Extractive distillation (ED) is a key technology for separating close-boiling and azeotropic mixtures by introducing an entrainer that modifies intermolecular interactions within the mixture. Through selective affinity toward specific components, the entrainer increases the non-ideality of the system, enhances relative volatility, and eliminates close-boiling and azeotropic behavior. However, conventional entrainers such as N-methyl-2-pyrrolidone (NMP) raise significant environmental and health concerns, including reproductive toxicity. Meanwhile, many greener candidates, including biobased and greener organic entrainers, as well as natural deep eutectic solvents (NADESs), remain insufficiently evaluated for ED applications. Nevertheless, systematic and validated entrainer selection strategies, supported by reliable vapor-liquid equilibrium (VLE) data and rigorous process performance comparisons for the close-boiling methylcyclohexane-toluene mixture and the azeotropic n-hexane-ethanol mixture containing these underexplored greener entrainers, are unavailable. Therefore, this thesis aims to develop a framework for screening greener entrainers, along with generating reliable VLE data and performing process performance comparison, to identify effective alternatives to NMP for these two representative separation challenges.
To achieve this objective, a multi-stage entrainer selection methodology was developed, integrating initial screening, predictive modelling, experimental validation, and process performance comparison. In Chapter 2, potential greener entrainers were screened using an initial screening phase, which identified potential greener entrainers based on high boiling temperatures, favorable solvency, and compliance with green chemistry principles. Subsequently, key separation metrics, such as selectivity and capacity at infinite dilution, and performance index, were predicted using quantum chemical calculations (COSMO-RS). In addition, relative volatility was predicted using both COSMO-RS and group contribution methods (UNIFAC and modified UNIFAC Dortmund). Promising candidates were then evaluated experimentally through miscibility tests and relative volatility measurements. Selected greener entrainer candidates, along with benchmark entrainer NMP in both mixtures, were examined for their vapor-liquid equilibrium (VLE) data. Chapters 3 and 4 focus on generating reliable VLE data for both mixtures in the presence of each selected greener entrainer at various entrainer-to-feed ratios (E/F) and operating pressures. The experimental data were examined through thermodynamic consistency tests. Moreover, the data were regressed using activity coefficient models (NRTL and UNIQUAC) to obtain the optimum binary interaction parameters. In Chapter 5, these parameters were implemented in Aspen Plus V.12 for ED process simulations. Greener entrainers were evaluated according their performance compared to NMP using economic indicator (total annual cost) and sustainability metrics, such as energy requirements, water consumption, and CO2 emissions. In addition, the use and limits of predictive tools for ED entrainer screening were evaluated.
The screening results in Chapter 2 identify promising greening entrainers. For the methylcyclohexane–toluene mixture, gamma-valerolactone (GVL), n-butyl-2-pyrrolidone (NBP), and dimethyl isosorbide (DMI) were selected for VLE data experimental evaluation, while NBP, DMI, and guaiacol were selected for the n-hexane–ethanol mixture. Some NADESs and other biobased and greener organic entrainers exhibited favorable predicted selectivity but showed immiscibility issues in the investigated mixtures and were therefore excluded from further evaluation. In Chapters 3 and 4, the measured VLE data for both mixtures containing each entrainer passed the thermodynamic consistency test, indicating the reliability of the data. The VLE data confirmed that the selected greener entrainers significantly increase the relative volatility of the mixtures and effectively remove close-boiling and azeotropic behavior. Process simulations discussed in Chapter 5 indicate that for the separation of methylcyclohexane-toluene, GVL reduces total annual cost (TAC) by 5.6% compared to NMP, while also having a lower energy intensity of 6.1%. In contrast, DMI and NBP exhibit slightly higher TAC values of 6.2% and 15.2%, respectively, along with slightly higher energy intensity of 3.0% and 18.2%. For CO2 emissions and water consumption, GVL remains comparable to NMP, with both exhibiting values of 0.04-0.05 kgCO2/kgproducts and 0.05 m3water/kgproducts. For the n-hexane-ethanol mixture, NBP shows a comparable TAC, with 1.6% slightly higher than that of NMP, with a 3.1% increase in energy intensity. Meanwhile, guaiacol and DMI demonstrate increasing TAC by 10.9% and 14.0%, respectively, along with energy intensity that are 12.5% and 18.8% higher. In addition, CO2 emissions for these options remain comparable at around 0.05-0.06 kgCO2/kgproducts and water consumption is similar at approximately 0.05-0.07 m3water/kgproducts. Importantly, these greener entrainers have significantly lower toxicity profiles than NMP. Furthermore, the TAC deviation threshold of 32% from predictive models compared to the experimental-based NRTL model makes them suitable for early-stage entrainer screening. However, experimental validation remains necessary for detailed process design.
Overall, this thesis provides a systematic and experimentally validated framework for selecting greener entrainers in extractive distillation. The work delivers new and reliable VLE data along with optimum binary interaction parameters and a comparison of process-level performance. The findings demonstrate that replacing conventional entrainers, such as NMP, with greener alternatives is technically feasible, economically viable, and environmentally sustainable. This supports the transition toward more eco-efficient extractive distillation processes.
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The rapid rise in global energy demands has accelerated the depletion of fossil fuel reserves, raising significant concerns about long-term energy security. Beyond resource exhaustion, this growing dependency on fossil fuels has contributed to severe environmental pollution and climate change, leading to strict environmental regulations. Consequently, extensive research efforts have been devoted to developing methods for producing a wide range of platform chemicals from renewable sources. In that respect, industrial biotechnology holds significant potential to replace fossil fuel-dependent production of various chemicals. Nonetheless, improvements in the fermentation and downstream processing are often necessary to enhance the competitiveness of large-scale bioprocesses. Significant research efforts have been put into genetic engineering to improve microorganisms’ performance and optimization of the fermentation process. However, downstream processing after fermentation has not been nearly as promptly addressed. A common limitation of the fermentation processes is the inhibition of microbial production by the products themselves which limits achievable product concentrations in the broth (often <10 wt%). Additionally, the formation of by-products and the presence of microorganisms complicate recovery process after fermentation. Consequently, downstream processing costs may significantly contribute to the total production costs (20-40% for the bulk biochemicals).
Process systems engineering is essential in developing competitive (bio)chemical processes, as it integrates process design and simulation in biotechnology. Hence, this thesis aims to advance industrial biotechnology by developing advanced, large-scale downstream processes for the recovery of fermentation products such as alcohols, diols, esters, carboxylic acids, and aromatic compounds. A systematic approach to downstream process development was undertaken through multiple case studies that were organized into chapters based on the characteristics of the primary product being recovered. Aspen Plus software was used as a computer aided process engineering tool for process design. Various process intensification techniques (e.g. dividing-wall column and reactive distillation), heat integration and heat pumping were studied to reduce energy requirements and decrease total process costs. The performance of the developed processes was assessed through economic analysis and the evaluation of key sustainability metrics, including energy requirements, greenhouse gas emissions, water consumption, water losses, and toxic materials and pollutants intensity.
Chapter 2 focuses on designing downstream processing strategies tailored for low-boiling alcohols produced through fermentation, including ethanol, isopropanol, isobutanol, and hexanol. Since these products are sufficiently volatile, the end-product inhibition can be mitigated by continuously removing the product from the broth using a distillation-based loop around the bioreactor. Heat pump-assisted vacuum distillation was demonstrated as an effective method for initial product recovery from the broth. Additionally, a novel pass-through distillation process was designed specifically for ethanol recovery. This innovative technique separates the evaporation and condensation parts of distillation by introducing an absorption-desorption loop between them. As a result, these operations can be conducted at different pressures, allowing the use of inexpensive cooling utilities while maintaining mild evaporation temperatures. Furthermore, a hybrid approach combining gas stripping with heat pump-assisted vacuum evaporation was developed for the recovery of isobutanol from fermentation broth. In all cases, the initial separation of the product from most of the broth under reduced pressure lowers the operational temperature, making it possible to reuse the remaining broth along with the microorganisms. This may improve fermentation performance by avoiding biomass loss, increasing substrate-to-product yield and reducing water requirements. Following this initial step, a preconcentration step using heat pump-assisted atmospheric distillation was carried out to remove most of the remaining water. The final purification method depended on the properties of the target product. Ethanol and isopropanol, which form homogeneous azeotropes with water, were purified using extractive distillation with ethylene glycol. In contrast, isobutanol and hexanol, which form heterogeneous azeotropes, were purified through a combination of simple distillation and liquid-liquid phase separation. Furthermore, a general methodology for recovering volatile alcohols from fermentation broths was developed and the performance of downstream processing was compared for the recovery of ethanol, isopropanol, isobutanol, and hexanol. Due to the higher hydrophobicity of longer-chain alcohols, their concentrations in the fermentation broth tend to be lower (e.g. 6.14 wt% for ethanol, 5.00 wt% for isopropanol, 1.61 wt% for isobutanol, and 0.24 wt% for hexanol). More dilute fermentation broths result in higher processing costs (0.08, 0.11, 0.16, and 0.53 $/kg, respectively) and increased energy requirements (0.96, 1.35, 2.02 and 3.07 kWthh/kg, respectively) of the downstream processing. Finally, it was concluded that the primary factor influencing downstream processing efficiency is the achievable product concentration in the fermentation broth, rather than the alcohol chain length.
Chapter 3 focuses on developing recovery processes for aliphatic diols that can be produced through fermentation, including 1,3-propanediol, 2,3-butanediol, 1,4-butanediol, and 1,3-butanediol. Due to their high boiling points, simple distillation is unsuitable for separating these compounds from the fermentation broth. Instead, initial separation steps are required to remove biomass, as well as large organic and inorganic molecules. These initial steps result in a clarified, desalted solution, which then undergoes further treatment through preconcentration and final purification. Since these final two steps contribute significantly to overall purification costs due to their high energy requirements, this research focuses on enhancing them to improve the efficiency of downstream processing for aliphatic diols. The preconcentration step was designed to remove most of water along with some light impurities using a heat pump-assisted vacuum distillation. The final purification step, which separates high-purity diol from residual light and heavy impurities, was effectively carried out in a dividing wall column. Furthermore, a general methodology for recovering high boiling components from dilute aqueous solutions was developed. Recovery processes for 1,3-propanediol, 2,3-butanediol, 1,4-butanediol, and 1,3-butanediol, designed according to this methodology, were compared. The performance of downstream processing was primarily determined by the product concentration in the fermentation broth, though the presence of impurities also played a significant role. Nonetheless, in all cases, the proposed methodology enabled the cost effective (total recovery costs of 0.29-0.70 $/kg) and energy-efficient (primary energy requirements of 1.35-2.01 kWthh/kg) recovery of valuable propanediol and butanediol from dilute aqueous solutions (7.0-10.0 wt%). Lastly, adaptable process design offers the possibility of using a single process configuration to produce various aliphatic diols depending on the market demand.
Chapter 4 discusses the development of recovery processes for various organic chemicals produced through different biotechnology-based processes, such as ethyl acetate, propionic acid, 2-phenylethanol, acetic acid, furfural, etc. While these processes differ due to the unique properties of each compound, they all rely on distillation as a primary recovery method. It was employed as the main separation technique to efficiently recover propionic, acetic, and succinic acids from dilute aqueous solutions. An adaptable dividing-wall column design was demonstrated to effectively recover propionic and acetic acids or perform esterification with methanol to recover methyl-propionate and methyl-acetate (total recovery costs of 0.40-0.47 $/kg). Distillation was also utilized as the primary technique in the recovery of ethyl acetate. Due to its high volatility, most of the ethyl acetate is separated in the fermenter off-gas. Consequently, product recovery was carried out from both the vapor and liquid phases, with an azeotropic dividing-wall column used effectively for final purification (total recovery costs of 0.61-1.09 $/kg). Furthermore, distillation-based downstream processing was effectively used for the solvent recovery and final purification of 2-phenylethanol after in-situ product recovery by liquid-liquid extraction. An adaptable azeotropic dividing-wall column was designed to recover high-purity 2-phenylethanol or perform esterification and recover 2-phenylethyl acetate (total recovery costs of 0.64-0.73 $/kg). Lastly, a sequence of distillation steps was developed to recover by-products (acetic acid, formic acid, furfural, 5-hydroxymethyl furfural) from the lignocellulosic biomass pretreatment process using liquid hot water (total recovery costs of 0.78 $/kg). This process could enhance the competitiveness of lignocellulosic biorefineries by enabling the valorization of additional products.
Furthermore, this thesis emphasizes the importance of advancing both upstream and downstream processes simultaneously to ensure the competitiveness and viability of entire bioprocesses. While the primary focus of this research is on recovery process development, it serves as an initial step toward achieving that broader goal. Chapter 5 highlights the significance of integrating upstream and downstream processes in bioprocess development. Isopropanol, along with acetone, and 2-phenylethanol, were selected as representative examples of low boiling and high-boiling biochemicals. Large-scale bioprocesses for their production were designed to showcase the practical application of integrated process design. Isopropanol and acetone were produced through gas fermentation, with different combinations of products (isopropanol and acetone together or separately) considered. Previously developed advanced recovery processes, including heat pump-assisted vacuum distillation, followed by heat pump-assisted atmospheric distillation and extractive distillation, were employed. Detailed techno-economic analysis and life cycle assessments demonstrated competitive economic performance (total production costs of 0.57-0.74 $/kg) and reduced environmental impacts compared to fossil fuel-based production (reduced global warming potential by 138-160%). 2-phenylethanol was produced de-novo through fermentation from glucose. Two different in-situ product recovery processes were compared: liquid-liquid extraction using oleyl alcohol and product adsorption. In both cases, distillation-based separations were used to effectively recover the solvent and obtain high-purity 2-phenylethanol. Additionally, a sensitivity analysis was conducted to examine the influence of 2-phenylethanol concentration on total production costs. This analysis revealed that minimal costs were achieved at a concentration of 1.5 g/L, with concentrations above 1 g/L not resulting in a significant reduction in costs due to increased fermentation costs. Regardless of the used in-situ recovery technique, the developed processes for producing 2-phenylethanol were found to be highly cost-effective (total production costs of 9.03-9.40 $/kg).
Summarizing, this thesis illustrates the significant impact that advancements in downstream processing can have on overall process performance. Specifically, it supports the development of novel advanced separation processes, based on process intensification principles, which have received relatively limited attention in industrial biotechnology. These innovations can play a decisive role in determining the feasibility of bioprocesses for industrial scale applications. Furthermore, the importance of incorporating downstream processing at the early stages of developing biotechnology-based processes is highlighted. The findings presented in this thesis have the potential to drive progress in industrial biotechnology and contribute to the successful commercialization of biotechnology-based products.
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The modern chemical industry faces many challenges, such as energy transition. However, energy transition alone will not provide enough improvements to the industry to maintain profitability and increase sustainability. To achieve these goals, chemical processes have to be appropriately optimised, and only the synergy of these two factors can improve existing processes. Epichlorohydrin production is an important industrial process, but it suffers from several drawbacks such as high energy consumption, significant wastewater production, and low atom efficiency. This is caused by chlorohydrin-based technology, which requires operations in very diluted solutions. In this thesis, a novel chlorohydrin-free technology for ECH production was investigated. This approach could allow operation in more concentrated solutions, but this route is in the early development stage. One of the most crucial design parameters for this process is proper solvent selection. On the one hand methanol appears to be the most suitable compound for this purpose. On the other hand, some papers reported the separation system for this case to be infeasible due to several azeotropes present in the post-rection mixture. However, with proper constraints and understanding of components' azeotropic behaviour, a separation system, which enables obtaining high purity ECH, was created and applied to the production process. To perform a comparison between HP route and chlorohydrin process an Aspen Plus simulation of both processes were created. For the hydrogen peroxide route with methanol as solvent a novel separation system which enables high purities of ECH were created. Furthermore, possibilities to optimise distillation in the given process were investigated because this unit operation requires significant expenses in terms of CAPEX and OPEX. A review of advanced distillation techniques concludes that Dividing Wall Column distillation is the most suitable technique for this purpose. This technology was then applied to replace two columns, which purifies the intermediate Allyl Chloride (ACH) from the process. Aspen Plus simulations of both processes with and without applied DWC distillation were created to evaluate the influence of these improvements. Moreover, to establish the impact of DWC distillation, an Aspen Plus model of this apparatus was created. Simulation results indicate that this novel epoxidation reaction produces 98% less wastewater than the traditional process. Additionally, the novel approach offers a 10% higher yield and a smaller amount of by-products than the chlorohydrin process. Energy consumption per unit of ECH is also lower for the novel route. Application of DWC distillation led to 3.5% decrease in OPEX, while the CAPEX was smaller by almost 5%. These results indicate that applying a novel epoxidation route and DWC may benefit a given plant. However, more research needs to be performed to implement a novel process in the industry. ... Read more