The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Marcus Center for Therapeutic Cell Characterization and Manufacturing, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
Lab Chip. 2021 Nov 25;21(23):4696-4706. doi: 10.1039/d1lc00884f.
Real-time, advanced diagnostics of the biochemical state within cells remains a significant challenge for research and development, production, and application of cell-based therapies. The fundamental biochemical processes and mechanisms of action of such advanced therapies are still largely unknown, including the critical quality attributes that correlate to therapeutic function, performance, and potency and the critical process parameters that impact quality throughout cell therapy manufacturing. An integrated microfluidic platform has been developed for in-line analysis of a small number of cells direct infusion nano-electrospray ionization mass spectrometry. Central to this platform is a microfabricated cell processing device that prepares cells from limited sample volumes removed directly from cell culture systems. The sample-to-analysis workflow overcomes the labor intensive, time-consuming, and destructive nature of existing mass spectrometry approaches for analysis of cells. By providing rapid, high-throughput analyses of the intracellular state, this platform enables untargeted discovery of critical quality attributes and their real-time, in-process monitoring.
实时、先进的细胞内生化状态诊断仍然是细胞疗法的研究、开发、生产和应用的重大挑战。这些先进疗法的基本生化过程和作用机制在很大程度上仍然未知，包括与治疗功能、性能和效力相关的关键质量属性，以及影响细胞治疗整个制造过程质量的关键工艺参数。已经开发出一种用于在线分析少量细胞的集成微流控平台 - 直接注入纳升电喷雾电离质谱法。该平台的核心是一种微加工细胞处理设备，可从直接从细胞培养系统中取出的有限样本量制备细胞。与现有的用于细胞分析的质谱方法相比，该样品分析工作流程克服了劳动强度大、耗时和破坏性的特点。通过提供对细胞内状态的快速、高通量分析，该平台能够实现关键质量属性的无目标发现及其实时、在线监测。
