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

TitleA sub cellular micro x ray fluorescence system for elemental imaging at fast acquisition times in biological tissue Project SummaryAbstract The ability to image elemental distribution and concentrations is increasingly critical to a variety of biomedical fieldsNearly all fundamental biological pathways have been found to require metal binding proteins and trace elementsand an increasing number of pathologies are now linkedor hypothesized to be linkedto trace element dysregulationincluding infertility and neurodegenerative diseases such as Alzheimer s and Wilson sMoreovernovel pharmaceuticals comprising metallodrugs and nanoparticle based treatments are on the riseand an improved rational design approach to such drugs necessitates chemical imaging to determine the uptake and removal mechanisms of such drugsCurrentlylaboratory approaches to elemental imaging are limited to aroundmicrometerswhich does not allow for the critical subcellular elemental understanding that could potentiate breakthrough insightsThe access of researchers to micron scale resolution chemical imaging is limited to work performed at the synchrotronwhich is a major bottleneckIn this small business innovation and research grantwe propose several major innovations to develop the first laboratory sub cellular microXRF for the biomedical communityopening the path forward for achieving laboratory nanoXRFThe 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 opticsThe proposed Phase Imonth project is a proof of principle demonstration of the capabilities of the x ray focusing optic componentThe proposed Phase IImonth project is to develop a complete prototype subcellular microXRF Project Narrative This project proposes to develop a laboratory micro x ray fluorescencemicroXRFfor subcellular elemental imagingto address emerging questions in the increasing number of pathologies hypothesized to be linked to trace element dysregulation and for the development of novel drugs such as metallodrugs and nanoparticle based therapeuticsSubcellularmicronscale chemical imaging currently requires the use of synchrotron x ray sources and is therefore a major bottleneck to the research communityThe proposed laboratory microXRF will accelerate critical research for understanding the relationship between trace elements with pathologies such as infertility and aging related neurodegenerative diseasesand it will be vital to help achieve rational design of metal based drugse ganti canceranti HIVand nanoparticlebased drug delivery techniques