Assuring SI traceable measurement results in Germany for organic, peptide and protein biomarkers

The international comparability of measurement results can be achieved by anchoring these measurements to the international System of Units (SI). Both the mechanisms and infrastructure for achieving this in the area of clinical chemistry are relatively new when compared to those for physical measurements. For the past two decades, PTB has been comparing the equivalence of its clinical measurement services with those of other NMIs. The development of high accuracy isotope dilution methods has enabled the provision of accurate results, whereby, all contributions to the measurement uncertainty can be appropriately estimated. These methods have been applied to priority clinical biomarkers, assuring the results provided by the German clinical reference laboratories are fully SI traceable. This, in turn, ensures the reference methods and routine clinical laboratories produce "fit for purpose" measurements as defined by RiLi-BÄK. Previously simple protein biomarkers were considered too complex for the application of the high accuracy methods developed by NMIs. Improvements in analytical technology combined with simpler protein expression systems that enabled the production of isotopically labelled peptides and proteins enabled these methods to be applied to this group of analytes for the first time. The developed methods enabled full traceability to the SI through a stepwise approach, whereby, protein-specific peptides can be used to determine the amount of protein present in a biological sample. These methods can be easily applied to simple proteins but alternative approaches using protein metal complexes, that could infer a protein's structural integrity are currently been investigated. The metrology community has developed and compared their measurement services at the highest level for several important clinical markers. Greater effort is required to further disseminate these services, with the final goal of improving the comparability of patient measurement results on a continuous and global basis, for a broader range of biomarkers. If this is to become a reality much greater collaboration is required between the NMIs, reference laboratories, IVDD manufactures, and routine laboratories. This collaboration is essential if the benefits of metrological traceability are to be realised in full.