Kidney stone in a chip: Understanding calcium oxalate kidney stone formation

Research output: ThesisDissertation (TU Delft)

121 Downloads (Pure)

Abstract

Kidney stone formation is a global health problem with increasing prevalence. Stone formation is a physiochemical process involving crystallization of inorganic salts in the presence of biological constituents in the urinary system. To inhibit kidney stone formation, a better understanding of the underlying physicochemical mechanism of stone formation in the kidney is required.
In this thesis, the solubility, nucleation and growth of calcium oxalate (CaOx), the most common inorganic constituent of kidney stones, were studied under different conditions such as ion concentration, pH value, and also the role of inhibitors in water or artificial urine was investigated. The first step towards this work was obtaining the solubility curve of calcium oxalate monohydrate (COM) in the solvent, such as ultrapure water and different buffers, to elucidate the physicochemical conditions which can cause the kidney stone formation (Chapter 2).
Beside the solubility study, advanced technology to observe crystal formation in small scale and a very short time was needed. The volume, structure and flow properties inside the kidney inspired us to use microfluidic technology with comparable volume and flow rate. The developed microfluidic devices that mimic pathways in the human kidney were used to study the nucleation and growth of calcium oxalate crystals. The developed devices rendered an alternate perspective to the study of kidney stone formation and showed that microfluidics can provide precise, simple and fast detection of stone formation under various experimental conditions.
Initially, the designed microfluidic device allowed us to build a testing platform for the study of nucleation kinetics of CaOx inside isolated environments provided by droplets. Preliminary experiments were performed by dissolving calcium chloride and sodium oxalate in ultrapure water. The aqueous solution, containing the ions, forms the droplet phase and oil were used as the continuous phase. Altering the pH values, as well as increasing the concentration of additives such as magnesium and osteopontin (OPN), were shown to slow down the nucleation kinetics, or even inhibit nucleation (Chapter 3).
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Delft University of Technology
Supervisors/Advisors
  • Padding, J.T., Supervisor
  • Eral, H.B., Advisor
Award date8 Jun 2022
DOIs
Publication statusPublished - 14 Apr 2022

Keywords

  • kidney stone
  • lab on a chip
  • calcium oxalate
  • nucleation
  • solubility
  • crystallization

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