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. 

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. 

Revealing 3D anatomy with lightsheet microscopy

3D spatial transcriptomics: Discovering new sub-cellular worlds in 3D brain samples

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

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.

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

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


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