Nevertheless, this method requires collection times of hours 7. 3D ptychography has recently been applied for imaging Chlamydomonas cells although with a resolution of 180 nm 7. Another alternative, which provides chemical and structural information at the same time, is 2D ptychography combined with 2D XRF that offers a way to study trace elements in their structural context 6. Alternatively, near edge X-ray absorption fine structure (NEXAFS) 5 allows to differentiate between elemental species, but in the case of biological samples its three-dimensional counterpart prevented by radiation damage.

Of the 3D X-ray approaches that can be used to quantify iron oxide nanoparticle distribution within a whole cell, 3D X-ray fluorescence (XRF) nanotomography 4 provides the greatest chemical sensitivity but lacks cell structural detail. Light microscopy combined with cytological staining is rapid 3, but resolution is very limited and bulk metal identification is possible only in few cases. Several methods are used to correlate cell morphology with specific metal identification and quantitation, each optimized for a specific sample size window and resolution 2. The recently increased use of superparamagnetic iron oxide nanoparticles (SPION) in nano-biomedicine for diagnosis, drug delivery and hyperthermia treatment 1 has underlined the need for quantitative data of the interaction of these particles with cells at nanometric resolution beyond classical microscopy approaches and bulk assays.

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