NMR as powerful technology for noninvasively monitoring cell health and expansion during bioprocessing.

Over the last decades, the success of advanced cell therapies and the increasing production volumes of vaccines, proteins, or viral vectors have raised the need of robust cell-based manufacturing processes for ensuring product quality and satisfying good manufacturing practice requirements. The cultivation process of cells needs to be highly controlled for improved productivity, reduced variability, and optimized bioprocesses. Cell cultures can be easily monitored using different technologies, which could deliver direct or indirect assessment of the cells' viability. Among these techniques, nuclear magnetic resonance (NMR) spectroscopy is a powerful technology that permits the evaluation and the identification of key endogenous metabolites. NMR can provide information on the cell metabolic pathways, on the bioprocesses, and is also capable to quickly test for impurities. In this study, NMR was successfully used as a technology for monitoring cell viability and expansion in different supports for cell growth (including bioreactors), to predict the bioprocess output and for the early identification of key metabolites linked to cell starvation. This investigation will allow the timely control of culture conditions and favor the optimization of the bioprocesses.

Low-Field Benchtop NMR to Discover Early-Onset Sepsis: A Proof of Concept.

Low-field (LF) benchtop NMR is a new family of instruments available on the market, promising for fast metabolic fingerprinting and targeted quantification of specific metabolites despite a lack of sensitivity and resolution with respect to high-field (HF) instruments. In the present study, we evaluated the possibility to use the urinary metabolic fingerprint generated using a benchtop LF NMR instrument for an early detection of sepsis in preterm newborns, considering a cohort of neonates previously investigated by untargeted metabolomics based on Mass Spectrometry (MS). The classifier obtained behaved similarly to that based on MS, even if different classes of metabolites were taken into account. Indeed, investigating the regions of interest mainly related to the development of sepsis by a HF NMR instrument, we discovered a set of relevant metabolites associated to sepsis. The set included metabolites that were not detected by MS, but that were reported as relevant in other published studies. Moreover, a strong correlation between LF and HF NMR spectra was observed. The high reproducibility of the NMR spectra, the interpretability of the fingerprint in terms of metabolites and the ease of use make LF benchtop NMR instruments promising in discovering early-onset sepsis.