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

Zhi Xian Chan1, Shruthi Pandi Chelvam1, Wei-Xiang Sin1

  • 1Critical Analytics for Manufacturing Personalized Medicine, Singapore MIT Alliance for Research and Technology Centre, Singapore, Singapore.

Frontiers in Bioengineering and Biotechnology
|August 18, 2025
PubMed
Summary
This summary is machine-generated.

An automated cell culture sampling system (Auto-CeSS) was developed to improve cell therapy manufacturing. This automated system accurately samples cell cultures, ensuring consistent quality and reducing manual labor and contamination risks.

Keywords:
asepticautosamplerbioreactorcar-tmicrobioreactorsamplingsmall-volume

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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.