State-of-the-art advanced lightsheet imaging center

Lightsheet microscopes can reveal the 3D anatomy of entire small organs. They image brain tissue down to individual neurons and offer unprecedented maps of nervous system structure and function. 

Revealing 3D anatomy with lightsheet microscopy

Revealing 3d Anatomy With Lightsheet Microscopy 2001 Highres 00300 01 11 12 Still004

ALICe, the Advanced Lightsheet Imaging Center, integrates a series of innovative fluorescence microscopy tools in a single pipeline to image whole organs with custom-built microscopes at high spatial and temporal resolution. 

The multidisciplinary ALICe team unites expertise from physics, cell biology, neuroscience and engineering, and joins forces with research teams around the world to image and draw insights into the central and peripheral nervous systems, innervation of organs including the brain and heart as well as human brain samples. Another focus area is brain and spinal cord organization for researchers working to restore movement after paralysis or to investigate neuronal networks involved in cognition, pleasure and drug addiction.

Unlike traditional microscopy in which specimens are cut in slices with a blade before being viewed on a slide under a microscope, lightsheet microscopes optically slice samples with a sheet of light. This optical sectioning captures slivers of image without damaging the sample. The images are then combined to reconstruct a detailed three-dimensional image of a whole organ or specimen.

The ALICe pipeline

ALICe’s capabilities cover the entire pipeline, from sample preparation to image capture and post-processing.  A variety of samples can be imaged from organoids to whole organs, labelled with genetically encoded fluorescent proteins or immuno-labeled with fluorescent antibodies.

Transparent brain in cuvette is placed in the lightsheet microscope by green gloved hand
A primer on lightsheet microscopy
transparent brain on a microscope slide
1) Sample preparation: Tissue clearing for entire large samples
lightsheet microscope with green light
2) Custom-built lightsheet image acquisition: high spatial and temporal resolution imaging
Vr Sp
3) Image and data analysis including 3D data-set exploration in virtual reality

Expansion microscopy: Visualizing the intricacies of the brain

female scientist looks down microscope
Expansion microscopy deepens our understanding of disease mechanisms to accelerate development of therapies for neurological and psychiatric disorders, like Parkinson’s and Alzheimer’s diseases. Chemical anchors in expanding gel attach to biomolecules, physically expanding the brain sample and allowing as much information as possible to be extracted from the tissue.
Prof. Holmaat, Unige
"Recent advances in microscopy have propelled the neurosciences into the era of connectomics, now allowing us to study single neurons with their synaptic connections in the whole brain."
D Huber
Prof. Daniel Huber, Unige
"The work at ALICe allowed us to reveal the distribution and anatomy of sensory receptors with unprecedented resolution and specificity. I was stunned by the quality of the images."
Marianne Web
Prof Fyhn - UiO
"Never before have we been able to visualise and quantify, in-depth, neuronal populations within the entire brain as we can now."
microscope image of brain in Alice Slider After
microscope image of brain in Alice Slider Before
Whole CNS lightsheet imaging of motor circuit and 3D surface rendering (Asboth et al. 2018). Courtine Lab, EPFL

Available resources

Colm Sped
COLM-SPED light-sheet
A brain sample in the lightsheet microscope
mesoSPIM light-sheet
210420503 Wc Creative 04
Clearscope Light-sheet MBF
Olympus VS120 Automated Slide Scanner
TissueScope - Huron Digital Pathology
Eclipse Ti2-U - Nikon
Confocal Lsm
Confocal LSM880 + Airyscan - Zeiss
Confocal Spinning
Confocal - Spinning Disk CSU-W1

We are always looking for innovative collaborations to advance the techniques, hardware and software related to ALICe.

Director of Neuroimaging: Stéphane Pagès, PhD

Microscopy Facility Manager: Laura Batti, PhD

If you would like to find out more, please contact us: microscopy@wysscenter.ch

microscope image of brain in Alice Slider Before
Whole CNS lightsheet imaging of motor circuit and 3D surface rendering (Asboth et al. 2018). Courtine Lab, EPFL
Lightsheet microscopy image Prof Fyhn Uio
Fluorescent interneurons in a whole brain - Fyhn Lab, University of Oslo
Lightsheet microscopy image of heart Chatelier Lab University Of Poitiers
Heart innervation, Chatelier Lab - University of Poitiers


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