Investigating CaOx Crystal Formation in the Absence and Presence of Polyphenols under Microfluidic Conditions in Relation with Nephrolithiasis

Abstract

Nephrolithiasis is a major health concern in western countries. Herein, we propose a microfluidic based approach to mimic the physical and physicochemical conditions encountered in the collecting duct in a nephron where calcium oxalate (CaOx) precipitation occurs. Our objective is to understand the parameters involved in the formation of such crystals. The microfluidic platform is reversible, allowing interfacial characterizations using scanning electron microscopy imaging and Raman spectroscopy. CaOx crystalline phases and morphologies were studied with respect to hydrodynamics and physicochemical conditions within the channel and at the outlet. While calcium oxalate monohydrate (COM) crystals were dominant within the channel, at the outlet, the crystals were calcium oxalate dihydrate (COD) crystals, which agrees with medical observations. Decreasing the flow rate lowered down the induction time for CaOx formation and enhanced the occurrence of COD crystals. The kinetics of COM crystals growth studied in situ showed two regimes, an initial surface-limited reaction, followed by a transport-limited growth with a dependency of the kinetics on the position of the crystal in the channel. Numerical modeling of CaOx formation in a microchannel using an in-house model considering the chemical reactions involved allowed to confirm the experimental observations on the location of precipitate formation but also to quantitatively match the scaling law related to the early growth of precipitate particles. Finally, the effect of polyphenols naturally found in green tea (GT) on modulating CaOx crystallization was studied in the microfluidic device in different scenarios where GT was initially mixed in solution with the Ca and/or the Ox precursors. The formation of COD crystals rather than COM ones was always predominant; however, depending on the conditions, CaOx crystals of different morphologies could be observed, including COD crystals with an elongated (100) crystalline face and COM crystals with a round-shaped morphology with a concave crystalline face.

Spatiotemporal Distribution of Calcium Oxalate Crystals in a Microchannel

“…The reaction rate ( r s ) of the solid particle formation in eq incorporates the nucleation ( r n ) and growth rate ( r g ) of the particles as r s = r n + r g = ( k normaln + k normalg ∑ j d j 2 ) ( Q − K sp ) where k n and k g are the rate coefficients for nucleation and growth, respectively, as dissolution and phase change are neglected on this time scale. In addition to supersaturation, the growth rate is proportional to the surface area of solid particles. ,, …”

“…A Y-shaped reversible microfluidic channel with a cross section of 100 × 100 μm 2 was produced using a standard soft lithographic process as described by us previously. 12 The fluid propagates laminarly in the channel, as the Reynolds number corresponding to the flow regime is Re = 0.33. The flow field is described by the Navier−Stokes equation for incompressible fluids (∇•u⃗ = 0) as…”

“…Since the supersaturation in the system is dominant, the dissolution of the precipitate can be neglected. 12 The temporal change of the homogeneous species (CaCl 2 , Na 2 C 2 O 4 , NaCl, CaC 2 O 4 ) is described by the component balance equation…”

“…In addition to supersaturation, the growth rate is proportional to the surface area of solid particles. 12,18,19 If the solution is supersaturated, CaC 2 O 4(aq) will accumulate in a ΔV volume of the unit cell unless a sufficient amount is formed according to…”

Preventing Biofilm Formation and Encrustation on Urinary Implants: (Bio)molecular and Physical Research Approaches

“…This leads to their reshaping by deposition and encrustation of chemical and biological species on their surface and the formation of bacterial biofilms and mineral crystals. Due to the continuous nature of biological fluids, these phenomena are in perpetual dynamics and self-organization, which can complicate their study in the human body [3,4]. Giving this complexity of the "system", a multidisciplinary input with different scientific approaches is needed to better understand and find solutions to this problem.…”