Construction Of Photofunctional Coatings For Bioanalysis

Bioanalysis is a powerful tool for human health management and life science research.Bioanalysis refers to the analysis of biological samples,to acquire information such as the type and concentration of specific bioactive molecules in the samples.Bioanalysis has been widely applied in the quantitative analysis of drugs,metabolites and biomarkers from various samples such as blood,urine,saliva,tear and tissue fluids.Among numerous bioanalysis methods,surface-enhanced Raman scattering(SERS)has attracted much attention as it can quickly profile the“fingerprints”of the sample with high sensitivity.SERS is highly dependent on the utilization of SERS substrates.However,currently SERS demonstrates limitations in the in-situ and real-time bioanalysis,due to the expensive fabrication process of SERS substrates and limited selection of SERS substrate materials.In this thesis,we firstly developed a photo-controllable SERS substrate preparation method based on biocompatible material TiO₂.Then we extended this method to polydopamine(PDA),a coating material with universal adhesive property and abundant functional groups,rendering the fabrication of SERS substrate available on various surfaces and the obtained SERS substrate with secondary modification feasibility.Finally,we applied such a photo-controllable SERS substrate fabrication method to glucose-responsive colloidal crystal microneedle patch,realizing a wearable bioanalysis device for multimode in vivo analysis.Detailed works are listed as follows:(1)Utilizing the photocatalytic property of TiO₂ coating,we demonstrated the photo-controllable fabrication of high-throughput SERS substrates.SERS substrate is the guarantee to obtain highly sensitive SERS signals of a sample.Meanwhile,high-throughput screening is an effective solution to a large sample volume.In this thesis,an Ag-nanoparticles-deposited discontinuous dewetting substrate was fabricated by locally UV irradiating hydrophobic TiO₂coating in AgNO₃ solution.The effects of experimental parameters on Raman enhancement and high-throughput sampling of the obtained SERS substrate were investigated.The sensitivity of the SERS substrate was significantly improved by introducing the photonic crystal structure.After trials,a sensitive SERS substrate capable of spontaneous formation of droplet arrays was obtained and applied to multiple analyses.The high-throughput SERS substrate fabrication method is equipment-independent,versatile,and suitable for various material surfaces,and the high-throughput SERS substrate could be recycled after use.(2)Discovering and leveraging the photo-metallization property of PDA coating,we reported the photo-controllable fabrication of material-independent,secondary-modification-available SERS substrates.In bioanalysis,SERS substrates often need to be constructed on complex interfaces(such as hydrogels,three-dimensional structures),and to be secondarily modified to capture and enrich biomolecules from tested samples.To achieve the goals above,we applied the photo-controllable fabrication method of SERS substates to PDA coated surface.The uniform PDA coating on versatile material interfaces could be easily obtained due to the“general adhesive”property of PDA and mild reaction conditions in solution.We discovered and investigated the photo-metallization phenomenon of PDA coating,therefore realizing photo-controllable fabrication of SERS substrates on various PDA modified surfaces.The abundant functional groups on PDA endow the SERS substrates with the feasibility of other secondary modifications(such as thiol and amine modifications),for the capture and enrichment of biomolecules in a sample.Besides,the photo-removal of the deposited metal on PDA was discovered for the first time.We proposed possible mechanisms for the reversible metallization on PDA and demonstrated its applications in SERS and metal recycle.(3)Leveraging the PDA-based photo-controllable SERS substrates fabrication method and colloidal crystal microneedle patch,a multifunctional bioanalysis device was constructed for glucose colorimetric monitoring and SERS analysis.With optimized glucose-responsive colloidal crystal formulation,the glucose concentration could be translated into naked-eye distinguishable color in an enzyme-free manner.The PDA induced metallization and the micro-nano structure of colloidal crystal rendered the formulated colloidal crystal with significant SERS effect.Through a colloidal crystal coating strategy,the gel-like colloidal crystal was coated on the surface of the tough microneedle,providing a feasible path for minimally invasive in vivo study with colloidal crystal.As demonstrated in a type 1 diabetic mouse model,the interstitial fluid extraction,sensing,and results display procedures were simultaneously achieved,realizing minimally invasive,painless,and enzyme-free bioanalysis.