Membrane Distillation and Related Operations—A Review

Abstract

Membrane contactors represent an emerging technology in which the membrane is used as a tool for inter phase mass transfer operations: the membrane does not act as a selective barrier, but the separation is based on the phase equilibrium. In principle, all traditional stripping, scrubbing, absorption, evaporation, distillation, crystallization, emulsification, liquid‐liquid extraction, and mass transfer catalysis processes can be carried out according to this configuration. This review, specifically addressed to membrane distillation (MD), osmotic distillation (OD), and membrane crystallization (MCr), illustrates the fundamental concepts related to heat and mass transport phenomena through microporous membranes, appropriate membrane properties, and module design criteria. The most significant applications of these novel membrane operations, concerning pure/fresh water production, wastewater treatment, concentration of agro food solutions, and concentration/crystallization of organic and biological solutions, are also presented and discussed.     

Online hyphenation of extraction,Sephadex LH‐20 column chromatography,and high‐speed countercurrent chromatography: A highly efficient strategy for the preparative separation of andrographolide from Andrographis paniculata in a single step

A novel isolation strategy, online hyphenation of ultrasonic extraction, Sephadex LH‐20 column chromatography combined with high‐speed countercurrent chromatography, was developed for pure compounds extraction and purification. Andrographolide from Andrographis paniculata was achieved only in a single step purification protocol via the present strategy. The crude powder was ultrasonic extracted and extraction was pumped into Sephadex LH‐20 column directly to cut the nontarget fractions followed by the second‐dimensional high‐speed countercurrent chromatography, hyphenated by a six‐port valve equipped at the post‐end of Sephadex LH‐20 column, for the final purification. The results yielded andrographolide with the amount of 1.02 mg and a purity of 98.5% in a single step, indicating that the present method is effective to harvest target compound from medicinal plant.     

Integrated process for the purification of antibodies combining aqueous two-phase extraction, hydrophobic interaction chromatography and size-exclusion chromatography

We have evaluated a process incorporating aqueous two-phase extraction, hydrophobic interaction chromatography (HIC) and size-exclusion chromatography (SEC) for the purification of human immunoglobulin G (IgG) from a Chinese hamster ovary (CHO) cell supernatant. These unit operations were chosen not only for allowing the removal of target impurities but also for facilitating the integration of different process units without the need for any conditioning step. Extraction in aqueous two-phase systems (ATPSs), composed of polyethylene glycol (PEG) and sodium citrate, allowed the concentration of the antibodies in the citrate-rich phase and the removal of the most hydrophobic compounds in the PEG-rich phase. An ATPS composed of 10% (w/w) PEG 3350 and 12% (w/w) citrate, at pH 6, allowed the recovery of IgG with a 97% yield, 41% HPLC purity and 72% protein purity. This bottom phase was then directly loaded on a phenyl-Sepharose HIC column. This intermediate purification step allowed the capture of the antibodies using a citrate mobile phase with 99% of the antibody recovered in the elution fractions, with 86% HPLC purity and 91% protein purity. Finally, SEC allowed the final polishing by removing IgG aggregates. HIC-eluted fractions were directly injected in a Superose 6 size-exclusion column affording a 100% pure IgG solution with 90% yield.     

Development of the protocol for purification of artemisinin based on combination of commercial and computationally designed adsorbents

A polymeric adsorbent for extraction of the antimalarial drug artemisinin from Artemisia annua L. was computationally designed. This polymer demonstrated a high capacity for artemisinin (120 mg g^?1), quantitative recovery (87%) and was found to be an effective material for purification of artemisinin from complex plant matrix. The artemisinin quantification was conducted using an optimised HPLC‐MS protocol, which was characterised by high precision and linearity in the concentration range between 0.05 and 2 μg mL^?1. Optimisation of the purification protocol also involved screening of commercial adsorbents for the removal of waxes and other interfering natural compounds, which inhibit the crystallisation of artemisinin. As a result of a two step‐purification protocol crystals of artemisinin were obtained, and artemisinin purity was evaluated as 75%. By performing the second stage of purification twice, the purity of artemisinin can be further improved to 99%. The developed protocol produced high‐purity artemisinin using only a few purification steps that makes it suitable for large scale industrial manufacturing process.     

萝芙木根中萝芙木碱的分离纯化

对萝芙木根中萝芙木碱的提纯与检测技术进行研究.利用萝芙木植物的根和皮为原料,对萝芙木碱的分离纯化过程进行了系统的研究,确立了固一液萃取、液一液萃取、等电点沉淀、甲醇重结晶提取萝芙木碱的优化方案,并用高效液相色谱法检测了萝芙木碱的含量.实验所得样品中萝芙木碱的含量不低于98%.结果表明该分离纯化技术生产成本低,操作简单,...     

Investigation of the solid phase synthesis of tyrosine‐derived diphenol monomers with resin‐bound carbodiimide coupling reagents

Tyrosine‐derived pseudo‐polypeptides have recently been established as potential biomaterials. The bulk production of these polymers is dependant upon the convenient synthesis of tyrosine‐derived diphenolic monomers. Suitable solution phase methods for the synthesis of such monomers, with transient activated esters, have been reported previously by Kohn, J.; Langer, R. In Biomaterials Science: An Introduction to Materials in Medicine; Ratner, B. D.; Hoffman, A. S.; Schoen, F. J.; Lemons, J. E., Eds.; Academic Press: New York, 1996; pp 64–72. However, for all the methods reported by them, purification and isolation of the diphenol monomer involves rigorous extraction, column purification, or an extensive aqueous workup. These may lead to the incorporation of solvent‐based as well as inorganic impurities and also may lead to difficulties in the process scale‐up. In this article, an alternate and relatively more convenient method for the synthesis of tyrosine‐based diphenol monomers is reported. This involved the investigation of polymer resin‐bound carbodiimide in the solid‐phase synthesis of L‐tyrosine‐based diphenolic monomers. This method was found to eliminate the need for rigorous purification processes and was found to maintain reasonable yield as well as maintain purity of the final monomer product. The monomer was able to produce polymers of a reasonably high‐molecular‐weight and a narrow polydispersity. The amide bond formation by such a polymer‐tethered reagent can be described to follow a reverse‐Merrifield sense and the method is relatively convenient to scale up. The L‐tyrosine‐based diphenolic monomeric compound formed by this method was analyzed by NMR, Fourier transform infrared, and elemental microanalysis techniques for chemical structure and composition. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4906–4915, 2004     

Chromatographic separation of papain evaluated by immunochemical methods

The chromatographic separation of crude papain preparations on Sephadex G-50 (fine) enables pure papain to be obtained in a single step. Immunochemical techniques have been found to be very convenient for testing the purity of the individual chromatographic fractions. A general approach is presented that makes it possible to follow the course of the chromatographic purification of any immunogenic compound by simple qualitative immunochemical techniques that can be applied in any laboratory.     

Downstream processing of antibodies: Single-stage versus multi-stage aqueous two-phase extraction

Single-stage and multi-stage strategies have been evaluated and compared for the purification of human antibodies using liquid–liquid extraction in aqueous two-phase systems (ATPSs) composed of polyethylene glycol 3350 (PEG 3350), dextran, and triethylene glycol diglutaric acid (TEG-COOH). The performance of single-stage extraction systems was firstly investigated by studying the effect of pH, TEG-COOH concentration and volume ratio on the partitioning of the different components of a Chinese hamster ovary (CHO) cells supernatant. It was observed that lower pH values and high TEG-COOH concentrations favoured the selective extraction of human immunoglobulin G (IgG) to the PEG-rich phase. Higher recovery yields, purities and percentage of contaminants removal were always achieved in the presence of the ligand, TEG-COOH. The extraction of IgG could be enhanced using higher volume ratios, however with a significant decrease in both purity and percentage of contaminants removal. The best single-stage extraction conditions were achieved for an ATPS containing 1.3% (w/w) TEG-COOH with a volume ratio of 2.2, which allowed the recovery of 96% of IgG in the PEG-rich phase with a final IgG concentration of 0.21 mg/mL, a protein purity of 87% and a total purity of 43%. In order to enhance simultaneously both recovery yield and purity, a four stage cross-current operation was simulated and the corresponding liquid–liquid equilibrium (LLE) data determined. A predicted optimised scheme of a counter-current multi-stage aqueous two-phase extraction was hence described. IgG can be purified in the PEG-rich top phase with a final recovery yield of 95%, a final concentration of 1.04 mg/mL and a protein purity of 93%, if a PEG/dextran ATPS containing 1.3% (w/w) TEG-COOH, 5 stages and volume ratio of 0.4 are used. Moreover, according to the LLE data of all CHO cells supernatant components, it was possible to observe that most of the cells supernatant contaminants can be removed during this extraction step leading to a final total purity of about 85%.     

New protocol to obtain spirolides from Alexandrium ostenfeldii cultures with high recovery and purity

The aim of this work was to develop a method to purify large amounts of spirolide toxins from cultures of Alexandrium ostenfeldii. The dinoflagellates grew in batches under controlled conditions of salinity, light and temperature. Analysis of the cultures demonstrated the existence of neurotoxins associated with paralytic shellfish poisoning toxins and two spirolides, 13‐desmethyl spirolide C and 13,19‐didesmethyl spirolide C. The protocol designed presents several stages of extraction, separation between spirolides and paralytic shellfish poisoning toxins, and cleanup in solid‐phase extraction. Finally, the purification of spirolides was conducted by a preparative high‐performance liquid chromatography system coupled to a mass spectrometer detector. The purity and the amount of both toxins in each step was monitored by analytical liquid chromatographic–mass spectrometry. Large amounts of 13‐desMeC, 97% pure, and 13,19‐didesMeC, 99% pure, were obtained. A novel and efficient method to separate and purify spirolide toxins from large amounts of phytoplankton is provided. The protocol proposed shows, for the first time, a complete and detailed methodology to separate and purify spirolide toxins with high purity, recovery, repeatability and stability. Copyright © 2010 John Wiley & Sons, Ltd.     

Purification of uranium product from plutonium contamination using acetohydroxamic acid (AHA) based process

Acetohydroxamic acid (AHA) based uranium product purification process to remove plutonium was optimized. For this process, equilibrium data was generated to optimize AHA concentration and acidity of stripping agent/scrubbing agent. Two options namely (i) Pu complexation in aqueous phase followed by extraction and scrubbing ii) extraction followed by scrubbing with AHA were studied. Results of these studies indicate that U product obtained in AHA purification is near to the table top specification and also quantitative Pu recovery from the AHA strip product is possible by oxalate precipitation.     

Neutron activation analysis of high purity noble metals (palladium,platinum, rhodium,gold and silver)

Methods of neutron activation analysis of high purity noble metals have been developed based on the selective extraction procedures for matrix activities separation. These procedures are shown to provide purification coefficients from matrix of about 10⁶–10⁸. High-resolution gamma-spectrometry makes possible the determination of 25–30 elements simultaneously in aqueous phases remained after matrix separation. Complex standard for NA analysis of pure materials has been described.     

Separation optimization for the recovery of phenyl ethyl alcohol

Phenyl ethyl alcohol is a compound that occurs naturally in flower petals and in many common beverages, such as beer. Desire for the floral, rose-like notes imparted by phenyl ethyl alcohol has created a unique niche for this chemical in flavor and fragrance industries. Phenyl ethyl alcohol can be produced by Saccharomyces cerevisiae via bioconversion. Often this method of production results in extremely low yields, thus placing a great deal of importance on recovery and purification of the valuable metabolite. To determine the best method for recovering the chemical, a primary recovery step and a secondary recovery step were developed. The primary recovery step consisted of comparing dead-end filtration with crossflow ultrafiltration. Crossflow ultrafiltration was ultimately selected to filter the fermentation broth because of its high flow rates and low affinity for the product. The secondary recovery step consisted of a comparison of liquid-liquid extraction and hydrophobic resin recovery. The hydrophobic resin was selected because of its higher rate of recovery and a higher purity than the liquid-liquid extraction, the current practice of Brown-Forman.     

Vapor phase matrix extraction of high purity di-boron trioxide and trace analysis using electrothermal AAS

A method has been developed for the determination of Al, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Sb, Sn and Zn at trace levels in high purity di-boron trioxide using ETAAS. The boron trioxide matrix was eliminated as trimethyl borate ester in a multiplex vapor phase matrix extraction (MVPME) device using a mixture of glycerol and methanol. In this MVPME device, in situ reagent purification, sample digestion and simultaneous matrix elimination were achieved by a single step in closed condition, which in combined effect reduce the process blanks. The matrix extraction procedure allows determination of trace elemental impurities by electrothermal atomic absorption spectrometry (ETAAS) with fast furnace analysis (without an ashing step and modifier) and calibration against aqueous standards. The performance and accuracy of the vapor phase matrix elimination technique are compared to those of suprapur grade hydrofluoric acid solution in two ways; (i) matrix separation as BF₃ over hot plate and (ii) in situ matrix elimination inside graphite furnaces. The method detection limits calculated from blank samples are in the range of 0.5 (Ni) and 2.9 (Al) ng g⁻¹. Thus the MVPME-based sample preparation approach is well suited for the trace analysis of high purity di-boron trioxide used in microelectronics applications.     

Purification of crude DNA oligonucleotides by solid-phase extraction and reversed-phase high-performance liquid chromatography

Purification of target oligodeoxyribonucleotides from failure sequence by-products of synthesis is often required for polymerase chain reaction primers, DNA sequencing and other oligonucleotide applications. We have developed purification protocols based on a reversed-phase mechanism ("trityl on" purification) using a 96-well Oasis HLB extraction plate. The Oasis HLB sorbent combines excellent pH stability with a high loading capacity allowing for single-step purification of 0.2 microM scale synthesis. After sample loading and washing, the oligonucleotide trityl group is cleaved on the plate with 2% trifluoroacetic acid. Target DNA is eluted with acetonitrile-0.36 mM triethylamine acetate, pH 11.3 (10:90, v/v). Typical yield of purified product is 60-95%. Final purity, measured by capillary gel electrophoresis, was found to be 90% or greater. Alternatively, highly pure oligonucleotides can be obtained by a RP-HPLC "trityl off" method using an XTerra C18 column. The use of volatile triethylamine acetate buffer as an ion-pair for RP-HPLC eliminates the need for further desalting.     

Isolation of ethanol from its aqueous solution by liquid phase adsorption and gas phase desorption using molecular sieving carbon

A novel bioethanol separation process was proposed in this study employing molecular sieving carbon (MSC) as an adsorbent, whose pore diameter is close to molecular size of ethanol. In the proposed process, fermentation broth is first introduced to the adsorption bed packed with MSC. In this step, ethanol is selectively adsorbed onto MSC, with highly enriching ethanol in the micropore of MSC. Subsequently, the concentrated ethanol is desorbed from MSC to gaseous phase, resulting in further purification of ethanol owing to a considerable difference in desorption rate between water and ethanol; Because of molecular sieving effect of MSC, the desorption rate of ethanol is much smaller than that of water. To establish this process, adsorption equilibrium and kinetics of ethanol on various MSCs were investigated in aqueous phase as the first step. Also, desorption kinetics of ethanol and water in gaseous phase were investigated. As a result, it was suggested that highly concentrated ethanol could be obtained with high recovery ratio through these simple operations, meaning the proposed process is quite promising.     

Method to obtain C-phycocyanin of high purity

A new approach is made for the purification of C-phycocyanin (C-PC), which is simple and more efficient than existing methods. The proposed method involves two steps: aqueous two phase extraction and ion-exchange chromatography. Crude extract of C-phycocyanin, of purity 1.18, obtained from Spirulina platensis is subjected to aqueous two phase extraction. C-phycocyanin obtained from this process showed a purity of 5.22, which is higher than the reported value till date. In order to explore the possibility of further purification, C-phycocyanin is subjected to ion-exchange chromatography and found that the purity increased from 5.22 to 6.69. The fluorescence, intactness of structure and purity of C-phycocyanin are confirmed using spectrofluorometry, circular dichroism spectra and sodium dodecyl sulfate-polyacrylamide gel, respectively.     

Concept and synthetic approach for a kilogram scale synthesis of octa-d-arginine amide nonahydrochloride salt

Oligomers of arginine, such as octa-d-arginine amide, are excellent transporters for active drugs through cell membranes and tissue. The synthesis of octa-d-arginine amide, as the nonahydrochloride salt, was approached via a solution phase synthetic route involving the preparation of an octa-d-ornithine intermediate, which was then converted into the desired octa-d-arginine compound through a guanidinylation step. The multi-step synthesis was carried out at pilot scale, resulting in the preparation of 700 g of the target molecule. No chromatographic purification was needed at any step of the process.     

In situ extraction of intracellular L-asparaginase using thermoseparating aqueous two-phase systems

The feasibility and generic applicability of directly integrating conventional discrete operations of cell disruption by high pressure homogenizer and the product capture by aqueous two-phase extraction (ATPE) system have been demonstrated for the extraction of intracellular L-asparaginase from E. coli. In a side-by-side comparison with the conventional ATPE process, including cell disruption, centrifugal clarification and following ATPE, purification of L-asparaginase via this novel in situ ATPE process yielded a product of L-asparaginase with a higher specific activity of 94.8 U/(mg protein) and a higher yield of 73.3%, both of which in the conventional ATPE process were 78.6 U/(mg protein) and 52.1%, respectively. In the purification of L-asparaginase (pI=4.9), product-debris interactions commonly diminish its recovery. It was demonstrated that immediate extraction of L-asparaginase in ATPE systems when it is released at pH 5.0 during cell disruption effectively increased its recovery in the top phase due to the reduced interaction between L-asparaginase and cell debris and the reduced degradation by contaminated protease. In addition, no clarification step and/or disruptate storage are required in this in situ ATPE, which reduced the number of unit operations and thus shortened the overall process time. This novel process has a good potential for the separation of other intracellular biological products.     

Prediction of Vapor–Liquid Equilibria for Pb–Pd and Pb–Pt Alloys Using Ab Initio Methods in Vacuum Distillation

The vapor–liquid equilibrium (VLE) phase diagrams of Pb–Pd and Pb–Pt alloy systems in vacuum distillation were obtained based only on pure-component properties and the structures of the atoms. The interaction energies between pairs of atoms were calculated from ab initio methods and were used as the input energy parameters for the Wilson equation. The calculated activity data of the components, using energy parameters which were obtained by ab initio methods, are in good agreement with the experimental data. It is revealed that a cluster size of eight atoms, optimized using the NVT ensemble at 300 K, a time step of 1 femtosecond, and the simulation time 10 ps gives a good representation of the liquid phase systems. This approach can be used to obtain accurate VLE predictions for alloy systems in vacuum distillation. The VLE phase diagram has a significant advantage in guiding experiment and industrial production in vacuum metallurgy.     

Development of a custom high-throughput preparative liquid chromatography/mass spectrometer platform for the preparative purification and analytical analysis of compound libraries

Solution-phase parallel synthesis has had a profound impact on the speed of compound synthesis delivering relatively pure compounds (>80%) in short order. However, to develop structure activity relationships (SAR) for a compound series, each library member should preferably be >95% pure. Historically, achieving and quantifying such high-purity criteria for each library member proved to be the slow step for most lead discovery groups. To address this issue, significant modifications have been made to a commercial Agilent preparative LC/MS system to allow for the general mass-guided purification of diverse compound libraries. The custom modifications include (1) the "DMSO slug" approach for the purification of samples with poor solubility; (2) an active splitter to reduce system back-pressure, reduce the delay volume, and allow for a variable split ratio; (3) a sample loading pump for the quick purification of large, dilute samples; (4) a preparative column-selection valve to quickly change column selectivity or sample loading; and (5) an analytical injector with a separate flow path for crude reaction or fraction analyses.