Antonio Casares

Modern microscopy labs are typically outfitted with a suite of instruments, capable of capturing data

across a range of length scales in 2D- and 3D, from the centimeters to the sub-nanometers.

These imaging instruments are often complimented by analytical techniques, such as spectroscopic

chemical characterization platforms or mass spectrometry and are designed to produce a comprehensive

depiction of the material under investigation.

 

Recently, a novel multi-beam SEM (MSEM) technology for imaging of large sample areas has been developed by ZEISS. The MultiSEM family features 61 or even 91 electron beams scanning in parallel, resulting in an imaging throughput of up to 3 TeraPixels per hour is now achievable, therefore enabling extremely large-scale imaging experiments in 2D and 3D.

 

Here, we present a unique advancement enabling correlativemicroscopy, which uses a centralized software platform to pull together data from light-, electron-, Ion-, andX-Ray Microscopy (XRM). Beyond just correlating the various datasets, the approach allows data fromone technique to be used to drive the hardware in another technique, facilitating easy transfer ofinformation between the suite of available microscopes and the operator.

In a proof-of-concept approach (Fig 1), we have started to develop brain preparation, scanning, and cross-correlation pipelines to utilize the virtues of complementary high-resolution neuroimaging techniques (MRI, 3D Polarized Light Imaging, X-ray tomography, 3D-SEM, mSEM, and FIB-SEM) serially applied to the same brain tissue. The main goal is to develop a multiscale approach that will enable, for example, the study of the human connectome from the millimetre to the nanometre scale, or in material sciences the study of batteries using the same technology.

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Fig. 1 Correlated multimodal imaging workflow of a mouse Brain section: (A) Polarize microscopy image; (B) Resin block prepared for electron microscopy; (C) X-ray image; (D) Image of the brain section taken with the SEM singlebeam; (E) Overview image taking with the MultiSEM multibeam microscope; (F) Image acquired with the focused ion beam.

Acknowledgement: BUILD is a partnering Project of the Human Brain Project (European Union’s Horizon 2020 Framework Programme for Research and Innovation, SGA3, No. 945539).