Advances in Bioprocess Technology

A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Biological Processes and Systems".

Deadline for manuscript submissions: 15 May 2024 | Viewed by 28705

Special Issue Editors

Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università degli Studi di Napoli Federico II, Piazzale Tecchio 80, 80125 Napoli, Italy
Interests: fermentation; bioreactors; bioprocesse engineering; biomass conversion
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Special Issue, “Advances in Bioprocess Technology”, will address the latest research in environmentally friendly bioprocess technology. Bioprocess technologies include bioenergy from lignocellulose materials, biomass gasification, biofuels/bioproducts production from agro-food waste, enzymatic bioprocess technology, food fermentation, bioprocesses optimization scale-up, and modeling.

Bioprocess technology is a vital part of biotechnology that deals with processes combining all living matter or its components with nutrients to produce specialty chemicals, reagents, and biotherapeutics. These processes form the backbone of translating discoveries of life sciences into useful industrial products. Different stages associated with bioprocess technology include substrates and media preparation, biocatalyst selection and optimization, volume production, downstream processing, purification, and final processing.

A bioprocess can commonly be divided in three stages:

  • Stage I: Upstream processing, which involves the preparation of liquid medium, separation of particulate and inhibitory chemicals from the medium, sterilization, air purification, etc. Upstream processes include the selection of a microbial strain characterized by the ability to synthesize a specific product with the desired commercial value. This strain is then subjected to improvement protocols to maximize its ability to synthesize economical amounts of the product.
  • Stage II: Fermentation, which involves the conversion of substrates to desired product with the help of biological agents such as microorganisms. Techniques for large-scale production of microbial products must provide both an optimum environment for the microbial synthesis of the desired product and be economically feasible on a large scale.
  • Stage III: Downstream processing, which involves the separation of cells from fermentation broth, purification and concentration of a desired product, and waste disposal or recycling.

Therefore, the objective of this Special Issue is to showcase the diversity and advances in research that contributes to developing effective bioprocess technologies.

Original papers on bioprocess technologies are solicited. We are particularly interested in receiving manuscripts that integrate biology and engineering research and/or experimental and theoretical studies. We invite researchers from all areas of bioengineering to submit manuscripts for this important Special Issue of Processes.

Dr. Francesca Raganati
Dr. Alessandra Procentese
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Processes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • upstream processing
  • fermentation
  • downstream processing
  • bioprocessing
  • biomass
  • bioreactors

Published Papers (10 papers)

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Research

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16 pages, 2863 KiB  
Article
Integrated Semi-Continuous Manufacturing of Lentiviral Vectors Using a HEK-293 Producer Cell Line
by Michelle Yen Tran, Shantoshini Dash, Zeyu Yang and Amine A. Kamen
Processes 2023, 11(12), 3347; https://0-doi-org.brum.beds.ac.uk/10.3390/pr11123347 - 01 Dec 2023
Viewed by 1144
Abstract
There have been considerable efforts on improving the lentiviral vector (LV) system and their production. However, there remains the persisting challenge of producing a sufficient quantity of LVs at manufacturing scale to support treatments beyond early clinical trials. Furthermore, their innately labile nature [...] Read more.
There have been considerable efforts on improving the lentiviral vector (LV) system and their production. However, there remains the persisting challenge of producing a sufficient quantity of LVs at manufacturing scale to support treatments beyond early clinical trials. Furthermore, their innately labile nature poses an equally important obstacle in LV production. As LVs lose function over time and they are sensitive to environmental factors in each unit operation in the bioprocess workflow, integrated continuous manufacturing is an attractive strategy for process intensification. This manuscript describes the implementation of nuclease treatment, clarification, and capture step in a semi-continuous mode. Combining the clarification and loading of the capture step as well as operating those steps in parallel to the purification of the capture step expedite the processing time, reducing it by 4-fold as compared to processing the same volume in batch mode using the same membrane size. This semi-continuous operation also improves the recoveries of functional vector particles and total vector particles by 26% and 18%, respectively, showing an added benefit in loading the capture membranes in series in continuous flow chromatography. Building on previously published upstream work using a scalable cell retention device in perfusion mode, this manuscript demonstrates the integration of upstream and downstream in a semi-continuous manner, reducing processing and hold times as well as showing improvements in LV product quality and recovery. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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14 pages, 6049 KiB  
Article
Study on Phase Change Flow and Heat Transfer Characteristics of Microalgae Slurry in the Absorber Tube of a Parabolic trough Solar Collector
by Wei Han, Nanhang Dong and Qicheng Chen
Processes 2023, 11(11), 3107; https://0-doi-org.brum.beds.ac.uk/10.3390/pr11113107 - 30 Oct 2023
Viewed by 602
Abstract
The study of gas–liquid two-phase flow and heat transfer in non-Newtonian fluids is of great significance for the research and development of refrigeration and energy storage. In this paper, the characteristics and influencing factors of the phase change reaction in microalgae slurry were [...] Read more.
The study of gas–liquid two-phase flow and heat transfer in non-Newtonian fluids is of great significance for the research and development of refrigeration and energy storage. In this paper, the characteristics and influencing factors of the phase change reaction in microalgae slurry were studied by numerical simulation and experimental verification. In order to further study the rheological and heat transfer characteristics of gas–liquid two-phase flow in the collector, the effects of wall heat flux, inlet velocity and microalgae slurry concentration on the phase change reaction in microalgae slurry were studied. The results show that when the boundary conditions of microalgae slurry with the same concentration change, the phase transition of microalgae slurry is different. The higher the wall heat flux, the more forward the phase transition occurs, and the smaller the flow rate, the more forward the phase transition occurs. When the boundary conditions remain unchanged, the phase transition point of microalgae slurry with different concentrations is the same, and the concentration of microalgae slurry will not be affected. However, the deviation between the fluid temperature and the thermal conductivity of high-concentration fluid after phase change is larger than that of low-concentration fluids. The deviation in the fluid temperature reaches approximately 10 K, and the deviation in thermal conductivity reaches approximately 0.025 W/(m·K). Therefore, the change in the fluid temperature and heat transfer intensity after phase change in microalgae slurry is more intense than that of Newtonian fluids. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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14 pages, 6658 KiB  
Article
Investigation of Synechocystis sp. CPCC 534 Motility during Different Stages of the Growth Period in Active Fluids
by Zahra Samadi, Malihe Mehdizadeh Allaf, Thomas Vourc’h, Christopher T. DeGroot and Hassan Peerhossaini
Processes 2023, 11(5), 1492; https://0-doi-org.brum.beds.ac.uk/10.3390/pr11051492 - 15 May 2023
Viewed by 1006
Abstract
The motility behavior of suspended microorganisms plays an essential role in the properties of active fluids. Despite the important progress in our understanding of microorganisms’ motility in recent years, there are still several open questions about the dynamics of cell motility in active [...] Read more.
The motility behavior of suspended microorganisms plays an essential role in the properties of active fluids. Despite the important progress in our understanding of microorganisms’ motility in recent years, there are still several open questions about the dynamics of cell motility in active suspensions. Of special interest is the relationship between cell motility and age. In this study, cyanobacterium Synechocystis sp. CPCC 534 was used as the model microorganism, and the cell trajectories were tracked for 78 days during the cell growth period. Results showed that the length of cell trajectories had substantially increased from the exponential growth phase to the stationary phase and had declined at the end of the stationary phase. Similar trends were observed for the cells’ mean squared displacement (MSD), the time-dependent diffusion coefficient of cell suspensions, and the cell displacement probability density function (PDF). These results suggest that the cellular age of microorganisms has a significant effect on various metrics of cell motility and, therefore, can impact the transport properties of active suspensions. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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13 pages, 2533 KiB  
Article
Optimization of the Cultivation Conditions of the Green Algae Dunaliella salina by Using Simplex Method
by Najah Al-Mhanna, Michael Pistorius and Lanah Al Sammarraie
Processes 2023, 11(1), 292; https://0-doi-org.brum.beds.ac.uk/10.3390/pr11010292 - 16 Jan 2023
Cited by 2 | Viewed by 2349
Abstract
The green algae Dunaliella salina offers great potential for the food industry due to its high β-carotene content. To guarantee the economic profitability of cultivation, growth conditions must be improved. Therefore, the effects of pH and salinity on the cultivation of the green [...] Read more.
The green algae Dunaliella salina offers great potential for the food industry due to its high β-carotene content. To guarantee the economic profitability of cultivation, growth conditions must be improved. Therefore, the effects of pH and salinity on the cultivation of the green alga D. salina were investigated and optimized. The simplex method was applied to find the optimum of these two parameters to maximize the biomass and the cell number of D. salina. The optimum pH was found at 7 and 8 at a salt content of 50 g/L, with a biomass content of 1.09 and 1.11 g/L, respectively. The highest biomass was found at a salinity of 50 g/L, with a final biomass of 1.11 g/L. However, by using the simplex method, an optimum product yield was found at a salinity of 64 g/L and an initial pH value of 7.2. Thus, a biomass of 1.23 mg/mL was achieved. In the single observation of both parameters, 14 experiments were conducted to obtain a satisfactory result, whereas eight runs only were required with the simplex method. This leads to the conclusion that using the simplex method is a useful way to drastically reduce the number of required experiments. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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17 pages, 5191 KiB  
Article
Influence of Brown’s Gas on Cracking Behavior of Gas-Phase Tar during Pine Wood Pyrolysis
by Shuo Yang, Yudong Fu, Jie Cui, Zhanzhi Liu, Daocheng Qin, Lin Xu and Youning Xu
Processes 2022, 10(7), 1231; https://0-doi-org.brum.beds.ac.uk/10.3390/pr10071231 - 21 Jun 2022
Viewed by 1302
Abstract
The effect of Brown’s gas on the gas-phase tar cracking behavior, carbonic oxide (CO) production rate, and gaseous product temperature during the pine wood pyrolysis was preliminarily explored. By the application of cold trapping and gravimetric methods, it was found that Brown’s gas [...] Read more.
The effect of Brown’s gas on the gas-phase tar cracking behavior, carbonic oxide (CO) production rate, and gaseous product temperature during the pine wood pyrolysis was preliminarily explored. By the application of cold trapping and gravimetric methods, it was found that Brown’s gas reduces the energy barrier of thermochemical conversion for gas-phase tar, widens the temperature range of gas-phase tar accelerated cracking, and increases the cracking rate. When the pyrolysis temperature increases by 1 °C, the average cracking rate of gas-phase tar increases from C = 4.58 g⋅Nm−3 (flow volume ratio of Brown’s gas to nitrogen, X(Brown’s gas):N2 = 0%) to C = 4.8 g⋅Nm−3 (X:N2 = 1%) and C = 5.02 g⋅Nm−3 (X:N2 = 5%). While participating in the deep cracking of gas-phase tar, Brown’s gas reduces the conversion energy barrier of the gas-phase tar to CO. The CO production rate rises from the initial 1.87% (X:N2 = 0%) to 4.22% (X:N2 = 1%) and 5.52% (X:N2 = 5%) per 1 °C of increased pyrolysis temperature. The consumption of Brown’s gas is 0.32 m3 per 1 g⋅Nm−3 of gas-phase tar cracking within the pyrolysis residence time of 30 min. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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16 pages, 2973 KiB  
Article
Techno-Economic Analysis on an Industrial-Scale Production System of Polyhydroxyalkanoates (PHA) from Cheese By-Products by Halophiles
by Ke Wang, Alex Michael Hobby, Yike Chen, Allan Chio, Bryan Martin Jenkins and Ruihong Zhang
Processes 2022, 10(1), 17; https://0-doi-org.brum.beds.ac.uk/10.3390/pr10010017 - 23 Dec 2021
Cited by 17 | Viewed by 4426
Abstract
Polyhydroxyalkanoates (PHA) are a family of biodegradable plastics used as an ecofriendly alternative for conventional plastics in various applications. In this study, an industrial-scale PHA production system was designed and analyzed for the material flows and economics with the use of SuperPro Designer. [...] Read more.
Polyhydroxyalkanoates (PHA) are a family of biodegradable plastics used as an ecofriendly alternative for conventional plastics in various applications. In this study, an industrial-scale PHA production system was designed and analyzed for the material flows and economics with the use of SuperPro Designer. Haloferax mediterranei was utilized to produce poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Byproduct streams from a local cheese plant, with an input of 168.7 metric ton/day (MT/day) lactose, were used as the feedstock. Three scenarios with different processes for the treatments of used enzyme and spent medium were investigated and the major factors that influence the overall economics were identified. The simulated system produces 9700 MT/year PHBV with a yield of 0.2 g PHBV/g lactose and an overall process efficiency of 87%. The breakeven price was found to be more sensitive to the lactose price than enzyme price. The scenario with enzyme reuse and spent medium recycling achieved the lowest breakeven price among others, which can be less than 4 $/kg PHA based on the delactosed permeate (DLP) unit price. The study suggests utilizing dairy derived feedstocks has the potential to make PHA competitive in the bioplastic market, which could be beneficial to both dairy and bioplastic industries. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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18 pages, 3267 KiB  
Article
An Experimental Investigation of Water Vapor Condensation from Biofuel Flue Gas in a Model of Condenser, (2) Local Heat Transfer in a Calorimetric Tube with Water Injection
by Robertas Poškas, Arūnas Sirvydas, Vladislavas Kulkovas, Hussam Jouhara, Povilas Poškas, Gintautas Miliauskas and Egidijus Puida
Processes 2021, 9(8), 1310; https://0-doi-org.brum.beds.ac.uk/10.3390/pr9081310 - 29 Jul 2021
Cited by 6 | Viewed by 1725
Abstract
In order for the operation of the condensing heat exchanger to be efficient, the flue gas temperature at the inlet to the heat exchanger should be reduced so that condensation can start from the very beginning of the exchanger. A possible way to [...] Read more.
In order for the operation of the condensing heat exchanger to be efficient, the flue gas temperature at the inlet to the heat exchanger should be reduced so that condensation can start from the very beginning of the exchanger. A possible way to reduce the flue gas temperature is the injection of water into the flue gas flow. Injected water additionally moistens the flue gas and increases its level of humidity. Therefore, more favorable conditions are created for condensation and heat transfer. The results presented in the second paper of the series on condensation heat transfer indicate that water injection into the flue gas flow drastically changes the distribution of temperatures along the heat exchanger and enhances local total heat transfer. The injected water causes an increase in the local total heat transfer by at least two times in comparison with the case when no water is injected. Different temperatures of injected water mainly have a major impact on the local total heat transfer until almost the middle of the model of the condensing heat exchanger. From the middle part until the end, the heat transfer is almost the same at different injected water temperatures. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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13 pages, 2167 KiB  
Article
Factors Affecting Detoxification of Softwood Enzymatic Hydrolysates Using Sodium Dithionite
by Dimitrios Ilanidis, Stefan Stagge, Björn Alriksson and Leif J. Jönsson
Processes 2021, 9(5), 887; https://0-doi-org.brum.beds.ac.uk/10.3390/pr9050887 - 18 May 2021
Cited by 2 | Viewed by 1671
Abstract
Conditioning of lignocellulosic hydrolysates with sulfur oxyanions, such as dithionite, is one of the most potent methods to improve the fermentability by counteracting effects of inhibitory by-products generated during hydrothermal pretreatment under acidic conditions. The effects of pH, treatment temperature, and dithionite dosage [...] Read more.
Conditioning of lignocellulosic hydrolysates with sulfur oxyanions, such as dithionite, is one of the most potent methods to improve the fermentability by counteracting effects of inhibitory by-products generated during hydrothermal pretreatment under acidic conditions. The effects of pH, treatment temperature, and dithionite dosage were explored in experiments with softwood hydrolysates, sodium dithionite, and Saccharomyces cerevisiae yeast. Treatments with dithionite at pH 5.5 or 8.5 gave similar results with regard to ethanol productivity and yield on initial glucose, and both were always at least ~20% higher than for treatment at pH 2.5. Experiments in the dithionite concentration range 5.0–12.5 mM and the temperature range 23–110 °C indicated that treatment at around 75 °C and using intermediate dithionite dosage was the best option (p ≤ 0.05). The investigation indicates that selection of the optimal temperature and dithionite dosage offers great benefits for the efficient fermentation of hydrolysates from lignin-rich biomass, such as softwood residues. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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15 pages, 2351 KiB  
Article
An Experimental Investigation of Water Vapor Condensation from Biofuel Flue Gas in a Model of Condenser, (1) Base Case: Local Heat Transfer without Water Injection
by Robertas Poškas, Arūnas Sirvydas, Vladislavas Kulkovas and Povilas Poškas
Processes 2021, 9(5), 844; https://0-doi-org.brum.beds.ac.uk/10.3390/pr9050844 - 12 May 2021
Cited by 8 | Viewed by 2038
Abstract
Waste heat recovery from flue gas based on water vapor condensation is an important issue as the waste heat recovery significantly increases the efficiency of the thermal power units. General principles for designing of this type of heat exchangers are known rather well; [...] Read more.
Waste heat recovery from flue gas based on water vapor condensation is an important issue as the waste heat recovery significantly increases the efficiency of the thermal power units. General principles for designing of this type of heat exchangers are known rather well; however, investigations of the local characteristics necessary for the optimization of those heat exchangers are very limited. Investigations of water vapor condensation from biofuel flue gas in the model of a vertical condensing heat exchanger were performed without and with water injection into a calorimetric tube. During the base-case investigations, no water was injected into the calorimetric tube. The results showed that the humidity and the temperature of inlet flue gas have a significant effect on the local and average heat transfer. For some regimes, the initial part of the condensing heat exchanger was not effective in terms of heat transfer because there the flue gas was cooled by convection until its temperature reached the dew point temperature. The results also showed that, at higher Reynolds numbers, there was an increase in the length of the convection prevailing region. After that region, a sudden increase was observed in heat transfer due to water vapor condensation. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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Review

Jump to: Research

13 pages, 1820 KiB  
Review
Protein L—More Than Just an Affinity Ligand
by Stefan Kittler, Mihail Besleaga, Julian Ebner and Oliver Spadiut
Processes 2021, 9(5), 874; https://0-doi-org.brum.beds.ac.uk/10.3390/pr9050874 - 17 May 2021
Cited by 4 | Viewed by 4936
Abstract
In the past 30 years, highly specific drugs, known as antibodies, have conquered the biopharmaceutical market. In addition to monoclonal antibodies (mAbs), antibody fragments are successfully applied. However, recombinant production faces challenges. Process analytical tools for monitoring and controlling production processes are scarce [...] Read more.
In the past 30 years, highly specific drugs, known as antibodies, have conquered the biopharmaceutical market. In addition to monoclonal antibodies (mAbs), antibody fragments are successfully applied. However, recombinant production faces challenges. Process analytical tools for monitoring and controlling production processes are scarce and time-intensive. In the downstream process (DSP), affinity ligands are established as the primary and most important step, while the application of other methods is challenging. The use of these affinity ligands as monitoring tools would enable a platform technology to monitor process steps in the USP and DSP. In this review, we highlight the current applications of affinity ligands (proteins A, G, and L) and discuss further applications as process analytical tools. Full article
(This article belongs to the Special Issue Advances in Bioprocess Technology)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Bio valorization through advanced process monitoring and control: challenges and opportunities in Bioprocess
Authors: Priyanka Priyankaa; Somesh Mishrab
Affiliation: Department of Chemical Engineering, University of Delaware, USA Department of Chemical Engineering, Indian Institute of Technology Delhi, India
Abstract: The production of biotherapeutics, nutraceuticals, food products “additives” and phytochemicals etc. all is bolstered by the biotech industries. The current progress in genomic related research, innovative methods to generate microbial cell factories, advanced process controller and a recent surge in consumer demand has propelled biotech sector to next level of Industry 4.0. In coming years, this transformation is anticipated to witness a rapid increase in expenditure in biotech sector. The vision of Industry 4.0 and profitability highly leverages the scale economies and scope critically reliant on product yields, titers, and productivity. It requires digitalization and automation, which is mostly missing in current biotech sector. Further, the regulatory bodies emphasize the manufacturing, especially in case of biotherapeutics and nutraceuticals, with in the frame work of Quality by design (QbD) and process analytical technology (PAT). This necessitates the implementation of advanced process control strategy that ensures high product yield (both in quality and quantity), more process understanding, meaningful data transformation, guide in decision making and encouraging digitalization and automation. Also, it helps in developing a knowledge base that can used to develop a control strategy or a “blueprint” of the process. Thus, in the coming years, advanced control algorithms (model predictive, neural networks, and hybrid) and data analytics are identified as vital activities to automate and digitalize the biotech sector. Therefore, in this review, advanced process algorithms and digitalization along with commercial control strategies are critically evaluated and discussed to provide a development path to biotech sector while meeting regulatory requirements with focus on biotherapeutic industry along with nutraceuticals and phytochemicals.

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