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

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

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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).

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

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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.

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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
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  22. Nicolas Renier
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  30. Fritjof Helmchen
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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.

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The authors declare no competing interests.

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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.

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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

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