With the increasing demand for biopharmaceuticals, a method to crystallize biomolecule products with high quality, high yield and uniform size distribution as well as regular crystal habit is needed. In this work, ultrasound was used as a nucleation accelerator to decrease the energy barrier for lysozyme crystal formation. Crystallization experiments on egg-white lysozyme were carried out with and without ultrasound. The effect of ultrasound on induction time, metastable zone width, crystal size and morphology and process yield was investigated in detail. The nucleation-promoting effect produced by ultrasound is illustrated by the reduction of metastable zone width and induction time. By inducing faster nucleation, ultrasound leads to protein crystals grow at lower supersaturation levels with shorter induction time. It was found that ultrasound could result in uniform size distribution of the product due to the preventing of aggregation. However, long time continuous application of ultrasound could result in smaller particle size. Hence, ultrasonic-stop method was found to be a more appropriate strategy to enhance the crystallization process of proteins such as lysozyme.

中文翻译：

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超声场下溶菌酶结晶的增强。

随着对生物药物需求的增加，需要一种使生物分子产品结晶的方法，该方法具有高质量，高收率和均匀的尺寸分布以及规则的晶体习性。在这项工作中，超声被用作成核促进剂以减少溶菌酶晶体形成的能垒。在有或没有超声波的情况下，对蛋清溶菌酶进行了结晶实验。详细研究了超声波对诱导时间，亚稳区宽度，晶体尺寸，形态和工艺产量的影响。超声产生的成核促进作用通过减少亚稳区宽度和诱导时间来说明。通过诱导更快的成核作用，超声导致蛋白质晶体以较低的过饱和水平和较短的诱导时间生长。已经发现，由于防止聚集，超声可以导致产物的均匀尺寸分布。但是，长时间连续使用超声波可能会导致粒径减小。因此，发现超声停止法是增强蛋白质例如溶菌酶的结晶过程的更合适的策略。