Enhanced Oxygenation of Bioreactors

描述(由申请人提供)： 该项目将通过显著增加生物反应器的无泡氧气输送，显著提高生物反应器产品的MTY。主要生物制药的销售额目前超过180亿美元。氧气限制通常控制细胞的生长和活力，从而控制产品的效价。喷雾广泛用于使用添加剂(如Pluronic化合物)氧化发酵液，以保护细胞免受剪切。高气体传输膜提供了一种实用的替代疏水的方法，减少了产品提纯步骤，并提高了细胞密度和产品效价。到目前为止，无孔硅橡胶管在占用大量体积的同时只能提供有限的增氧作用。疏水性微孔膜虽然最初工作良好，但会迅速湿化或使细胞生长到毛孔中，从而显著减少流量。我们建议使用一种新型的无孔全氟中空纤维膜来显著提高生物反应器的氧合。我们提出了一种创新的结构，使用了一种新型的高气体通量的无孔全氟膜涂层，以提供所需的湿出阻力和多孔性载体顶部的高气体流量。通过这样做，我们可以优化多孔支撑体和整体系统，以实现高通量或蒸汽灭菌，并结合抗湿性。CMS膜的无孔全氟化特性表明，湿化和细胞生长到载体中不应该是问题。在这个第一阶段的项目中，我们将：a)用CMS全氟化膜制造中空纤维膜模块，b)评估它们对生物反应器发酵液和实际细胞培养物的氧气输送能力，c)展示促进细胞和杂交瘤的生长，d)展示增强对生物反应器的氧气输送，e)展示蒸汽灭菌非润湿中空纤维系统。还将进行经济评估，以确定膜式氧合器的总体价值。

DESCRIPTION (provided by applicant): This project will significantly enhance bioreactor product Mty by significantly increasing the bubbleless oxygen delivery to bioreactors. Sales of major biopharmaceuticals currently exceed $18 billion. Oxygen limitations often control cell growth and viability and therefore product titer. Sparging is extensively used to oxygenate fermentation broths using additives (e.g. Pluronic compounds) to 3rotect cells from shear. High gas transfer membranes provide a practical alternative to sparging, reducing product purification steps and allowing increased cell densities and product titer. To date, non-porous silicone rubber tubing provides limited oxygen enhancement while occupying much volume. Hydrophobic microporous membranes, while working well initially, quickly wet out or have cells grow into the pores and dramatically reduce flow. We propose using a novel family of non-porous perfluorinated hollow fiber membranes to dramatically enhance bioreactor oxygenation. We propose an innovative structure using a novel high gas flux non-porous perfluoromembrane coating to provide the needed wet-out resistance and high gas flux on top of a porous support. By doing this we can optimize the porous support and overall system for high flux or steam sterilization in combination with wet-out resistance. The non-porous perfluorinated nature of CMS membranes suggests that wet-out and cells growing into the support should not be an issue. In this Phase I program we will: a) fabricate hollow fiber membrane modules with CMS perfluorinated membranes, b) evaluate their oxygen delivery capability to both bioreactor broth and actual cell cultures, c) demonstrate enhanced growth of both cells and hybridoma, and d) demonstrate enhanced oxygen delivery to bioreactors and e) demonstrate a steam sterilizability non-wetting hollow fiber system. Economic evaluation will also be done to determine overall value of membrane oxygenators.