Upconversion nanoparticles (UCNPs) is a series of lanthanoid ions doped nanocrystals that are of great interest for biomedical applications, including nanoscale optical sensing and imaging, benefiting from its bright, stable, multicolour emission. Each of the nanoparticles contains thousands of Lanthanide ions, which works as both sensitizers and activators to absorb the near-infrared photons and transfer the energy from sensitizers to activators through nonlinear energy transferring process for an upconverting emission. A few new super-resolution imaging methods have been developed recently based on UCNPs’ unique nonlinear energy transferring process. Most recently, upon these advances, we have found that the thousands of Lanthanide ions provide a strong dielectric resonance effect in a single UCNP. In this work, we will review using the nonlinear response of lanthanoid ions to improve super-resolution nanoscopy. We will also report the ion resonance effect in UCNPs could substantially increase the permittivity and polarizability of nanocrystals, leading to an enhanced optical force on a single 23.3 nm radius UCNP, more than 30 times stronger than the reported value for gold nanoparticles with the same size. The enhanced optical force also provides a way to bypass the optical trapping requirement of “refractive index mismatch”. We further report that the resonance effect could engineer the Rayleigh scattering of UCNPs. These applications suggest a new potential of UCNPs as force probe, scattering probe and fluorescence probe simultaneously for multiplexed imaging.
Organoid, an in vitro model to study cell behaviours in a living organism, holds great potential for human cellular biology study, especially in disease pathology, drug delivery and drug efficacy trials. However, it remains challenging to track subcellular features inside organoid, as organoid are clusters of high-density cells that highly scatters and absorbs both excitation and emission light. Here we report a strategy on nanoscopy that applying “non-diffractive” beam and near-infrared imaging probe to minimize the light scattering and absorption inside scattering bio-tissue. Using a single Bessel-doughnut beam excitation from a 980nm diode laser and detecting at 800nm, we achieved a near-infrared, “non-diffractive” nanoscopy with high resolution under-diffractive limit in water solution. We further demonstrate that this method can image single upconversion nanoparticles inside spheroids, as deep as half-100μm, with resolution of 113nm. This method provides simple solution to inspect inter-and intra-cellular trafficking and drug release of single nanoparticles in 3D biological systems.
Bright and photo-stable luminescent nanoparticles held great potential for bioimaging, long-term molecular tracking. Rare-earth-doped upconversion nanoparticles (UCNPs) have been recently discovered with unique properties for Stimulated Emission Depletion (STED) super-resolution microscopy imaging. However, this system strictly requires optical alignment of concentric excitation and depletion beams, resulting in cost, stability, and complicity of the system. Taking the advantage of intermediate state saturation in UCNPs, emission saturation nanoscopy has been developed as a simplified modality by using a single doughnut excitation beam. In this work, we report that the emission saturation curve of fluorescence probes can modulate the performance of multi-photon emission saturation nanoscopy. With the precise synthesis of UCNPs, we demonstrate the resolution of this new imaging approach can be improved with five parameters, including emission band, activator doping, excitation power, sensitizer doping, core-shell. This approach opens a new strategy to a simple solution for super-resolution imaging and single molecule tracking at low cost, suggesting a large scope for materials science community to improve the performance of emission saturation nanoscopy.
Biology and medicine sample measurement takes an important role in the microscopic optical technology. Optical tweezer has the advantage of accurate capture and non-pollution of the sample. The SPR(surface plasmon resonance) sensor has so many advantages include high sensitivity, fast measurement, less consumption of sample and label-free detection of biological sample that the SPR sensing technique has been used for surface topography, analysis of biochemical and immune, drug screening and environmental monitoring. If they combine, they will play an important role in the biological, chemical and other subjects. The system we propose use the multi-axis cage system, by using the methods of reflection and transmiss ion to improve the space utilization. The SPR system and optical tweezer were builtup and combined in one system. The cage of multi-axis system gives full play to its accuracy, simplicity and flexibility. The size of the system is 20 * 15 * 40 cm3 and thus the sample can be replaced to switch between the optical tweezers system and the SPR system in the small space. It means that we get the refractive index of the sample and control the particle in the same system. In order to control the revolving stage, get the picture and achieve the data stored automatically, we write a LabVIEW procedure. Then according to the data from the back focal plane calculate the refractive index of the sample. By changing the slide we can trap the particle as optical tweezer, which makes us measurement and trap the sample at the same time.
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