Light-sheet microscopy is an ideal technique for imaging large cleared samples; however, the community is still lacking instruments capable of producing volumetric images of centimeter-sized cleared samples with near-isotropic resolution within minutes. Here, we introduce the mesoscale selective plane-illumination microscopy initiative, an open-hardware project for building and operating a light-sheet microscope that addresses these challenges and is compatible with any type of cleared or expanded sample (www.mesospim.org).
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
BMC Biology Open Access 08 November 2023
Communications Biology Open Access 10 October 2023
Neuroscience Bulletin Open Access 16 September 2023
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Data was deposited to the Image Data Resource (http://idr.openmicroscopy.org) under accession number idr0066.
Richardson, D. S. & Lichtman, J. W. Cell 162, 246–257 (2015).
Ertürk, A. et al. Nat. Protoc. 7, 1983–1995 (2012).
Renier, N. et al. Cell 159, 896–910 (2014).
Pan, C. et al. Nat. Methods 13, 859–867 (2016).
Cai, R. et al. Nat. Neurosci. 22, 317–327 (2018).
Chung, K. et al. Nature 497, 332–337 (2013).
Susaki, E. A. et al. Cell 157, 726–739 (2014).
Murakami, T. C. et al. Nat. Neurosci. 21, 625–637 (2018).
Dodt, H.-U. et al. Nat. Methods 4, 331–336 (2007).
Huisken, J., Swoger, J., Del Bene, F., Wittbrodt, J. & Stelzer, E. H. Science 305, 1007–1009 (2004).
Tomer, R., Ye, L., Hsueh, B. & Deisseroth, K. Nat. Protoc. 9, 1682–1697 (2014).
Keller, P. J., Schmidt, A. D., Wittbrodt, J. & Stelzer, E. H. K. Science 322, 1065–1069 (2008).
Fahrbach, F. O., Simon, P. & Rohrbach, A. Nat. Photon 4, 780–785 (2010).
Dean, K. M., Roudot, P., Welf, E. S., Danuser, G. & Fiolka, R. Biophys. J. 108, 2807–2815 (2015).
Buytaert, J. A. N. & Dirckx, J. J. J. Biomed. Opt. 12, 014039 (2007).
Hörl, D. et al. Nat. Methods https://doi.org/10.1038/s41592-019-0501-0 (2018).
Hildebrand, S., Schueth, A., Herrler, A., Galuske, R. & Roebroeck, A. Sci. Rep. 9, 10880 (2019).
Pitrone, P. G. et al. Nat. Methods 10, 598–599 (2013).
Gualda, E. J. et al. Nat. Methods 10, 599–600 (2013).
Sharpe, J. et al. Science 296, 541–545 (2002).
This work was supported by grants from the Swiss National Science Foundation (grant nos. 31003A-149858, 31003B-170269 to F.H.; no. 31003A_170037 to T.K.; nos. 31003A-153448, 31003A_173125, CRSII3_154453 and NCCR Synapsy no. 51NF40-158776 to A.H.), the European Research Council (ERC Advanced Grant BRAINCOMPATH, project no. 670757 to F.H.), ERC Starting Grants (InterWiring, project no. 679175 to T.K. and MULTICONNECT, project no. 639938 to A.R.), the Dutch science foundation (NWO VIDI Grant, project no. 14637 to A.R.), a PhD fellowship by the Swiss Foundation for Excellence in Biomedical Research (to R.K.), a gift from a private foundation with public interest through the International Foundation for Research in Paraplegia (to A.H. and S.P.), and a Distinguished Scientist Award of the Nomis Foundation (to A.A.). In addition, we would like to thank D. Göckeritz-Dujmovic and S. Bichet for help with sample preparation and M. Wieckhorst for help with custom electronics.
The authors declare no competing interests.
Peer review information Rita Strack was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Figs. 1–14, Supplementary Notes 1–6, Supplementary Tables 1–5
About this article
Cite this article
Voigt, F.F., Kirschenbaum, D., Platonova, E. et al. The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue. Nat Methods 16, 1105–1108 (2019). https://doi.org/10.1038/s41592-019-0554-0
This article is cited by
BMC Biology (2023)
Nature Biotechnology (2023)
Communications Biology (2023)
Efficient 3D light-sheet imaging of very large-scale optically cleared human brain and prostate tissue samples
Communications Biology (2023)
Nature Protocols (2023)