Multiplexed Microfluidic Cartridge for At-Line Protein Monitoring in Mammalian Cell Culture Processes for Biopharmaceutical Production
| العنوان: | Multiplexed Microfluidic Cartridge for At-Line Protein Monitoring in Mammalian Cell Culture Processes for Biopharmaceutical Production |
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| المؤلفون: | Pinto, Ines Fernandes, Soares, Ruben R. G., Mäkinen, Meeri, Chotteau, Veronique, Russom, Aman, Prof., 1976 |
| المصدر: | ACS Sensors. 6(3):842-851 |
| مصطلحات موضوعية: | microfluidics, streptavidin beads, immunoassay, colorimetric, monoclonal antibodies, host cell proteins |
| الوصف: | The biopharmaceutical market has been rapidly growing in recent years, creating a highly competitive arena where R&D is critical to strike a balance between clinical safety and profitability. Toward process optimization, the recent development and adoption of new process analytical technologies (PAT) highlight the dynamic complexity of mammalian/human cell culture processes, as well as the importance of fine-tuning and modeling key metabolites and proteins. In this context, simple, rapid, and cost-effective devices allowing routine at-line monitoring of specific proteins during process development and production are currently lacking. Here, we report the development of a versatile microfluidic protein analysis cartridge allowing the multiplexed bead-based immunodetection of specific proteins directly from complex mixtures with minimal hands-on time. Colorimetric quantification of Chinese hamster ovary (CHO) host cell proteins as key impurities, monoclonal antibodies as target biopharmaceuticals, and lactate dehydrogenase as a marker of cell viability was achieved with limits of detection in the 1-10 ng/mL range and analysis times as short as 30 min. The device was further demonstrated for the monitoring of a Rituximab-producing CHO cell bioreactor over the course of 8 days, providing comparable recoveries to standard enzyme-linked immunosorbent assay (ELISA) kits. The high sensitivity combined with robustness to matrix interference highlights the potential of the device to perform at-line measurements spanning from the bioreactor to the downstream processing. |
| وصف الملف: | electronic |
| URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-294016 https://doi.org/10.1021/acssensors.0c01884 https://kth.diva-portal.org/smash/get/diva2:1553076/FULLTEXT01.pdf |
| قاعدة البيانات: | SwePub |
| تدمد: | 23793694 |
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| DOI: | 10.1021/acssensors.0c01884 |