Evaluation of a prototype bioreactor based on slowly rotating drum

Area of Science:

• Biotechnology
• Biochemical Engineering
• Cell Culture Technology

Background:

• Chinese hamster ovary (CHO) cells are crucial for producing monoclonal antibodies (mAbs).
• Optimizing bioreactor design is essential for enhancing cell growth, viability, and product yield.
• Conventional stirred-tank bioreactors face challenges in achieving efficient oxygen transfer and controlled hydrodynamic conditions.

Purpose of the Study:

• To evaluate an innovative rotating-drum bioreactor against a conventional stirred-tank system for CHO cell fed-batch culture.
• To compare oxygen transfer, hydrodynamic conditions, and overall bioprocess performance.
• To assess the impact of the novel bioreactor on cell growth, viability, and mAb production.

Main Methods:

• Fed-batch culture of CHO cells in both rotating-drum and stirred-tank bioreactors.
• Monitoring of oxygen transfer coefficient (kLa), dissolved oxygen (DO) levels, and tip speeds.
• Measurement of viable cell density (VCD), cell viability, and monoclonal antibody (mAb) titer.
• Analysis of hydrodynamic conditions within the bioreactors.

Main Results:

• The rotating-drum bioreactor achieved a higher volumetric mass transfer coefficient (kLa = 0.1087 min⁻¹) at lower rotational speeds.
• Stable DO levels (~40%) were maintained, supporting enhanced cell growth (peak VCD of 2.55 × 10⁷ cells mL⁻¹).
• Monoclonal antibody production was nearly doubled (1.3 ± 0.09 g L⁻¹) compared to the stirred-tank reactor.

Conclusions:

• The innovative rotating-drum bioreactor demonstrates superior performance for CHO cell fed-batch culture.
• Efficient oxygenation and favorable hydrodynamic conditions contribute to improved cell growth and mAb yield.
• Further studies are needed to define operational limits, optimize conditions, and assess critical quality attributes at larger scales.