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Protein instability following transport or storage on dry ice

Nature Methods volume 10, pages 278–279 (2013)Cite this article

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To the Editor:

It is common practice to place protein solutions on dry ice for storage or transport, but this may lead to an unrecognized problem. A series of assay failures after short-term storage of antibody solutions on dry ice led to our observation that the pH of the thawed solutions was between 5.5 and 6.0 even though they had been formulated at pH 7.2. We hypothesized that exposure of the solutions to CO2 caused the formation of carbonic acid, resulting in protein damage from the pH drop. Protein properties affected by pH include tertiary and quaternary structure, enzymatic rate constants, solubility, tendency to aggregate, susceptibility to chemical degradation and propensity to adsorb to surfaces1. We therefore examined possible interactions between dry ice and sealed frozen protein solutions.

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Figure 1: Effect of dry ice on pH and aggregation index.

References

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Author information

Authors and Affiliations

  1. Legacy BioDesign LLC, Johnstown, Colorado, USA

    Brian M Murphy & Mark C Manning

  2. Department of Chemistry, Colorado State University, Fort Collins, Colorado, USA

    Brian M Murphy & Mark C Manning

  3. Department of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA

    Spencer Swarts & Peter van der Geer

  4. Torrey Pines Institute for Molecular Studies, San Diego, California, USA

    Barbara M Mueller

  5. Somatek Inc., San Diego, California, USA

    Mark I Fitchmun

  6. Accelagen Inc., San Diego, California, USA

    Mark I Fitchmun

Authors
  1. Brian M Murphy
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  2. Spencer Swarts
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  3. Barbara M Mueller
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  4. Peter van der Geer
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  5. Mark C Manning
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  6. Mark I Fitchmun
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Corresponding author

Correspondence to Mark I Fitchmun.

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Competing interests

B.M. Murphy and M.C.M. performed research related to this manuscript while employed by Legacy BioDesign. M.I.F. performed research related to this manuscript while employed by Somatek.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1 and 2 and Supplementary Methods (PDF 184 kb)

CO2-induced acidification of sample upon thaw

Acidification is seen as a color shift from yellow to red starting at the sample-headspace interface. (MOV 443 kb)

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Murphy, B., Swarts, S., Mueller, B. et al. Protein instability following transport or storage on dry ice. Nat Methods 10, 278–279 (2013). https://doi.org/10.1038/nmeth.2409

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