Developing Adsorptive Protein Separations

这项研究将加快吸附蛋白质分离的设计，重点是高效放大。重点放在直接测量关键分离参数的仪器技术上：O颗粒内扩散系数，这是预测任何吸附过程的有效性所必需的，在商业分离器的高负荷下尤其重要。脉冲场梯度核磁共振技术将用于这一目的。O吸附动力学，需要预测分辨率和产量损失，在高溶质负载量时也是最重要的。O对流弥散系数，以表征系统几何形状和流动条件的影响。将使用磁共振成像。成功将允许根据基本的运输和反应原理进行合理的设计，从而不仅优化工艺条件，而且还考虑替代的工艺模式和设备配置。这项研究将促进治疗性蛋白质和其他重要新药的开发，并通过提供改进的程序来从发酵液或其他粗品来源中进行下游加工、分离和纯化，从而降低生产成本。下游加工占总生产成本的50%至80%，但相对于生产过程的其他方面，工程师往往会忽视这一点。这里的注意力集中在吸附分离上，例如层析，因为这对两类至关重要的治疗药物特别有效：蛋白质和合成有机物。如果我们要防止竞争对手利用美国医学和生物研究人员的发现，加快商业开发是必要的。

This study will speed the design of adsorptive protein separations, with emphasis on efficient scale-up. The focus is on instrumental techniques for direct measurement of key separation parameters: o Intraparticle diffusion coefficients, needed to predict effectiveness of any adsorptive process and especially important at the high loadings of commercial separators. Pulsed field gradient NMR techniques will be used for this purpose. o Adsorption kinetics, needed to predict resolution and yield losses, and again most important at high solute loading. o Convective dispersion coefficients, to characterize the effects of system geometry and flow conditions. Magnetic resonance imaging will be used. Success will permit rational design based on underlying transport and reaction principles, and thus not only to optimize process conditions but also to consider alternate processing modes and equipment configurations. This research will enhance the development of therapeutic proteins and other important new drugs and also reduce the cost of producing them by providing improved procedures for downstream processing, isolation, and purification from fermentation broths or other crude sources. Downstream processing accounts for 50 to 80 percent of total production costs but has tended to be neglected by engineers relative to other aspects of the production process. Attention is focused here on adsorptive separations, such as chromatography, because these are particularly effective for two critically important classes of therapeutic agents: proteins and synthetic organics. Speeding commercial development is necessary if we are to prevent competitors from capitalizing on the discoveries of American medical and biological researchers.