Understanding gradients in industrial bioreactors

Nadal-Rey, Gisela; McClure, Dale D.; Kavanagh, John M.; Cornelissen, Sjef; Fletcher, David F.; Gernaey, Krist V.

doi:10.1016/j.biotechadv.2020.107660

“…Using a conventional single-point top feed (left-most part of Figure 4) created a slowly-dissolving concentration gradient across the working height: the tracer concentration remained higher close to the feeding point and lower in the rest of the tank. Similar highly segregated concentration fields have been observed in many other simulations of tall multi-impeller vessels [3][4][5]29], and the phenomenon has also been experimentally confirmed in bioreactors [1,2,5]. As can be seen in the middle and right-most parts of Figure 4, the segregation can be efficiently abolished by using as little as two appropriately placed feed points, leading to superior homogenization.…”

Section: Multi-port Feed Simulationssupporting

confidence: 81%

“…The presented simulation results imply that the feed-related gradients found for example in large-scale bioprocesses [1][2][3][4][5] could be diminished considerably by dividing the feed into multiple symmetrically positioned points. Similar benefits could also be anticipated in other contexts.…”

Section: Discussionmentioning

confidence: 99%

“…In aerobic bioprocesses they are especially prevalent and find use in the production of antibiotics, enzymes, and therapeutic proteins, to name a few. However, macromixing in a large-scale (cubic meters) multi-impeller tank tends to be severely limited, which leads to heterogeneities if the time-scale of reaction competes with that of mixing [1][2][3][4][5]. Some reductions in the macromixing time have been realized in experiments by relocating the single feed point from the top to the middle [6,7].…”

Section: Introductionmentioning

confidence: 99%

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A Multi-Point Feed Increases Macromixing Rate by an Order of Magnitude in Simulated Multi-Impeller Vessels

Losoi¹,

Konttinen²,

Santala³

2021

Preprint

0

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Tall vessels equipped with multiple impellers, such as many gas-liquid contactors in bioprocessing, often suffer from poor macromixing of feeds, which leads to heterogeneities and complicates the scale-up. Here, a diffusion equation was used as a simple model of macromixing in multi-impeller tanks, and the model fitted previously published experimental tracer curves. The model was then noted to predict that the macromixing time-scale is decreased to a quarter by relocating the feed point from the top to the middle. Furthermore, dividing the vessel axially in symmetric proportions and locating a feed point in the center of each compartment was found to reduce the time-scale even further. These theoretical results were put to test by compartment model simulations of 17 L to 22 m3 tanks with one to four impellers. Order-of-magnitude improvements were seen in the multi-impeller setups: up to 29-fold macromixing rates compared to a single-point top feed were realized with multiple feed points in a 22 m3 bioreactor stirred with four Rushton turbines. Considerable improvements were observed also in the other scales and geometries with fewer than four impellers, which suggests that the herein proposed division of feed points may greatly facilitate the scale-up of tall multi-impeller vessels.

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“…The bioreactor is the core of the biological process with four major functions. They are: (1) to contain the substrate; (2) to contain the processed microorganism; (3) to protect the processed microorganism against contamination and (4) to control parameters and environmental conditions to optimise growth and product formation [39][40][41].…”

Section: Introductionmentioning

confidence: 99%

Performance of Fungal Growth Through Integrated Gompertz Model and Respiratory Quotient by Solid State Fermentation in Multi-Layer Squared Tray Solid State Bioreactor with Aeration Strategies

Manan

¹

,

Webb

²

2021

Preprint

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A newly designed, laboratory-scaled and multi-layer squared tray solid state bioreactor (SSB), was developed and successfully operated in solid state fermentation (SSF) conditions. The bioreactor was divided into eight layers of squared perforated trays. Wheat bran was used as a solid substrate for the growth of Aspergillus awamori and Aspergillus oryzae. The SSB was equipped with an oxygen (O2)/carbon dioxide (CO2) gas analyser and a thermocouple. Continuous on-line monitoring of fungal growth could be performed by indirect methods that measure O2 consumed, production of CO2 and metabolic heat. The advantage of using this method is that there are no tedious and time-consuming sampling processes. The evolution of CO2, which represents an accumulation term, was integrated with time and fitted to the Gompertz model in a log-like equation. The Gompertz model generated values that may be used to stimulate and verify the experimental data. Results strongly suggest that the evolved and accumulated CO2, excellently described fungal growth. Simulated results agreed with experimental results. The respiratory quotient (RQ), which is the ratio of CO2 evolution rate (CER) to O2 uptake rate (OUR), was determined by the gas balance method. CER and OUR confirmed that measurements correlated to fungal activity. Each RQ values can explain the differences of each SFF process carried out. Yet, heat evolved by fungal activity also described fungal growth. The current findings is an excellent pre-liminary experimental work, evidencing that multi-layer squared tray SSB with forced moistened aeration present a promising alternative of instrumented bioreactors for SSF processes.

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“…In aerobic bioprocesses they are especially prevalent and find use in the production of antibiotics, enzymes, and therapeutic proteins, to name a few. However, macromixing in a large-scale (cubic meters) multi-impeller tank tends to be severely limited, which leads to heterogeneities if the time-scale of reaction competes with that of mixing [1][2][3][4][5]. Some reductions in the macromixing time have been realized in experiments by relocating the single feed point from the top to the middle [6,7].…”

Section: Introductionmentioning

confidence: 99%

A Multi-Point Feed Increases Macromixing Rate by an Order of Magnitude in Simulated Multi-Impeller Vessels

Losoi

¹

,

Konttinen²,

Santala³

2021

Preprint

0

View full text Add to dashboard Cite

Tall vessels equipped with multiple impellers, such as many gas-liquid contactors in bioprocessing, often suffer from poor macromixing of feeds, which leads to heterogeneities and complicates the scale-up. Here, a diffusion equation was used as a simple model of macromixing in multi-impeller tanks, and the model fitted previously published experimental tracer curves. The model was then noted to predict that the macromixing time-scale is decreased to a quarter by relocating the feed point from the top to the middle. Furthermore, dividing the vessel axially in symmetric proportions and locating a feed point in the center of each compartment was found to reduce the time-scale even further. These theoretical results were put to test by compartment model simulations of 17 L to 22 m3 tanks with one to four impellers. Order-of-magnitude improvements were seen in the multi-impeller setups: up to 29-fold macromixing rates compared to a single-point top feed were realized with multiple feed points in a 22 m3 bioreactor stirred with four Rushton turbines. Considerable improvements were observed also in the other scales and geometries with fewer than four impellers, which suggests that the herein proposed division of feed points may greatly facilitate the scale-up of tall multi-impeller vessels.

show abstract

Understanding gradients in industrial bioreactors

Cited by 70 publications

References 148 publications

A Multi-Point Feed Increases Macromixing Rate by an Order of Magnitude in Simulated Multi-Impeller Vessels

A Multi-Point Feed Increases Macromixing Rate by an Order of Magnitude in Simulated Multi-Impeller Vessels

Performance of Fungal Growth Through Integrated Gompertz Model and Respiratory Quotient by Solid State Fermentation in Multi-Layer Squared Tray Solid State Bioreactor with Aeration Strategies

A Multi-Point Feed Increases Macromixing Rate by an Order of Magnitude in Simulated Multi-Impeller Vessels

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