A sub-cellular micro x-ray fluorescence system for elemental imaging at fast acquisition times in biological tissue

The ability to image elemental distribution and concentrations is increasingly critical to a variety of biomedical fields. Nearly all fundamental biological pathways have been found to require metal-binding proteins and trace elements, and an increasing number of pathologies are now linked – or hypothesized to be linked – to trace element dysregulation, including infertility and neurodegenerative diseases such as Alzheimer’s and Wilson’s. Moreover, novel pharmaceuticals comprising metallodrugs and nanoparticle-based treatments are on the rise, and an improved rational design approach to such drugs necessitates chemical imaging to determine the uptake and removal mechanisms of such drugs. Currently, laboratory approaches to elemental imaging are limited to around 10 micrometers, which does not allow for the critical subcellular elemental understanding that could potentiate breakthrough insights. The access of researchers to micron-scale resolution chemical imaging is limited to work performed at the synchrotron, which is a major bottleneck. In this small business innovation and research grant, we propose several major innovations to develop the first laboratory sub-cellular microXRF for the biomedical community, opening the path forward for achieving laboratory nanoXRF. The system will achieve micron-scale resolution at high throughput and will be enabled through several major advances to the x-ray source and x-ray optics. The proposed Phase I 6-month project is a proof-of-principle demonstration of the capabilities of the x-ray focusing optic component. The proposed Phase II 24-month project is to develop a complete prototype sub- cellular microXRF.