A digital light-sheet microscope for the analysis of biological processes under almost natural conditions

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Biological imaging has been moving consistently towards experimentation employing increasingly physiologically relevant systems for many years, and new technologies are making such experimental approaches progressively feasible. Such systems, comprising whole model organisms, tissue explants, and three-dimensional (3D) cell cultures, must be imaged in a way that minimises perturbations in order to maintain their physiological integrity as experimental models. Light-induced photodamage and phototoxicity have long been challenging in the field of biological imaging and can have quite a dramatic effect on health and function at all biological levels of organisation. Imaging such large and sensitive specimens thus demands an efficient approach to 3D imaging that lessens exposure of the sample to light.The light-sheet microscope stands for a planar illumination technique that has revolutionised how optical imaging of biological specimens can be performed. Basically, the light-sheet technique is made possible by decoupling the illumination and detection optical pathways, allowing for novel illumination strategies that optimise the light exposure and signal collection efficiency. With light-sheet microscopy, lower illumination intensities can be used in combination with planar illumination to provide improved signal with minimal sample light exposure, enabling imaging with high frame rates and over long periods of time. Fields that have already benefited considerably from such an imaging modality include developmental biology, neurobiology, drug discovery, plant biology, and beyond.However, custom-made light-sheet microscopes can be very difficult to use, usually requiring two or more objectives, non-standard sample preparation protocols, difficult alignment procedures, and a well-planned workflow for dealing with the massive amounts of data generated by such techniques. Our aim is to purchase a commercial light-sheet microscope that is the simplest, most intuitive and most reliable system available that in combination with a straightforward data handling and analysis platform can empower researchers to investigate biological processes under almost natural conditions.