Facility
ALICe
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
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.
1) Sample preparation: Tissue clearing for entire large samples
2) Custom-built lightsheet image acquisition: high spatial and temporal resolution imaging
3) Image and data analysis including 3D data-set exploration in virtual reality
Creating elastic brains
To image brain samples, fluorescent tags are used so that structures are visible with a microscope. To help these tags penetrate thick samples, the team is exploring a new method - ELAST (entangled link-augmented stretchable tissue-hydrogel). They embed the sample in an elastic polymer gel that allows it to deform and reshape. Then they stretch the sample over hundreds of cycles while it bathes in a solution of antibodies. The process makes labeling of thick samples more efficient.
Expansion microscopy
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. 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.
![Holtmaat]()
"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]()
"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]()
"Never before have we been able to visualise and quantify, in-depth, neuronal populations within the entire brain as we can now."
Whole CNS lightsheet imaging of motor circuit and 3D surface rendering (Asboth et al. 2018).
Courtine Lab, EPFL
Available resources
COLM-SPED light-sheet
mesoSPIM light-sheet
Clearscope Light-sheet MBF
Olympus VS120 Automated Slide Scanner
TissueScope - Huron Digital Pathology
Eclipse Ti2-U - Nikon
Confocal LSM880 + Airyscan - Zeiss
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
Nikita Vladimorov - University of Zurich
A section of human cerebellum from the Lamylab at the University of Geneva imaged with the Wyss Center’s mesoSPIM lightsheet microscope. The image shows blood vessels labelled with the marker lectin. Blood supplies energy to the brain and is known to be disregulated in some diseases. Imaging brain vasculature with advanced microscopes helps drive research into neurodegenerative diseases and stroke. Credit: Tomàs Jordà - Lamylab, University of Geneva - Human Brain Mapping project
Whole CNS lightsheet imaging of motor circuit and 3D surface rendering (Asboth et al. 2018). Courtine Lab, EPFL
Fluorescent interneurons in a whole brain - Fyhn Lab, University of Oslo
Heart innervation, Chatelier Lab - University of Poitiers
Team
Updates
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23.02.2023New project: Repairing the spinal cord
Gene therapy to boost rehabilitation success following spinal cord injury.
Collaboration -
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15.01.2023New project: STAR - Solutions Through Astrocyte Research
The STAR team is pursuing new strategies, focused on astrocytes, to identify biomarkers and new therapeutic targets to treat neurological and psychiatric disorders.
Wyss Center -
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16.11.2022In conversation with Jules Scholler, PhD, Software Engineer in Bioimaging
Software Engineer in Bioimaging, Jules Scholler, describes what it's like to work at the boundary of biology, optics and computer science. The ‘in conversation’ series features members of the Wyss Center community discussing their work, their collaborations and imagining the future.
Insight
