Project

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Automated Magnetic Collection of Ultrathin Sections for High-Throughput Microscopy

Applicant Templier Thomas
Number 173825
Funding scheme Bridge - Proof of Concept
Research institution
Institution of higher education EPF Lausanne - EPFL
Main discipline Neurophysiology and Brain Research
Start/End 01.02.2018 - 30.11.2019
Approved amount 176'754.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Other disciplines of Engineering Sciences

Keywords (7)

Connectomics; Automation; Microscopy; High Throughput; Neuroscience; Ultrathin sectioning; Electron microscopy

Lay Summary (French)

Lead
Une branche de l'étude des tissus biologiques requiert la découpe de ces derniers en très fines tranches. En recherche comme en industrie, ce procédé de découpe est lent, peu fiable et requiert une grande expertise manuelle. Pour tirer toute l'information possible de tissus complexes tels que le cerveau ou une tumeur, j'ai développé et m'apprête à commercialiser durant ce projet une technique de collection de très fines tranches qui permettra d'analyser ces tissus biologiques avec de hauts rendements et à haute résolution avec de la microscopie.
Lay summary
Les neurones de personnes autistes sont-ils branchés différemment ? Quel effet sur les connexions synaptiques du cerveau une drogue contre Alzheimer a-t-elle ? Quelle est la répartition spatiale d'agents pathogènes dans une tumeur ?

Pour répondre à ces questions, des centaines de laboratoires industriels et de recherche tranchent des tissus biologiques en sections ultrafines (quelques dizaines de nanomètres d'épaisseur) pour les analyser volumétriquement avec de la microscopie à haut rendement et haute résolution telle que la microscopie électronique multifaisceau. Les procédés de découpe actuels sont fastidieux, chers et requièrent une expérience considérable.

Pour pallier ce manque j'ai développé une technique de collection automatique de centaines de sections ultrafines sur des substrats tels que des plaquettes de silicium pour de la microscopie à haute résolution. Pendant le project Bridge Proof of Concept differentes voies de commercialisation de la technologie ont ete etudiees. Nous avons cree une entreprise afin de vendre des machines qui permettent aux laboratoires d'utiliser eux-memes la technologie.
Direct link to Lay Summary Last update: 16.01.2020

Responsible applicant and co-applicants

Employees

Publications

Publication
MagC, magnetic collection of ultrathin sections for volumetric correlative light and electron microscopy
Templier Thomas (2019), MagC, magnetic collection of ultrathin sections for volumetric correlative light and electron microscopy, in eLife, 8, 1.

Datasets

MagC - Datasets 1 and 2

Author Templier, Thomas
Publication date 11.07.2019
Persistent Identifier (PID) 10.7554/eLife.45696
Repository Neurodata
Abstract
The non-destructive collection of ultrathin sections onto silicon wafers for post-embedding staining and volumetric correlative light and electron microscopy traditionally requires exquisite manual skills and is tedious and unreliable. In MagC introduced here, sample blocks are augmented with a magnetic resin enabling remote actuation and collection of hundreds of sections on wafer. MagC allowed the correlative visualization of neuroanatomical tracers within their ultrastructural volumetric electron microscopy context.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Institute seminar - HHMI Janelia Research Campus Individual talk Combining magnetic collection (MagC) of ultrathin sections with broad ion beam (BIB) milling for volumetric correlative light and electron microscopy 24.10.2019 Ashburn, United States of America Templier Thomas;
Interdisciplinary Symposium on 3D microscopy Talk given at a conference Combining Magnetic Collection (MagC) of ultrathin sections with wafer-wide Broad Ion Beam (BIB) milling for volumetric correlative light and electron microscopy 04.10.2019 Engelberg, Switzerland Templier Thomas;
Electron Microscopy Facility Course 2019 Talk given at a conference Magnetic collection (MagC) and Broad Ion Beam (BIB) milling of ultrathin sections on silicon wafers for biological electron microscopy 02.05.2019 Lausanne, Switzerland Templier Thomas;
EPFL CIME Day 2019 Talk given at a conference Magnetic collection (MagC) and Broad Ion Beam (BIB) milling of ultrathin sections on silicon wafers for biological electron microscopy 18.02.2019 Lausanne, Switzerland Templier Thomas;


Use-inspired outputs


Start-ups

Name Year
Collectome 2019

Abstract

Are neurons miswired in autistic brains? How are the pathogenic agents of a developing tumor spatially arranged? To answer such questions hundreds of academic and industrial laboratories scrutinize ultrathin (a few dozens of nanometers thick) tissue sections at high resolution for volumetric analysis. Current methods for the collection of ultrathin sections are semi-manual, expensive, cumbersome to use, slow and inflexible. I have developed a technology (PCT-patent-pending) that allows the automated and fast collection of consecutive ultrathin sections onto flat, conductive substrates with an unprecedentedly high packing density, all of which ideally supports sample handling, chemical treatment, and provides for unparalleled speed, quality, and flexibility of imaging in electron microscopy (EM), fluorescent light microscopy (LM) and next-generation microscopy (multi-beam EM, super-resolution fluorescent LM) with full CLEM compatibility. My technology will enable customers to handle routinely orders of magnitude more sections than previously possible and to perform truly high-throughput experiments. To realize the potential of my technology, a company has been created to sell devices enabling the technology.
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