Traceability for biologically relevant molecules and entities

Short Name: Bio-SITrace, Project Number: SIB54
Scientist with DNA copying, Real-time cycler, wide

Better biological measurements: Removing barriers to traceable measurements in biology 


Many medical diagnosis techniques, such as those for identifying heart attack risk or detecting cancer, depend on accurately determining the amount of DNA, proteins and cells in biological samples. Improved diagnoses lead to earlier interventions and improved treatment monitoring.

 

Diagnostics based on polymerase chain reaction (PCR) including next generation sequencing (NGS) amplify trace amounts of mutated DNA, enabling them to be measured within complex biological samples. But these, and other clinical methods that are used to measure lipoprotein levels and to count cells, lack traceable reference methods and materials. This leads to inconsistent results across different laboratories and means that borderline cases can be missed. It also makes it difficult to gather the quality of data needed for new medical device regulations. Recent developments using techniques based on biomolecular and cell counting require rigorous characterisation to establish SI traceability and to demonstrate their reproducibility when performed in different laboratories.

 

This project demonstrated for the first time, the potential for achieving SI traceability through determining the basis for clinical reference measurement procedures to support comparability in critical healthcare measurements.

 

The project:

 

Established digital PCR (dPCR) as a primary reference measurement procedure for DNA copy number quantification, through comprehensive evaluation of sources of error and comparison with mass spectrometry measurements. This was successfully applied to improve the accuracy of a clinical study on cancer biomarker diagnostics

 

Developed a new application of electrospray-differential mobility analysis (ES-DMA) for analysing lipoprotein particle sizes in blood, which are associated with cholesterol levels that create cardiovascular disease risks

 

Improved SI links for impedance counting flow cytometry, which is used to count individual particles, linking electrical charge to cell size to enable its use for comparing cell measurement instruments

 

Applied NGS as a novel method for the assessment of DNA reference material purity and defined limits for the quantification of minority sequences impurities.

 

This project has made a significant contribution to the growing global movement, led by the Joint Committee for Traceability in Laboratory Medicine (JCTLM), for greater assay standardisation and global harmonisation in the clinical laboratory measurement community. A European Metrology Network is being formed to address the needs of stakeholders in this area of medical science. The project’s highly precise reference method for a cancer genetic marker, the first for nucleic acids, has been added to the JCTLM database, and project results improving SI traceability through biomolecular counting have contributed to the revision of ISO 17511 – a key standard for increasing measurement harmonisation in healthcare. Other project inputs to normative standards include quality criteria for dPCR and NGS and flow cytometry advances, whilst a new working group, instigated by the International Federation of Clinical Chemistry, is pursuing project advances on the improvement of routine cholesterol measurements.

 

For more information, please contact the EURAMET Management Support Unit

Phone: +44 20 8943 6666

E-mail: empir.msu@euramet.org