for the detection of biomarkers.The research contents were as follow:1.It is still a very challenging work to develop new and more effective methods for detecting Hepatitis B virus(HBV).In this work,a novel simple electrochemical biosensor with high sensitivity and stability was constructed for detecting HBV DNA by using the electroactive Cu-MOF([Cu_2.5(btca)_1.5(Hbtca)_0.5(?-Cl)_0.5(?-OH)-(H₂O)]·3H₂O)as a signal nanoprobe and multi-site matrix and combing with electroreduced graphene oxide(Er GO)as signal amplification material.Cu-MOF exhibited good affinity to probe DNA through cross-linker reaction,which could further stabilize the DNA probe.The probe DNA density and the hybridization efficiency of this electrochemical DNA biosensor were 9.48×10¹³ molecules cm^-2and 89.9%,respectively.Under optimal conditions,the electrochemical DNA biosensor had an excellent performance toward HBV DNA determination with a wide linear range of 50.0 f M to10.0 n M,and a low limit of detection(LD)of 5.2 f M,which was more sensitive than other reported electrochemical HBV DNA biosensors.Moreover,the deveolped sensor was used to measure HBV DNA in human serum and urine samples with sound results.Moreover,this work also provides some insights for the construction of other electrochemical DNA biosensors.2.Acute myocardial infarction(AMI)is one of the diseases with the highest mortality at present.Simultaneous detection of multiple biomarkers of AMI can greatly improve the accuracy of early diagnosis of AMI.Herein,a novel and simple multianalyte electrochemical immunosensor for simultaneous determination of high-sensitivity C-reactive protein(hs-CRP)and heart fatty acid-binding proteins(h-FABP)were developed based on electroactive substance-modified metal-organic framework materials(Ui O-66-NH₂,denoted as NMOF)as distinguishable signal labels and Au nanoparticles deposited reduced graphene oxide(Au/r GO)as a sensor platform.In view of the distinct difference of redox potentials between copper ions and ferricyanide ions,we loaded these two ions on NMOF to fabricate a multianalyte immunosensor,which greatly simplified the labeling procedure.Meanwhile,Au/r GO could immobilize antibodies and amplify electrochemical signals,making it an ideal material for sensing platforms.This immunosensor could simultaneously detect hs-CRP and h-FABP with LD down to 0.15 and 0.59 pg m L^-1,respectively,which showed better sensitivity than those of reported methods.The developed immunosensor provided a simple and cost-efficient signal transduction platform with high sensitivity and selectivity for the simultaneous detection of multiplex AMI biomarkers.Moreover,the results of clinical serum samples detected by the designed assay had satisfactory correlations with commercially available ELISA,indicating that the designed strategy had a broad prospect in the clinical screening of AMI.3.As a neurotransmitter,dopamine(DA)plays a crucial role in physiological or pathological processes.Therefore,rapid and accurate detection of DA can realize the monitoring and clinical evaluation of some diseases.In this work,a novel ratiometric electrochemical sensor based on Au NPs modified MOF is developed for DA detection with high sensitivity and excellent selectivity.Au NPs could be deposited into the pore of MOF-74(Cu)without additional reductants owing to redox activity of the ligand in MOF-74,which could effectively avoid the agglomeration of Au NPs,thus improving the catalytic activity of Au NPs and the stability of the biosensor.In addition,the metal center(Cu²⁺)of MOF-74 could be served as the inner reference electrochemical signal.The oxidation current intensity(I)of DA at 0.23 V increased with the increasing concentration of DA,while I of MOF-74 at-0.18 V almost unchanged,thus forming a novel ratiometric electrochemical biosensor for the detection of DA.This sensor demonstrated satisfactory biocompatibility with a wide detection range(0.001-100?M)and a low LD(0.12n M),which was successfully used for the detection of DA in human serum and injection,as well as in the secretion of PC12 cell.4.H₂O₂ is a kind of endogenous reactive oxygen in organisms.The level of H₂O₂ is closely related to human health.It is of great clinical significance to develop an effective,rapid,simple and reliable method for the detection of H₂O₂.In this work,the novel colorimetric and electrochemical biosensing based on Cu,N doping carbon materials encapsulated in MIL-101(Cr)(CuNC@MIL-101 composite material)were developed for the detection of H₂O₂ in human serum.MIL-101 with large porosity and good thermal stability could be used as a nano-reactor for wet chemical synthesis of CuNC,which could effectively prevent the agglomeration of active sites in CuNC,resulting significantly improving the catalytic activity to H₂O₂.Considering that CuNC@MIL-101 composite had good mimetic enzyme activity,we established colorimetric(linear range from 10 to 600?M,a LD of 7.8?M)and electrochemical(linear range from 1 to600?M,a LD of 0.89?M)biosensors for the detection of H₂O₂ in human serum.Here,this work developed a new biosynthesis strategy to obtain CuNC@MIL-101 composite material with good peroxidase activity,broadening the application prospects of MOF in biological biosensors and medical fields.