Enhanced Oxygenation of Bioreactors

生物反应器的增强氧化

• 批准号: 6689919
• 负责人: Stuart Nemser
• 金额: $ 11.82万
• 依托单位: COMPACT MEMBRANE SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-03-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6689919
• 关键词: artificial membranes; bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial evaluation; biomedical equipment development; bioreactors; hybridomas; oxygen transport; surface coating; tissue /cell culture

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.

描述（由申请人提供）： 该项目将通过显着增加向生物反应器的无泡氧气输送来显着提高生物反应器产品 Mty。目前主要生物制药的销售额超过180亿美元。氧气限制通常控制细胞生长和活力，从而控制产物滴度。鼓泡广泛用于使用添加剂（例如 Pluronic 化合物）对发酵液进行充氧，以保护细胞免受剪切力的影响。高气体传递膜提供了喷射的实用替代方案，减少了产品纯化步骤，并提高了细胞密度和产品滴度。迄今为止，无孔硅橡胶管在占据大量体积的同时提供有限的氧气增强。疏水性微孔膜虽然最初工作良好，但很快就会被润湿或细胞生长到孔中并显着减少流量。我们建议使用新型无孔全氟化中空纤维膜家族来显着增强生物反应器的氧合作用。我们提出了一种创新结构，使用新型高气体通量无孔全氟膜涂层，在多孔支撑体顶部提供所需的抗润湿性和高气体通量。通过这样做，我们可以优化多孔支撑和整个系统，以实现高通量或蒸汽灭菌与防潮性相结合。 CMS 膜的无孔全氟化性质表明，润湿和细胞生长到支持物中不应成为问题。在此第一阶段计划中，我们将：a) 制造带有 CMS 全氟化膜的中空纤维膜模块，b) 评估其向生物反应器肉汤和实际细胞培养物的氧气输送能力，c) 证明细胞和杂交瘤的生长增强，d) 证明增强的生物反应器氧气输送，e) 证明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氧合器的总体价值。