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Development of stirred well filtration as a high-throughput technique for downstream bioprocessing

Micro-scale processing (MSP) techniques are miniaturized version of upstream and downstream conventional unit operations that are designed to accelerate the pace of bioprocess design and development. Previous ‘dead end’ filtration studies have demonstrated the usefulness of this concept for membrane filtration processes. However, these experiments were performed without stirring which is the most common strategy to control the effects of concentration polarization and fouling on filtration performance.
In this work, the pressure-driven stirred conditions of a conventional stirred-cell module were integrated with a 96-well filter plate to develop a high throughput technique called ‘stirred-well filtration’ (SWF). The design allowed for up to eight constant flux filtration experiments to be conducted at once using a multi-rack programmable syringe pump and a magnetic lateral tumble stirrer. An array of pressure transducers was used to monitor the transmembrane pressure (TMP) in each well. The protein sieving behavior and fouling propensity of Omega™ ultrafiltration membranes were assessed via a combination of hydraulic permeability measurements and protein sieving tests in constant filtrate flux mode. The TMP profile during filtration of bovine serum albumin (BSA) solution was strongly dependent on the stirring conditions – for example the maximum TMP in the stirred wells were an average of 7.5, 3.8, and 2.6 times lower than those in the unstirred wells at filtrate fluxes of 12, 36, and 60 LMH (5, 15, and 25 μL/min) respectively. The consistency of the data across different wells for the same stirring condition was very good. To demonstrate the effectiveness of the SWF technique, the eight tests for a simple 2^2 factorial design-of-experiments (DOE) test with duplicates was run to evaluate the effect of solution pH and salt concentration on protein filtration. The combination of SWF with statistical methods such as DOE is shown to be an effective strategy for high-throughput optimization of membrane filtration processes. / Dissertation / Master of Applied Science (MASc)

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/16153
Date11 1900
CreatorsKazemi, Amir Sadegh
ContributorsLatulippe, David, Chemical Engineering
Source SetsMcMaster University
Languageen_US
Detected LanguageEnglish
TypeThesis

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