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X-ray absorption spectroscopy (XAS) is a technique which is frequently used in metallomics research, providing a valuable tool for the elucidation of element-specific electronic and geometric structural information. Recent decades have seen the development of related synchrotron-based X-ray techniques with enhanced analytical capabilities, including X-ray emission spectroscopy (XES), resonant inelastic X-ray scattering (RIXS), and high energy resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS). With appropriate experimental configuration, HERFD-XAS can generate spectra with significantly improved spectroscopic resolution and background rejection compared to conventional XAS, providing a substantial advantage in the analysis of dilute analytes in biological samples. These improvements arise from the capability to interrogate selected fluorescence lines with the use of multiple crystal analyzers, minimizing the effects of core-hole lifetime broadening. Herein, we review a range of existing and emerging applications of HERFD-XAS for the study of metals and metalloids in biology and medicine. Direct comparisons of conventional XAS and HERFD-XAS spectra highlight the substantial improvements in resolution, and greater potential for the interpretation of metal speciation in complex and dilute biological samples. We also discuss current challenges with the design of HERFD-XAS experiments.
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George et al. (2025) studied this question.
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