Automated, aseptic sampling with small-volume capacity from microbioreactors for cell therapy process analysis.

Area of Science:

• Biotechnology
• Process Engineering
• Cell Therapy Manufacturing

Background:

• Current autologous cell therapy manufacturing relies on manual processes, hindering scalability.
• High-throughput bioreactors require robust bioprocess monitoring for quality control.
• Existing commercial sampling systems are often bioreactor-specific and not adaptable to various scales.

Purpose of the Study:

• To develop an automated cell culture sampling system (Auto-CeSS) for cell therapy manufacturing.
• To eliminate manual sampling, reduce sterility risks, and enable process intensification.
• To integrate Auto-CeSS with diverse bioreactor types and scales.

Main Methods:

• Developed and integrated an automated, aseptic cell culture sampling system (Auto-CeSS).
• Tested Auto-CeSS with a 2 mL perfusion microbioreactor and an 8 mL gas-permeable well-plate for T cell culture.
• Collected daily supernatant samples (200 μL) for metabolite analysis and compared with manual sampling.

Main Results:

• Auto-CeSS accurately and aseptically samples a minimum of 30 μL with periodic sampling intervals as short as 15 minutes.
• Metabolic profiles (glucose, lactate, glutamine, glutamate) from Auto-CeSS samples showed insignificant differences compared to manual sampling.
• Demonstrated Auto-CeSS as a viable at-line sampling platform for real-time T cell production monitoring.

Conclusions:

• Auto-CeSS effectively automates cell culture sampling, minimizing sterility risks and manual labor.
• The system's compatibility with various bioreactors supports process intensification in cell therapy.
• Auto-CeSS facilitates reliable in-process monitoring, crucial for ensuring cell therapy product quality and scalability.