A flow injection analysis system for fermentation monitoring and control

Abstract

An automated analysis system for on-line fermentation monitoring is presented. The modular system consists of an in-line sterilizeable crossflow microfilter, a selection valve that allows injection of sample or standards, a degassing unit, a dilution module, and a FIA manifold with a spectrophotometric UV/VIS detector. In the dilution module samples are conditioned and diluted depending upon concentration of analyte and the working range of the analyzer. Methods for the monitoring of glucose, ethanol, ammonia and phosphate are described. Results from the monitoring of glucose and their use in fermentation control are presented. The maximal analysis frequency is 30 samples per hour including the dilution of 1 : 200. Detection limits are 5 mg/L for ethanol and glucose, 1 mg/L for phosphate and 50 mg/L for ammonia.

Bioprocess monitoring and computer control: Key roots of the current PAT initiative

“…Required broth stream filtration Kobayashi et al (1987) Anchorage-dependent mammalian cells Stable and reproducible only up to 7 days Male et al (1997) Glucose Recominant E. coli Maximized biomass for protein yields Garn et al (1989) Ciba-Geigy …”

Development of Bioreaction Engineering

“…Later on, UF membrane filtration was used for sampling and analysis of low molecular-weight analytes, and MF membrane filtration for sampling and analysis of proteins. The first external cross-flow aseptic membrane module that was integrated into a medium recirculation loop [141] was commercialized by B. Braun Melsungen (BIOPEM®); another system [142] was produced by Millipore. The first internal in situ filter for sampling [143] was commercialized by ABC Biotechnologie/Bioverfahrenstechnik GmbH.…”

Semi-on-line analysis for fast and precise monitoring of bioreaction processes

“…Some of the most often used sample preparation steps include dilution, enzymatic conversion of the analyte, and separation steps such as filtration or gas diffusion. Table I Ogbomo et al, 1991;Rank et al, 1995Carlsen et al, 1994Christensen et al, 1991aLukkari et al, 1993;Palsson et al, 1993Baxter et al, 1994Benthin et al, 1991;Nielsen et al, 1990;Schulze, 1995Munch, 1992 Steube and Spohn, 1994a,b Buttler et al, 1994Joksch et al, 1991;Kunnecke and Schmid, 1991;Rank et al, 1993Rank et al, , 1995Schulze, 1995Benthin et al, 1991, 1992aFilippini et al, 1991;Garn et al, 1989;Nielsen et al, 1990;Nikolajsen et al, 1988;Min et al, 1995;Schulze, 1995;Spohn et al, 1994Spohn et al, 1991Palsson et al, 1993 Rank Schulze, 1995Benthin et al, 1992aNielsen et al, 1990;Nikolajsen et al, 1988;Ogbomo et al, 1991;Min et al, 1995Ogbomo et al, 1991Carlsen et al, 1993Rank et al, 1993, Nielsen et al, 1990 the versatility of the flow injection technique with regard to bioreaction monitoring. The following discussion w...…”