Device for automated aseptic sampling: Automated sampling solution for future cell and gene manufacturing

Front Bioeng Biotechnol. 2024 Nov 20:12:1452674. doi: 10.3389/fbioe.2024.1452674. eCollection 2024.

Abstract

Cell sampling is a key step performed regularly throughout the cell manufacturing process to gather cell samples for cell growth, progress, and characteristics analysis. While the current method of sampling by pipetting in a biosafety cabinet is commonly used, it is labour-intensive and susceptible to contamination risks. We have developed Device for Automated Aseptic Sampling (DAAS), to enable automated, small volume (0.02-1.00 mL) aseptic sampling with minimal dead volume primarily for cell and gene therapy manufacturing. The aim of DAAS is to enable an accurate and consistent sampling process, with minimal contamination risks and interruption to the cells in culture. DAAS can potentially interface with other automated solutions to enable automated and streamlined cell manufacturing workflow and reduce overall manufacturing costs. DAAS has been verified as an aseptic sampling solution via repeated microbial ingression tests. It has also been tested for achieving comparable cell density and viability compared to manual pipetting, with negligible cross-sample carryover when used to sample Jurkat cells of different cell concentrations. The application of using DAAS to sample cell periodically and monitor cell growth and viability continuously for prolonged cell culture was successfully demonstrated with Jurkat cell culture in a static culture flask and donor T cell culture in an automated bioreactor system over a culture duration of 10 days in a Biosafety Level-2 laboratory. Overall, DAAS presents great potential as an automated and aseptic sampling solution, offering cell and gene therapy manufacturers easier and more frequent access to cell samples with minimal interruptions to the cell culture. This enables close monitoring of cell culture and a more automated, connected and cost-effect cell and gene therapy manufacturing process.

Keywords: aseptic sampling; automated sampling; automation; cell and gene therapy; cell manufacturing; process analytical technology.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work is funded by core fund from Bioprocessing Technology Institute (BTI), Singapore Agency for Science, Technology and Research (A*STAR), and Integrated Manufacturing Programme for Autologous Cell Therapy (IMPACT), an Industry Alignment Fund—Pre-Positioning Programme (Grant Number: H18/01/a0/022) funded by Agency for Science, Technology and Research (A*STAR).