Jeremy T. Lant, Jurgen Frasheri, Taehong Kwon, Camille M. N. Tsang, Bingyu B. Li, Sheldon Decombe, Alexandros A. Sklavounos, Samin Akbari and Aaron R. Wheeler
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引用次数: 0
摘要
近年来,单克隆抗体(mAbs)已成为治疗人类疾病的有力工具。目前,美国已批准 100 多种 mAbs 用于治疗,其应用范围广泛,从癌症到传染病。生产治疗用抗体的主要方法是在哺乳动物细胞系中表达。在 mAb 生产过程中,通常要进行大量优化工作,以最大限度地提高在生物反应器中生长的细胞的抗体滴度。因此,能使细胞系测试(如活力和抗体生产测定)微型化和自动化的系统对降低治疗用 mAb 的开发成本非常有价值。在此,我们介绍一种利用数字微流控技术优化细胞系以生产 mAb 的新型平台。该平台可对 6-8 μL 液滴中的细胞培养样本进行半自动活力、培养基 pH 值和抗体生产检测。该系统在细胞生长和生产指标之间架起了一座独特的桥梁,同时最大限度地减少了日常测试所需的培养基体积。我们认为,这项技术及其未来的迭代有望帮助缩短抗体生产细胞系的上市时间并降低开发成本。
A multimodal digital microfluidic testing platform for antibody-producing cell lines†
In recent years, monoclonal antibodies (mAbs) have become a powerful tool in the treatment of human diseases. Currently, over 100 mAbs have received approval for therapeutic use in the US, with wide-ranging applications from cancer to infectious diseases. The predominant method of producing antibodies for therapeutics involves expression in mammalian cell lines. In the mAb production process, significant optimization is typically done to maximize antibody titres from cells grown in bioreactors. Therefore, systems that can miniaturize and automate cell line testing (e.g., viability and antibody production assays) are valuable in reducing therapeutic mAb development costs. Here we present a novel platform for cell line optimization for mAb production using digital microfluidics. The platform enables testing of cell culture samples in 6–8 μL droplets with semi-automated viability, media pH, and antibody production assays. This system provides a unique bridge between cell growth and productivity metrics, while minimizing culture volume requirements for daily testing. We propose that this technology and its future iterations has the potential to help reduce the time-to-market and development costs of antibody-producing cell lines.
期刊介绍:
Lab on a Chip is the premiere journal that publishes cutting-edge research in the field of miniaturization. By their very nature, microfluidic/nanofluidic/miniaturized systems are at the intersection of disciplines, spanning fundamental research to high-end application, which is reflected by the broad readership of the journal. Lab on a Chip publishes two types of papers on original research: full-length research papers and communications. Papers should demonstrate innovations, which can come from technical advancements or applications addressing pressing needs in globally important areas. The journal also publishes Comments, Reviews, and Perspectives.