Abstract:Mass cytometry (MC) relies on the identification of intracellular or surface-expressed targets using antibodies coupled to metal isotope chelates.
Detection is based on the difference in the time-of-flight of metal ions when placed in an electric field.
For several years, MC technology was restricted to the analysis of cells in suspension, but thanks to a major development, its connection to a laser ablation system now makes it possible to analyse tissues: the samples are ionised, and their isotopic composition is then mapped to produce high-precision images comparable to fluorescence microscopy.
Theorically, IMC technology has the unique capability to simultaneously stain, acquire and analyze more than 100 markers of interest on a tissue section without interference from autofluorescent tissues or management of spectral overlap.
However, at present, this technology is limited to the analysis of 40 markers associated solely with the 40 metal isotopes that are actually used, which are lanthanide isotopes.
This is associated to the current chemistry of MC tags those can only be loaded with few elements.
To make full use of IMC and ensure a more detailed characterisation of biological samples (i.e. to increase the number of parameters that can be analysed simultaneously), it is therefore crucial to open up new detection channels, that is, to introduce new metal isotopes.
In theory, any exogenous metal isotope with a mass between 77 and 209 uma can be utilised.
However, adding new channels is not so straightforward, as some isotopes may produce a signal of low sensitivity or significantly increase background noise and their chemistry is not compatible with the current reagents.
The aim of this project is therefore to design new labelling agents for MC, enabling the opening of new detection channels to significantly improve IMC technology and facilitate a more comprehensive study of complex biological systems.
More specifically, the objective will be to design bifunctional chelators capable of strongly coordinating new metals for use in IMC, and to develop grafting methodologies on innovative platforms to replace the
MAXPAR polymers currently in use.
Laboratory:The research programme will be carried out within the
COSM team at the
CEMCA laboratory (UMR 6521, UBO, Brest, France).
The
COSM team is developing several research areas focused on Health and/or Materials.
More specifically, the ‘Nitrogen-containing Macrocycles and Coordination’ research group is dedicated to the synthesis and study of nitrogen-containing macrocycles intended for applications in the field of health: medical imaging (MRI, PET, etc.) and therapy (radioimmunotherapy, leukaemia, etc.).
The
CEMCA laboratory is equipped with all the facilities required for high-level organic chemistry: automated chromatographic purification systems, HPLC, NMR and
HR-MS platforms, etc.