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Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing

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

Deadline for manuscript submissions: 5 July 2026 | Viewed by 46822

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Special Issue Editors

Dr. Giannis Penloglou

E-Mail Website1 Website2
Guest Editor

1. Department of Environmental Engineering, International Hellenic University (IHU), Sindos, EL-57400 Thessaloniki, Greece
2. Chemical Process and Energy Resources Institute—CPERI/LPRE, Centre for Research and Technology Hellas—CERTH, 57001 Thessaloniki, Greece
Interests: photobioreactors; fermentation; microalgae; biopolymers; biorefinery; biofuels; nanocellulose; bioprocess modeling; techno-economic analysis; biomass
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Dr. Alexandros Pavlou

E-Mail Website
Guest Editor Assistant

Chemical Process and Energy Resources Institute—CPERI/LPRE, Centre for Research and Technology Hellas—CERTH, Thessaloniki 57001, Greece
Interests: microalgae; photobioreactors; CO₂ capture; techno-economic analysis; biopolymers; biomolecules; nanomaterials; agro-industrial wastes; colloids; emulsifying agents

Special Issue Information

Dear Colleagues,

Bioreactors are increasingly essential for various industries such as pharmaceuticals, food and beverages, agriculture, environmental remediation, and bioenergy. Specifically, novel design and optimization of bioreactors are critical for enhancing efficiency and productivity within biorefineries and bioprocessing systems, addressing contemporary challenges in the bioeconomy. This entails consideration of parameters such as reactor type, agitation, aeration, temperature, pH control, and nutrient supply. Optimization techniques, including mathematical modeling and statistical analysis, aid in maximizing product yield, minimizing production costs, and ensuring process robustness.

In biorefineries, where multiple products are derived from biomass and wastes, integrated bioreactor systems are indispensable. These systems should be adaptable to various feedstocks and capable of handling complex microbial communities. Advanced monitoring and control strategies enable real-time adjustments to optimize performance. Furthermore, the integration of downstream processing units enhances product purification and recovery. Beyond technical advancements in bioreactors, ensuring their economic and environmental sustainability is of paramount importance.

In this context, the aim of this Special Issue of Processes is to attract high-quality original research contributions and review articles in the field of “Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing”. This could include individual experimental and theoretical studies or combined approaches.

Specific topics for the Special Issue include, but are not limited to, the following:

Design of innovative bioreactor configurations, including photo-bioreactors.
2G and 3G biorefineries for energy, fuels and materials.
Fermentative production of biofuels, biochemicals, and biopolymers.
Hybrid (photo-)bioreactor systems for bioremediation and wastewater treatment.
Microbial activity towards bioprocessing and downstream processing.
Experimental and model-based intensification and scale-up of bioproduction systems.
Advanced multi-scale modeling and simulation of complex bioreactor phenomena.
Versatile monitoring and efficient control systems for bioreactors.
Techno-economic assessment and Life Cycle Analysis (LCA) of multi-purpose bioreactors.

Dr. Giannis Penloglou
Guest Editor

Dr. Alexandros Pavlou
Guest Editor Assistant

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 250 words) can be sent to the Editorial Office for assessment.

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 semimonthly 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

bioreactor
photobioreactor
fermentation
biorefinery
bioprocessing
microbial production
monitoring and control
mathematical modeling and simulation
techno-economic assessment
life cycle analysis

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Published Papers (10 papers)

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Research

Jump to: Review

17 pages, 5016 KB

Open AccessArticle

Bioprocess Scale-Up: A Computational Fluid Dynamics Approach for the Bioproduction of Succinic Acid from Glycerol

by Ioannis Zacharopoulos and Constantinos Theodoropoulos

Processes 2026, 14(5), 870; https://doi.org/10.3390/pr14050870 - 9 Mar 2026

Viewed by 190

Abstract

In this work, we present the scale-up of a batch anaerobic fermentation system for the production of succinic acid from glycerol using A. succinogenes. The system has been successfully scaled up from an initial bioreactor working volume of 1 L (laboratory scale) to a working volume of 100 L (pilot scale). At the same time, we have developed a hybrid model, combining the intrinsic kinetics of the microbial growth, with a computational fluid dynamics model (CFD) of the bioreactor. The proposed model is able to predict the productivity drop, usually observed while scaling up a bioprocess. In our process, this is a result of the limitations on the mass transfer of CO₂ between the gas and the liquid phase of the system. The model is successfully used to predict the amount of aeration needed in order to achieve increased succinic acid productivity. Using the model, the final succinic acid increased by 4.3%, and the succinic acid productivity increased by 8.5%, while the fermentation by-products decreased by approxiamtely 3% each. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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26 pages, 934 KB

Open AccessArticle

Superstructure-Based Process and Supply Chain Optimization in Sugarcane–Microalgae Biorefineries

by Jorge Eduardo Infante Cuan, Victor Fernandes Garcia, Halima Khalid, Reynaldo Palacios, Dimas José Rua Orozco and Adriano Viana Ensinas

Processes 2026, 14(2), 188; https://doi.org/10.3390/pr14020188 - 6 Jan 2026

Viewed by 490

Abstract

The worldwide transition to renewable energy systems is motivated by diminishing fossil fuel availability and the intensifying consequences of climate change. This study presents a Mixed-Integer Linear Programming (MILP) model for designing and optimising the bio-fuel and electricity supply chain in Colombia, using sugarcane as the main feedstock and integrating microalgae cultivation in vinasse. Six alternative biorefinery configurations and four microalgae conversion pathways were evaluated to inform strategic planning. The optimisation results indicate that microalgae achieve higher energy yields per unit of land than sugarcane. Ethanol production from sugarcane could meet all of Colombia’s gasoline demand, while diesel and sustainable aviation fuel derived from microalgae could supply around 9% and 16%, respectively, of the country’s consumption. Further-more, pelletised bagasse emerges as a viable alternative to replace part of the coal used in thermoelectric plants. From an economic perspective, all scenarios achieve a positive net present value, confirming their profitability. Sensitivity analysis highlights the critical factors influencing the deployment of distilleries as ethanol price, algae productivity, and sugarcane cost. Furthermore, transportation costs play a decisive role in the geographic location of microalgae-based facilities and the distribution of their products. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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25 pages, 3932 KB

Open AccessFeature PaperArticle

Improving the Circularity of Sugarcane Mills: Evaluation of Technologies for Obtaining Isoamyl Acetate from Fusel Oil

by Claudia Liz García Aleaga, Arletis Cruz Llerena, Lourdes Zumalacárregui de Cárdenas, Leandro Vitor Pavão, Mauro Antonio da Silva Sá Ravagnani, Caliane Bastos Borba Costa and Osney Pérez Ones

Processes 2026, 14(1), 37; https://doi.org/10.3390/pr14010037 - 22 Dec 2025

Viewed by 474

Abstract

The commitment to the Sustainable Development Goals and the need for increasing the circularity of industrial processes call for the exploitation of byproducts to generate value-added chemicals in cost- and energy-advantageous processes. In this process simulation-based research, two technologies were evaluated for the synthesis of isoamyl acetate from fusel oil: (A) an indirect process, and (B) a direct process using reactive distillation. Aspen Hysys v14.0 was used for simulation. A sensitivity analysis was performed to identify the influence of operating parameters on product purity, isoamyl acetate recovery and productivity, and energy consumption. Technology B was found to be the most favorable, obtaining 22.27 kg/h of isoamyl acetate with a purity of 98%. The total consumption values of cooling water and heating were 24.33 kW and 24.50 kW, respectively. Based on the best conditions, a technical–economic analysis was performed that demonstrated the viability of the process, obtaining a net present value (NPV) of US$3,587,110/year, an internal rate of return (IRR) of 38.95% and a payback period (PP) of 5.05 years. If acid recirculation is considered in the process, an NPV of US$7,232,950, an IRR of 56.34%, and a PP of 3.56 years are obtained. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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18 pages, 24817 KB

Open AccessArticle

An Open-Source Modular Bioreactor Platform for Cultivation of Synechocystis sp. PCC 6803 and Extraction of Intracellular Glucose

by Ingie Baho, Yitong Tseo, Yuexuan Zu, Vineet Padia and Ian Hunter

Processes 2025, 13(9), 2985; https://doi.org/10.3390/pr13092985 - 18 Sep 2025

Viewed by 1235

Abstract

Synechocystis sp. PCC 6803 is a photosynthetic microbe with high potential for capturing excessive atmospheric carbon while generating valuable bioproducts, like glucose. Current cultivation technologies remain expensive, closed-source, and poorly suited for downstream processing. This study presents a low-cost, open-source bioreactor platform with integrated modules for Synechocystis cultivation and glucose extraction. The system incorporates a photobioreactor, a lysis module, and a pressure-driven filtration setup. Optical density was continuously monitored using a custom-built module, and glucose was quantified using high-performance liquid chromatography (HPLC). Under an incident light intensity of approximately 400

μ m o l

m^{- 2}

s^{- 1}

, cultures reached a biomass productivity of 90 mg

L^{- 1} {day}^{- 1}

, with a specific growth rate of

0.166 {day}^{- 1}

and glucose concentrations up to

5.08

m g L^{- 1}

. A model was developed to predict the growth based on measured environmental parameters, achieving a strong predictive accuracy with a mean absolute error and variance of

0.0009 \pm 0.0003

. The system demonstrates up to 65% reduction in cost compared to commercial alternatives. This modular platform provides an accessible solution for biomanufacturing research and serves as a template for sustainable cyanobacteria-derived glucose production. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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13 pages, 4379 KB

Open AccessArticle

Optimizing Chlorella vulgaris Bioremediation of Wastewater via Advanced Aeration Systems: A Pilot-Scale Implementation

by Lamprini Malletzidou, Eleni Kyratzopoulou, Evangelos Nerantzis, Nikoletta Kyzaki, Nestor C. Tsirliganis and Nikolaos A. Kazakis

Processes 2025, 13(6), 1709; https://doi.org/10.3390/pr13061709 - 30 May 2025

Cited by 1 | Viewed by 2668

Abstract

Towards the bioremediation of toxic compounds from aquatic environments using living microalgae, Chlorella vulgaris has emerged as a promising candidate for the removal of heavy metals. The present study advances the scale-up of the microalga’s culture and investigates its efficiency in multi-metal removal (Cu, Cd, Ni, Pb, and Zn at 1 ppm each). Two aeration conditions were investigated: standard/conventional aeration (SA), and an innovative, custom-built micro-bubble aeration (MBA), which optimizes CO₂ residence time to enhance photosynthesis. Conducted in a pilot-scale 30 L photobioreactor (PBR) over a cultivation period of 7 days, control and multi-metal treated cultures were monitored for pH, cell population growth, and pigment content. Heavy metal removal efficiency was evaluated by means of atomic absorption spectroscopy (AAS) on Days 3 and 7 of cultivation. The comparative results reveal that MBA significantly enhances both the population and the photosynthetic pigment content of the cultures. Furthermore, the heavy metal removal efficiency under MBA reached up to 95% even by Day 3 of cultivation, remarkably higher than the 67% of the SA treated culture. These findings not only demonstrate Chlorella vulgaris’s effectiveness in multi-metal treated systems but also highlight the potential of advanced aeration systems to enhance bioremediation efficiency in larger-scale aquatic environments. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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21 pages, 3614 KB

Open AccessArticle

Process Synthesis, Design and Techno-Economic Assessment of Malonic Acid Production

by Virginia Ioannidou, Nikiforos Misailidis, Demetri Petrides and Michael C. Georgiadis

Processes 2024, 12(11), 2559; https://doi.org/10.3390/pr12112559 - 16 Nov 2024

Cited by 3 | Viewed by 3265

Abstract

This work focuses on the design and techno-economic evaluation of an industrial facility for the production of malonic acid. The raw material utilized is commercial glucose syrup with a concentration of 95%. Based on a patent of Lygos, Inc., an innovative biotechnology research company, this study presents a comprehensive synthesis, design, and simulation framework for the production of malonic acid through oligosaccharide fermentation. An integrated process flowsheet is proposed and simulated using SuperPro Designer™. The analysis indicates that for an installation capacity of about 8000 MT/yr of the final product with a purity of 99.5%, the production cost is estimated at USD 7.92/kg. A comprehensive study of the capacity’s impact on economics reveals that this cost could decrease to as low as USD 6.05/kg. A parametric analysis and optimization conducted at the flowsheet level identifies opportunities for further reducing production costs, laying the groundwork for a potential decrease in the product’s selling price. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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Review

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23 pages, 1415 KB

Open AccessReview

Composting of Biodegradable Packaging Materials: A Review of Available Technology for Biopolymer Degradation

by Tea Sokač Cvetnić, Frédéric Debeaufort, Nasreddine Benbettaieb, Iva Pavlinić Prokurica and Mia Kurek

Processes 2026, 14(5), 850; https://doi.org/10.3390/pr14050850 - 6 Mar 2026

Viewed by 284

Abstract

Over the past few decades, the extensive use of plastics has led to significant environmental challenges due to their limited biodegradability and long-term persistence. Consequently, biodegradable materials have attracted considerable attention as sustainable alternative solutions to mitigate these environmental concerns. Also, the use and disposal of these materials present some sustainability challenges. Biopolymers have some advantages over standard polymers, such as biodegradability, non-toxicity and environmental sustainability, and they can be used in various industries. Taking into account the fact that the biopolymers are produced by living organisms and microorganisms, they are considered as the natural materials that can be composted. This review paper explores the increased demand for biopolymers and summarizes their benefits along with application. Overall, the focus is on the composting process as the promising sustainable technology for recovery of biodegradable waste as well as for biopolymers. Also, some biopolymers and their degradation in different conditions are presented, and the biodegradation test methods for these materials are mentioned in accordance with relevant international standards. This review aims to provide a comprehensive overview of current developments and future development directions for the biopolymer field. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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28 pages, 1224 KB

Open AccessReview

A Review of Artificial Intelligence Applications for Biorefineries and Bioprocessing: From Data-Driven Processes to Optimization Strategies and Real-Time Control

by Alex Butean, Iulia Cutean, Ruben Barbero, Juan Enriquez and Alexandru Matei

Processes 2025, 13(8), 2544; https://doi.org/10.3390/pr13082544 - 12 Aug 2025

Cited by 25 | Viewed by 9790

Abstract

This paper reviews the integration of artificial intelligence (AI) and machine learning in biorefineries and bioprocessing, with applications in biocatalysis, enzyme optimization, real-time monitoring, and quality assurance. AI contributes to predictive modeling and allows the precise forecasting of process outcomes, resource management, and energy utilization. AI models, including supervised, unsupervised, and reinforcement learning, support improvements in important bioprocess stages, such as fermentation, purification, and microbial biosynthesis. Digital twins and soft-sensing technologies enable real-time control and increase operational precision in complex bioprocess environments. Hybrid modeling integrates data-driven AI techniques with common scientific principles, improving scalability and adaptability under dynamic operational conditions. This review addresses challenges in AI implementation, such as data standardization, model transparency, and the need for interdisciplinary collaboration. The discussion concludes with future directions and sustainable AI strategies, highlighting the potential of AI to strengthen scalable, efficient, and environmentally sustainable biorefinery operations. These findings highlight how AI-driven methodologies improve operational efficiency, reduce resource waste, and facilitate sustainable innovation in bioprocesses, thereby strengthening sustainability within the bioeconomy. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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22 pages, 840 KB

Open AccessReview

Advanced Optimization of Bioprocess Parameters for Exopolysaccharides Synthesis in Extremophiles

by Nadja Radchenkova and Songül Yaşar Yıldız

Processes 2025, 13(3), 822; https://doi.org/10.3390/pr13030822 - 11 Mar 2025

Cited by 7 | Viewed by 3272

Abstract

Exopolysaccharides (EPSs) represent versatile biopolymers finding diverse applications in food, pharmaceuticals, and bioremediation industries. Extremophiles, thriving under extreme environmental conditions, have emerged as a promising source of novel EPSs with better stability and bioactivity. The present work reviews the complex influence of various abiotic factors and bioprocess parameters such as temperature, pH, carbon and nitrogen sources, C/N ratios, and oxygen transfer dynamics on the production of EPSs from extremophilic microorganisms. Results underline the important role of temperature for structural and functional properties of EPSs, from the synthesis of cryoprotective polymers in psychrophiles to the production of thermostable EPSs in thermophiles under cold stress. The pH has an extensive effect on enzymatic activities: optimal neutral to slightly acidic conditions exist for most strains. Carbon sources determine not only the yield of EPSs but also its structural features, while nitrogen sources and C/N ratios regulate the balance between biomass production and polymer biosynthesis. Besides that, oxygen transfer limitations—which may happen in particularly viscous or saline media—are overtaken by optimized bioreactor configuration and stirring strategies. These findings are highly relevant to the development of tailored cultivation conditions enabling the maximization of EPS yields and adaptation of its properties to comply with industrial requirements. This study provides a framework for enhancing EPS production by leveraging the adaptive traits of extremophiles. This approach supports the sustainable use of biopolymers, advances fermentation production processes, and helps uncover the underlying mechanisms involved. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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18 pages, 3187 KB

Open AccessReview

Recent Advancements in Photo-Bioreactors for Microalgae Cultivation: A Brief Overview

by Giannis Penloglou, Alexandros Pavlou and Costas Kiparissides

Processes 2024, 12(6), 1104; https://doi.org/10.3390/pr12061104 - 28 May 2024

Cited by 85 | Viewed by 21854

Abstract

Inspired by the vast potential of microalgae in the bioeconomy and the numerous applications and benefits associated with their cultivation, a multitude of pilot- and industrial-scale microalgae production systems have been developed in recent years. Both open and closed cultivation systems have been successfully utilized, with closed photo-bioreactors (PBRs) emerging as the most versatile option for various applications and products, enabling the implementation of advanced optimization strategies. Therefore, this short review provides a comprehensive overview of the different PBR configurations and their recent applications, primarily in large-scale but also in pilot- and laboratory-scale microalgae cultivation. A detailed discussion of the advantages, limitations, specific applications and recent advancements of each type of PBR is presented to aid researchers, engineers and industry stakeholders in selecting the most suitable PBR design for their specific goals and constraints. Moreover, this review highlights the major challenges impeding the full commercialization of microalgal products and forecasts future trends in the microalgae-based industry. The diverse potential applications of microalgae in various sectors, including biofuels, nutraceuticals, pharmaceuticals, agriculture and environmental remediation, underscore the versatility and significance of the relevant cultivation technologies. By offering valuable insights into the future commercial scale and trends of microalgal biotechnology, this work sheds light on the challenges and opportunities facing this burgeoning industry. Full article

(This article belongs to the Special Issue Innovative Bioreactor Design and Advanced Optimization Strategies for Biorefineries and Bioprocessing)

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