Construction And Application Of Neodymium Sensitized NIR â…¡ Luminescence Lifetime Probe

Because of the reduced photon scattering,absorption and tissue autofluorescence,the newly emerging fluorescence imaging technique in the near-infrared second biological window（NIR â…¡,1000-1700 nm）allows a high signal-to-noise ratio and deep penetration depth in tissue.Although NIR â…¡ probes have been widely used in imaging and biosensing,there are still some problems to be resolved.Especially,tissue autofluorescence remains in the spectral range of 1000-1300 nm,resulting in reduced the signal-to-noise ratio.Furthermore,the luminescence intensity is dependent on the concentration of nanoprobes,power density,tissue penetration depth and tissue types,rendering quantitative assessment difficult.In this thesis,we aim to solve these problems through time domain detection and imaging.Benefiting from the characteristics of tunable emission wavelength and long luminescence lifetime of rare earth ions,Nd³⁺-sensitized down-shifting nanoparticles（NPs）are used for this purpose.To optimize the luminescence performance of NPs,the core/shell,the core/shell/shell and the core/multi-shell nanostructure were constructed,in which NIR â…¡ lifetimes were tailored via changing the doping concentration and prolonging energy transfer distance,and their uses for autofluorescence elimination,accurate biosensing and multi-channel encoding were investigated.The main research contents are summarized as follows:Autofluorescence-free and multiplexing in vivo imaging in time domain was realized with Nd³⁺-Yb³⁺core/shell NPs.The impact of doping concentration on the energy transfer efficiency and luminescence lifetime of the NaYF₄:Yb³⁺,Nd³⁺@CaF₂core/shell/shell NPs were investigated via changing the doping concentration of Yb³⁺and Nd³⁺ions.The optimal doping concentrations of Yb³⁺and Nd³⁺in the system were determined to be 10%and 30%,respectively,reaching an optimal NIR emission of 1000 nm.At the same time,activation of Yb³⁺→Nd³⁺energy back-transfer processes was regulated via changing Nd³⁺ion doping concentration,and the energy migration among Yb³⁺-sublattices was changed by changing the Yb³⁺ion concentration.Finally,the luminescence lifetime of Yb³⁺ion at1000 nm was adjustable from 0.1 ms to 1.4 ms.Polyacrylic acid modified NPs with a luminescence lifetime of up to 833μs were applied in vivo,the autofluorescence generated by fur and eyes can be completely eliminated by performing time-gated imaging with a time delay of 1μs.And the demonstration of in vivo animal multiplexed lifetime imaging herein provided enables an accurate and unequivocal distinction between NPs and allows the determination of the different biodistribution pathways followed by NPs administrated via different routes.In vivo thermal sensing was realized with the 1000 nm lifetime of Nd³⁺-Yb³⁺core/shell/shell NPs.We revealed that both Nd³⁺and Yb³⁺concentration play an important role in tuning the thermal sensitivity of luminescence lifetime at 1000 nm of NaYF₄@NaYF₄:Yb³⁺,Nd³⁺@CaF₂core/shell/shell NPs.This is because concentration changes can regulate the temperature-dependent back energy transfer process from Yb³⁺to Nd³⁺ions and the energy migration process between Yb³⁺and Yb³⁺ions.The relative temperature sensitivity can reach as high as 1.4%℃^-1.The luminescence lifetime thermosensitive nanoprobes were shown to be stable against intense laser exposure,independent of nanoprobe concentration,having reliable repeatability,and pH-stability.Importantly,the nanoprobes are able to probe precise temperature at varied tissue depths and allow an accurate thermographic mapping of temperature distribution in nanoparticles-probed area in vivo.Lifetime-encoding in simulated biological tissue was realized with the 1532 nm lifetime of Nd³⁺-Yb³⁺-Er³⁺core/multi-shell NPs.A method was developed to regulate the fluorescence lifetime of Er³⁺ions at 1532 nm.In the NaYF₄:Yb³⁺/Er³⁺@NaYbF₄@NaYF₄@NaYF₄:Nd³⁺core/multi-shell NPs,the shell thickness of NaYF₄layer was adjusted between 0 and 8.5 nm to prolong the energy transfer distance and delay the time of energy transferred to the Er³⁺ions in the core.When setting Er³⁺doping concentration at 40%or 2%,this method resulted in the lifetime of 1532 nm of Er³⁺ions changing from 3 and 9 ms.When the NaYF₄ layer is placed between the NaYbF₄and NaYF₄:Yb³⁺/Er³⁺layer,the Er³⁺lifetime was also prolonged due to the retardment of Yb³⁺-Yb³⁺energy migration process.Finally,combined with the advantages of high resolution and deep penetration of the emission in NIR â…¡b region,optical lifetime-encoded patterns of these 1532 nm NPs were visulalized through scattering media.