Nonlinear Spectral Fusion Super-Resolution Fluorescence Microscopy based on Progressively Saturated Upconversion Nanoparticles

TL;DR

This paper introduces a novel super-resolution microscopy technique using nonlinear upconversion nanoparticles combined with deep learning to achieve 33 nm resolution with simplified optical setup.

Contribution

It presents a new computational super-resolution method leveraging nonlinear saturation responses and deep learning for high-quality imaging with a single beam.

Findings

Achieved 33 nm spatial resolution, 1/29th of excitation wavelength.

Enhanced signal-to-noise ratio from 55 dB to 7 dB in Gaussian imaging.

Applicable to any wavelength with simplified optical system.

Abstract

Single-beam scanning microscopy (SBSM) is one of the most robust strategies for commercial optical systems. Although structured illumination combined with Fourier-domain spatial spectrum fusion can enhance SBSM resolution beyond the diffraction limit, a sophisticated detection system is still required to optimize both effective resolution and signal-to-noise ratio.Here, we report that the diverse nonlinear responses of upconversion nanoparticles can unlock a new mode of Computational Progressively Emission Saturated Nanoscopy (CPSN), which employs a single doughnut-shaped excitation beam assisted by deep learning to simplify conventional microscopy. By modulating the excitation power, the smooth transition of the point spread function (PSF) from doughnut-shaped to Gaussian can be achieved, allowing for accessing different spatial frequency components of the sample. Then, in order to enhance time resolution, the doughnut-shaped beam at low power and the saturated Gaussian-like image were predicted by the doughnut-shaped beam at low saturation threshold based on the power dependence curve. Furthermore, a deep recursive residual network (DRRN) is employed to fusion these progressively complementary spatial frequency information into a final super-resolved image that encompasses the full frequency wwinformation. This approach can achieve high-quality super-resolution imaging with a spatial resolution of 33 nm, corresponding to 1/29th of the excitation wavelength, 55 dB of SNR ratio contracted to 7 dB in Gaussian imaging and applicable to any wavelength. The unique combination of nonlinear saturation and deep learning computational reconstruction could open a new avenue for simplifying the optical system and enhancing imaging quality in single-beam super-resolution nanoscopy.