Water Flow-NMR—A Prospective Contact-Free In-Line Analytical Tool for Continuous Biomanufacturing

Abstract

Continuous manufacturing of biopharmaceuticals paves way to much faster and higher quality products compared to conventional batch manufacturing. One of the most critical impediments for a wider use of continuous biomanufacturing is the lack of noninvasive analytical tools for process monitoring. We have already demonstrated that water proton transverse relaxation rate R2(1H2O) could be used to noninvasively monitor a number of important aspects of a solute state, such as protein concentration and aggregation. Here, we present the results obtained using compact low-field benchtop flow-NMR instrument capable to measure R2(1H2O) within a wide range of flow rates. Our measurements confirmed the sensitivity of R2(1H2O) to flow rate changes, protein concentration, and the content of the protein aggregates in stressed protein solutions.