Altair-LSFM: An Easy-to-Build Light-Sheet Microscope for Subcellular Imaging
A team from UT Southwestern Medical Center has published Altair-LSFM in eLife: an open-source, sample-scanning light-sheet microscope that brings subcellular resolution to laboratories without specialist optical expertise. The system’s four excitation wavelengths are provided by a fiber-coupled Oxxius MixxWave L4Cc laser combiner.
The challenge
Light-sheet fluorescence microscopy (LSFM) images biological samples quickly and with low photodamage. Open-source platforms such as mesoSPIM or OpenSPIM, however, are built for large specimens and cannot resolve organelles or cytoskeletal structures. Lattice light-sheet microscopy does reach that resolution, but its open-source version requires precise alignment of around 29 optical components in the illumination path and regular expert maintenance, while turnkey commercial systems remain expensive and hard to modify.
The method
The authors optimised the full illumination path in silico, then translated it into a custom-machined baseplate whose dowel pins fix each optical element in place. Only nine elements in the illumination path need alignment. Detection uses a high-NA (1.1) water-dipping objective, and the whole system runs on the lab’s open-source navigate software.
- Excitation is supplied by a fiber-coupled [Oxxius MixxWave L4Cc laser combiner] delivering four wavelengths (405, 488, 561 and 638 nm). Its output is collimated at the entrance of the illumination path and used both to align the system and to characterise the light sheet.
- The same four lines drive multicolour imaging, each matched to one label: nuclei (405 nm), microtubules (488 nm), actin (561 nm) and the Golgi apparatus (638 nm).
The result
After deconvolution, Altair-LSFM reaches about 235 nm lateral and 350 nm axial resolution across a 266 µm field of view, on par with the original open-source lattice light-sheet microscope. The team demonstrates four-colour imaging of fixed mouse embryonic fibroblasts and dual-colour live imaging of migrating cells. The estimated cost of a complete system, optical table and laser source included, is around $150,000, and the full parts list, CAD files and assembly guide are openly available.
Why it matters for researchers
Open-source instruments only succeed if every lab that builds them gets the same performance from the same parts. A single fiber-coupled source that delivers several co-aligned wavelengths removes a whole stage of beam combining and alignment from the build, which fits the philosophy of Altair-LSFM. This is the kind of integration Oxxius L4Cc combiners are designed for.
Source :
- Haug, J., Gałecki, S., Lin, H.-Y., Wang, X. & Dean, K.M. A high-resolution, easy-to-build light-sheet microscope for subcellular imaging.
- eLife 14, RP106910 (2026).
- Read the full article: https://doi.org/10.7554/eLife.106910
- Photo: © 2025, Haug et al.
