Isotope metallomics approaches for medical research

Abstract

Metallomics is a rapidly evolving field of bio-metal research that integrates techniques and perspectives from other "-omics" sciences (e.g. genomics, proteomics) and from research vocations further afield. Perhaps the most esoteric of this latter category has been the recent coupling of biomedicine with element and isotope geochemistry, commonly referred to as isotope metallomics. Over the course of less than two decades, isotope metallomics has produced numerous benchmark studies highlighting the use of stable metal isotope distribution in developing disease diagnostics-e.g. cancer, neurodegeneration, osteoporosis-as well as their utility in deciphering the underlying mechanisms of such diseases. These pioneering works indicate an enormous wealth of potential and provide a call to action for researchers to combine and leverage expertise and resources to create a clear and meaningful path forward. Doing so with efficacy and impact will require not only building on existing research, but also broadening collaborative networks, bolstering and deepening cross-disciplinary channels, and establishing unified and realizable objectives. The aim of this review is to briefly summarize the field and its underpinnings, provide a directory of the state of the art, outline the most encouraging paths forward, including their limitations, outlook and speculative upcoming breakthroughs, and finally to offer a vision of how to cultivate isotope metallomics for an impactful future.

Keywords: Biomarkers; Disease diagnostics; Geochemistry; Isotope metallomics; Metallomics; Neurodegeneration; Stable metal isotopes.

Fig. 1

Future-shaping research areas: a theoretical predictions of isotope fractionation at the molecular and cellular level; b measurements of natural stable isotope fractionation at the molecular and cellular level; c in situ analyses in soft tissues (e.g. LA-MC-ICP-MS); d high-throughput techniques and scalable workflow

Fig. 2

Strategies for high-throughput IEC: a sequential element extraction (SIEC); b vacuum-assisted IEC (VIEC); c pressure-assisted IEC (PIEC); and d automated/hyphenated systems