Investigation of Calcium Oxalate Crystallization under Microfluidic Conditions for the Understanding of Urolithiasis

Axe 1 - Biominéralisation

Thèse de Karol Rakotozandriny

Appel à projet 2016.

Soutenance de thèse le 27 septembre 2019 à 9h30 - Salle 2 du Collège de France 

Laboratoires co-porteurs

• Laboratoire de Chimie de la Matière (LCMCP)
  Directeur de thèse : Christian Bonhomme
• Physicochimie des Electrolytes et Nanosystèmes interfaciaux (PHENIX)
  Co-Directeur de thèse : Ali Abou Hassan

Keywords

calcium oxalate - hydroxyapatite - microfluidics - in situ characterization - growth kinetics

Projet de recherche (abstract)

Over the past decades, the increase in kidney stone formers has raised the importance to understand the biomineralization process responsible for urolithiasis. Calcium oxalate (CaOx) crystallization – kidney stone main inorganic compound – has largely been characterized under batch synthesis conditions that cannot be regarded as biomimetic with respect to the microscale environment in the kidney and to the urinary flow.

In this work, we used a reversible microchannel to mimic the collecting duct in the nephron where CaOx stones can form due to supersaturated levels in calcium and oxalate ions. Within the channel, CaOx crystallization was induced under co-laminar mixing of Ca²_(aq) and Ox^2-_(aq) ions matching pathological concentrations – i.e. hypercalciuria and moderate hyperoxaluria. Scanning electron microscopy and Raman spectroscopy were used to support our investigations. They showed that CaOx crystals precipitate in a mixture of monohydrated whewellite (CaC₂O₄.2H₂O, COM) and dihydrated weddellite (CaC₂O₄.2H₂O, COD) in the microchannel, similar to what is observed by the physicians. In situ information on the kinetics of CaOx crystal growth could be acquired in our microfluidic system. They confirmed the effect of the hydrodynamic and chemical conditions on the growth kinetics and the final chemistry (phase, shape) of the formed CaOx crystals. In a trial to achieve a more complex biomimetic model (formation of kidney stones on a Randall’s plaque), hydroxyapatite was grown also in the microchannel and the CaOx crystal formation was investigated.

Conférences et interventions

• FlowMat workshop
  Paris, Juin 2019
  Communication orale
• MRS Spring Meeting
  Phoenix (AZ), Avril 2019
  Communication orale
• Division du Solide de la Société Chimique de France
  Montpellier, Octobre 2017
  Communication orale
• Flow17
  Paris, Juillet 2017
  Poster presentation