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 4000X 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 II project aims to build a working prototype of the microXRF system. Key deliverables of this project include completing: system engineering design, final prototype of the x-ray source, prototype of Wolter x-ray mirror lens, integration of the system components, and experimental demonstration of ppm detection sensitivity at a spatial resolution of 10 m.
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 both aging-related diseases such as cancer and neurodegenerative diseases and developmental diseases such as autism, as well as due to the importance of mapping cellular and tissue uptake of metal-based drugs in new metal-based (e.g. anti-cancer and anti-HIV) therapeutic drugs and nanoparticle-based drug delivery techniques.