IMPROVING UPSTREAM BIOPROCESSING BY ENABLING PROCESS SCOUTING DEVICES WITH LOW COST, DISPOSABLE OXYGEN AND pH SENSORS

Title	IMPROVING UPSTREAM BIOPROCESSING BY ENABLING PROCESS SCOUTING DEVICES WITH LOW COST, DISPOSABLE OXYGEN AND pH SENSORS
Author	Vallejos, Jose Reynaldo
Advisors	Moreira, Dr. Antonio ; Rao, Dr. Govind ;
Program	Engineering, Chemical and Biochemical
UMBC Department	Chemical and Biochemical Engineering
Document Type	dissertation
Sponsors	University of Maryland, Baltimore County (UMBC)
Keywords	Cell culture; kla; optical sensors; process development; process transfer; scale-up Cell culture; kla; optical sensors; process development; process transfer; scale-up Cell culture; kla; optical sensors; process development; process transfer; scale-up
Date Issued	2011-01-01
Abstract	Bioprocess information generated at the Process Scouting Devices (PSDs)-scale (<100mL) constitutes the initial building block upon which an industrial bioprocess is developed. Despite the key role that they play in bioprocess development, PSDs often lack the capability of monitoring the critical cell culture process parameters (e.g. dissolved oxygen (DO), pH, substrate consumption, product formation, etc.), and measuring certain engineering physical characteristics (e.g. , , mixing time). As a result there is a process information gap between un-instrumented PSDs and fully instrumented lab cell culture devices that makes the process transfer from research to manufacturing scale more of an art than a science. In this project we have equipped T-flasks, small-scale spinner flasks and novel PSDs such as SuperSpinner D 1000® with low cost disposable dissolved oxygen and pH sensors which can convert these un-instrumented PSDs to cell culture devices that can provide greater quantitative process information. By taking this approach, we have been able to 1) Convert T-flasks into novel upstream bioprocessing tools for scale-up/down applications such as cell clone stability testing. We observed from DO and pH profiles that after cell vial thaw significant biochemical pathway changes can occur during extended cell passaging in static T-flasks. Our on-line monitoring of pH and DO profiles picked the metabolic shifts ten passages earlier that the off-line sampling methods. 2) Develop empirical mass transfer correlations for rocking and shaken T-flasks and compare the oxygen transfer capabilities of these sensor enabled T-flasks with other PSDs such as spinner flasks. We observed that rocking/shaken T-flasks have superior mass transfer coefficient (kLa) than novel and traditional PSDs such as CultiFlask 50, SuperSpinner D 1000® and standard spinner flasks. 3) Provide a novel vial thaw and inoculum expansion train (rocking) with on-line monitoring capabilities for critical cell culture parameters such as DO and pH. We have observed that a design space based on kLa or DO can be developed at the PSDs-scale and integrated with bench-scale devices (and beyond). As a first step, this project shows how patch-based disposable optical technology can aid integrating research and manufacturing scales by using chemical engineering principles (mass transfer). We hypothesize that a robust and predictable bioprocess can be obtained by providing the cells with similar DO levels (or mass transfer coefficients) at every step of the bioprocess development cycle and thereby enabling implementation of Process Analytical Technology (PAT).
Identifier	10516
Format	application:pdf application:pdf application:pdf
Language	en
Collection	UMBC Theses and Dissertations.
Rights Statement	This item may be protected under Title 17 of the U.S. Copyright Law. It is made available by UMBC for non-commercial research and education. For permission to publish or reproduce, please see http://aok.lib.umbc.edu/specoll/repro.php or contact Special Collections at speccoll(at)umbc.edu.
Source	Vallejos_umbc_0434D_10516.pdf

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IMPROVING UPSTREAM BIOPROCESSING BY ENABLING PROCESS SCOUTING DEVICES WITH LOW COST, DISPOSABLE OXYGEN AND pH SENSORS

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