Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue

Nature Methods volume 16, pages 1105–1108 (2019)Cite this article

Subjects

Abstract

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Example demonstrations of the mesoSPIM light-sheet microscope.
Fig. 2: Large-scale dataset acquired with the mesoSPIM.

Data availability

Data was deposited to the Image Data Resource (http://idr.openmicroscopy.org) under accession number idr0066.

Code availability

The mesoSPIM software and documentation are available as Supplementary Software. Updated versions can be found on Github (https://github.com/mesoSPIM). mesoSPIM-control is licensed under the GNU General Public License v.3.0 (GPL v.3).

References

  1. Richardson, D. S. & Lichtman, J. W. Cell 162, 246–257 (2015).

    Article  CAS  Google Scholar 

  2. Ertürk, A. et al. Nat. Protoc. 7, 1983–1995 (2012).

    Article  Google Scholar 

  3. Renier, N. et al. Cell 159, 896–910 (2014).

    Article  CAS  Google Scholar 

  4. Pan, C. et al. Nat. Methods 13, 859–867 (2016).

    Article  CAS  Google Scholar 

  5. Cai, R. et al. Nat. Neurosci. 22, 317–327 (2018).

    Article  Google Scholar 

  6. Chung, K. et al. Nature 497, 332–337 (2013).

    Article  CAS  Google Scholar 

  7. Susaki, E. A. et al. Cell 157, 726–739 (2014).

    Article  CAS  Google Scholar 

  8. Murakami, T. C. et al. Nat. Neurosci. 21, 625–637 (2018).

    Article  CAS  Google Scholar 

  9. Dodt, H.-U. et al. Nat. Methods 4, 331–336 (2007).

    Article  CAS  Google Scholar 

  10. Huisken, J., Swoger, J., Del Bene, F., Wittbrodt, J. & Stelzer, E. H. Science 305, 1007–1009 (2004).

    Article  CAS  Google Scholar 

  11. Tomer, R., Ye, L., Hsueh, B. & Deisseroth, K. Nat. Protoc. 9, 1682–1697 (2014).

    Article  CAS  Google Scholar 

  12. Keller, P. J., Schmidt, A. D., Wittbrodt, J. & Stelzer, E. H. K. Science 322, 1065–1069 (2008).

    Article  CAS  Google Scholar 

  13. Fahrbach, F. O., Simon, P. & Rohrbach, A. Nat. Photon 4, 780–785 (2010).

    Article  CAS  Google Scholar 

  14. Dean, K. M., Roudot, P., Welf, E. S., Danuser, G. & Fiolka, R. Biophys. J. 108, 2807–2815 (2015).

    Article  CAS  Google Scholar 

  15. Buytaert, J. A. N. & Dirckx, J. J. J. Biomed. Opt. 12, 014039 (2007).

    Article  Google Scholar 

  16. Hörl, D. et al. Nat. Methods https://doi.org/10.1038/s41592-019-0501-0 (2018).

    Article  Google Scholar 

  17. Hildebrand, S., Schueth, A., Herrler, A., Galuske, R. & Roebroeck, A. Sci. Rep. 9, 10880 (2019).

    Article  Google Scholar 

  18. Pitrone, P. G. et al. Nat. Methods 10, 598–599 (2013).

    Article  CAS  Google Scholar 

  19. Gualda, E. J. et al. Nat. Methods 10, 599–600 (2013).

    Article  CAS  Google Scholar 

  20. Sharpe, J. et al. Science 296, 541–545 (2002).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

  1. Brain Research Institute, University of Zurich, Zurich, Switzerland

    Fabian F. Voigt, Rahel Kastli, Ladan Egolf, Alexander van der Bourg, Philipp Bethge, Theofanis Karayannis & Fritjof Helmchen

  2. Neuroscience Center Zurich, University of Zurich, ETH Zurich, Zurich, Switzerland

    Fabian F. Voigt, Rahel Kastli, Martina Schaettin, Ladan Egolf, Alexander van der Bourg, Philipp Bethge, Karen Haenraets, Noémie Frézel, Esther T. Stoeckli, Hanns Ulrich Zeilhofer, Theofanis Karayannis & Fritjof Helmchen

  3. University Hospital Zurich, Zurich, Switzerland

    Daniel Kirschenbaum & Adriano Aguzzi

  4. Center for Microscopy and Image Analysis, University of Zurich, Zurich, Switzerland

    Evgenia Platonova & Urs Ziegler

  5. Wyss Center for Bio- and Neuroengineering, Geneva, Switzerland

    Stéphane Pagès & Laura Batti

  6. Department of Basic Neurosciences, Geneva Neuroscience Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Stéphane Pagès, Anthony Holtmaat & Christian Lüscher

  7. Sainsbury Wellcome Centre for Neural Circuits and Behaviour, London, UK

    Robert A. A. Campbell

  8. Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland

    Martina Schaettin & Esther T. Stoeckli

  9. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland

    Karen Haenraets, Noémie Frézel, Nicolas Renier & Hanns Ulrich Zeilhofer

  10. ICM—Brain & Spine Institute, Paris, France

    Thomas Topilko

  11. Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy

    Paola Perin

  12. Hungarian Academy of Sciences Research Centre for Natural Sciences, Budapest, Hungary

    Daniel Hillier

  13. Faculty of Information Technology and Bionics, Pazmany Peter Catholic University, Budapest, Hungary

    Daniel Hillier

  14. Faculty of Psychology & Neuroscience, Maastricht University, Maastricht, Netherlands

    Sven Hildebrand, Anna Schueth & Alard Roebroeck

  15. Friedrich Miescher Institute Basel, Basel, Switzerland

    Botond Roska

  16. Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland

    Botond Roska

  17. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Roberto Pizzala

  18. Clinic of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland

    Christian Lüscher

Authors
  1. Fabian F. Voigt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Kirschenbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evgenia Platonova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stéphane Pagès
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert A. A. Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rahel Kastli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martina Schaettin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ladan Egolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alexander van der Bourg
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Philipp Bethge
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Karen Haenraets
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Noémie Frézel
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Thomas Topilko
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Paola Perin
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Daniel Hillier
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Sven Hildebrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Anna Schueth
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Alard Roebroeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Botond Roska
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Esther T. Stoeckli
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Roberto Pizzala
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Nicolas Renier
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Hanns Ulrich Zeilhofer
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Theofanis Karayannis
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Urs Ziegler
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Laura Batti
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Anthony Holtmaat
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Christian Lüscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Adriano Aguzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Fritjof Helmchen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

F.F.V. and F.H. designed the project. F.F.V designed the microscope, wrote control software and documentation, coordinated the mesoSPIM initiative and analyzed data. F.F.V., E.P. and P.B. imaged samples. D.K., E.P., R.K., M.S., L.E., A.v.d.B., K.H., N.F., T.T., N.R., H.U.Z., T.K., P.P., R.P., D.H., B.R., S.H., A.S. and A.R. prepared samples for imaging. F.F.V., S.P., E.P., D.K., R.A.A.C., F.M., U.Z., L.B. A.H., C.L. and A.A. set up the mesoSPIM instruments. F.F.V. and F.H. wrote the manuscript with input from all coauthors.

Corresponding author

Correspondence to Fabian F. Voigt.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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 information

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41592-019-0554-0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing