A Novel 5mm NMR-Compatible Micro-Spindle Bioreactor for Steady-State and Dynamic in Cell NMR

INTRODUCTION: To present, NMR-compatible bioreactors have been utilized as a platform to explore the metabolism of cells non-invasively. These systems have utilized standard 10–25mm coils to exploit filling factor and ease of construction [1-3]. For immortalized cell lines, densities on the order of 10 cells are achievable, requiring extensive cell culture, but this is nearly impossible to achieve for stem cells as we all as other primary cells and tissues. Cultures of immortalized cells, the traditional platform for metabolic study, exhibit an unnaturally rapid mitotic rate, while primary cells and tissues more closely mimic in vivo metabolism [4]. Combing hyperpolarized MR with NMR-compatible 3D cell and tissue culture bioreactors allows for kinetic monitoring of metabolism on a second timescale without any background signals from the culture media under very controlled conditions. The use of primary cell and tissue cultures provides a more clinically relevant platform for testing new hyperpolarized MR probes and therapies. With this in mind, the goal of this study was to develop and implement a 5mm bioreactor system, which would provide comparable performance to 10 mm bioreactors while reducing the necessary cell/tissue and perfusate volume and thus facilitate the study of primary cells and tissues.