SWEDEN

Swedish National Microscopy Infrastructure (NMI)

The National Microscopy Infrastructure (NMI) is a distributed infrastructure of five specialized, complementary, and interlinked sites located across Sweden: Stockholm, Uppsala, Göteborg, and Umeå. The mission of NMI is to provide access to innovative technologies and competence in microscopy and image analysis to all scientists that have a need for advanced imaging in fundamental and translational biomedical research projects. Annually, the NMI serves more than 500 national and international users. The Swedish Euro-BioImaging Node has strong expertise in super-resolution microscopy, correlative and multimodal microscopy, intravital microscopy as well as image processing and analysis. The infrastructure is coordinated by KTH (Royal Institute of Technology) which provides the single-entry point from which users are directed to the relevant imaging technologies.

Specialties and expertise of the Node

The NMI has been designed as a multi-sited infrastructure with five specialized imaging facilities distributed in Sweden with complementary expertise and technologies:

Advanced light microscopy (ALM) at the Royal Institute of Technology (KTH): Super-resolution, FCS/FCCS, lattice light-sheet and CODEX (CoDetection by indEXing) technology - high parametric imaging of cells in a tissue context.

Centre for Cellular Imaging (CCI), at University of Gothenburg: Correlated multimodal imaging and automated high content screening microscopy for live cell imaging

Biochemical Imaging Centre Umeå (BICU) and Umeå Core facility for Electron Microscopy (UCEM), at the University of Umeå: Correlative microscopy and electron tomography.

Intravital Microscopy at Stockholm University (IVMSU): Intravital imaging with an integrated animal house

BioImage Informatics Facility (BIIF) at Uppsala University: Image and data analysis

The sites are supported by an administrative team at KTH that is responsible for project management, the project web portal, the website, software license servers and data handling. They also coordinate the activity of NMI to support users in finding the best technology for their research questions and help combine techniques from different sites.

The application experts in NMI have long experience in supporting projects in many different scientific areas, including: Neurobiology, Structural Biology, Mucosal biology and Immunology, Cardiovascular and Metabolic diseases, Cancer biology, Oral biochemistry, Virology, Cell Biology, Physiology, Endocrinology, Organotypic cultures, Dermatology and Molecular Skin Research, Pathology, Drug delivery, Developmental Biology and Regenerative medicine, Plant Biology, Botany, and Microbiology.

All of these research applications cover a wide spectrum of model organisms and in vitro models. There is also an increased interest from other scientific fields to utilize advanced microscopic imaging and analysis. Projects from researchers in e.g., nano- and material science, wood and fibre technology, chemistry, marine research, fuel research, food research, archaeology, palaeontology and cultural heritage have been supported.

Bioimage informatics and image analysis are another area of expertise of the Swedish Euro-BioImaging Node. The BIIF at the Uppsala site of the NMI is responsible for developing new computational technologies and provides access to expertise and state-of-the art software for processing and quantitative analysis of all kinds of microscopy image data for applications in the life sciences.

Technologies

• Laser scanning confocal microscopy (LSCM/CLSM)
• Multiphoton microscopy systems (MMS)
• Total internal reflection fluorescence microscopy (TIRF)
• Fluorescence Correlation Spectroscopy (FCS)
• Fluorescence Cross-Correlation Spectroscopy (FCCS)
• Fluorescence-lifetime imaging microscopy (FLIM)
• Fluorescence resonance energy transfer (FRET)
• Fluorescence recovery after photobleaching (FRAP)
• High-throughput microscopy (HTM))
• Super-resolution Structured illumination microscopy (SIM)
• Stimulated emission depletion microscopy (STED)
• Stochastic optical reconstruction microscopy (STORM)
• Photo activated localization microscopy (PALM)
• Reversible Saturable Optical Fluorescence Transitions (RESOLFT)
• Digital scanned laser light-sheet fluorescence microscopy (DSLM)
• Selective plane illumination microscopy (SPIM)
• Atomic Force Microscopy (AFM)
• Mass spectrometry-based imaging
• Correlative Light and Electron microscopy (CLEM)

Biological Technologies

Technologies	Euro-BioImaging	ISIDORe
Laser scanning confocal microscopy (LSCM/CLSM)
Multiphoton microscopy systems (MMS)
Total internal reflection fluorescence microscopy (TIRF)
Fluorescence Correlation Spectroscopy (FCS)
Fluorescence Cross-Correlation Spectroscopy (FCCS)
Fluorescence-lifetime imaging microscopy (FLIM)
Fluorescence resonance energy transfer (FRET)
Fluorescence recovery after photobleaching (FRAP)
High-throughput microscopy (HTM))
Super-resolution Structured illumination microscopy (SIM)
Stimulated emission depletion microscopy (STED)
Stochastic optical reconstruction microscopy (STORM)
Photo activated localization microscopy (PALM)
Reversible Saturable Optical Fluorescence Transitions (RESOLFT)
Digital scanned laser light-sheet fluorescence microscopy (DSLM)
Selective plane illumination microscopy (SPIM)
Correlative Light and Electron microscopy (CLEM)

Medical Technologies

Technologies	Euro-BioImaging	ISIDORe
Atomic Force Microscopy (AFM)
Mass spectrometry-based imaging

• Electron Microscopy:
• Focused Iom Beam Scanning Electron Microscopy (FIB-SEM)
• Immuno-electron microscopy (immunogold labeling of Tokuyasu cryosections)
• 3D Scanning Electron Microscopy (SEM)
• Serial section Transmission Electron Microscopy (ssTEM)
• TEM Tomography

Additional services offered by the Node

BioImage Informatics

• Guidance on image analysis assay development, including image processing algorithm development and software engineering to address challenging project goals.

All NMI nodes have supporting routines and infrastructure for tissue, cell and molecular biology laboratory work including:

• Wet lab
• Cell culture facilities
• Probes
• Animal facilities
• Other model organisms
• Biosafety level BSL-2
• Workstations
• High-performance computers

All nodes also offer:

• Methodological setup (e.g. design of study protocols and standard operation procedures
• Technical assistance to run instruments

Instrument highlights

Special feature of the Intravital microscopy facility at the Stockholm University (IVMSU): This facility operates as an “open access” facility, by combining state-of-the-art imaging and animal facility together, to enable users from academy and industry to visualize biological processes at the molecular and cellular levels within intact living rodent models. Being “open access” makes this facility unique both at the national and international levels. To enable this unique feature, IVMSU is localized within its own biological containment barrier integrated into the state-of-the-art animal facility (Experimental Core Facility) at Stockholm University.
To guarantee highest-quality service and access to cutting-edge instrumentation the NMI nodes are constantly implementing and development new technology and methods:

• Lattice light-sheet microscopy for single cell fast volumetric imaging of biological processes
• CODEX (CoDetection by indEXing) technology - high parametric imaging of cells in a tissue context
• Correlated multimodal imaging: laser scanning confocal microscopy and matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS)
• Cryo-CLEM integrated in the Focused Ion Beam scanning electron microscopy
• Developing new techniques for high-throughput/high content imaging and analysis of zebrafish embryos, an important model organism in large-scale studies of e.g. cardiovascular disease. Building up a set of state-of-the art learning-based analysis and visualization tools for whole-slide tissue images/digital pathology.

Contact details