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 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

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

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."

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."

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 — Whole CNS lightsheet imaging of motor circuit and 3D surface rendering (Asboth et al. 2018). Courtine Lab, EPFL

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 light-sheet

A brain sample in the lightsheet microscope

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

mesoSPIM

Christophe Lamy - UNIGE

Mackenzie Mathis - EPFL

Renier Lab - Paris Brain Institute

Michel Paques - Institut de la Vision

Nikita Vladimorov - University of Zurich

Daniel Huber - UNIGE

Valérie Dutoit, UNIGE, HUG

Luc Stoppini - HEPIA

Jérôme Extermann - HEPIA

Dotphoton

Yanik Mehmet Fatih Lab - ETH Zürich

G-LAB UPCOURTINE

3D image of intestinal villi. Villi are controlled by the enteric nervous system (ENS) our gut’s own little brain. The team is using the three-dimensional microscopic imaging of the intestinal wall to better understand the involvement of enteric neurons in gut function and their connection with the brain. Image acquired with Clarity Optimised Lightsheet Microscope. Gut section cleared with iDisco+ protocol. Data are processed with a depth coding algorithm - the color represents the depth of the 3D image.