首页> 外文期刊>Biotechnology Journal: Healthcare,Nutrition,Technology >Systematic interpolation method predicts protein chromatographic elution from batch isotherm data without a detailed mechanistic isotherm model
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Systematic interpolation method predicts protein chromatographic elution from batch isotherm data without a detailed mechanistic isotherm model

机译:系统内插法可从批量等温线数据预测蛋白质色谱洗脱,而无需详细的机械等温线模型

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Predicting protein elution for overloaded ion exchange columns requires models capable of describing protein binding over broad ranges of protein and salt concentrations. Although approximate mechanistic models are available, they do not always have the accuracy needed for precise predictions. The aim of this work is to develop a method to predict protein chromatographic behavior from batch isotherm data without relying on a mechanistic model. The method uses a systematic empirical interpolation (EI) scheme coupled with a lumped kinetic model with rate parameters determined from HETP measurements for non-binding conditions, to numerically predict the column behavior. For two experimental systems considered in this work, predictions based on the EI scheme are in excellent agreement with experimental elution profiles under highly overloaded conditions without using any adjustable parameters. A qualitative study of the sensitivity of predicting protein elution profiles to the precision, granularity, and extent of the batch adsorption data shows that the EI scheme is relatively insensitive to the properties of the dataset used, requiring only that the experimental ranges of protein and salt concentrations overlap those under which the protein actually elutes from the column and possess a +/- 10% measurement precision.
机译:预测过载离子交换柱的蛋白质洗脱需要能够描述蛋白质在广泛的蛋白质和盐浓度范围内结合的模型。尽管可以使用近似的机械模型,但是它们并不总是具有精确预测所需的精度。这项工作的目的是开发一种无需依赖机械模型即可从批量等温线数据预测蛋白质色谱行为的方法。该方法使用系统的经验插值(EI)方案和集总动力学模型,该模型具有从HETP测量中确定的非结合条件下的速率参数,以数字方式预测色谱柱的行为。对于这项工作中考虑的两个实验系统,基于EI方案的预测与高度过载条件下的实验洗脱曲线非常吻合,而无需使用任何可调参数。对预测蛋白质洗脱曲线对批吸附数据的精度,粒度和范围的敏感性的定性研究表明,EI方案对所用数据集的属性相对不敏感,仅要求蛋白质和盐的实验范围浓度与蛋白质实际从色谱柱上洗脱下来的浓度重叠,并具有+/- 10%的测量精度。

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