Dan Liu, Ying Ying Wu, Prabhu Akshaya V, Bin Abdul Rahim Ahmad Amirul, Jia Sheng Zach Lee
Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Front Bioeng Biotechnol. 2024 Nov 20;12:1452674. doi: 10.3389/fbioe.2024.1452674. eCollection 2024.
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.
细胞采样是细胞制造过程中定期进行的关键步骤，用于采集细胞样本以进行细胞生长、进展和特性分析。虽然目前在生物安全柜中通过移液管进行采样的方法被普遍使用，但它劳动强度大且易受污染风险影响。我们开发了自动无菌采样装置（DAAS），主要用于细胞和基因治疗生产，以实现自动化、小体积（0.02 - 1.00 mL）无菌采样，死体积最小。DAAS的目标是实现准确且一致的采样过程，污染风险最小，对培养中的细胞干扰最小。DAAS有可能与其他自动化解决方案对接，以实现自动化和简化的细胞制造工作流程并降低总体制造成本。通过反复的微生物侵入测试，DAAS已被验证为一种无菌采样解决方案。与手动移液相比，它在实现可比的细胞密度和活力方面也经过了测试，用于对不同细胞浓度的Jurkat细胞进行采样时，交叉样本残留可忽略不计。在生物安全2级实验室中，在静态培养瓶中的Jurkat细胞培养以及自动生物反应器系统中的供体T细胞培养中，成功证明了使用DAAS定期对细胞进行采样并在长时间细胞培养过程中持续监测细胞生长和活力的应用。总体而言，DAAS作为一种自动化无菌采样解决方案具有巨大潜力，为细胞和基因治疗制造商提供了更便捷、更频繁获取细胞样本的途径，对细胞培养的干扰最小。这使得能够密切监测细胞培养，并实现更自动化、连贯且经济高效的细胞和基因治疗制造过程。
