1. PPT 206 Instrumentation, Measurement and Control SEM 2 (2012/2013) Dr. Hayder Kh. Q. Ali hayderali@unimap.edu.my 1

2. 2 Overview WHY measure online? WHAT is measured? HOW is biomass measured? Applications System configurations Capacitance vs Optical density Maintenance / Validation / Calibration Application examples Case studies

3. 3 Why Measure Biomass On-line? PROCESS DEVELOPMENT MONITOR: Real-time measurement of VIABLE cell mass CONTROL: Process automation SAFETY: Decreases risk of contamination. COST: Eliminate offline sampling (labor, eliminate errors) CONVENIENCE: no more weekend sampling VOLUME LOSS: Eliminate loss from off-line sampling

4. 4 Why Measure Biomass On-line? MANUFACTURING Reduce risk = huge cost savings Eliminate contamination risk from sampling Eliminate offline sampling error Eliminate “non-conformance” events Automation: feed rates, proactive realtime corrections Reduce excursions from process limits Increase productivity

5. 5 What is measured? Viable cells only Bio-volume Online, real-time Standard units: cells/ml, OD, wet cell weight.

6. 6 How?  Capacitance.  Probes.

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8. 8 Dead cells / debris

9. 9 Non Cellular debris

10. 10 Applications Immobilised Cells & Microcarriers Filamentous bacteria and fungi Animal Cell Culture Suspension Cells Control in Cell Culture Solid Substrates Industrial bacterial fermentations Controlling perfusion bioreactors Bacteria-E.Coli High Density Yeast Fermentations

11. 11 Cell concentration vs Capacitance LINEAR

12. 12 MethodsAdvantagesDis Advantages CAPACITANCE ♦ measures viable cells ♦ insensitive to media, cell debris and gas bubbles. ♦ works in complex industrial media ♦ linear response over a wide concentration ♦ suitable for suspension and attached cells ♦ works in high density biomass. ♦ multiplexable so low cost for multiple fermenters. ♦ higher detection limit than od probes. ♦ single channel system more expensive than od probes. OPTICAL TECHNIQUES sensitive at low concentrations in clean media low cost for single channel. measures dead and live cells affected by media, debris and gas bubbles. non-linear at high cell concentrations. unsuitable with high density biomass. cannot be multiplexed. probe liable to foul

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15. 15 cGMP – MULTI-CHANNEL Biomass Monitor 230

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