Nucleation kinetics of calcium oxalate monohydrate as a function of pH, magnesium, and osteopontin concentration quantified with droplet microfluidics

Journal Article (2021)
Author(s)

Fatma Ibis (TU Delft - Complex Fluid Processing)

Tsun Wang Yu (Student TU Delft)

Frederico Marques Penha (KTH Royal Institute of Technology)

Debadrita Ganguly (Student TU Delft)

Manzoor Alhaji Nuhu (Student TU Delft)

Antoine van der Heijden (TU Delft - Complex Fluid Processing)

HJM Kramer (TU Delft - Complex Fluid Processing)

Hüseyin Burak Eral (Universiteit Utrecht, TU Delft - Complex Fluid Processing)

Copyright
© 2021 F. Ibis, Tsun Wang Yu, F. Marques Penha, Debadrita Ganguly, Manzoor Alhaji Nuhu, A.E.D.M. van der Heijden, H.J.M. Kramer, H.B. Eral
DOI related publication
https://doi.org/10.1063/5.0063714
More Info
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Publication Year
2021
Language
English
Copyright
© 2021 F. Ibis, Tsun Wang Yu, F. Marques Penha, Debadrita Ganguly, Manzoor Alhaji Nuhu, A.E.D.M. van der Heijden, H.J.M. Kramer, H.B. Eral
Bibliographical Note
Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.@en
Issue number
6
Volume number
15
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Abstract

A droplet-based microfluidic platform is presented to study the nucleation kinetics of calcium oxalate monohydrate (COM), the most common constituent of kidney stones, while carefully monitoring the pseudo-polymorphic transitions. The precipitation kinetics of COM is studied as a function of supersaturation and pH as well as in the presence of inhibitors of stone formation, magnesium ions (Mg2+), and osteopontin (OPN). We rationalize the trends observed in the measured nucleation rates leveraging a solution chemistry model validated using isothermal solubility measurements. In equimolar calcium and oxalate ion concentrations with different buffer solutions, dramatically slower kinetics is observed at pH 6.0 compared to pHs 3.6 and 8.6. The addition of both Mg2+ and OPN to the solution slows down kinetics appreciably. Interestingly, complete nucleation inhibition is observed at significantly lower OPN, namely, 3.2 × 10-8 M, than Mg2+ concentrations, 0.875 × 10-4 M. The observed inhibition effect of OPN emphasizes the often-overlooked role of macromolecules on COM nucleation due to their low concentration presence in urine. Moreover, analysis of growth rates calculated from observed lag times suggests that inhibition in the presence of Mg2+ cannot be explained solely on altered supersaturation. The presented study highlights the potential of microfluidics in overcoming a major challenge in nephrolithiasis research, the overwhelming physiochemical complexity of urine.

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