2026/03/23 by Safe Khan, Jonas Albers, Artem Vorobyev +13 · 1 voice
Biochemistry, Genetics and Molecular Biology · Physics and Astronomy · #Advanced Electron Microscopy Techniques and Applications #Advanced X-ray Imaging Techniques #Crystallography and Radiation Phenomena
paper · doi:10.1107/s1600577526001402
openalex publication_date 2026/03/23 · openalex created_date 2026/03/24 · openalex updated_date 2026/08/01
X-ray phase-contrast tomography can efficiently image brain tissue at subcellular resolution. However, current sample preparation methods are not optimized to exploit the full potential of X-ray contrast mechanisms. Here we propose to replace interstitial material by air to enhance X-ray phase contrast of the ultrastructural features. Critical point drying (CPD) of heavy-metal-stained mouse brain tissue produced samples with preserved ultrastructure, a nanofoam-like material that remains compatible with follow-up conventional resin embedding. Using two synchrotron-based setups, namely, a high-throughput microtomography beamline and a nanoscale holographic tomography beamline, we found that CPD samples consistently showed 2–4× stronger phase-shift signal than samples embedded in resin. CPD offers a versatile route for preparing tissue for subcellular and ultrastructural-resolution X-ray imaging. It retains structural detail while improving signal, and is compatible with follow-up protocols involving femtosecond laser milling or electron microscopy, paving the path for biological tissue imaging beyond the mm 3 scale.