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J Phys D Appl Phys. 2018 Nov 7;51(44):443001. doi: 10.1088/1361-6463/aad055. Epub 2018 Aug 31.

The 2018 correlative microscopy techniques roadmap.

Author information

1
Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
2
Department of Life Sciences & Chemistry, Jacobs University, Bremen, Germany.
3
Ionovation GmbH, Osnabrück, Germany.
4
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, OX3 9DS Oxford, United Kingdom.
5
Francis Crick Institute, London, United Kingdom.
6
INM-Leibniz Institute for New Materials, 66123 Saarbrücken, Germany.
7
Saarland University, 66123 Saarbrücken, Germany.
8
Dpto. Física de la Materia Condensada Universidad Autónoma de Madrid 28049, Madrid, Spain.
9
Instituto de Física de la Materia Condensada IFIMAC, Universidad Autónoma de Madrid 28049, Madrid, Spain.
10
KU Leuven, Department of Chemistry, B-3001 Heverlee, Belgium.
11
Institute of Applied Optics, Friedrich-Schiller University, Jena, Germany.
12
Leibniz Institute of Photonic Technology (IPHT), Jena, Germany.
13
christian.eggeling@rdm.ox.ac.uk.
14
Department of Mechanical Engineering, University of Wisconsin-Madison, 1513 University Ave, Madison, WI 53706, United States of America.
15
Kennedy Institute for Rheumatology, University of Oxford, Oxford, United Kingdom.
16
Debye Institute, Utrecht University, Utrecht, Netherlands.
17
Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
18
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
19
Centre of Structural Systems Biology Hamburg and University of Hamburg, Hamburg, Germany.
20
Heinrich-Pette-Institute, Leibniz Institute of Virology, Hamburg, Germany.
21
Imaging Physics, Delft University of Technology, Delft, Netherlands.
22
J.P.Hoogenboom@tudelft.nl.
23
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
24
Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584CX Utrecht, Netherlands.
25
Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD 4072, Australia.
26
University Hospital Jena, Jena, Germany.
27
Faculty of Medicine, Saarland University, 66421 Homburg, Germany.
28
University of Göttingen, Third Institute of Physics-Biophysics, 37077 Göttingen, Germany.
29
KU Leuven, Department of Bioscience Engineering, B-3001 Heverlee, Belgium.
30
University of Göttingen, Institute for X-Ray Physics, 37077 Göttingen, Germany.
31
SmarAct GmbH, Schütte-Lanz-Str. 9, D-26135 Oldenburg, Germany.
32
Schaap@smaract.com.
33
Institute for Theoretical Physics and BioQuant, Heidelberg University, Heidelberg, Germany.
34
School of Biochemistry, University of Bristol, Bristol, United Kingdom.
35
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.

Abstract

Developments in microscopy have been instrumental to progress in the life sciences, and many new techniques have been introduced and led to new discoveries throughout the last century. A wide and diverse range of methodologies is now available, including electron microscopy, atomic force microscopy, magnetic resonance imaging, small-angle x-ray scattering and multiple super-resolution fluorescence techniques, and each of these methods provides valuable read-outs to meet the demands set by the samples under study. Yet, the investigation of cell development requires a multi-parametric approach to address both the structure and spatio-temporal organization of organelles, and also the transduction of chemical signals and forces involved in cell-cell interactions. Although the microscopy technologies for observing each of these characteristics are well developed, none of them can offer read-out of all characteristics simultaneously, which limits the information content of a measurement. For example, while electron microscopy is able to disclose the structural layout of cells and the macromolecular arrangement of proteins, it cannot directly follow dynamics in living cells. The latter can be achieved with fluorescence microscopy which, however, requires labelling and lacks spatial resolution. A remedy is to combine and correlate different readouts from the same specimen, which opens new avenues to understand structure-function relations in biomedical research. At the same time, such correlative approaches pose new challenges concerning sample preparation, instrument stability, region of interest retrieval, and data analysis. Because the field of correlative microscopy is relatively young, the capabilities of the various approaches have yet to be fully explored, and uncertainties remain when considering the best choice of strategy and workflow for the correlative experiment. With this in mind, the Journal of Physics D: Applied Physics presents a special roadmap on the correlative microscopy techniques, giving a comprehensive overview from various leading scientists in this field, via a collection of multiple short viewpoints.

KEYWORDS:

atomic force microscopy; correlative microscopy; electron microscopy; fluorescence microscopy; magnetic resonance imaging; super-resolution microscopy; x-ray microscopy

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