The Application Of Metal-organic Framework In Solid-phase Microextraction Of Biomarkers In Lung Cancer Exhaled Breath

Lung cancer is one of the most common malignant tumors,and the incidence rate has increased in recent years.Early diagnosis of lung cancer can improve patient survival.Exhaled breath analysis is a method by judging the changes of human exhaled breath components and then judging the physiological metabolic processes and disease states of human beings.It has the advantages of non-invasive,convenient,relatively low-cost,and reproducible.However,the concentration of biomarkers in exhaled breath is low(10^-1212 mol/L-10^-9 mol/L)and the matrix is complex,which makes it difficult to achieve direct measurement.Therefore,it is necessary to adopt an effective pretreatment method to separate,enrich and purify the target before the actual analysis and determination to improve the accuracy and sensitivity of the detection.Solid-phase microextraction?SPME?is a sample preparation method that combines sampling,extraction,concentration and injection into one step.It has the advantages of simple operation,low solvent consumption,and easy combine with other instruments,so it is widely used in environmental,food,clinical,pharmaceutical and biological sample analysis.The adsorbent material coated on the extracted fiber is the core component of SPME,which determines the extraction efficiency of SPME.Therefore,an important development direction of SPME is to develop a fiber coating with high enrichment effect and high selectivity for the target.Metal-organic frameworks?MOFs?are a new type of porous materials with rich structure,adjustable pores,large specific surface area,good thermal stability and good solvent stability.In recent years,MOFs have been prepared into coatings for solid phase microextraction.The field is favored by researchers.In the past,the preparation of MOFs coatings on the surface of stainless steel wire fibers was usually carried out by deposition or physical coating.However,due to high temperature desorption and repeated extraction,the coating will fall off,thereby reducing the service life of the extracted fibers,affecting reproducibility and extraction efficiency.However,its application field does not involve the enrichment detection of biomarkers in exhaled breath from major diseases.Based on the above research,this work aims to explore the preparation method of MOFs coating and expand the application of MOFs coating in the early diagnosis of lung cancer.Its main innovations and research contents are as follows:1.ZIF-7 coating was prepared on the surface of stainless steel wire by sol-gel method.The prepared ZIF-7 fiber coating was used for solid-phase microextraction analysis of five aldehydes in exhaled breath of lung cancer patients.The extraction conditions were optimized.Under the optimal conditions,the method has high enrichment factor,low detection limit and good reproducibility.The extraction mechanism was discussed.The excellent extraction efficiency of the extracted fiber may be due to the combination of the high specific surface area of ZIF-7 and the porosity of the skeleton and the specific selectivity of the ZIF-7 skeleton window.2.ZIF-8,ZIF-8-90 and ZIF-90 ZIFs were synthesized by adjusting the ratio of two organic ligands.The coatings preparated by epoxy resin adhesive method were used for detecting 9 biomarkers in lung cancer exhaled breath?acetone,1-propanol,cyclohexane,toluene,hexanal,ethylbenzene,styrene,octanal,furfural?.The adsorption study showed that the ZIF-90 has a better adsorption than the ZIF-8 and ZIF-8-90,this may caused by the larger pore size.This may also be due to the fact that the presence of imidazole-2-carbaldehyde induces the opening effect of ZIF-90 and improves the adsorption efficiency of ZIF-90 on the target.3.The stainless steel wire was modified by dopamine self-assembly,and the covalently bonded ZIF-90 coating was prepared on the surface of the stainless steel wire with 3-aminopropyltriethoxysilane as the covalent bridge.The chemical bonding method greatly improves the stability and lifespan of the fiber coating.The extraction temperature,extraction time,desorption temperature and desorption time were optimized,and the ZIF-90 coating was successfully applied to the determination of 5 biomarkers in lung cancer exhaled breath.