灌流是上游连续生物工艺的基石，自 1980 年代以来一直应用至今，它大大提高了设施利用率、拓展了工艺灵活性并最大程度降低了成本。如今，新型细胞截留设备和一次性使用技术结合成熟的控制逻辑，让实施变得简便易行。
Perfusion cell culture utilizes a cell retention device and continuous media exchange to achieve and maintain high cell densities and viabilities over extended periods of time. The cell retention device retains cells inside the bioreactor, while fresh media is added, and products of interest, waste products and spent (or depleted) media are continuously removed. Fresh media is provided at the same rate that product and spent media are removed from the bioreactor. Hollow fiber-based membrane filters act as the most reliable and commonly used membrane type. Long-term perfusion is typically performed in weeks.
Technology innovations, such as XCell ATF®, solved historical challenges, shifting the paradigm towards perfusion as a key platform for modern upstream process intensification and continuous processing.
Repligen solutions help overcome key challenges in perfusion cell culture, with hands-on process and implementation consultation from global Field Applications Specialists.
Long-term Perfusion Cell Culture Workflow
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Perfusion enabled 10X VCD and 10X product than Fed-Batch
Perfusion achieved 100-130 million viable cell density (VCD) compared to 13 million for Fed-Batch. Perfusion culture viability was maintained above 90% over a period of 17 days. Fed-Batch viability began to drop after day 9 to approximately 70% at days 14-15. Higher VCD and viability of perfusion cultures translated to an increase in total product yield. The perfusion process yielded approximately 30-35 g, while the Fed-Batch process achieved 3 g in approximately 15 days.
Higher cell density, higher viability
- Unoptimized perfusion process achieved up to 10X VCD over optimized Fed-Batch
- Perfusion enabled higher cell growth rates and healthier cultures
- Higher cell density and viability of perfusion culture enabled 10X yield increase over Fed-Batch
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