Structured detection microscopy

TL;DR

This paper introduces a novel super-resolution microscopy technique called Structured Detection Microscope (SDM) that enhances resolution beyond the diffraction limit without relying on saturation or stochastic emitter switching.

Contribution

The work demonstrates a new spatial mode demultiplexing approach that improves sensitivity to sub-diffraction separations, enabling faster, less phototoxic super-resolution imaging.

Findings

Achieved imaging of DNA nanorulers with 50 nm separation.

Surpassed 40 nm resolution, five times below diffraction limit.

Enabled super-resolution imaging without emitter saturation or stochastic processes.

Abstract

Super-resolution microscopy is crucial for imaging sub-wavelength biological structures. However, most techniques rely on nonlinear saturation or stochastic switching of emitters, limiting imaging speed and increasing phototoxicity. Here, we achieve deep super-resolution without employing saturation or stochastic dynamics, instead using a form of spatial mode demultiplexing. By shaping the point-spread function of the emitted light, our Structured Detection Microscope (SDM) redistributes information away from high shot-noise regions of the image, enhancing sensitivity to sub-diffraction emitter separations in two-dimensions and without mode-sorting optics. Implementing SDM within a high-numerical aperture total internal reflection fluorescence microscope, we demonstrate imaging of fluorophores attached to DNA nanorulers with separations as small as 50 nm at resolutions surpassing 40 nm - fivefold below the diffraction limit. This shows that spatial mode demultiplexing can achieve far sub-wavelength resolution and is applicable to biologically relevant samples. By enabling super-resolution biomolecular imaging without emitter saturation and stochasticity, our work opens the door to better understanding biological structure, function and dynamics.