All optical microscopes, regardless of how well they are constructed, exhibit some degree of mechanical drift. This drift corresponds to an uncontrolled relative motion between the sample and the objective lens, which can distort images and reduce spatial resolution.
A basic research‑grade microscope typically shows a drift on the order of 10–50 nm/min, whereas a high‑end research microscope can achieve improved stability, with drift values around 2–10 nm/min. In conventional optical or fluorescence microscopy, which is fundamentally limited to a spatial resolution of approximately 200 nm and usually involves image acquisition times shorter than one second, such levels of drift are entirely negligible.
The situation changes dramatically in super‑resolution microscopy, particularly in techniques based on single‑molecule localization, where nanometer‑scale resolution is sought and total acquisition times extend over several minutes or even tens of minutes. Under these conditions, even small amounts of mechanical drift can severely compromise image quality, making drift correction unavoidable.
In our recent publication in Light: Science & Applications by Florencia Edorna, Lucía Lopez, Andrés Zelcer and co-workers, we present an open-source / open-hardware stabilization system that delivers sub-nanometer precision over hours. We have implemented this system in all our for super-resolution microscopes: STED, RASTMIN, SMLM and p-MINFLUX. We believe this simple and affordable design, together with the modularity and user-friendly open-source software will facilitate that more research groups build and apply ultraprecise single-molecule localization methods like MINFLUX, p-MINFLUX or RASTMIN, making these powerful tools for discovery more accessible and increasing their impact in fields such as materials science, nanophotonics, and chemistry, among others.
Software
GitHub – Stefani-Lab/takyaq: Stabilization module for microscopy and photolithography
Publication
- Florencia Edorna, Florencia D. Choque, Giovanni Ferrari, Luciano A. Masullo, Piotr Zdańkowski, Guillermo P. Acuna, Philip Tinnefeld, Alan M. Szalai, Lucía F. Lopez, Andrés Zelcer & Fernando D. Stefani
“Open-source sub-nanometer stabilization system for super-resolution fluorescence microscopy”
