Isotope Metallomics Quality Assurance Program (IMQAP) Consortium

Summary

The National Institute of Standards and Technology (NIST) is establishing the Isotope Metallomics Quality Assurance Program (IMQAP) Consortium. This initiative focuses on developing and evaluating measurement methods and reference standards, including reference materials, to enhance the quality and comparability of measurements within the isotope metallomics measurement community. The IMQAP Consortium unites stakeholders to identify and address the measurement and standards needs related to isotopic measurements of clinical and biological materials and products. The Consortium's efforts aim to enhance measurement capabilities, establish quality assurance strategies, support the creation of reference materials for clinical and biological matrices, and gather data to develop best practices and standardized methods.

TO BECOME A MEMBER

• View the Federal Register Notice for the IMQAP Consortium.
• Complete the Consortium Letter of Interest.
• Sign the Cooperative Research and Development Agreement (CRADA).
  • The CRADA will be sent after submission of Consortium Letter of Interest is submitted.

Applications will be accepted on an on-going basis. Consortium activities will commence October 1, 2025.

Please direct all Consortium questions to imqap [at] nist.gov (imqap[at]nist[dot]gov).

Description

Credit: J.L.Mann/Adobestock

The use of stable metal isotopes in the health and medical sciences, known as Isotope Metallomics, shows promise for developing clinical biomarkers and improving diagnostics and prognostics. This field is grounded in the idea that certain pathologies trigger physiological responses which lead to isotope fractionation—the separation of isotopes based on their atomic mass differences. This process creates unique isotope signatures in biological samples, such as blood, tissues, and organs, that are specific to the pathology.  Isotopic biomarkers show greater sensitivity and specificity for certain pathologies compared to standard biochemical markers, as they are less influenced by complex biochemical processes than molecular-based biomarkers.  For example, isotopes of Calcium (Ca) found in blood and urine can be utilized to identify musculoskeletal disorders like osteoporosis well in advance of the conventional Dual X-ray absorptiometry (DXA) method (Eisenhauer et al., 2019; 2024).

Credit: https://material-properties.org/

Chronic diseases like diabetes, cardio-vascular diseases, and cancers are the leading cause of death worldwide. It is estimated that by 2030 the cost of these diseases will reach $47 trillion worldwide (World Economic Forum, 2011). The annual financial burden of these diseases on the American healthcare system exceeds $1 trillion and is projected to continue to increase (Waters and Graf, 2018). With rising costs, healthcare is shifting from a reactive model toward predictive, preventive, and personalized medicine (PPPM) for optimal and cost-effective healthcare. This new model requires a new generation of biomarkers capable of early detection and effective monitoring of targeted therapies. Isotope analytics are emerging as powerful tools to meet this need.

IMQAP CONSORTIUM GOALS AND IMPACTS

The IMQAP Consortium aims to assist its members in improving the methods used to measure metal isotopes in clinical and biological materials. The goal is to enhance the accuracy and precision and the overall comparability of these measurements, thereby building confidence in the use of metal isotopes as a tool for clinical applications.

Credit: J.L.Mann/Powerpoint

 

     GOALS

• Develop new reference materials to support the isotope metallomics measurement community
• Evaluate the suitability of current measurement approaches by using interlaboratory exercises based on candidate clinical/biological reference materials.  Samples may include NIST Standard Reference Materials® (SRMs), NIST Reference Materials (RMs) Research Grade Test Materials (RGTMs)) and commercial products.
• Propose tests(s) that can be standardized through the clinical lab standards organizations or similar consensus process, using outcomes from Consortium efforts as a foundation.

     DELIVERABLES

• A suite of fit-for-purpose (e.g., matrix-matched) clinical/biological reference materials value-assigned for various metal isotopes (e.g., Ca, Cu, Fe, Mo, Sr, Zn) for isotope method development and validation, and for ensuring measurement accuracy and comparability.
• A series of publications and presentations related to standardized measurement methods for high accuracy and low uncertainty of metal isotope measurements in clinical/biological samples.
• Enable the adoption of metal isotopes as an early detection/biomarker and treatment monitoring tool by clinical labs and practitioners.

     CONSORTIUM MODEL

• Convenes academia, government, and industry to identify and address measurement and standards needs across the isotope metallomics field.
• Enables members to work with NIST to develop measurement solutions and standards.
• Leverages NIST expertise in measurement science, standards development, reference materials, technology development, and basic research.

     WHY NIST?

• Cross-disciplinary expertise in physical, information, chemical, and biological sciences.
• As a non-regulatory agency of the U.S. Department of Commerce, NIST does not impose standards; standards are accepted by consensus.
• Neutral convener for consortia, standards development organizations, federal labs, universities, public workshops, and interlaboratory comparability testing.

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References

Eisenhauer, A., Müller, M., Heuser, A., Kolevica, A., Glüer, C.-C., Both, M., Laue, C., Hehn, U.v., Kloth, S., Shroff, R. and Schrezenmeir, J., 2019, Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis, Bone Reports, 10, doi: 10.1016/j.bonr.2019.100200.

Eisenhauer, A., Hastuti, A., Heuser, A., Kolevica, A., Brandt, B., Shroff, R., Oehme, J. and Müller, M., 2024, Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis, Bone, 188, doi: 10.1016/j.bone.2024.117210.

Morgan, J.L.L., Skulan, J.K., Gordon, G.W., Romaniello, S.J., Smith, S.M. and Anbar, A.D., 2012, Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes, PNAS, 109(25), 9989-9994.

Waters, H. and Graf, M. eds. 2018, The costs of chronic disease in the U.S. 1st ed. Milken Institute.

World Economic Forum and The Harvard School of Public Health, Methodological Appendix: The Global Economic Burden of Non-communicable Diseases 2013-2020 1st ed. World Health Organization; 2013.