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Establishment and optimization of a high-throughput mimic perfusion model in ambr® 15
Biotechnology Letters ( IF 2.0 ) Pub Date : 2020-11-13 , DOI: 10.1007/s10529-020-03026-5
Lu Jin 1 , Zhen-Shou Wang 2 , Yun Cao 2 , Rui-Qiang Sun 2 , Hang Zhou 2 , Rong-Yue Cao 1
Affiliation  

OBJECTIVES To establish an automated high-throughput mimic perfusion scale-down model (SDM) in ambr® 15 system. RESULTS An optimized SDM for mimic perfusion was developed in ambr® 15 system. Cell retention in ambr® 15 was realized by sedimentation and supernatant removal with a retention rate > 95%. Although the SDM couldn't reach the viable cell density (VCD) at a bench scale bioreactor (BR), it maintained VCD at approximately 30 × 106 cells/mL with a cell bleeding rate estimated theoretically and predicted the cell specific perfusion rate (CSPR). A base-feeding strategy was developed to alleviate the pH drop during sedimentation which would adversely have an impact on cell growth, and showed an apparent cell viability improvement from 79.6% (control) to 90.1% on Day 18. The optimized SDM for mimic perfusion was employed for media screening in two cell lines. CONCLUSIONS A small-scale high-throughput perfusion model in ambr® 15 was developed, optimized to improve cell viability, and as a result, utilized for media screening in two cell lines.

中文翻译:

ambr® 15中高通量模拟灌注模型的建立和优化

目标 在 ambr® 15 系统中建立自动化的高通量模拟灌注缩小模型 (SDM)。结果 在 ambr® 15 系统中开发了用于模拟灌注的优化 SDM。ambr® 15 中的细胞保留是通过沉淀和上清液去除实现的,保留率 > 95%。尽管 SDM 无法在实验室规模的生物反应器 (BR) 中达到活细胞密度 (VCD),但它仍将 VCD 维持在大约 30 × 106 个细胞/mL,理论上估计了细胞出血率,并预测了细胞特异性灌注率 (CSPR) )。开发了一种基础喂养策略来缓解沉淀过程中的 pH 值下降,这会对细胞生长产生不利影响,并在第 18 天显示出明显的细胞活力从 79.6%(对照)提高到 90.1%。用于模拟灌注的优化 SDM 用于两种细胞系的培养基筛选。结论 开发了 ambr® 15 中的小规模高通量灌注模型,优化以提高细胞活力,因此可用于两种细胞系的培养基筛选。
更新日期:2020-11-13
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