Bioreactors: Control, Optimization and Applications

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Applied Sciences applsci	2.7	4.5	2011	16.9 Days	CHF 2400	Submit
Bioengineering bioengineering	4.6	4.2	2014	17.7 Days	CHF 2700	Submit
Fermentation fermentation	3.7	3.7	2015	14.3 Days	CHF 2600	Submit
Processes processes	3.5	4.7	2013	13.7 Days	CHF 2400	Submit
Water water	3.4	5.5	2009	16.5 Days	CHF 2600	Submit

16 pages, 1983 KiB

Open AccessFeature PaperArticle

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

by Vivian Ott, Jan Ott, Dieter Eibl and Regine Eibl

Processes 2024, 12(4), 806; https://doi.org/10.3390/pr12040806 - 17 Apr 2024

Viewed by 623

Modern production processes for biopharmaceuticals often work with very high cell densities. Moreover, there is a trend towards moving from fed-batch to continuous perfusion processes; a development that is influencing the requirements for bioreactor design and process control. In this study, the transfer [...] Read more.

Modern production processes for biopharmaceuticals often work with very high cell densities. Moreover, there is a trend towards moving from fed-batch to continuous perfusion processes; a development that is influencing the requirements for bioreactor design and process control. In this study, the transfer of fed-batch and perfusion experiments between different cylindrical stirred lab-scale bioreactors and Thermo Scientific’s^TM (Waltham, MA, USA) cubical HyPerforma^TM DynaDrive^TM Single-Use Bioreactor was investigated. Different scaling parameters were used, which were selected based on the requirements of the respective processes. Peak cell densities of up to 49 × 10⁶ cells mL⁻¹ and antibody titers of up to 5.2 g L⁻¹ were achieved in 15- to 16-day fed-batch experiments. In 50-day perfusion cultivations, a viable cell volume of >100 mm³ mL⁻¹ was maintained and more than 1 g L⁻¹ d⁻¹ of antibodies were harvested. The perfusion processes were automated with both cell bleed control and glucose concentration control. Cell retention was performed using Repligen’s (Waltham, MA, USA) XCell^® ATF perfusion systems and single-use devices. In summary, approaches for successfully scaling highly productive fed-batch and perfusion processes between geometrically dissimilar lab and pilot scale bioreactors were demonstrated. The advantages of perfusion in comparison to fed-batch processes were also observed. Full article

(This article belongs to the Topic Bioreactors: Control, Optimization and Applications - 2nd Volume)

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13 pages, 1201 KiB

Open AccessArticle

Improved Performance of Sulfur-Driven Autotrophic Denitrification Process by Regulating Sulfur-Based Electron Donors

by Jiang Xu, Zhikun Lu, Yifeng Xu, Chuanzhou Liang and Lai Peng

Water 2024, 16(5), 730; https://doi.org/10.3390/w16050730 - 29 Feb 2024

Viewed by 729

Abstract

Sulfur-driven autotrophic denitrification (SADN) has demonstrated efficacy in nitrate (NO₃⁻) removal from the aquatic environment. However, the insolubility of elemental sulfur (S⁰) (maximum 5 μg/L at 25 °C) limited the NO₃⁻ removal rate. In this study, [...] Read more.

Sulfur-driven autotrophic denitrification (SADN) has demonstrated efficacy in nitrate (NO₃⁻) removal from the aquatic environment. However, the insolubility of elemental sulfur (S⁰) (maximum 5 μg/L at 25 °C) limited the NO₃⁻ removal rate. In this study, we investigated the performance of a laboratory-scale S⁰-packed bed reactor (S⁰-PBR) under various volumetric NO₃⁻ loading rates. By filling with smaller S⁰ particles (0.5–1 mm) and introducing chemical sulfide (30–50 mg S²⁻-S/L), a high NO₃⁻ removal rate (1.44 kg NO₃⁻-N/(m³·d)) was achieved, which was substantially higher than previously reported values in SADN systems. The analysis of the average specific NO₃⁻ removal rates and the half-order kinetic constants jointly confirmed that the denitrification performance was significantly enhanced by decreasing the S⁰ particle sizes from 10–12 mm to 1–2 mm. The smaller S⁰ particles with a larger specific surface area improved the mass-transfer efficiency. Dosing chemical S²⁻ (20 mg S²⁻-S/L) to trigger the abiotic polysulfuration process increased the specific NO₃⁻ removal rate from 0.366 to 0.557 g NO₃⁻-N/g VSS/h and decreased the portion of removed NO₃⁻-N in the form of nitrous oxide (N₂O-N) from 1.6% to 0.7% compared to the S²⁻-free group. Full article

(This article belongs to the Topic Bioreactors: Control, Optimization and Applications - 2nd Volume)

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15 pages, 8430 KiB

Open AccessArticle

Process Intensification in Human Pluripotent Stem Cell Expansion with Microcarriers

by Misha Alexander Teale, Samuel Lukas Schneider, Dieter Eibl and Regine Eibl

Processes 2024, 12(3), 426; https://doi.org/10.3390/pr12030426 - 20 Feb 2024

Viewed by 1073

Abstract

Given the demands human induced pluripotent stem cell (hiPSC)-based therapeutics place on manufacturing, process intensification strategies which rapidly ensure the desired cell quality and quantity should be considered. Within the context of antibody and vaccine manufacturing, one-step inoculation has emerged as an effective [...] Read more.

Given the demands human induced pluripotent stem cell (hiPSC)-based therapeutics place on manufacturing, process intensification strategies which rapidly ensure the desired cell quality and quantity should be considered. Within the context of antibody and vaccine manufacturing, one-step inoculation has emerged as an effective strategy for intensifying the upstream process. This study therefore evaluated whether this approach could be applied to the expansion of hiPSCs in flasks under static and in microcarrier-operated stirred bioreactors under dynamic conditions. Our findings demonstrated that high density working cell banks containing hiPSCs at concentrations of up to 100 × 10⁶ cells mL⁻¹ in CryoStor^® CS10 did not impair cell growth and quality upon thawing. Furthermore, while cell distribution, growth, and viability were comparable to routinely passaged hiPSCs, those subjected to one-step inoculation and expansion on microcarriers under stirred conditions were characterized by improved attachment efficiency (≈50%) following the first day of cultivation. Accordingly, the process development outlined in this study establishes the foundation for the implementation of this intensified approach at L-scale. Full article

(This article belongs to the Topic Bioreactors: Control, Optimization and Applications - 2nd Volume)

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24 pages, 2508 KiB

Open AccessReview

A Review of AI-Driven Control Strategies in the Activated Sludge Process with Emphasis on Aeration Control

by Celestine Monday, Mohamed S. Zaghloul, Diwakar Krishnamurthy and Gopal Achari

Water 2024, 16(2), 305; https://doi.org/10.3390/w16020305 - 16 Jan 2024

Cited by 1 | Viewed by 1203

Abstract

Recent concern over energy use in wastewater treatment plants (WWTPs) has spurred research on enhancing efficiency and identifying energy-saving technologies. Treating one cubic meter of wastewater consumes at least 0.18 kWh of electricity. About 50% of the energy consumed during this process is [...] Read more.

Recent concern over energy use in wastewater treatment plants (WWTPs) has spurred research on enhancing efficiency and identifying energy-saving technologies. Treating one cubic meter of wastewater consumes at least 0.18 kWh of electricity. About 50% of the energy consumed during this process is attributed to aeration, which varies based on treatment quality and facility size. To harness energy savings in WWTPs, the transition from traditional controls to artificial intelligence (AI)-based strategies has been observed. Research in this area has demonstrated significant improvements to the efficiency of wastewater treatment. This contribution offers an extensive review of the literature from the past decade. It aims to contribute to the ongoing discourse on improving the efficiency and the sustainability of WWTPs. It covers conventional and advanced control strategies, with a particular emphasis on AI-based control utilizing algorithms such as neural networks and fuzzy logic. The review includes four key areas of wastewater treatment AI research as follows: parameter forecasting, performance analysis, modeling development, and process optimization. It also points out potential disadvantages of using AI controls in WWTPs as well as research gaps such as the limited translation of AI strategies from research to real-world implementation and the challenges associated with implementing AI models outside of simulation environments. Full article

(This article belongs to the Topic Bioreactors: Control, Optimization and Applications - 2nd Volume)

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12 pages, 1925 KiB

Open AccessArticle

Maximizing Bio-Hydrogen and Energy Yields Obtained in a Self-Fermented Anaerobic Bioreactor by Screening of Different Sewage Sludge Pretreatment Methods

by Alaa A. El-kebeer, Usama F. Mahmoud, Sayed Ismail, Abu Abbas E. Jalal, Przemysław Kowal, Hussein E. Al-Hazmi and Gamal K. Hassan

Processes 2024, 12(1), 118; https://doi.org/10.3390/pr12010118 - 02 Jan 2024

Viewed by 1143

Abstract

Egypt faces significant challenges in managing its sewage sludge generated in large quantities from wastewater treatment plants. This study investigates the feasibility of utilizing sewage sludge as a renewable resource for hydrogen production through anaerobic digestion at the 100 L bioreactor level. Hydrogen [...] Read more.

Egypt faces significant challenges in managing its sewage sludge generated in large quantities from wastewater treatment plants. This study investigates the feasibility of utilizing sewage sludge as a renewable resource for hydrogen production through anaerobic digestion at the 100 L bioreactor level. Hydrogen is considered a promising alternative energy source due to its high energy content and environmental benefits. To optimize the microbial degradation process and maximize hydrogen production from sewage sludge, a specialized pretreatment is necessary. Various pretreatment methods have been applied to the sewage sludge, individually and in combination, to study the bio-hydrogen production from sewage sludge. The four methods of treatment were studied in batch assays as a pilot scale. Thermal pretreatment of sewage sludge significantly increases bio-hydrogen production yield compared to other sewage sludge pretreatment methods, producing the highest H₂ yield (6.48 LH₂/g VS). In general, the hydrogen yield of any type of pretreated inoculum was significantly higher than the untreated inoculum. At the same time, alkaline pretreatment improved the hydrogen yield (1.04 LH₂/g VS) more than acid pretreatment (0.74 LH₂/g VS), while the hydrogen yield for the combination of pretreatments (shock alkali pretreatment) was higher than both (1.73 LH₂/g VS), On the other hand, untreated sewage sludge (control) had almost no hydrogen yield (0.03 LH₂/g VS). The self-fermented anaerobic bioreactor improved sewage sludge utilization, increased bioenergy yields, and seems to be promising for treating complex wastes at this scale. Full article

(This article belongs to the Topic Bioreactors: Control, Optimization and Applications - 2nd Volume)

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21 pages, 3859 KiB

Open AccessArticle

Optimizing Mass Transfer in Multiphase Fermentation: The Role of Drag Models and Physical Conditions

by Yannic Mast, Moritz Wild and Ralf Takors

Processes 2024, 12(1), 45; https://doi.org/10.3390/pr12010045 - 23 Dec 2023

Viewed by 904

Abstract

Detailed knowledge of the flow characteristics, bubble movement, and mass transfer is a prerequisite for the proper design of multiphase bioreactors. Often, mechanistic spatiotemporal models and computational fluid dynamics, which intrinsically require computationally demanding analysis of local interfacial forces, are applied. Typically, such [...] Read more.

Detailed knowledge of the flow characteristics, bubble movement, and mass transfer is a prerequisite for the proper design of multiphase bioreactors. Often, mechanistic spatiotemporal models and computational fluid dynamics, which intrinsically require computationally demanding analysis of local interfacial forces, are applied. Typically, such approaches use volumetric mass-transfer coefficient (k_La) models, which have demonstrated their predictive power in water systems. However, are the related results transferrable to multiphase fermentations with different physicochemical properties? This is crucial for the proper design of biotechnological processes. Accordingly, this study investigated a given set of mass transfer data to characterize the fermentation conditions. To prevent time-consuming simulations, computational efforts were reduced using a force balance stationary 0-dimension model. Therefore, a competing set of drag models covering different mechanistic assumptions could be evaluated. The simplified approach of disregarding fluid movement provided reliable results and outlined the need to identify the liquid diffusion coefficients in fermentation media. To predict the rising bubble velocities u_B, the models considering the Morton number (Mo) showed superiority. The mass transfer coefficient k_L was best described using the well-known Higbie approach. Taken together, the gas hold-up, specific surface area, and integral mass transfer could be accurately predicted. Full article

(This article belongs to the Topic Bioreactors: Control, Optimization and Applications - 2nd Volume)

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14 pages, 2950 KiB

Open AccessArticle

Scalable and High-Throughput In Vitro Vibratory Platform for Vocal Fold Tissue Engineering Applications

by Andreea Biehl, Ramair Colmon, Anastasia Timofeeva, Ana Maria Gracioso Martins, Gregory R. Dion, Kara Peters and Donald O. Freytes

Bioengineering 2023, 10(5), 602; https://doi.org/10.3390/bioengineering10050602 - 17 May 2023

Viewed by 1225

Abstract

The vocal folds (VFs) are constantly exposed to mechanical stimulation leading to changes in biomechanical properties, structure, and composition. The development of long-term strategies for VF treatment depends on the characterization of related cells, biomaterials, or engineered tissues in a controlled mechanical environment. [...] Read more.

The vocal folds (VFs) are constantly exposed to mechanical stimulation leading to changes in biomechanical properties, structure, and composition. The development of long-term strategies for VF treatment depends on the characterization of related cells, biomaterials, or engineered tissues in a controlled mechanical environment. Our aim was to design, develop, and characterize a scalable and high-throughput platform that mimics the mechanical microenvironment of the VFs in vitro. The platform consists of a 24-well plate fitted with a flexible membrane atop a waveguide equipped with piezoelectric speakers which allows for cells to be exposed to various phonatory stimuli. The displacements of the flexible membrane were characterized via Laser Doppler Vibrometry (LDV). Human VF fibroblasts and mesenchymal stem cells were seeded, exposed to various vibratory regimes, and the expression of pro-fibrotic and pro-inflammatory genes was analyzed. Compared to current bioreactor designs, the platform developed in this study can incorporate commercial assay formats ranging from 6- to 96-well plates which represents a significant improvement in scalability. This platform is modular and allows for tunable frequency regimes. Full article

(This article belongs to the Topic Bioreactors: Control, Optimization and Applications - 2nd Volume)

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25 pages, 8837 KiB

Open AccessArticle

Study on Scale-Up of Anaerobic Fermentation Mixing with Different Solid Content

by Zhe Li, Hancheng Lu, Zixuan Zhang and Baoqing Liu

Fermentation 2023, 9(4), 375; https://doi.org/10.3390/fermentation9040375 - 14 Apr 2023

Cited by 1 | Viewed by 2279

Abstract

The scale-up technology of anaerobic fermentation stirring equipment is worthy of attention. Computational fluid dynamics (CFD) simulations were used to study the scale-up of anaerobic fermentation mixing under different solid content conditions. The applicability of different scale-up criteria was analyzed by investigating the [...] Read more.

The scale-up technology of anaerobic fermentation stirring equipment is worthy of attention. Computational fluid dynamics (CFD) simulations were used to study the scale-up of anaerobic fermentation mixing under different solid content conditions. The applicability of different scale-up criteria was analyzed by investigating the relative parameters, such as the blade tip speed and the Reynolds number. On this basis, the scale-up index was optimized and verified. The results revealed the applicability of five common scale-up criteria under different solid content conditions. When the solid content is less than 5%, the anaerobic fermentation tank should be scaled up according to the same Weber number. When the solid content is between 5% and 10%, the anaerobic fermentation tank should be scaled up according to the same blade tip speed; it was especially suitable for anaerobic fermentation and other conditions that limit the shear rate. Scaling up according to the Reynolds number was not recommended due to the poor mixing effect. When the scale-up index x reached 0.75, there was no need to further reduce it. For anaerobic fermentation systems, the suitable scale-up indices selected for 5%, 10%, and 15% solid content were 1.1, 1, and 0.75, respectively. Full article

(This article belongs to the Topic Bioreactors: Control, Optimization and Applications - 2nd Volume)

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