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Bright-field TEM of thin sections

Bright-field TEM of thin sections

Most biological samples require extensive processing prior to TEM as they have a high water content and little inherent contrast due to being composed predominantly of elements with a low atomic number, meaning they are not electron-dense.

The general processing steps are: a) fixation - to preserve the specimen in as ‘life-like’ a state as possible; b) staining with heavy metals, such as osmium tetroxide, uranyl acetate and lead citrate - to introduce contrast; and c) dehydration and resin embedding - in preparation for thin sectioning.

Due to the large range of organisms and types of tissue, there is no universal ‘one-size-fits-all’ method of specimen processing. Especially if samples contain inorganic inclusions to be preserved for imaging and/or analysis by EDX or EELS (e.g. nanoparticles), or if the samples are intended for use in immuno-TEM, the processing protocol usually needs adapting in order to preserve the chemistry of inclusions or the antigenicity of target antigens. Please discuss your projects with us prior to sample drop-off.



Rakesh Rajan, Prof. Melinda Duer Group, Department of Chemistry, University of Cambridge – Pathways of ECM calcification 

Culture of M3T3 cells induced in-vitro to produce extracellular matrix (ECM) and matrix calcifications (C). Low-magnification overview image; the knife mark striations are caused by the inherent calcium phosphate crystals (

Higher magnification reveals the banding of individual collagen fibres and the electron-dense crystals of calcium phosphate platelets (arrow) marking the start of matrix calcification.



Prof. Slawomir Boncel, Silesian University of Technology, Poland – Exploring MWCNTs as vehicles for drug targeting

Uptake of multi-walled carbon nanotubes by human macrophages in culture; arrowheads indicate MWCNTs, m = mitochondria, v = intracellular vesicles; scale bar is 100 nm (doi: 10.1021/acsbiomaterials.6b00197).



Karin Müller, Department of PDN and Chemistry (Duer Group), University of Cambridge – Uptake of hydroxyapatite nanoparticles in human macrophages (then

SCC overview
Low magnification overview of macrophage taking up vast amounts of HA nanoparticles. The particles are sequestered in large, interconnected vacuoles (arrows) that form a surface-connected compartment; n = nucleus.


HA NP degradation
HA nanoparticles are subject to degradation inside these vesicles changing from a thin platelet-like appearance to a smooth, round morphology; scale bars are 100 nm.