Process Intensification Strategies Research Articles

The design and control of heat-integrated EDWC processes for the separation of THF/IPA/water

Extractive dividing wall columns (EDWC) and heat integration are effective process intensification strategies for separating azeotropes. In this study, the steady-state and dynamic control for the separation of tetrahydrofuran/isopropanol/water using a combination of EDWC and heat integration with intermediate reboilers are systematically investigated. The feasibility of the extractive distillation process is evaluated by analyzing the thermodynamic characteristics of the mixture through phase diagrams, and the three-column extractive distillation (TCED) process is established as the basic process. To enhance the energy and economic efficiencies, as well as environmental sustainability, three improved processes are proposed. Compared with TCED, the optimal process (E-EDWC-HI2) reduces the total annual costs, energy consumption, and CO2 emissions by 22.35 %, 41.77 %, and 26.28 %, respectively. In addition, a dynamic control structure is proposed for the E-EDWC-HI2, which exhibits robustness against disturbances in the feed flow rate and composition. This study provides guidance for the design and dynamic control of complex distillation processes.

Hydrodynamics of liquid–liquid parallel flow in novel microextractors: Review

Parallel flows on microfluidic platforms enable continuous liquid–liquid operations and inline separation of effluent streams, bearing immense scope in integration of miniaturized separation processes. However, these flows face major challenges including low mass transfer efficiency due to lack of transverse convection and flow instability at low flow rates, which undermine their operating range and utility. The limitations have inspired dedicated research, delving into the fundamentals of fluid flow and transport mechanism and exploring novel configurations of microextractors. The current article summarizes the hydrodynamics of parallel flows and relevant process intensification strategies in microfluidic extractors, evolving from the use of straight to curved and helical geometries, besides elucidating unique secondary flow patterns observed in-state-of-the-art designs. It includes exclusive sections addressing various aspects of parallel flows: (i) flow inception and theoretical modeling of flow fields and phase hold up, (ii) challenges concerning interfacial stability and flow intensification, (iii) curvature effects in planar curved geometries, and (iv) curvature cum torsional effects in unique multi-helical configurations. The theoretical perspective of this review presents a roadmap that can provide further insights into design modifications for developing improved integrated microextractors based on parallel flows.

Energy-efficient separation of a ternary azeotropic mixture via azeotropic reflux-induced sequences based on the intensified pressure-swing distillation

The recovery and separation of chloroform, acetonitrile and ethanol from waste water involving two azeotropes and a distillation boundary has emerged as a pivotal concern in the pursuit of environmental protection and resource conservation. Herein, the energy-efficient separation design of the ternary azeotropic mixture based on a triple-column pressure-swing distillation (TCPSD) process with five azeotropic reflux induced sequences is comprehensively investigated. The suitable operating pressure range of the distillation columns and the potential optimal distillation sequence is investigated based on the thermodynamic intrinsic probe. According to the optimal distillation sequence, further process intensification strategies are proposed to improve the thermodynamic efficiency encompassing the heat integration pressure-swing distillation (HI-PSD), heat pump assisted pressure-swing distillation (HP-PSD), and a combination of heat pump assisted and heat integration pressure-swing distillation (HPHI-PSD). It unveils the economic preeminence of the HI-PSD process, characterized by the lowest total annual cost (TAC) in a shorter payback period (3 to 7 years). Conversely, both the HP-PSD and HPHI-PSD processes exhibit superior environmental performance on CO2 emissions of 111.46 kg/h and 119.78 kg/h respectively, with the HP-PSD demonstrating prolonged economic viability and the HPHI-PSD showcasing heightened thermodynamic efficiency of a 65.12 % improvement. This study potentially provides a theoretical basis for devising industrial separation schemes for analogous pressure-sensitive ternary azeotropic systems.

A mini‐review of intensified synthesis of 1st and 2nd generation biofuels in the presence of perovskite catalysts

AbstractEnhancement of a sustainable environment through the choice of a selective catalyst with high activity, regeneration nature, and high stability is an important aspect to be focused on to achieve a high yield and maximum conversion of feedstock to biodiesel (1st generation biofuel), and also in the biomass valorization/pyrolysis (2nd generation biofuel synthesis). Depending on the nature of the catalyst and synthesis method adopted for biofuel production and biomass valorization, the variations in the process conditions, final yield, and conversion are varied accordingly. A prospective development and application of perovskite catalysts in the synthesis of 1st and 2nd generation biofuels using various process intensification strategies for the development of a clean and green environment is reviewed in this study. The synthesis of types of perovskite catalysts polycrystalline, nano‐sized, and powdered oxide are also discussed in this review. It is also concluded that, apart from other process parameters, molar ratio is one of the most influencing sensitive factors in the case of 1st generation biofuel synthesis, whereas during the production of 2nd generation biofuels, catalyst concentration and liquid–solid ratio are more significant process parameters that change based on the nature of the catalyst selected for the reaction.

Plasma-Assisted One-Step Direct Methanol Conversion to Ethylene Glycol and Hydrogen: Process Intensification

This perspective reports a process intensification strategy that converts methanol into ethylene glycol (MeOH-2-EG) in a single step to circumvent multi-step naphtha cracking into ethylene followed by ethylene epoxidation to ethylene oxide (EO) and the subsequent hydrolysis of EO to ethylene glycol (EG). Due to the thermodynamic restriction for the direct MeOH-2-EG, plasma-assisted catalysis was introduced, and platinum group metals were identified as prospective transition metal catalysts that can achieve the formation of strong metal hydride bonds and guarantee the controlled C–C coupling of two plasma-activated hydroxymethyl radicals (*CH2OH) from methanol, both of which are essential for the single-step MeOH-2-EG.

Enhancing swine manure treatment: A full-scale techno-economic assessment of nitrogen recovery, pure oxygen aeration and effluent polishing

In regions with intensive livestock production, managing the environmental impact of manure is a critical challenge. This study, set in Flanders (Belgium), evaluates the effectiveness of integrating process intensification measures into the treatment of piggery manure to mitigate nitrogen (N) surplus issues. The research investigates the techno-economic benefits of implementing three key interventions: pure oxygen (PO) aeration, ammonia (NH3) stripping-scrubbing (SS) pretreatment, and tertiary treatment using constructed wetlands (CW), within the conventional nitrification-denitrification (NDN) process.Conducted at a full-scale pig manure treatment facility, our analysis employs steady-state mass balances for N and phosphorus (P) to assess the impact of these process intensification strategies. Findings indicate that the incorporation of advanced treatment steps significantly enhances the efficiency and cost-effectiveness of the manure management system. Specifically, the application of PO aeration is shown to reduce overall treatment costs by nearly 4%, while the addition of an NH3 SS unit further decreases expenses by 1–2%, depending on the counter acid utilized. Moreover, the implementation of a CW contributes an additional 4% in cost savings.Collectively, these measures offer substantial improvements in processing capacity, reduction of by-product disposal costs, and generation of additional revenue from high-quality fertilising products. The study highlights the potential of advanced treatment technologies to provide economically viable and environmentally sustainable solutions for manure management in livestock-dense regions, emphasizing the cumulative economic benefit of a holistic approach to process intensification (10%).

Process Intensification in Human Pluripotent Stem Cell Expansion with Microcarriers

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.

Triple Space-Time Yield in Discontinuous Antibody Biomanufacturing by Combination of Synergetic Process Intensification Strategies.

Monoclonal antibodies are the workhorse of the pharmaceutical industry due to their potential to treat a variety of different diseases while providing high specificity and efficiency. As a consequence, a variety of production processes have been established within the biomanufacturing industry. However, the rapidly increasing demand for therapeutic molecules amid the recent COVID-19 pandemic demonstrated that there still is a clear need to establish novel, highly productive, and flexible production processes. Within this work, we designed a novel discontinuous process by combining two intensification strategies, thus increasing inoculation density and media exchange via a fluidized bed centrifuge, to fulfill the need for a flexible and highly productive production process for therapeutic molecules. To establish this new process, firstly, a small-scale experiment was conducted to verify synergies between both intensification strategies, followed by a process transfer towards the proof-of-concept scale. The combination of these two-process intensification measures revealed overall synergies resulting in decreased process duration (-37%) and strongly enhanced product formation (+116%) in comparison to the not-intensified standard operation. This led to an impressive threefold increase in space-time yield, while only negligible differences in product quality could be observed. Overall, this novel process not only increases the ways to react to emergency situations thanks to its flexibility and possible short development times, but also represents a possible alternative to the current established processes due to high increases in productivity, in comparison to standard fed-batch operations.

Integrated Semi-Continuous Manufacturing of Lentiviral Vectors Using a HEK-293 Producer Cell Line

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.

Kinetic effect of in situ water adsorption during CO2 hydrogenation: An experimental investigation

Sorption enhancement exhibits great potential as process intensification strategy to improve the extent of chemical reactions.Particularly, the selective removal of products or inhibiting components from the reactive gas mixture via in situ adsorption ontosolid sorbents may reducethermodynamic and kinetic constraints. Consequently, the present work investigates the kinetic effect of sorption-enhanced CO2 hydrogenation via dynamic experimentation under reaction conditions in the kinetic regime with sufficient distance from chemical equilibrium. In particular, H2O is selectively removed by adsorption at 280 and 330 °C and 2 bar on zeolite 3A. The experimental data are evaluated based on stoichiometric analysis for quantification of the kinetic effect of in situ water removal on CO2 hydrogenation. The results reveal that an improvement in reaction extent is obtained, which is caused by enhancement of the reaction rate in the kinetic regime, probably due to the less pronounced blockage of catalytic sites by water adsorption.

Chemical looping CO2 capture and in-situ conversion as a promising platform for green and low-carbon industry transition: Review and perspective

Industrial flue gas and solid waste with the characteristics of large emissions and complicated distributions are two issues for industry, due to that sequential CO2 capture and utilization for flue gas shows high energy-cost penalties and solid waste faces with low reutilization ratio. As a powerful process intensification strategy, chemical looping CO2 capture and in-situ conversion (CL-ICCC) provides an effective solution to handle those two issues. However, current researches on CL-ICCC aim to develop process configurations, design bifunctional materials, and reveal reaction mechanisms, which ignore how to apply CL-ICCC for realizing flue gas purification and solid waste reutilization simultaneously in industry. Herein, after reviewing the current status of CL-ICCC for flue gas upgrade, industrial solid waste reutilization and industrial system integration, a perspective is proposed to highlight CL-ICCC as a promising platform for green and low-carbon industry transition. In the proposed system, industrial flue gas enters the capture reactor and reacts with industrial solid waste derived bifunctional materials to separate CO2 from other impurities. In the conversion reactor, reduction agents are introduced to spill CO2 over bifunctional materials and convert it into value-added chemicals. This review and perspective provide a new pathway to establish a low-carbon and self-digestion industrial system.

Separation performance evaluation of green crystallization technique: Model configuration and process design

Layer melt crystallization (LMC) is deemed a green separation technique and is widely used in the purification of crude chemical products. This work optimizes the separation of LMC based on process design and model configurations. Firstly, we monitor the central temperature with the crystal layer growth, where the temperature change can be divided into two stages. The main heat exchange and crystal growth occur in stage 1. Then we establish two kinetics models based on the temperature and concentration difference, to describe the features of crystal layer growth. Both kinetic models can successfully correlate the driving force and kinetic parameters. Further, the temperature effect and composition of the feed mixture on the separation performance are analyzed. The proposed separation coefficients accurately figure out the underlying correlations of the technical variables and target products. The optimized operating trajectory based on the model analyses and experiments is given to guide the separation process. Finally, four process intensification strategies are proposed to improve separation efficiency, where the incorporation of the stirring operation into LMC is more suitable for industrial production.

Multiscale Process Intensification of Waste Valorization Reactions.

ConspectusThe central theme of this Account is the development of intensified and sustainable chemical processes for the sequestration of CO2 in synergism with the utilization of wastes of industrial, urban, and agricultural origins. A challenge when working with solid waste-fluid reactions is that mass transfer limitations across solid-liquid, solid-gas, and gas-liquid interfaces and unfavorable thermodynamics lead to slow reaction rates, incomplete reaction conversions, high energy expenditure and processing costs, and inadequate product properties. The traditional macroscale approaches to overcoming slurry reaction limitations can be effective; however, they come at a cost to the environment. In the treatment or valorization of low-grade and waste resources, such conventional approaches are often unfeasible on an industrial scale. Sustainable solutions are thus needed.In the last six years, we have been exploring and developing approaches to overcoming reaction rate limitations of slurry reactions of environmental relevance by concurrently applying process intensification strategies and multiscale engineering approaches. The scientific approach has relied on laboratory-scale experiments to test and refine the devised multiscale process intensification strategies, with thermodynamic and computational modeling work supporting the experimental work and with advanced characterization techniques being used to elucidate reaction and transport mechanisms and aid the development of nanoscale reaction models and micro- and macroscale process models. The research streams, associated with the four key references, discussed next are (a) brine carbonation; (b) mineral carbonation and enhanced weathering; (c) process intensification and integration; and (d) characterization techniques.Within the four research streams, a number of mineral carbonation processes have been investigated and can be classified as (i) ambient weathering and carbonation; (ii) gas-(wet) solid accelerated carbonation; (iii) aqueous accelerated carbonation; (iv) supercritical accelerated carbonation; and (v) CO2 mineralization from brine. In some cases, the research was aimed at producing valuable products with reduced environmental risk or a reduced carbon footprint, such as an organomineral fertilizer and zeolites. In other cases, the aim was to assess the reactivity of minerals to match the right feedstock with the right carbonation process, in view of maximizing net carbon sequestration. There were also cases where the carbonation process was reimagined by the use of innovative reaction conditions, reactors, and reagents. The experience with accelerated weathering and carbonation in engineered processes has been translated into the field of enhanced rock weathering (ERW) in agriculture, where the multidisciplinary approach used has served to advance ERW science and technology in ways that have had a resounding effect on recent commercial deployment.The completed research serves to encourage the adoption of process intensification technologies in place of conventional processes, in industry and among the research community, and to catalyze the development of the types of sustainable processes required by the chemical, metallurgical, and minerals industries (which are critical to the green transition) to reduce their environmental impact and carbon emissions. Moreover, the multiscale process intensification approaches developed may also be extended to other industrial, urban, and agricultural processes where the reduction of energy intensity, carbon intensity, and environmental footprint could be achieved.

An investigation of the Ni/carbonate interfaces on dual function materials in integrated CO2 capture and utilisation cycles

CO2 capture and utilisation (CCU) is a promising strategy to effectively mitigate the adverse greenhouse effects caused by CO2 emissions at an industrial scale. Through a process intensification strategy known as integrated CO2 capture and utilisation (ICCU), CO2 capture and catalytic CO2 conversion can be achieved in a single process with the use of dual function materials (DFMs), which are both CO2 sorbents and CO2 conversion catalysts. Given the significantly different operating conditions of ICCU from conventional catalytic CO2 hydrogenation, the catalytic mechanism of DFMs, especially during CO2 hydrogenation, needs to be thoroughly investigated. In this study, the relationship between the nature of the Ni/carbonate interfaces and the performance of Ni-based DFMs over ICCU cycles is systematically investigated. A series of Ni/alkaline earth carbonate DFMs were synthesised with varying Ca:Mg ratios to simulate different metal-carbonate model interfaces. At 400 °C, CH4 formation with nearly 100% CH4 selectivity was achieved on Ni/CaCO3 over 15 ICCU cycles. In general, Ni/CaCO3 interfaces correspond to higher CO2 conversion and higher CH4 selectivity than Ni/MgCO3 interfaces. Such trend may be attributed to the higher surface basicity of CaO and the higher thermal stability of CaCO3. As a consequence, the hydrogenation of the Ni/CaCO3 interface proceed via the formate pathway, in which carbonates are consecutively converted to surface formates, methoxyl, methyl species and eventually desorb as methane. This reaction model is applicable to the hydrogenation of both surface carbonate and bulk carbonates, although the former proceeds with much faster kinetics. On the weakly alkaline Ni/MgCO3 interface, MgCO3 preferentially decomposes to form gaseous CO2, which is subsequently hydrogenated via the reverse-water-gas-shift pathway, with CO as the key reaction intermediate. Interestingly, in situ infrared spectroscopy shows similar surface significant species during the direct hydrogenation of DFMs and during the conventional catalytic hydrogenation of molecular CO2, suggesting that the catalytic mechanisms during the two operating regimes are highly correlated.

Enhancing and upgrading biogas and biomethane production in anaerobic digestion: a comprehensive review

Anaerobic digestion (AD) processes can face operational challenges or flaws such as substrate structure and characteristics complexity, process complexity, low productivity, inefficient biodegradability, and poor stability, which suppresses or reduces biogas and biomethane production. As a result of the need to overcome these challenges/shortcomings and improve or enhance biogas and biomethane yield, process intensification methods have gained attention. There is some literature review on pretreatment and co-digestion as a means of improving AD performance; however, there is no systematic information on the various strategies required for improving AD performance and, in turn, increasing biogas/biomethane yield. The AD process produces biogas, a valuable renewable biofuel. Biogas is composed primarily of biomethane and other undesirable components such as carbon dioxide, oxygen, hydrogen sulphide, water vapour, ammonia, siloxanes, nitrogen, hydrocarbons, and carbon monoxide, which act as impurities or contaminants and tend to reduce the biogas specific calorific value while also causing various problems with machine operation. As a result, various technologies are used to improve raw biogas quality by removing contaminants during biogas transformation to biomethane. As a result, this paper provides a comprehensive review of the various systematic process intensification strategies used to overcome AD process challenges/shortfalls, improve or enhance biogas and biomethane production, and conventional and emerging or advanced technologies for biogas purification, cleaning, and upgrading.

Intensification of the Oligomerization and Hydrogenation Stage for Biojet Fuel Production: Preliminary Outlines

The environmental conditions generated by the consumption of fossil fuels have created a growing interest in alternative energy sources for various sectors of society. In the case of the aviation sector, one solution is biojet fuel as a sustainable fuel for direct application in flights. The alcohol to jet (ATJ) fuel process has high expectations due to its performance and for revalorizing alcohols from fermentation. Starting from ethanol, the ATJ process consists of four stages: dehydration, oligomerization, hydrogenation, and separation. On the other hand, process intensification philosophy promotes process efficiency, reducing the number of equipment used, reducing land use, and combining different phenomenologies. In this sense, this work researches the outlines of implementing intensification ideas to the ATJ process using reactive distillation (RD) to improve the sustainable performance of jet fuel production. Particularly, the oligomerization and hydrogenation stages will be subject to process intensification strategies. Both strategies were evaluated considering various sustainability indicators (global warming potential, mass intensity, energy intensity, economic impact, etc.). The most intensified alternative presented is an RD column with two reactive sections. Once a distillation column with two reactive zones was implemented, an improvement in the return on investment value of close to 50% and a decrease in the total annual cost of close to 90% were observed. The global warming potential value improved by 70%. Likewise, an improvement of close to 30% was observed in efficiency, mass intensity, and thermodynamic efficiency.

Impact of membrane engineering on the process engineering progresses: Towards a sustainable development

The fast growing of membrane systems in industrial applications suggests the dissemination of last results, particularly in the areas of strategic interest. In this contribution, the role of membrane engineering for more sustainable industrial cycles, following the Process Intensification strategy, is reported. The development of Membrane Crystallizers (MCr) with specific focus on their application to the treatment of brines is presented, together with the use of molecular dynamic simulation to help in the selection of the most appropriate membrane material. The potential of membrane reactors for CO2 valorization through new designs is also highlighted. Moreover, tools like exergy analyses and new metrics to compare the performance of membrane operations to conventional ones in the logic of Process Intensification are discussed.

Process intensification strategies towardcell culture-based high-yield production of a fusogenic oncolytic virus.

We present a proof-of-concept study for production of a recombinant vesicular stomatitis virus (rVSV)-based fusogenic oncolytic virus (OV), rVSV-Newcastle disease virus(NDV), at high cell densities (HCD). Based on comprehensive experiments in 1 L stirred tank reactors (STRs) in batch mode, first optimization studies at HCD were carried out in semi-perfusion in small-scale cultivations using shake flasks. Further, a perfusion process was established using an acoustic settler for cell retention. Growth, production yields, and process-related impurities were evaluated for three candidate cell lines (AGE1.CR, BHK-21, HEK293SF)infected at densities ranging from 15 to 30 × 106 cells/mL. The acoustic settler allowed continuous harvesting of rVSV-NDV with high cell retention efficiencies (above 97%) and infectious virus titers (up to 2.4 × 109 TCID50 /mL), more than 4-100 times higher than for optimized batch processes. No decrease in cell-specific virus yield (CSVY) was observed at HCD, regardless of the cell substrate. Taking into account the accumulated number of virions both from the harvest and bioreactor, a 15-30 fold increased volumetric virus productivity for AGE1.CRand HEK293SF was obtained compared to batch processes performed at the same scale. In contrast to all previous findings, formation of syncytia was observed at HCD for the suspension cells BHK 21 and HEK293SF. Oncolytic potency was not affected compared to production in batch mode. Overall, our study describes promising options for the establishment of perfusion processes for efficient large-scale manufacturing of fusogenic rVSV-NDV at HCD for all three candidate cell lines.

Boosting Productivity for Advanced Biomanufacturing by Re-Using Viable Cells.

Monoclonal antibodies (mAb) have gained enormous therapeutic application during the last decade as highly efficient and flexible tools for the treatment of various diseases. Despite this success, there remain opportunities to drive down the manufacturing costs of antibody-based therapies through cost efficiency measures. To reduce production costs, novel process intensification methods based on state-of-the-art fed-batch and perfusion have been implemented during the last few years. Building on process intensification, we demonstrate the feasibility and benefits of a novel, innovative hybrid process that combines the robustness of a fed-batch operation with the benefits of a complete media exchange enabled through a fluidized bed centrifuge (FBC). In an initial small-scale FBC-mimic screening, we investigated multiple process parameters, resulting in increased cell proliferation and an elongated viability profile. Consecutively, the most productive process scenario was transferred to the 5-L scale, further optimized and compared to a standard fed-batch process. Our data show that the novel hybrid process enables significantly higher peak cell densities (163%) and an impressive increase in mAb amount of approximately 254% while utilizing the same reactor size and process duration of the standard fed-batch operation. Furthermore, our data show comparable critical quality attributes (CQAs) between the processes and reveal scale-up possibilities and no need for extensive additional process monitoring. Therefore, this novel process intensification strategy yields strong potential for transfer into future industrial manufacturing processes.

Process intensification strategies for green solvent mediated biomass pretreatment

Demonstrated to be highly effective for lignocellulosic biomass pretreatment, deep eutectic solvent (DES) has attracted increasing attention owing to its advantages of simple synthesis, relatively low chemical cost, and better biocompatibility as compared to certain ionic liquids. Here we provide a critical review of the status of the design/selection of DES for the pretreatment of biomass feedstocks with an emphasis on the process intensification strategies: 1) integration of microwave, ultrasound, and high solid extrusion for pretreating biomass, 2) one-pot DES pretreatment, enzymatic hydrolysis, and fermentation, 3) strategies for DES recycling and product recovery; and 4) recent progress on molecular simulations toward understanding the interactions between DES and biomass compounds such as lignin and cellulose. Lastly, we provide perspectives toward cost-effective, continuous, high-solid, environmental-benign, and industrial-relevant applications and point to future research directions to address the challenges associated with DES pretreatment.