Magnified Image Spatial Spectrum (MISS) microscopy for nanometer and millisecond scale label-free imaging

TL;DR

MISS microscopy is a novel label-free imaging technique that enables nanometer-scale resolution and millisecond temporal resolution for dynamic, transparent nanoscale structures, with broad applications in biology and materials science.

Contribution

The paper introduces MISS microscopy, a new interferometric method that provides quantitative phase imaging and high sensitivity for fast, label-free visualization of nanoscale particles and live cell dynamics.

Findings

Achieves 0.95 nm sensitivity at 833 fps

Can detect particles as small as 20 nm in diameter

Successfully measures live neuron membrane dynamics

Abstract

Label-free imaging of rapidly moving, sub-diffraction sized structures has important applications in both biology and material science, as it removes the limitations associated with fluorescence tagging. However, unlabeled nanoscale particles in suspension are difficult to image due to their transparency and fast Brownian motion. Here we describe a novel interferometric imaging technique referred to as Magnified Image Spatial Spectrum (MISS) microscopy, which overcomes these challenges. The MISS microscope provides quantitative phase information and enables dynamic light scattering investigations with an overall optical path length sensitivity of 0.95 nm at 833 frames per second acquisition rate. Using spatiotemporal filtering, we find that the sensitivity can be further pushed down to 0.001-0.01 nm. We demonstrate the instrument's capability through colloidal nanoparticle sizing down to 20 nm diameter and measurements of live neuron membrane dynamics. MISS microscopy is implemented as an upgrade module to an existing microscope, which converts it into a powerful light scattering instrument. Thus, we anticipate that MISS will be adopted broadly for both material and life sciences applications.