Nephrolithiasis is a disease of the urinary tract system, caused by accumulating waste products which form small stones. It is known to affect people all over the world, with a prevalence in populations as high as 16.7 % in North East Thailand and 18.5 % in uranium workers in Eastern Tennessee, USA. The most found stones are Calcium (𝐶𝑎)Oxalate (𝑂𝑥)based crystals, which form when their concentrations are supersaturated in the kidney, thus exceeding their solubility limit. The most common forms of CaOxcrystals in urine are the stable Calcium Oxalate Monohydrate (COM) and the metastable Calcium Oxalate Dihydrate (COD). If they grow too large and get stuck, medical surgery is necessary to prevent kidney failure. It is therefore necessary to understand this form of biomineralization within the human body to ensure proper treatment and prevention. This study focuses on mimicking the situation in the collecting duct of the kidney. This is done in a 295𝑥45 𝜇𝑚T-shaped microchannel, wherin a 𝐶𝑎solution enters through one inlet and an 𝑂𝑥solution through a second, such that the combined fluid flowing through the main channel is supersaturated. 𝐶𝑎 and 𝑂𝑥 are dissolved in either water or artificial urine based on the works of Streit et al. In this manner, the following effects are studied: the effect of varying average velocity, the effect of adding an amount of the natural inhibitor Osteopontin in the 𝑂𝑥-inlet, and the effect of changing the 𝐶𝑎 to 𝑂𝑥 ratio in urine conditions. Besides the microfluidic experiments, three models are applied to understand the ongoing phenomena: the Surface Reaction Model (SRM)as an analytical model of the transport-reaction kinetics at the crystal surface, the Analytical Microchannel Model (AMM) as an analytical model of the momentum and mass transport through the microchannel, and the COMSOL model as a numerical model of the microchannel made in the Matlab program COMSOL. With the latter momentum and mass transport through the channel are calculated and the mass transport results are combined with Jess Urine Expert to calculate supersaturation profiles at the channel bottom, where the crystals grow. The number for the transport reaction kinetics of the crystal surface points out that the surface reaction limits the growth, not the mass transport. LowDamköhler numbers for the transport-reaction kinetics in the entire microchannel also point this out.

Kidney stone disease influences 10% of people in the world [36]. Calcium oxalate (CaOx) stones are the most common stones found in the kidney stone. In this research, ANSYS/Fluent CFD was used to determine the supersaturation profile in the microchannel for different constant flow rates and Ca and Ox inlet concentrations. The growth of the CaOx stones is studied by performing experiments in a microfluidic channel under an optical microscopy. The growth of the CaOx stones is also investigated by using a combined transport-kinetics model which couple both mass transport and CaOx precipitation
reaction at the surface of the crystal. It is shown that the crystal growth rate increases with solution supersaturation increasing and decreases with the crystal size increasing. The findings also indicated that in cases of low bulk solution supersaturation and low surface reaction constant values,
the crystal growth rates are controlled by the surface reaction kinetics and independent on the species transport. When the bulk solution supersaturation and surface reaction constant values are high, the Ca and Ox surface concentrations become lower than the bulk solution concentration values. Thus,
the crystal growth rates are controlled by the species transport. The presented study also shows that in the presence of inhibitor osteopontin, the crystal growth rate was decreased.

Kidney stones may be uncommon is certain parts of the world. On the other hand, considering the percentage of cases in the western world, one can say it is worrisome. Anyone can have kidney stones, which may be easily passed out of the kidney through the urine. It only becomes a cause for concern when the stones grow beyond a certain size. They can cause flank and abdominal pains, fever, painful urination, etc., and can subsequently result in kidney failure if the patient has only one kidney present. In that case, a kidney stone patient may require the attention of a nephrologist. Advancement in technology has provided conventional techniques such as ureteroscopy (URS), percutaneous nephrolithotomy (PNL) and shockwave lithotripsy (SWL) for treating kidney stones. One may wonder what exactly these stones are. They are nothing extraordinary but rather made of calcium oxalate (CaOx) crystals which are formed from a supersaturated urine. CaOx crystal which is a product of crystallization occurs in two forms, calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD). Crystallization is a very simple and effective purification and phase separation process used in the chemical and pharmaceutical industry. This process is usually influenced by many factors such as concentration, temperature, mixing, impurities, etc. The presence of oxalate in urine is a major contributor to the formation of kidney stones. High concentration of oxalate combines with calcium to form CaOx. On the other hand, injury to the kidney tubular epithelial cells results in the expression of Hyaluronic acid (HA). HA has since been considered as a binding agent which causes the retention of kidney stones. Furthermore, some scientists are of the idea that HA may also influence the formation of kidney stones. A novel method was developed to study the nucleation kinetics of CaOx in artificial urine under the influence of varying oxalate and HA concentrations. The method involved crystallizing CaOx (COM, COD) in emulsions (micro-droplets) that were generated by and stored in a microfluidic device. Incorporating polarized lightmicroscopy also allowed COM and COD to be detected at the same time. The cumulative probability distribution as a function of induction time for COM and COD was determined and fitted to the Weibull model. The induction time is the average time at which the first crystal is detected in the droplets. As was expected, higher oxalate concentration shortened the induction time for both COM and COD. Surprisingly, increasing HA concentration induced the formation of COM whiles inhibiting the formation of COD. In general, the frequency of COD was always less than that of COM. In conclusion, the idea that HA played a role in the formation of kidney stones was confirmed. This was the most important part of the research.

Kidney stones disease is a serious healthy issue in modern society. The amount of patients getting kidney stones are increasing every year. This trend can be caused my numerous reasons like dietary and living conditions. The main point is that the number of kidney stone disease patients need to be lowered. The first step to achieve this is by getting a better understanding of the process of kidney stone formation. The focus will be on calcium oxalate which is the main constituent of kidney stones. In this study we present a microfluidic method to quantify nucleation kinetics of calcium oxalate as function of supersaturation, pH and in the presence of inhibitors (Magnesium, Osteopontin). We have optimized the design of the microfluidic device to minimize the droplet coalescence. Kinetic parameters were obtained through fitting of the probability of nucleation curves measured for over a hundred microdroplets. Nucleation kinetics was seen to increase with an increase in supersaturation, as expected. At pH 6.0 the kinetics dramatically slows down compared to pH’s 3.6 and 8.6. As the inhibitor concentration increases the kinetics will decrease, this is the case for both magnesium and osteopontin.