Preparation Of Functionalized MOFs Based SERS Substrates For The Rapid Detection Of Antibiotics

Antibiotics are widely used in the prevention and treatment of infectious diseases in humans and livestock,due to their good therapeutic effect on bacterial and fungal infections.At the same time,they are widely used as growth promoting agents to reduce production costs in modern animal husbandry.Their large-scale unregulated use will accelerate the generation of bacterial resistance,bringing great potential harm to human health.Therefore,it is crucial to develop rapid antibiotic detection methods to guide the rational use of antibiotics.However,due to the complex sample matrix,low antibiotic concentration and many interfering components,complex sample pretreatment is often required,resulting in a time-consuming and costly detection process relying on traditional detection techniques.Surface-enhanced Raman spectroscopy（SERS）based on the precious metal nanostructure substrate is an ultra sensitive vibration spectroscopy technique with remarkable characteristics such as fingerprint recognition,high resolution,strong anti-interference and non-destructive to samples.Combined with a miniaturized portable Raman spectrometer,it can rapid and sensitively detect trace targets.It has great application potential in environmental monitoring,food safety,biomedicine detection and other fields.In view of this,in this paper,metal-organic frameworks（MOFs）combined with noble metal nanostructures were used to construct functionalized MOFs based SERS substrates to develop rapid detection methods for antibiotic residues in actual samples.The main research content was as follows:1.Preparation of magnetic UiO-66-NH₂ based SERS substrate for rapid detection of enrofloxacin in milkFirstly,magnetic UiO-66-NH₂（Fe₃O₄@UiO-66-NH₂,MMOFs）are prepared by a microwave-assisted method and popcorn-like gold nanoparticles（Au NPs）are prepared by sacrificial template approach and galvanic displacement reaction.Then,Au NPs were uniformly loaded on the surface of MMOFs to construct a composite SERS substrate through electrostatic interaction.Due to the good magnetism of Fe₃O₄,the good adsorption effect of UiO-66-NH₂on enrofloxacin,and the excellent SERS performance of popcorn-like Au NPs,a novel rapid and sensitive detection method for enrofloxacin in milk was successfully constructed combining with a portable Raman spectrometer.The detection linear range was 1.0×10^-11～5.0×10^-6 M,and the detection limit was as low as 1.0×10^-11 M.The whole process from sample pretreatment to the SERS detection result took about 45 min,enabling rapid,sensitive and accurate determination of enrofloxacin in milk samples.2.Preparation of MIL-88B-NH₂ based ratiometric SERS substrate for rapid detection of doxorubicin in human serumFirstly,silver coated gold core-shell nanorods embedded with 4-mercaptobenzoic acid（Au-MBA@Ag NRs）were prepared by seed-mediated growth method and served as internal standard SERS nanoprobes,octahedral MIL-88B-NH₂ were prepared by a microwave-assisted method.Then,internal standard SERS nanoprobes were modified with 0.5%poly（sodium 4-styrene sulfonate）（PSS）and loaded onto the surface of MIL-88B-NH₂ through electrostatic interaction to construct ratiometric SERS substrate.Due to the good adsorption effect of MIL-88B-NH₂on doxorubicin,the excellent Raman enhancement effect and the self-correction ability of internal standard SERS nanoprobes,a ratiometric composite SERS substrate based onMIL-88B-NH₂ was constructed for the rapid detection of doxorubicin in human serum.The composite SERS substrate combined with portable Raman spectrometer showed a good linear relationship（R² were 0.9995 and 0.9977,respectively）for doxorubicin at the concentration of50 nM～10μM and 10μM～100μM,the detection limit was as low as 29.6 nM,and the recovery in human serum was good（99.98-106.35%）.This method is expected to be used for therapeutic drug monitoring to guide the dosage,periodicity and route of drug administration,thereby improving drug efficacy and avoiding or reducing toxic side effects.