Trace elements are well known to have critical roles in a wide variety of diseases, including cancer and neurodegenerative diseases such as Alzheimer's and Wilson's diseases. Due to their biological importance, there have been numerous studies performed with spectroscopy techniques such as laser ablation inductively coupled mass spectrometry (LA-ICP-MS) to understand absolute concentration values in tissue. More recent developments in synchrotron X-ray Fluorescence (XRF) have enabled rapid high resolution mapping of absolute concentration values, and, significantly, the quantitative distribution analysis of multiple trace elements at once. Such systems provide up to parts-per-billion sensitivity to map trace elements at micron- scale resolution in diseased tissue. We propose to develop a laboratory scanning X-ray fluorescence microprobe for the biomedical community that will make it possible for the first time to bring trace elemental mapping at the cellular level currently only achievable at synchrotron facilities. This will be achieved by bringig vast improvements to standard laboratory XRF by key innovations on the source, optics, and detector. Up to 7200X fluorescence signal gain over existing commercial micro-XRF systems will be achieved, enabling key capabilities for biomedical application x-ray fluorescence mapping within the laboratory. The proposed Phase I project is a proof-of-principle demonstration that the novel XRF source required can be manufactured and to complete design of the optics. Key deliverables of this project are finite element analysis of the source thermal performance, five prototypes of the novel source anode, and a design specification for the Wolter optics.
This project proposes to develop the first biomedical x-ray fluorescence microprobe for laboratory use with outstanding trace element mapping capability and comprising three main innovations on the source, optics, and detector. The system's capabilities are intended to enable high sensitivity mapping of trace elements in diseases, to further understand the relationship between trace element distribution and disease progression. The pursuit of this understanding is motivated by the growing evidence of relationships between trace amounts of specific elements with diseases such as cancer and neurodegenerative diseases.