Controlling nucleation and crystal growth during reactive crystallization of monosodium urate monohydrate from simulated synovial fluid by N2 fine bubble injection

Abstract

To control the nucleation and growth of monosodium urate monohydrate (MSU) crystals, we studied the reactive crystallization of MSU from simulated synovial fluid using the gas–liquid interfaces around N2 fine bubbles as novel crystallization fields. In the regions near the gas–liquid interfaces, local supersaturation is generated because of the accumulation of Na+ resulting from the negative electric charge on the fine bubble surface. Hence, the micronization of MSU crystals is expected to occur via growth suppression through the enhancement of nucleation. N2 fine bubbles were continuously supplied to the simulated synovial fluid with 140 mmol/L-Na+ and 3.6 mmol/L-uric acid using a pressurized dissolution-type fine bubble generator. The injection time of the N2 fine bubbles was varied within 60 min to control the volume density of the fine bubbles. The simulated synovial fluid containing N2 fine bubbles was sampled and sealed on a microscope slide, and the reactive crystallization of MSU was performed by standing operation. When the volume density of fine bubbles was increased, the crystal growth was suppressed because of the increasing effective nuclei number and the decreasing consumption of supersaturation for crystal growth caused by the acceleration of nucleation, which led to the generation of numerous fine crystals of needle-shaped MSU.