# Reinforced optical cage systems enable drift-free single-molecule localization microscopy

## TL;DR

A new mechanical design for microscopes prevents sample drift during imaging, enabling high-resolution microscopy without complex corrections.

## Contribution

Reinforced optical cage systems mechanically eliminate drift instead of relying on post-processing techniques.

## Key findings

- The reinforced optical cage system achieved 5 nm lateral drift over 2 hours in widefield fluorescence microscopy.
- The system showed 11-16 nm lateral drift over 15 minutes in single-molecule localization microscopy with no axial drift.
- This approach offers a cost-effective and accessible solution for high-resolution imaging.

## Abstract

Single-molecule localization microscopy achieves nanometer-scale resolution but is compromised by sample drift during image acquisition. Here we present reinforced optical cage systems, a novel approach that eliminates drift at its mechanical source rather than correcting it through complex image post-processing or fiducial markers. Reinforced optical cage systems employ perforated optomechanical components interconnected by tungsten-steel rods in a design proven by mechanical stability simulations. Our bench-top microscope, built with reinforced optical cage systems, demonstrated exceptional three-dimensional stability, with mean cumulative lateral drift of approximately 5 nanometers over 2 h in widefield fluorescence microscopy and 11-16 nanometers over 15 min in single-molecule localization microscopy, free from measurable axial drift. This development allows super-resolution microscopy to reach its full resolution without the necessity of sample drift correction, offering a straightforward, cost-effective, low-maintenance, and readily accessible solution to high-performance super-resolution microscopy. By addressing the fundamental issue of mechanical instability, reinforced optical cage systems enable improved precision instrumentation for the broader scientific and engineering community.

Single-molecule localization microscopy visualizes individual biological molecules but suffers from sample drift that degrades resolution. Hao Qiu and colleagues present reinforced optical cage systems to readily prevent drift for uncompromised resolution