Polarization-insensitive Micro-metalens For Miniaturized Multi-photon Fluorescence Endoscopy Imaging

At present,the incidence of neurological diseases such as depression,epilepsy and Alzheimer's disease is rapidly increasing.The pathological section proves that the reason of those diseases is inseparable from the morphological changes of neuronal cell bodies and synapses.Therefore,the quality of imaging technology is particularly important for the study of pathogenesis.The current mainstream method for high-resolution imaging of nerve tissue in vivo is two-photon microscopic(TPM)imaging.Unfortunately,the imaging depth of TPM is limited to 1000?m below the surface with a resolution of 1?m because of the high scattering and absorption of biological tissues.In order to overcome the imaging depth limit,a two-photon endoscopic fluorescence imaging system has been emerged.However,the structure and function of tissues would be damaged seriously by implanting a large-diameter gradient refractive index(GRIN)lens.A class of metasurface lens has caused a great sensation owing to its ability to completely control the phase,polarization and amplitude of incident light,this ultrathin,size adjustable and high efficiency component is suitable for micro-optical systems.A high resolution imaging of ultra-depth tissue will be obtained under the less tissue damage if combined with two-photon endoscopic imaging and high-NA micro-metalens for biological tissue imaging.In this paper,micro-metalens has been designed for micro-endoscopic imaging system,then the resolution and signal-to-background(SBR)ratio of two-photon and three-photon fluorescence imaging ware calculated based on the focusing results of polarization-insensitive micro-metalens in the mouse cortex model.Firstly,the Richards-Wolf vector diffraction theory of high-NA objective lens and the calculation method of multiphoton fluorescence imaging were introduced in theoretical.Then,a multi-photon fluorescence endoscopic imaging system based on polarization-insensitive micro-metalens was proposed,which can be inserted into the interest region for multiphoton fluorescence imaging with less tissue damage.A single wavelength polarization-insensitive micro-metalens was designed according to the generalized Snell's law of refraction.The focusing results of high-order hollow Gaussian beam(HGB)with linearly polarized and radially polarized show that the ability of designed micro-metalens is basically consistent with that of the conventional high-NA objective.Comparing the light field distributions and the size of linearly polarized and radially polarized focal spots indicate that the distribution of focus for the radially polarized light is more uniform with a small full width at half maximum(FWHM).The focus spot is close to the resolution limit with a FWHM of 0.56?m when the radially polarized 5th-order HGB is focused by the micro-metalens at wavelength 915 nm.In order to meet the requirements of two-photon and three-photon fluorescence imaging,the 915-510 and 1280-510 polarization-insensitive dual-wavelength micro-metalenses ware designed and simulated in theoretically.The focusing results show that the designed dual-wavelength lens can achieve the ability of control two wavelengths simultaneously.Finally,a fine model of mouse cortex with volume of 400×400×850?m~3 is designed according to the mouse cortex parameters in FDTD software,The radially polarized 5th-order HGB was focused by polarization-insensitive dual-wavelength micro-metalens to imaging in the model of cortex,the resolution and SBR of two-photon and three-photon fluorescence imaging ware calculated based on the multi-photon excitation theory.Two-photon fluorescence imaging with a resolution of0.75?m and SBR of 1.9 were obtained at excitation wavelength 915 nm.Three-photon fluorescence imaging with resolution of 0.908?m and SBR of 5.65 was realized at1280 nm.The results of this paper prove that the designed polarization-insensitive micro-metalens can replace the conventional objective lens for imaging.The feasibility of using two materials to design dual-wavelength micro-metalenses based on large-scale spatial division multiplexing is verified.Besides,high resolution and ultradeep imaging of mouse cortex can be achieved by multi-photon fluorescence endoscopy imaging system with dual-wavelength polarization insensitive micro-metalens.Meanwhile,the micro-endoscopic system can be used for tumor detecting and treating if combined with colonoscopy or gastroscopy and high-energy source.