M4IMaastricht MultiModal Molecular Imaging institute

Contact details:

Prof. Dr Ron Heeren
Universiteitssingel 50, 6229ER Maastricht
+31 43-3881492

M4I is a unique facility that allows high-resolution molecular imaging, centered around two major imaging techniques, i.e. Nanoscopy and Imaging Mass Spectrometry. The core of the nanoscopy lab is a set of cryo-light and cryo-electron microscopes that allows imaging of 3D-structures at nanometer resolution by means of electron tomography and allows to study cellular processes close to the in vivo situation. The Imaging Mass Spectrometry division devises, implements and applies technologies that allow high-resolution detection of biomolecules as proteins, lipids and drugs directly in cells and tissues. The facility hosts state-of-the-art mass spectrometers, including several systems for high-throughput molecular histology.

The core of the division Nanoscopy is a workflow for electron tomography. The workflow starts on
the CorrSight with live cell imaging of cell cultures on an EM carrier which can be used throughout
the complete workflow in order to prevent loss of orientation and sample contamination or
destruction. The CorrSight is a unique and dedicated light microscope for correlative microscopy
including a fully integrated spinning disk system (Andromeda) with a patented optical design for 3D
Live Cell imaging. Once a specific event or location has been identified by means of light microscopy
and preserved by means of cryo-fixation, the vitrified sample can be re-examined on the CorrSight
in a dedicated cryo-stage in order to precisely determine the position of interest. After transferring
the sample to the Scios DualBeam, the identified region will thinned down to the appropriate
thickness of about 200-300 nm without artifacts using the focused ion beam. The correlative MAPS
software allows the transfer of all data from the CorrSight, such as positions of interest and recorded
images, to the Scios DualBeam in order to know exactly where to prepare the lamella for subsequent high resolution cryo-TEM imaging.
After thinning the samples to the proper thickness, the grids will be loaded in the autoloader on the
Tecnai Arctica for high resolution cryo-tomography. The Tecnai Arctica is equipped with FEI’s high
sensitive Falcon direct electron detector for low-dose imaging, FEI tomography software for
automated low-dose tomography and EPU software for automated single particle data acquisition.
The division Imaging Mass Spectrometry at M4I offers a unique infrastucture for state-of-the-art
mass spectrometry-based atomic and molecular imaging. Complementary instruments allow the
determination of the spatial distribution of biomolecules from cellular and tissue surfaces with spatial
resolutions ranging from 200 nm to 200 μm. The range of desorption and ionization methods
available allow the analysis of a variety of complex surfaces from single cells to larger histological
tissue sections. In addition various proteomics and metabolomic technologies are used to investigate
the structure-function relation of biomolecules in their native environment. The infrastructure
encompasses a variety of different mass spectrometers that offer different molecular imaging
modalities. 9.4T and 7T FTICR systems with different ionization technologies offer high molecular
resolution imaging and identification. High throughput tissue typing can be achieved by several
systems, including a Bruker Rapiflex MALDI Tissue typer. TRIFT II based mass microscopes are
employed for submicron imaging. A NanoTOF SIMS system equipped with a variety of ion guns is
employed for high resolution molecular 3D imaging and depth profiling and tandem mass
spectrometry for structural identificationThe institute has recently invested in 3 Xevo G2S systems
as part of an intraoperative diagnostic system for imaging and iKnife applications. High resolution,
high throughput imaging proteomics is achieved with Orbitrap Elite and MALDI enabled q-Exactive
HF Orbitrap systems. The infrastructure is equipped with several HPLC systems, and robots, image
processing and analysis tools, including tissue classification and correlation software and protein
data basing tools and a large scale data storage and cluster computing facility.

Connection to strategic developments
High Tech Systemen en Materialen
Life Sciences & Health
Health and Food
Personalised medicine
Regeneratieve geneeskunde
Gezondheidszorgonderzoek, preventie en behandeling