249th American Chemical Society National meeting, Division for Biochemical Technology (BIOT) BIOT 315: Process Analytical Technology Solutions for Robust Measurement and Control of Upstream Bioprocesses Elizabeth R. Gibson1, Kaylee Lanz1, Edwin Koerperick1, Daniel Cooley1, Jonathon T. Olesberg1, Chris Evans1, Gary W. Small1,2, Mark A. Arnold1,2 1
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ASL Analytical, Inc., Coralville, IA Optical Science and Technology Center and Department of Chemistry, University of Iowa, Iowa City, IA Analytical sensing technologies that can measure key chemicals in real‐time during cell expansion and protein expression phases of upstream processes have been of interest to the biotechnology community for some time. The driving goal for the development of these technologies, in addition to enhanced process efficiency, is consistent product quality through discovery, process development, scale up, and manufacturing. Real‐time chemical monitoring is recognized as being particularly important during these complex processes, where multiple parameters including media composition, dissolved oxygen levels, and reactor scale are known to impact product quality. A novel on‐line bioprocess monitor is presented for the simultaneous, real‐time measurement of key analytes during recombinant protein production. This automated monitor, developed initially for the yeast Pichia pastoris and recently expanded to include the CHO protein expression platform, uses a completely sealed and sterilized closed loop to continuously circulate a small sample from the bioreactor, through the monitor, and back to the bioreactor. There is zero sample lost from monitoring and the measurement method is completely nondestructive. In contrast with some previous approaches, very little operator expertise is required and long‐term stability without repeated calibration is demonstrated. Results will be presented showing robust operation and accurate monitoring for more than 3 months post‐calibration. The ability of the monitor to maintain closed‐loop feedback control at multiple concentration set points will be presented. DIVISION: Division of Biochemical Technology SESSION: Poster Session SESSION TIME: Tuesday, March, 24, 2015, 6:00 PM ‐ 9:00 PM ROOM & LOCATION: Imperial Ballroom ‐ Grand Hyatt Denver BIOT 458: Real‐time, Continuous Monitoring of Cellular Nutrients and Metabolites for Optimization of Upstream Bioprocesses Mark A. Arnold,1,2 Elizabeth R. Gibson1, Kaylee Lanz1, Edwin Koerperick1, Daniel Cooley1, Jonathon T. Olesberg1, Chris Evans1, and Gary W. Small1,2 1
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ASL Analytical, Inc., Coralville, IA Department of Chemistry, University of Iowa, Iowa City, IA This presentation will focus on the analytical utility of a robust monitor designed for continuous, real‐time measurements of cellular nutrients and metabolites during upstream bioprocesses. Measurements are based on non‐destructive near infrared spectroscopy where a small volume of the bioprocessing broth is continuously circulated from the reactor, through the monitor, and back to the reactor within a sterilized closed loop. Near infrared spectra are collected as the sample passes through the monitor and the concentrations of targeted analytes are determined automatically from the resulting spectrum. Unlike traditional near infrared systems, the RTBio™ monitor eliminates the need for the user to develop and maintain an instrument calibration function for each analyte. Data showing extended operation in industrial environments will be presented including real‐time measurements of glycerol and methanol concentrations, as well as relative cell density, for bioprocesses using Pichia pastoris yeast. Real‐time measurements of glucose and lactate during CHO cultivations will also be presented. The robustness of this approach will be demonstrated by assessing measurement accuracy for multiple bioprocesses implemented over many months. Lastly, the unique information that real‐time, continuous monitoring provides will be highlighted. DIVISION: Division of Biochemical Technology SESSION: Upstream Processes SESSION TIME: Thursday, March 26, 2015, 9:30 AM – 9:50 AM ROOM & LOCATION: Mt. Evans ‐ Grand Hyatt Denver