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Conductive mechanism
Published in Stanley A. Gelfand, Hearing, 2017
Subsequent experiments led to the abandonment of this principle, since studies of drum movement were inconsistent with it, and since Helmholtz's results were not replicated (Wever and Lawrence, 1954). Bekesy (1941) used a capacitance probe to measure human eardrum displacement at various frequencies. The capacitance probe used a very fine wire as one plate of a capacitor and the drum surface as the other plate. Sound causes the drum to vibrate, which in turn varies its distance from the wire. If a current is passed through this capacitor, the movement of the drum will affect current flow. Monitoring the current flow at different spots on the drum enabled Bekesy to determine its displacement with considerable accuracy.
Engineering death resistance in CHO cells for improved perfusion culture
Published in mAbs, 2022
Michael A. MacDonald, Matthias Nöbel, Verónica S. Martínez, Kym Baker, Evan Shave, Peter P. Gray, Stephen Mahler, Trent Munro, Lars K. Nielsen, Esteban Marcellin
The antibody titer was monitored in the reactor supernatant and permeate stream throughout the runs (Supplementary material Figure 2). Cell-specific productivity qp and biomass-specific productivity qp,biomass were calculated for cultures during and after a capacitance probe-controlled bleed, designated as phase I and phase II, respectively (Figure 6).
Biomanufacturing evolution from conventional to intensified processes for productivity improvement: a case study
Published in mAbs, 2020
Jianlin Xu, Xuankuo Xu, Chao Huang, James Angelo, Christopher L. Oliveira, Mengmeng Xu, Xia Xu, Deniz Temel, Julia Ding, Sanchayita Ghose, Michael C. Borys, Zheng Jian Li
For Process C, the same CHO2 (GS−/-) cell line was used for vial thaw and seed expansion in the B2 basal medium. Cells were passaged every 3 days prior to N-2 seed inoculation. N-2 perfusion seed culture was run in a 50-L wave bioreactor (GE Healthcare) with a 25 L working volume containing the B2 basal medium and a SD of 2.3 × 106 cells/mL. The perfusion wave bioreactor was equipped with a 0.2-µm filter to remove the spent culture medium while retaining the cells. Perfusion was initiated on day 1 with fresh B2 medium continuously added (media-in) and spent culture medium withdrawn (media-out) at the same rate through peristaltic pumps for media exchange. The perfusion rate was controlled in the step-wise mode with 0.5 vessel volume per day (VVD) from day 1 to day 3 and 1 VVD from day 3 to day 4. Temperature was set to 36.5°C. Rocking speed was controlled at 28 rpm with a 7° rocking angle. Air and CO2 gas flow rates were properly controlled to ensure good cell growth with a final VCD targeted at 26–42 × 106 cells/mL and cell viability at >90% on day 4. N-1 perfusion seed culture was run in a 500-L disposable bioreactor (Xcellerex, GE Healthcare) with a 195 L working volume containing the B2 medium and with a SD of 3.3 × 106 cells/mL. A single-use XCELLTM ATF 6 unit (Repligen) was connected to the 500-L bioreactor to perfuse the culture. Fresh B2 medium was continuously added while spent culture medium was continuously removed at the same rate. Perfusion rate, started on day 1 at 0.04 nL/cell/day, was controlled as a function of VCD as measured by an online capacitance probe (Hamilton). Temperature was maintained at 36.5°C. pH was set to 7.2 and controlled via carbon dioxide or sodium carbonate addition, as needed. Agitation was set to 100 rpm. Air overlay was set to 2.9 LPM, while bottom air was set to 1.0 LPM. Dissolved oxygen was set to 40% by cascade control of oxygen. A final VCD was targeted at 90–120 × 106 cells/mL with >90% cell viability on day 6. An intensified fed-batch production (Process C) inoculated with the perfusion N-1 seed was run in a 2000-L disposable bioreactor (Xcellerex, GE Healthcare) with an initial 1210 L working volume containing a B3 basal medium and with a SD of 16 × 106 cells/mL. Temperature was initiated at 36.5°C with a temperature shift to 32.0°C from day 3 on. pH was set to 7.2 and controlled via carbon dioxide or sodium carbonate addition, as needed. Agitation was set to 90 rpm. Air overlay was set to 13.3 LPM, while bottom air was set to 25 LPM. Dissolved oxygen was set to 40% by cascade control of oxygen. A proprietary feed F3 was initiated from day 2 and fed daily by a single bolus addition for the rest of the duration. The cell culture was harvested with about 1800 L final volume by depth filtration on day 14 post inoculation. The harvested bulk was then clarified by 0.22 µm filtration.