MeXpose – A Modular Imaging Pipeline for the Quantitative Assessment of Cellular Metal Bioaccumulation
Braun et. al.
JACS Au, 2024
DOI: 10.1021/jacsau.4c00154
In this recent publication, led by the University of Vienna, our icpTOF 2R was used in combination with a newly developed imaging analysis tool, MeXpose, to study metal exposure at single cell resolution for the first time.
Metal exposure in humans is increasing due to industrial activities and medical applications, with significant bioaccumulation in tissues that can affect health. The toxicity of metals depends on factors such as chemical form, dosage, and exposure route, with different metals accumulating in various tissue types. Accumulation can also alter cellular behavior, such as cancer cells becoming resistant to metal-based therapies. Single-cell resolution of metal distribution offers insights into metal toxicity but remains challenging to achieve.
MeXpose is a newly developed advanced image analysis pipeline for studying metal exposure at single-cell resolution using using the icpTOF 2R coupled to an Iridia laser ablation system with a 193 nm laser. It combines high-resolution laser ablation with immunohistochemistry using metal-labeled antibodies, enabling precise cellular phenotyping and quantitative metal bioaccumulation analysis (in the sub-femtogram range per cell). Using our time-of-flight technology, the system covers a wide mass range (m/z 14−256), allowing comprehensive single-cell metallomics.
In a proof-of-concept study, MeXpose analyzed cobalt chloride (CoCl2) exposure in an ex vivo human skin model. For the first time, metal permeation was quantified at single-cell resolution, revealing high cobalt accumulation in the epidermis, particularly in mitotic basal cells, which was linked to DNA damage. Cobalt deposits were also detected in vascular cells, with lower levels in dermal fibers.
MeXpose, in combination with the laser ablation capabilities of the icpTOF, provides insights into metal bioaccumulation and its effects on cellular behavior, making it a valuable tool for toxicological and therapeutic research.
