Fluorescence light-sheet microscopy such as Selective Plane Illumination Microscopy (SPIM)  is a powerful tool to image developmental processes in vivo with high-resolution over large tissue volumes . The main advantages of the technology are the minimal phototoxicity due to the confined fluorescence excitation and the fast full-frame image acquisition. Recently, we have shown that even the intact beating zebrafish heart can be reconstructed at 400 frames/s . One key innovation for such applications has been the integration of fast scanners and liquid lenses in our light sheet microscope setups  for almost instantaneous imaging of up to 120 three-dimensional volumes/s. This technology does not require any scanning of the sample anymore; it is essentially contactless and motionless. Without modifying any component of a typical SPIM setup, we also managed to perform a multimodal acquisition that integrates the high-resolution SPIM fluorescence data with optical tomography, purely based on bright-field contrast .
The enormous amounts of data from these instruments (TB/hour) now require a new approach to imaging: we cannot blindly image large samples with uniformly high spatial and temporal resolution. We propose smart microscopy as a solution, in which illumination and detection are adaptively adjusted to obtain meaningful information at any time without any a priori knowledge about the sample . Only the regions in the sample that change over time or exhibit interesting new information will be illuminated and detected. This presentation will give an overview of the latest developments in light sheet microscopy that lead towards a smart and gentle microscope. With the fabrication and computing facilities at the Morgridge Institute we now hope to develop novel, custom and smart light sheet based microscopes.
 Huisken et al., Science, 2004
 Weber et al., Methods Cell Biol., 2014
 Mickoleit et al., Nat. Methods, 2014
 Fahrbach et al., Opt. Express, 2013
 Bassi et al., Development, 2015
 Scherf & Huisken, Nat. Biotech., 2015
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