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Light Sheet Theta Microscopy for High-resolution Quantitative Imaging of Large Biological Systems

Bianca Migliori, Malika S. Datta, Christophe Dupre, Mehmet C. Apak, Shoh Asano, Ruixuan Gao, Edward S. Boyden, Ola Hermanson, Rafael Yuste, Raju Tomer
doi: https://doi.org/10.1101/119289
Bianca Migliori
1Department of Biological Sciences
4Department of Neuroscience, Karolinska Institut, Sweden
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Malika S. Datta
1Department of Biological Sciences
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Christophe Dupre
1Department of Biological Sciences
2NeuroTechnology Center
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Mehmet C. Apak
1Department of Biological Sciences
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Shoh Asano
5MIT Media Lab and McGovern Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, MIT, Cambridge, MA USA
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Ruixuan Gao
5MIT Media Lab and McGovern Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, MIT, Cambridge, MA USA
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Edward S. Boyden
5MIT Media Lab and McGovern Institute, Departments of Biological Engineering and Brain and Cognitive Sciences, MIT, Cambridge, MA USA
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Ola Hermanson
4Department of Neuroscience, Karolinska Institut, Sweden
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Rafael Yuste
1Department of Biological Sciences
2NeuroTechnology Center
3Data Science Institute Columbia University
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Raju Tomer
1Department of Biological Sciences
2NeuroTechnology Center
3Data Science Institute Columbia University
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  • For correspondence: raju.tomer@columbia.edu
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Abstract

Advances in tissue clearing and molecular labelling methods are enabling unprecedented optical access to large intact biological systems. These advances fuel the need for high-speed microscopy approaches to image large samples quantitatively and at high resolution. While Light Sheet Microscopy (LSM), with its high planar imaging speed and low photo-bleaching, can be effective, scaling up to larger imaging volumes has been hindered by the use of orthogonal light-sheet illumination. To address this fundamental limitation, we have developed Light Sheet Theta Microscopy (LSTM), which uniformly illuminates samples from same side as the detection objective, thereby eliminating limits on lateral dimensions without sacrificing imaging resolution, depth and speed. We present detailed characterization of LSTM, and show that this approach achieves rapid high-resolution imaging of large intact samples with superior uniform high-resolution than LSM. LSTM is a significant step in high-resolution quantitative mapping of structure and function of large intact biological systems.

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Posted August 30, 2017.
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Light Sheet Theta Microscopy for High-resolution Quantitative Imaging of Large Biological Systems
Bianca Migliori, Malika S. Datta, Christophe Dupre, Mehmet C. Apak, Shoh Asano, Ruixuan Gao, Edward S. Boyden, Ola Hermanson, Rafael Yuste, Raju Tomer
bioRxiv 119289; doi: https://doi.org/10.1101/119289
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Light Sheet Theta Microscopy for High-resolution Quantitative Imaging of Large Biological Systems
Bianca Migliori, Malika S. Datta, Christophe Dupre, Mehmet C. Apak, Shoh Asano, Ruixuan Gao, Edward S. Boyden, Ola Hermanson, Rafael Yuste, Raju Tomer
bioRxiv 119289; doi: https://doi.org/10.1101/119289

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