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）： 该项目将通过显著增加输送至生物反应器的无泡氧气来显著提高生物反应器产品Mty。主要生物制药的销售额目前超过180亿美元。氧限制通常控制细胞生长和活力，因此控制产物滴度。鼓泡广泛用于使用添加剂（例如Pluronic化合物）将发酵液从剪切中除去以保护细胞。高气体转移膜提供了一种实用的替代鼓泡，减少产品纯化步骤，并允许增加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，但很快就会被浸湿或使细胞生长到孔中并显著降低流动。我们建议使用一种新型的无孔全氟中空纤维膜，以显着提高生物反应器的充氧。我们提出了一种创新的结构，使用一种新的高气体通量的非多孔全氟膜涂层，以提供所需的润湿阻力和高气体通量的多孔支持的顶部。通过这样做，我们可以优化多孔载体和整个系统，以实现高通量或蒸汽灭菌以及抗润湿性。CMS膜的无孔全氟化性质表明，润湿和细胞生长到载体中不应成为问题。在该I期项目中，我们将：a）使用CMS全氟膜制造中空纤维膜组件，B）评价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）证明向生物反应器的氧气输送增强，e）证明蒸汽灭菌性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。