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).
Subscribe to Journal
Get full journal access for 1 year
only $21.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
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
ACS Chemical Neuroscience (2021)
Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy
Nature Communications (2021)
Sensory and Behavioral Components of Neocortical Signal Flow in Discrimination Tasks with Short-Term Memory
Applied Sciences (2021)