Light sheet microscopy in biomedical imaging (360G-Wellcome-208276_Z_17_Z)

We want to purchase a LaVision Ultramicroscope II, the only commercially available light sheet microscope capable of imaging immunofluorescence or endogenous fluorescence in tissues cleared with novel organic solvent-based techniques, including iDISCO (Cell 2014; 159(4); 896-910) and uDISCO (Nature Methods 2016; 13(10): 859-867). The system uses triple sheet optics to create a focused plane of light from a white laser, used in conjunction with appropriate excitation/emission filters. The sample is imaged with specially protected dipping objectives (2x and 20x), which allow rapid 3-dimensional visualisation of multi-colour fluorescence in tissues exceeding 10mm in each dimension, achieving 1-2 micron resolution in all axes. Imaging is conducted using a high-specification workstation, with a separate workstation requested for processing-intensive offline analyses. In view of the large datasets produced, we have applied for 50 terabytes of server storage capacity, managed by IT staff already running the Wellcome Trust funded Astbury cryo-EM facility. We also request support for a half-time grade 5 technician to train new users in the tissue preparation and imaging approaches required to maximise the potential of this equipment. We will use this technological advance to better understand disease mechanisms, test novel therapeutics, and define the potential of 3-dimensional imaging in clinical diagnostics.