Metals are essential to life and, in excess or in the wrong place, they can cause disease. We map them, at the scale of a single organelle or of a whole biopsy, to understand what they do in cells and tissues and to turn this knowledge into diagnosis and treatment.
Metals inside the cell
We took part in the development of X-ray fluorescence imaging at the subcellular scale. With the nanoimaging group of the ESRF, we showed for the first time quantitative 2D and 3D elemental maps inside a single frozen-hydrated human cell, with a resolution down to about 30 nm.
- Following a drug. Correlative 2D and 3D nano-fluorescence revealed the path of a metal-based drug (a metallocifen) in triple-negative breast cancer cells.
- Painting organelles. Metal-based probes now allow several organelles to be “painted” at once in the X-ray fluorescence image, a new benchmark for cryo-nanoscale studies.
- Understanding contrast. The same approach helped explain why X-ray phase-contrast imaging detects amyloid-β plaques without any contrast agent.
Seeing elements in tissue with LIBS
Laser-induced breakdown spectroscopy (LIBS) images the chemical elements of a sample, light and heavy, natural or introduced, in a fast benchtop instrument. We built, with industrial and academic partners, the first LIBS microscope dedicated to biomedical samples to be installed in a hospital: the Bio-LIBS platform .
Chasing the causes of idiopathic diseases
Exposure to fumes, dust and metals can lead to diseases that are labelled “idiopathic” because no cause is known. LIBS imaging can reveal what is in the tissue.
A case reclassified
In a patient with emphysema, LIBS identified silicon in the lung tissue. The disease was reclassified from idiopathic to occupational (sandblasting).- First clinical trial using LIBS (MEDICO-LIBS, NCT03901196): multi-elemental imaging of lung specimens from patients with idiopathic interstitial lung diseases, including sarcoidosis and idiopathic pulmonary fibrosis, compared with control lungs from autopsies.
- Lung and skin sarcoidosis, a rare disease of unknown origin. We combine elemental imaging, autofluorescence, biochemistry and 3D cryo-XRF nano-imaging on biopsies to look for the causative agent, then test the immune response ex vivo. The questions: which metal or protein, what link with occupational or environmental exposure, which immune mechanism, which genetic predisposition.
- Other pathologies of interest include skin sarcoidosis, occupational diseases and the toxicity of tattoo inks.
What comes next
- Metal-based probes applied to LIBS imaging.
- Artificial intelligence for spectroscopy and for the automatic processing of large LIBS data sets, with partners in Lille.
- Copper-based strategies against cancer, with a new class of copper ionophores developed with chemists in Belgium and the Netherlands.