Development and Characterization of a Portable Flow Microreactor for Enhanced Bioconjugation Applications

• Published in: Organic process research & development 2024-05, Vol.28 (5), p.1806-1813
• Main Authors: Endo, Yuta, Nakahara, Yuichi, Shiroma, Ryo, Takimoto, Kiyotaka, Matsuda, Yutaka
• Format: Article
• Language: English
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/acs.oprd.3c00384

The reliance of pharmaceutical production on batch reactors dating back to the 20th century has exposed vulnerabilities in the supply chains of essential medicines, which were exacerbated by recent global challenges such as the COVID-19 pandemic and geopolitical tensions. Modern alternatives such as flow microreactors (FMRs) promise streamlined chemical production in small channels, enabling precise local production with advantages such as efficiency, environmental friendliness, and potential cost reduction. In particular, the field of bioconjugate synthesis has expanded rapidly alongside traditional small-molecule drugs. This study describes the development and optimization of a Portable FMR system designed to fit the size constraints of a suitcase. The system was successfully tuned to withstand practical applications, and the performance was stabilized by using a feedback mechanism based on actual flow measurements relative to the pressure (or viscosity). The mixing capability was verified by using the Villermaux–Dushman reaction. Bioconjugate synthesis, exemplified by the PEGylation of interleukin-6, showcased successful mono-PEGylation while reducing aggregation rates. Additionally, the synthesis of antibody–drug conjugates was efficiently accomplished by using a tandem-mode reactor system, highlighting advancements in this field. To the best of our knowledge, this is the first report on the development of a Portable suitcase-sized FMR device using bioconjugate syntheses.