Design And Preparation Of Host-Guest Fluorescent Encoding Particles Of Encapsulated Lanthanide Complexes With Shielding Structure

With the increasing variety of tumor markers(TM),medical workers and researchers in different countries have realized the importance of developing diagnostic technologies with the advantages of rapid detection,high sensitivity and low detection limit.For the detection of tumor markers,Luminex x MAP(?)technology based on fluorescence encoding microspheres has been applied in medical diagnosis due to its advantages of large sample capacity,high throughput and high sensitivity.Simultaneously,the development of new fluorescent encoding microspheres has become the primary research direction to optimize this technology.Compared with the typical fluorescent encoding dyes(quantum dots and organic fluorescent dyes),Lanthanide complexes(Lnx)have better fluorescence characteristics,including long fluorescence lifetimes and narrow half-peak width.However,due to the lack of good porous carrier materials,the coordination structure of Lnx is damaged and fluorescence quenched in the environment of aqueous phase and physiological medium,which greatly limits the application of Lnx as fluorescent dyes in fluorescent encoding microspheres.Silica particles and polystyrene microspheres are currently used as encoding carrier at the market,and dye molecules easily form aggregates to affect the luminescence performance of fluorescent encoding microspheres.Metal-organic framework(MOF)materials with significant physical properties,structural and functional diversity have attracted great attention in medical diagnostics.In addition,fluorescent dyes achieve efficient loading and independent luminescence without interfering based on the microporous structure of the MOF carrier.In this paper,combined with the advantages of Lnx and MOF materials,the composite fluorescent particles loaded with Lnx that maintain fluorescence stability in the physiological medium environment were successfully prepared through a strategy of constructing a protective shell.Fluorescent encoding particles were synthesized through different coding strategies.The main research contents are as follows:(1)Composite fluorescent particles loaded with Lnx were prepared on the construction of organic-inorganic composite shell.With Lnx(Tbx and Eux),zinc nitrate hexahydrate and 2-methylimidazole as precursors and sodium formate as regulating ligand,Lnx@ZIF-8 particles(size:?3?m)were prepared by the static synthesis method.Lnx@ZIF-8 particles were coated with tetraethyl orthosilicate(TEOS),dopamine hydrochloride(DA)and polyethyleneimine(PEI)to obtain Lnx@ZIF-8@Si O₂-PDA-PEI particles.The results of structure and optical characterization showed that compared with the traditional fluorescent dyes,the fluorescent particles based on Tbx(shell thickness:100 nm)have high quantum yield(85.8%)and long fluorescence lifetime(1.9 ms).Photoluminescence of the fluorescent particles in PBS buffer solution can be maintained for up to eight hours,and it has very strong fluorescence stability.In addition,the single/double-color encoding particles were successfully obtained by adjusting the type and quantity of Lnx in the synthesis process.Although Lnx@ZIF-8@Si O₂-PDA-PEI microparticles can be used as fluorescent coding materials in suspension array detection technology,Lnx@ZIF-8nanoparticles coated organic-inorganic composite shells cannot avoid agglomeration,which further limits the application of host-guest structure fluorescent coding microspheres.(2)Preparation of Lnx-loaded composite particles based on superhydrophobic shell for fluorescence encoding.In this study,Lnx(Tbx and Eux)were encapsulated in the interior of ZIF-8 by in-situ synthesis to obtain Lnx@ZIF-8 nanoparticles with primary host-guest structure.Then,Lnx@ZIF-8@F-ZIF-90 nanoparticles were obtained by forming a ZIF-90 shell layer on the surface of the core particle and performing fluorination modification.The target fluorescent particles(secondary object particles)were obtained by coating the hydrophilic coating(polydopamine,PDA).Through the structure and fluorescence characterization,the object particles based on Tbx with a superhydrophobic shell(thickness:?10 nm)have long fluorescence lifetime(1.8 ms),high quantum yield(19.1%)and remarkable fluorescence stability in the physiological medium.Therefore,PDA-mediated guest particles and amino polystyrene microspheres are encoded through the host-guest structure,and the single/double-color fluorescent encoding microspheres(SEMs/DEMs)are successfully obtained by changing the type and quantity of the guest particles.Subsequently,the application value of fluorescent encoding microspheres as carrier material was verified by alpha-fetoprotein(AFP)test.All the results in this thesis show that single/double-color host-guest structured fluorescently encoding microspheres can be successfully synthesized through a novel construction strategy of Lnx as fluorescent dyes and MOF as carrier materials.In addition,the organic-inorganic composite shell/superhydrophobic shell was constructed to protect the fluorescence of MOF particles loaded with Lnx.Fluorescence encoding microspheres as detection carrier also successfully detected AFP.The research work provides new strategies and materials for the construction of new fluorescent coding microspheres in suspension array detection technology.