Continuous Liquid-liquid Extraction Research Articles

Evaluating bottle liquid-liquid extraction technique for monitoring residual levels of organochlorine pesticides in wastewater treatment-associated matrices

The gold standard for recovering residual organochlorine pesticides from wastewater and aqueous environmental matrices is the continuous liquid-liquid extraction (CLLE) technique that requires methylene chloride (CH2Cl2) as solvent at its refluxing temperature. In light of a recent USEPA proposed prohibitions and workplace protections for CH2Cl2 (due to its toxicity) and the fact that CLLE requires expensive and hard-to-acquire glassware, an alternative to CLLE as currently practiced is needed. The bottle liquid-liquid extraction (BLLE) technique, demonstrated for extracting semi-volatile organic contaminants from surface water, is potentially a low cost and high throughput alternative for such recovery. BLLE is cheaper and has a smaller laboratory footprint. The technique, performed at ambient temperature in a tightly capped bottle, requires less amount of solvent and contains solvent vapor within the bottle. The latter means less CH2Cl2 is encountered in the workplace. In this study, BLLE was performed directly in 1-L amber sampling bottles and shown to recover 21 organochlorine pesticides as efficiently as CLLE from influents and effluents of two wastewater treatment plants Because no statistical differences were found between CLLE (mean = 77.4, SD = 9.28) and BLLE (mean = 79.1, SD = 14.3); t(22) = 0.548, p(same mean) = 0.58, even though CLLE recovered more pesticides than BLLE by 5.18 ± 8.15%, these techniques are amenable to interchangeable usage. The systematic bias so far detected fits the expression BLLE = 1.4[CLLE] – 35 (r = 0.88). Both CLLE and BLLE recoveries were consistently higher for 4,4′-DDD and lower for aldrin, heptachlor and endrin aldehyde. Diethyl ether addition, as some suggested, did not improve BLLE.Synopsis: There is need to find a cheap, reliable and high throughput technique for purifying SVOCs from aqueous environmental media efficiently. BLLE, a little known technique, fulfils this need.

Modeling of continuous hydrogen fermentation integrated with continuous in-line liquid-liquid extraction

Hydrogen, a promising source of green energy, can be produced via fermentation. However, its productivity is often limited due to accumulation and inhibition of organic acid byproducts (e.g., acetic, propionic, butyric, and lactic acids). To alleviate the inhibitory effect, acids must be continuously removed. Continuous liquid-liquid extraction (LLE) can be used as an in-line removal, which also allows for recycle of remaining substrates. In this work, an integrated process of fermentation and continuous LLE was evaluated for its feasibility. The methodology involved collection of empirical fermentation data, formulation of a kinetic model, and simulation of the integrated process design in SuperPro Designer®. A fermentation process integrated with continuous in-line LLE and recycle (RS-LLE) can increase a production yield by up to 4.5-fold from the single-pass (SP) fermentation while maintaining a comparable productivity. Back extraction is found to reduce the amount of extractants required considerably, eventually improving feasibility of the process.

Enhanced, continuous, liquid-liquid extraction and in-situ separation of volatile fatty acids from fermentation broth

In 2018 alone, the US landfilled 35.3 million tons of food waste, about 24% of the total landfilled mass. In addition to the negative impacts landfills have demonstrated on the environment and human health, some states have begun to outlaw or dissuade the disposal of food waste and sewage sludge into landfills altogether. An urgent need has thus been created for the development of digestion processes like anaerobic digestion (AD) and arrested methanogenesis (AM) to convert food waste into valuable chemical products. Unfortunately, the buildup of volatile fatty acids (VFAs) during these processes eventually halts the reaction, and energy efficient methodologies for VFA removal are critical for the operation of fermenters. Additionally, VFAs themselves can serve as valuable chemical precursors, and recently AD processes have been modified to increase VFA production during fermentation. However, even with significant research over the past three decades, the separation of VFAs from the fermenter broth has remained expensive. Moreover, the separation of these VFAs from the fermenter broth may cost up to 50% of the entire process budget, hindering the widespread commercial adoption of AD and AM. In this work, we present a novel liquid–liquid extraction process termed CLEANS (Continuous Liquid-liquid Extraction And iN-situ Separation) as a highly efficient method for continuously separating VFAs from a real fermentation broth solely under gravity. Our optimized process (using an aqueous broth feed pH of 2.5, tri-n-octylamine as an extractant, and a 10:1 ratio of aqueous broth to organic extractant), achieved a VFA distribution constant KD = 44.5 ± 7.9, a single-pass recovery = 81.3 ± 2.5%, and an extraction factor = 8.1 ± 0.3. These KD values are over an order of magnitude higher than what has been previously reported for comparable processes. A high aqueous-to-organic flowrate ratio, enabled for the first time by CLEANS, was found to be particularly crucial for achieving optimal extraction. Our separation process demonstrates excellent reproducibility and potential for scalability. The economic and environmental implications of this work are briefly discussed.

Continuous extraction of 2-chloroethyl isocyanate for 1-(2-chloroethyl)-3-cyclohexylurea purification

This study details the development of simulation-aided design, development, and successful operation of a continuous liquid-liquid extraction platform made with 1.5 mm tubing for the extraction of 2-chloroethyl isocyanate, an important reagent in the synthesis of cancer drugs. Preliminary solvent screening was carried out with partition coefficient calculations to determine solvents of interest. Next, batch and flow extraction experiments of 2-chloroethyl isocyanate in 2-methyl tetrahydrofuran and water were conducted to estimate extraction parameters. Following parameter estimation, experimental and model values for KLa were determined in the range of 1.13 × 10−3 to 36.0 × 10−3 s−1. Simulations of the extraction of 2-chloroethyl isocyanate were found to agree with experimental data resulting in a maximum efficiency of 77% and percent extraction of 69% for the continuous platform. Finally, model selection and discrimination was implemented for design space generation with experimental and model determined KLa values to guide lab-scale operation.

Liquid-liquid extraction using combined hydrophilic-hydrophobic emulsion templated macroporous polymer micromixer-settlers

Continuous liquid-liquid extraction and separation of 4-aminoacetophenone, a product of the hydrogenation of 4-nitroacetophenone, was performed within emulsion templated macroporous polymer (polyHIPE) extraction units combined with a miniaturized gravity-based settler. PolyHIPEs with interconnected and tailorable macroporous structures are effective micromixers allowing to mix fluids in both axial and radial directions. We fabricated extraction units by combining hydrophilic and hydrophobic polyHIPEs, which improved the extraction efficiency by inverting the liquid/liquid dispersion type from oil/water to water/oil (or vice versa) during the extraction. The dispersion type is governed by the wettability of the porous medium. The extraction efficiency of our combined polyHIPE micromixer reached 98%, while that of control experiments performed using a blank tube or commercial Kenics® static mixer was 78%. The overall volumetric mass transfer coefficient kLa in polyHIPE micromixer-settlers was significantly higher 0.011 s−1 reaching interfacial areas a of 17900 m2/m3, much larger compared to a blank tube (kLa = 0.0035 s−1 and a = 5700 m2/m3) and static mixer (kLa = 0.0041 s−1 and a = 6800 m2/m3). PolyHIPE micromixer-settlers could be potentially useful to intensify continuous L-L extractions.

In-stream product recovery of p-coumaric acid heterologously produced: Implementation of a continuous liquid-liquid extraction assisted by hollow fiber membrane contactor

This work aims to intensify trans-p-coumaric acid (p-CA) heterologous production. p-CA exhibits antimicrobial properties, low hydrosolubility, and retro-inhibition activity, making its heterologous production limited due to its accumulation in the broth. To overcome these limitations, an in-stream product recovery process (ISPR) is proposed and consists in a liquid-liquid extraction assisted by a hollow fiber membrane contactor. pH, medium composition, and solvent impacts on extraction performances, were investigated prior to the implementation. The coupling of the fermentation and the membrane-assisted extraction was then studied. Although cells were impaired by shear stress with only 15% of viable cells at the end in the extractive fermentation, the final p-CA concentration was approximatively 89% of the control one, suggesting an intensification of p-CA heterologous production if one factors the proportion of viable cells.

Continuous Liquid-Liquid Extraction and in-Situ Membrane Separation of Miscible Liquid Mixtures.

Separation operations are critical across a wide variety of manufacturing industries and account for about one-quarter of all in-plant energy consumption in the United States. Conventional liquid-liquid separation operations require either thermal or chemical treatment, both of which have a large environmental impact and carbon footprint. Consequently, there is a great need to develop sustainable, clean methodologies for separation of miscible liquid mixtures. The greatest opportunities to achieve this lie in replacing high-energy separation operations (e.g., distillation) with low-energy alternatives such as liquid-liquid extraction. One of the primary design challenges in liquid-liquid extraction is to maximize the interfacial area between two immiscible (e.g., polar and nonpolar) liquids for efficient mass transfer. However, this often involves energy-intensive methods including ultrasonication, pumping the feed and the extractant through packed columns with high tortuosity, or using a supercritical fluid as an extractant. Emulsifying the feed and the extractant, especially with a surfactant, offers a large interfacial area, but subsequent separation of emulsions can be energy-intensive and expensive. Thus, emulsions are typically avoided in conventional extraction operations. Herein, we discuss a novel, easily scalable, platform separation methodology termed CLEANS (continuous liquid-liquid extraction and in-situ membrane separation). CLEANS integrates emulsion-enhanced extraction with continuous, gravity-driven, membrane-based separation of emulsions into a single unit operation. Our results demonstrate that the addition of a surfactant and emulsification significantly enhance extraction (by >250% in certain cases), even for systems where the best extractants for miscible liquid mixtures are known. Utilizing the CLEANS methodology, we demonstrate continuous separation of a wide range of miscible liquid mixtures, including soluble organic molecules from oils, alcohols from esters, and even azeotropes.

Continuous Liquid-Liquid Extraction of Lomustine Synthesis

Continuous Liquid-Liquid Extraction of Lomustine Synthesis

On-Demand Continuous Manufacturing of Ciprofloxacin in Portable Plug-and-Play Factories: Development of a Highly Efficient Synthesis for Ciprofloxacin

The experimental approach taken and challenges overcome in developing a high-purity production (>100 g) scale process for the telescoped synthesis of the antibiotic ciprofloxacin is outlined. The process was first optimized for each step sequentially with regard to purity and yield, with necessary process changes identified and implemented before scaling for longer runs. These changes included implementing a continuous liquid–liquid extraction (CLLE) step and eliminating and replacing the base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) initially used in the ring-closure step due to DBU plausibly forming a decomposition side product that negatively impacted the final product purity. Process conditions were scaled 1.5–2-fold in order to enable the ultimate project goal of producing enough crude ciprofloxacin within 24 h to manufacture 1000 250 mg tablets. Working toward this goal, several production-scale runs were carried out to assess the reproducibility and robustness of the finalized process conditions, with the first three steps being run continuously up to 22 h and the last two steps being run continuously up to 10 h. The end result is a process with a throughput of ∼29 g/h (∼700 g/24 h) with a crude product stream profile of 94 ± 2% and 34 ± 3 mg/mL after five chemical transformations across four reactors and one continuous CLLE unit operation with each intermediate step maintaining a purity >95% by HPLC.

Polymers for electronics: a new process under development

The experts at Seqens are working on the implementation of a continuous liquid-liquid extraction process. In OPE journal, the company provides an update on the development

Sinomenine Purification by Continuous Liquid-Liquid Extraction Process with Centrifugal Extractors

Continuous manufacturing is considered as one of the future trends of pharmaceutical engineering. In this work, continuous liquid-liquid extraction for sinomenine purification was realized with the usage of centrifugal extractors. Chloroform was used as the extractant because of the high distribution coefficient (>100). Higher extraction ratio can be obtained when using the centrifugal extractor of Model CWL50-N. The extraction ratio of the second-stage extraction was higher than that of the first-stage extraction. The extraction ratio of the second-stage countercurrent extraction was higher than that of second-stage cross-flow extraction. When chloroform phase was recycled for liquid-liquid extraction, the extraction ratio was also higher than 95%. This work can also be an example of continuous liquid-liquid extraction for the separation of other Chinese medicine components.

Visualization of Type-J counter current chromatography: Hydrodynamic behavior in a helical column

In counter-current chromatography (CCC), the hydrodynamic motion of a two-phase solvent system in the column/coil is very important. There are some previous visualization studies on CCC using stroboscopic photography. As CCC separation is a continuous liquid-liquid extraction process, observing the distribution and movement of the solvent system on-line will be helpful to understand the hydrodynamic behavior during the whole CCC separation process. In the present study, a high-speed imaging camera was employed to take videos of a running CCC bobbin (visualized continuously on-line). The dynamic motion and phase distribution of conventional quaternary solvent system hexane/ethyl acetate/methanol/water (HEMWat) and ternary solvent system dichloromethane/methanol/water were both investigated. Wave-like mixing was observed in the area where the centrifugal force is minimum in different diameter columns. When the coil rotated, the mixing zone was “fixed” at the minimum centrifugal force position. Several photographs of the rotating coiled tube were taken which revealed that the phase dispersion hardly changes once equilibrium is established. Finally, the sample dispersion process was also recorded. These results will help us to understand the separation process in a CCC column/coil and also present some more interesting questions related to separation efficiency which are shown in discussion part of this paper.

Separation/preconcentration of chromium species with continuous liquid-liquid extraction device and its determination by AAS

A chromium speciation and preconcentration method was developed for graphite furnace atomic absorption spectrometry (GFAAS). This method was based on a continuous liquid-liquid extraction technique. For the separation and enrichment of the chromium species, an ion-pair forming quaternary ammonium compound was used. The sample and chloroform with the ion-pair forming agent were introduced into a patented extraction glass device. After the extraction, the Cr(VI) content of real water samples was determined by GFAAS. The optimized extraction conditions were as follows: the detection limit (S/N = 3) of 0.01 μg L−1, linear range of 0.04–5.00 μg L−1 and precision (RSD, n = 3) ≤ 3.0%. The advantages of this method are its simplicity, cost efficiency, the high enrichment factor of chromium species and easy usage with the GFAAS technique. Thus, the concentration of the chromium species can be determined at sub μg L−1 level.

Membrane assisted continuous production of solvents with integrated solvent removal using liquid-liquid extraction

The aim of this work was to demonstrate an industrially relevant pilot scale integrated process to produce butanol and other solvents from lignocellulosic sugars produced with AVAP® biomass fractionation technology from southern pine wood. The concentrated sugars were concurrently fermented using genetically engineered Clostridium acetobutylicum to n-butanol, acetone, isopropanol and ethanol in continuous membrane assisted cell recycle fermentation with steady-state solvent productivity exceeding 10 g/L/h. The solvents from the cell free permeate were recovered with extractant of butyl butyrate in a continuous liquid-liquid extraction column and aqueous product (raffinate) along with unused sugars, nutrients, and metabolic intermediates were recycled back to the fermentors. The total solvent yield approached 0.30 g/g sugars.

Process modelling, design and technoeconomic Liquid–Liquid Extraction (LLE) optimisation for comparative evaluation of batch vs. continuous pharmaceutical manufacturing of atropine

Continuous Pharmaceutical Manufacturing (CPM) can revolutionise industrial efficiency via potential operational and economic benefits over currently dominant batch methods. Process modelling and optimisation are valuable towards rapid design space evaluation and elucidation of optimal process design configurations, without expensive and time-consuming experimental campaigns. This paper pursues total cost minimisation via nonlinear optimisation of different separation design options for atropine, a product of great societal importance. The study considers a demonstrated continuous flow synthesis, presents reaction kinetic parameter estimation towards reactor design, and illustrates a comparative analysis of the subsequent batch vs. continuous liquid–liquid extraction (LLE) for product purification, using published partition coefficient data and UNIFAC-modelled ternary liquid–liquid equilibria. Original optimisation results show that toluene is the best continuous LLE solvent, attaining the lowest total costs at both plant capacities considered and the greatest total cost savings with respect to the batch LLE design for varying solvent recovery, at acceptable material efficiencies.

Continuous Liquid-Liquid Extraction of Uranium from Uranium-containing Wastewater Using an Organic Phase-refining-type Emulsion Flow Extractor.

A previously reported emulsion flow (EF) extraction system does not equip the refining device for any used organic phase. Therefore, the processing of large quantities of wastewater by using the EF extractor alone could lead to the accumulation of extracted components into the organic phase, and a lowering of the extraction performance. In the present study, we developed an organic phase-refining-type EF system, which is equipped with a column for refining a used organic phase to prevent accumulation, and successfully applied it for treating uranium-containing wastewater.

Kinetic study of continuous liquid-liquid extraction of wine with real-time detection

Kinetic optimization of continuous liquid-liquid extraction (CLLE) can shorten sample preparation times and reduce losses of labile or volatile analytes. Here, we coupled a downscaled CLLE apparatus with atmospheric pressure chemical ionization interface of triple quadrupole mass spectrometer. Real-time sampling was guided by an Arduino-based programmable logic controller. The recorded datasets were processed to compute the extraction rate constants for the target analytes. The extraction time in subsequent on-line experiments was set to 180 min as a compromise between the reduction of the analysis time and maximizing its yield. Interestingly, off-line analysis of the extract produced different results than on-line analysis pointing to the immanent degradation of the collected extract aliquots. Next, we implemented this hyphenated system in the analysis of red wine samples, which were stored during different periods of time after opening the bottle. The results reveal differences in the depletion of the volatile wine components during storage.

Steroid hormones in environmental matrices: extraction method comparison.

The U.S. Environmental Protection Agency (EPA) has developed methods for the analysis of steroid hormones in water, soil, sediment, and municipal biosolids by HRGC/HRMS (EPA Method 1698). Following the guidelines provided in US-EPA Method 1698, the extraction methods were validated with reagent water and applied to municipal wastewater, surface water, and municipal biosolids using GC/MS/MS for the analysis of nine most commonly detected steroid hormones. This is the first reported comparison of the separatory funnel extraction (SFE), continuous liquid-liquid extraction (CLLE), and Soxhlet extraction methods developed by the U.S. EPA. Furthermore, a solid phase extraction (SPE) method was also developed in-house for the extraction of steroid hormones from aquatic environmental samples. This study provides valuable information regarding the robustness of the different extraction methods. Statistical analysis of the data showed that SPE-based methods provided better recovery efficiencies and lower variability of the steroid hormones followed by SFE. The analytical methods developed in-house for extraction of biosolids showed a wide recovery range; however, the variability was low (≤7% RSD). Soxhlet extraction and CLLE are lengthy procedures and have been shown to provide highly variably recovery efficiencies. The results of this study are guidance for better sample preparation strategies in analytical methods for steroid hormone analysis, and SPE adds to the choice in environmental sample analysis.

Efficient purification of halide-based ionic liquids by means of improved apparatus for continuous liquid-liquid extraction

The purity level of Ionic liquids (ILs) is a question of immense importance both from fundamental and applied standpoint. In order to improve the purification process of halide-based ILs, the latter being starting materials for the synthesis of a vast number of other ILs, we constructed an apparatus for continuous liquid-liquid extraction to be used as a tool for purification after the quaternisation step. The apparatus employs the heat of the evaporating solvent to heat up the extraction chamber, thus allowing the liquid-liquid extraction to be conducted at elevated temperature. The latter improves the process efficiency due to facilitated mass transfer. The purification carried out with this tool proved successful in the removal of impurities such as residual starting compounds (N-methylimidazole and haloalkanes) under mild conditions and was shown to give ILs of high purity for considerably reduced consumption of organic solvent and technological time.

Identification of active anti-inflammatory principles of betabeta wood (<i>Lunasia amara</i> Blanco) from Siawung Barru- South Sulawesi, Indonesia

Purpose: To identify the anti-inflammatory components of beta-beta (Lunasia amara Blanco.) wood.Methods: The wood material was extracted with 96 % ethanol and fractionated with dichloromethane using a liquid-liquid continuous extraction (LLCE). The fractions were subjected to silica gel column chromatography. Components of the extracts were identified by thin layer chromatography (TLC) scanner and UV-visible spectroscopy, using scopoletin as standard.Results: TLC results for Lunasia amara extract showed the same spot as standard scopoletin. UVvisible spectrum for scopoletin displayed maximum absorption at 213, 228, 255 and 344 nm, while betabeta wood extract showed characteristic bands at 344, 336, 299 and 255 nm. The results indicate that the main components of the extracts are scopoletin and its derivatives.Conclusion: The active anti-inflammatory compound in beta-beta (Lunasia amara) wood is scopoletin.Keywords: Beta-beta wood (Lunasia amara Blanco.), Scopoletin, Thin layer chromatography