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Abstract

Non-invasive magnetic resonance imaging and spectroscopy techniques have been used to monitor the growth and distribution of Chinese hamster ovary K1 cells growing in a fixed bed bioreactor composed of macroporous carriers. Diffusion-weighted 1H magnetic resonance spectroscopy was used to monitor the volume fraction of the bioreactor occupied by the cells and diffusion-weighted 1H magnetic resonance imaging was used to map cell distribution. The imaging measurements demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the surface of the carriers. The increase in the volume fraction occupied by the cells during cell growth showed a close correlation with bioreactor ATP content measured using 31P magnetic resonance spectroscopy. These magnetic resonance measurements, in conjunction with measurements of bioreactor glucose consumption, allowed estimation of the specific glucose consumption rate. This declined during the culture, in parallel with medium glucose concentration.

In-cell NMR: Why and how?

“…The diameter and composition of gel threads or beads has of course an impact on diffusion of ions [167]. Adherent cells can be grown on micro-carrier polymer beads [167,778,779,792,793,1093,1099,1100,1112,1800,1865,[1868][1869][1870][1871][1872][1873][1874], on fibers [1800] or even on polyethylene terephthalate (PET) scaffolds [1875]. Cell spheroids and plant cells or root nodules have convenient characteristics: unlike single bacterial or mammalian cells, they do not require any immobilization to be retained in the NMR tube, and simple perfusion systems can be used [882,964,1876,1877], possibly equipped with loose nets and completed by stirring devices [1878].…”

Intracellular Sodium Changes in Cancer Cells Using a Microcavity Array-Based Bioreactor System and Sodium Triple-Quantum MR Signal

“…The non-invasive capability of the MR technique to obtain a variety of physiological information resulted in a large effort to investigate living cells in bioreactor systems by MR [31][32][33]35,[61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]. In general, the low sensitivity of the MR technique requires a high cell density/number, which can be obtained by densely packed 3D cell cultures, to achieve a sufficient SNR within a high temporal resolution.…”

Bioreactor systems for the production of biopharmaceuticals from animal cells

“…There are numerous advantages to using HFBRs and they have received attention for the commercial production of mAbs and recombinant proteins [41–43]. The main advantage of HFBRs is the high cell densities that can be achieved.…”