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A new anion exchange purification method for Cu stable isotopes in blood samples

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Abstract

The isotopic composition of iron, zinc, copper, and cadmium (δ56Fe, δ66Zn, δ65Cu, and δ114Cd) are novel and promising tools to study the metabolism and homeostasis of trace metals in the human body. Serum δ65Cu has been proposed as a potential tool for diagnosis of cancer in liquid biopsy, and other metals may have similar utility. However, accurate analysis of trace metal isotopes is challenging because of the difficulties in purifying the metals from biological samples. Here we developed a simple and rapid method for sequential purification of Cu, Fe, Zn, and Cd from a single blood plasma sample. By using a combination of 11 M acetic acid and 4 M HCl in the first steps of column chemistry on AG-MP1 resin, we dramatically improve the separation of Cu from matrix elements compared to previous methods which use concentrated HCl alone. Our new method achieves full recovery of Cu, Fe, Zn, and Cd to prevent column-induced isotope fractionation effects, and effectively separates analytes from the matrix in order to reduce polyatomic interferences during isotope analysis. Our methods were verified by the analysis of isotope standards, a whole blood reference material, and a preliminary sample set including five plasma samples from healthy individuals and five plasma samples from cancer patients. This new method simplifies preparation of blood samples for metal isotope analysis, accelerating multi-isotope approaches to medical studies and contributing to our understanding of the cycling of Fe, Zn, Cu, and Cd in the human body.

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References

  1. Dauphas N, John SG, Rouxel O. Iron isotope systematics. Rev Mineral Geochem. 2017;82:415–510.

    Article  CAS  Google Scholar 

  2. Moynier F, Vance D, Fujii T, Savage P. The isotope geochemistry of zinc and copper. Rev Mineral Geochem. 2017;82:543–600.

    Article  CAS  Google Scholar 

  3. Teng FZ, Dauphas N, Watkins JM. Non-traditional stable isotopes: retrospective and prospective. Rev Mineral Geochem. 2017;82:1–26.

    Article  CAS  Google Scholar 

  4. Albarède F, Télouk P, Balter V, Bondanese VP, Albalat E, Oger P, et al. Medical applications of Cu, Zn, and S isotope effects. Metallomics. 2016;8:1056–70.

    Article  CAS  PubMed  Google Scholar 

  5. Albarède F, Telouk P, Lamboux A, Jaouen K, Balter V. Isotopic evidence of unaccounted for Fe and Cu erythropoietic pathways. Metallomics. 2011;3:926–33.

    Article  CAS  PubMed  Google Scholar 

  6. Balter V, da Costa AN, Bondanese VP, Jaouen K, Lamboux A, Sangrajrang S, et al. Natural variations of copper and sulfur stable isotopes in blood of hepatocellular carcinoma patients. Proc Natl Acad Sci U S A. 2015;112:982–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Télouk P, Puisieux A, Fujii T, Balter V, Bondanese VP, Morel AP, et al. Copper isotope effect in serum of cancer patients. A pilot study. Metallomics. 2015;7:299–308.

    Article  CAS  PubMed  Google Scholar 

  8. Dauphas N, Janney PE, Mendybaev RA, Wadhwa M, Richter FM, Davis AM, et al. Chromatographic separation and multicollection-ICPMS analysis of iron. Investigating mass-dependent and-independent isotope effects. Anal Chem. 2004;76:5855–63.

    Article  CAS  PubMed  Google Scholar 

  9. Maréchal CN, Télouk P, Albarède F. Precise analysis of copper and zinc isotopic compositions by plasma-source mass spectrometry. Chem Geol. 1999;156:251–73.

    Article  Google Scholar 

  10. Heghe LV, Engström E, Rodushkin I, Cloquet C, Vanhaecke F. Isotopic analysis of the metabolically relevant transition metals Cu, Fe and Zn in human blood from vegetarians and omnivores using multi-collector ICP-mass spectrometry. J Anal At Spectrom. 2012;27:1327–34.

    Article  CAS  Google Scholar 

  11. Borrok DM, Wanty RB, Ridley WI, Wolf R, Lamothe PJ, Adams M. Separation of copper, iron, and zinc from complex aqueous solutions for isotopic measurement. Chem Geol. 2007;242:400–14.

    Article  CAS  Google Scholar 

  12. Conway TM, Rosenberg AD, Adkins JF. John SG. A new method for precise determination of iron, zinc and cadmium stable isotope ratios in seawater by double-spike mass spectrometry. Anal Chim Acta. 2013;793:44–52.

    Article  CAS  PubMed  Google Scholar 

  13. Zhu ZY, Jiang SY, Yang T, Wei HZ. Improvements in Cu–Zn isotope analysis with MC-ICP-MS: a revisit of chemical purification, mass spectrometry measurement and mechanism of Cu/Zn mass bias decoupling effect. Int J Mass Spectrom. 2015;393:34–40.

    Article  CAS  Google Scholar 

  14. Korkisch J. CRC handbook of ion exchange resins, vol. 6: CRC Press; 1988. 154pp

  15. Chapman JB, Mason TF, Weiss DJ, Coles BJ, Wilkinson JJ. Chemical separation and isotopic variations of Cu and Zn from five geological reference materials. Geostand Geoanal Res. 2006;30:5–16.

    Article  CAS  Google Scholar 

  16. Larner F, Rehkämper M, Coles BJ, Kreissig K, Weiss DJ, Sampson B, et al. A new separation procedure for Cu prior to stable isotope analysis by MC-ICP-MS. J Anal At Spectrom. 2011;26:1627–32.

    Article  CAS  Google Scholar 

  17. Fritz JS, Pietrzyk DJ. Non-aqueous solvents in anion-exchange separations. Talanta. 1961;8:143–62.

    Article  CAS  Google Scholar 

  18. Korkisch J, Hazan I. Anion exchange separations in hydrobromic acid-organic solvent media. Anal Chem. 1965;37:707–10.

    Article  CAS  Google Scholar 

  19. Klakl E, Korkisch J. Anion-exchange behaviour of several elements in hydrobromic acid-organic solvent media. Talanta. 1969;16:1177–90.

    Article  CAS  PubMed  Google Scholar 

  20. Marrinucci D, Bethel K, Kolatkar A, Luttgen MS, Malchiodi M, Baehring F, et al. Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers. Phys Biol. 2012;9:016003.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gault-Ringold M, Stirling CH. Anomalous isotopic shifts associated with organic resin residues during cadmium isotopic analysis by double spike MC-ICPMS. J Anal At Spectrom. 2012;27:449–59.

    Article  CAS  Google Scholar 

  22. Takano S, Tanimizu M, Hirata T, Shin KC, Fukami Y, Suzuki K, et al. A simple and rapid method for isotopic analysis of nickel, copper, and zinc in seawater using chelating extraction and anion exchange. Anal Chim Acta. 2017;967:1–11.

    Article  CAS  PubMed  Google Scholar 

  23. Mason TF, Weiss DJ, Horstwood M, Parrish RR, Russell SS, Mullane E, et al. High-precision Cu and Zn isotope analysis by plasma source mass spectrometry part 2. Correcting for mass discrimination effects. J. Anal Atom Spectrom. 2004;19:218–26.

    Article  CAS  Google Scholar 

  24. Siebert C, Nägler TF, Kramers JD. Determination of molybdenum isotope fractionation by double-spike multicollector inductively coupled plasma mass spectrometry. Geochem Geophys Geosyst. 2001;2:2000GC000124.

    Article  Google Scholar 

  25. Hou Q, Zhou L, Gao S, Zhang T, Feng L, Yang L. Use of Ga for mass bias correction for the accurate determination of copper isotope ratio in the NIST SRM 3114 Cu standard and geological samples by MC-ICPMS. J Anal At Spectrom. 2015;31:280–7.

    Article  CAS  Google Scholar 

  26. Strelow FW. Distribution coefficients and anion exchange behavior of some elements in hydrobromic-nitric acid mixtures. Anal Chem. 1978;50:1359–61.

    Article  CAS  Google Scholar 

  27. Abouchami W, Galer SJ, Horner TJ, Rehkämper M, Wombacher F, Xue Z, et al. A common reference material for cadmium isotope studies–NIST SRM 3108. Geostand Geoanal Res. 2012;37:5–17.

    Article  CAS  Google Scholar 

  28. Stevenson EI, Fantle MS, Das SB, Williams HM, Aciego SM. The iron isotopic composition of subglacial streams draining the Greenland ice sheet. Geochim Cosmochim Acta. 2017;213:237–54.

    Article  CAS  Google Scholar 

  29. Miller KA, Keenan CM, Martin GR, Jirik FR, Sharkey KA, Wieser ME. The expression levels of cellular prion protein affect copper isotopic shifts in the organs of mice. J Anal At Spectrom. 2016;31:2015–22.

    Article  CAS  Google Scholar 

  30. Costas-Rodríguez M, Anoshkina Y, Lauwens S, Van Vlierberghe H, Delanghe J, Vanhaecke F. Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis? Metallomics. 2015;7:491–8.

    Article  CAS  PubMed  Google Scholar 

  31. Anoshkina Y, Costas-Rodríguez M, Speeckaert M, Van Biesen W, Delanghe J, Vanhaecke F. Iron isotopic composition of blood serum in anemia of chronic kidney disease. Metallomics. 2017;9:517–24.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Nick Hawco, Paulina Pinedo-Gonzalez, and Irit Tal for technical support. We would also like to thank Editor Alfredo Sanz-Medel and two anonymous referees for their helpful comments.

Funding

This work was supported by NSF award 1636332.

Author information

Authors and Affiliations

  1. Department of Earth Sciences, University of Southern California, 3651 Trousdale Pkwy, Los Angeles, CA, USA

    Shun-Chung Yang, William M. Berelson, A. Joshua West & Seth G. John

  2. Bridge Institute, University of Southern California, 1002 Childs Way, Los Angeles, CA, 90089, USA

    Lisa Welter, Anand Kolatkar & Peter Kuhn

  3. Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA

    Jorge Nieva & Peter Kuhn

  4. Billings Clinic, 801 North 29th St, Billings, MT, 59101, USA

    Kathryn R. Waitman

  5. Institute of Earth Sciences, Academia Sinica, 128 Section 2 Academia Rd, Nangang District, Taipei, 11529, Taiwan

    Kuo-Fang Huang

  6. Research Center for Environmental Changes, Academia Sinica, 128 Section 2 Academia Rd, Nangang District, Taipei, 11529, Taiwan

    Wen-Hsuan Liao

  7. Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-011, Japan

    Shotaro Takano

Authors
  1. Shun-Chung Yang
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  2. Lisa Welter
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  3. Anand Kolatkar
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  8. Shotaro Takano
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  9. William M. Berelson
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  11. Peter Kuhn
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  12. Seth G. John
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Corresponding author

Correspondence to Shun-Chung Yang.

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Conflict of interest

The authors declare that they have no conflict of interest.

All sampling procedures were approved by the University of Southern California, University Park Institutional Review Board (FWA no. 00007099), and the Scripps Health Green Hospital Institutional Review Board (FWA no. 00000411). All study participants provided written informed consent.

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Yang, SC., Welter, L., Kolatkar, A. et al. A new anion exchange purification method for Cu stable isotopes in blood samples. Anal Bioanal Chem 411, 765–776 (2019). https://doi.org/10.1007/s00216-018-1498-4

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  • DOI: https://doi.org/10.1007/s00216-018-1498-4

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