A quartz crystal microbalance (QCM) is used as a novel in situ strategy for analyzing the supersaturation profile during cooling crystallization. The main concept is based on preventing any solid mass loading on the QCM sensor by modifying the sensor surface. As a result, the QCM responses only depend on the solution concentration changes during the crystallization. The proposed strategy is confirmed on the basis of an analysis of sulfamerazine (SMZ) crystallization. When the QCM sensor is modified using 11-amino-1-undecanethiol (AUT), crystal formation on the sensor is completely prevented due to a repulsive interaction between the -NH2 functional groups of the AUT and SMZ crystals. Thus, the QCM responses reflect only the property changes in the solution phase during the crystallization. The supersaturation in the solution is then estimated on the basis of the difference in the frequency shifts between the SMZ solution and a blank solution. The accuracy of the in situ QCM analysis of supersaturation is confirmed using an off-line gravimetric method.
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