Practical Techniques for Improving the Performance of Polymeric Membranes and Processes for Protein Separation and Purification

Document Type: Review Article


1 Department of Chemical & Petroleum Engineering, Sharif University of Technology, P.O. Box 11365-11155 Tehran, I.R. IRAN

2 Department of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115-114 Tehran, I.R. IRAN


Protein separation and purification technologies play an essential role in various industries including but not limited to pharmaceuticals, dairy as well as the food sector. Accordingly, a wide variety of techniques such as chromatography and electrophoresis has been developed and utilized extensively over the years for this purpose. Despite their widespread acceptance, conventional techniques still suffer from major limitations and complexities such as short lifetime, low productivity, high-pressure drop and difficulty in scale-up among others. Membrane separation processes have received significant attention in recent years as a promising alternative that can potentially overcome the problems associated with conventional technologies due to their spectacular features. The prime advantages offered by the membrane-based processes for protein separation and purification include tunable properties, cost-effectiveness, superb productivity, as well as energy efficiency. The present manuscript aims to highlight the significant aspects of the established protein separation and purification technologies by addressing the principal concepts and highlighting their characteristics. Special attentions are paid to the membrane-based processes by providing detailed features and specifications involved in each individual process, especially from the industrial perspective. Furthermore, the recent and ongoing progress on strategies and practical techniques towards improvement in the performance of membranes for separation and purification of various proteins are introduced and discussed in details.


Main Subjects

[1] Ahmad S., Ahmed S.M., Application of Membrane Technology in Food Processing, in: A. Malik, Z. Erginkaya, S. Ahmad, H. Erten (Eds.) “Food Processing: Strategies for Quality Assessment”, Springer New York, New York, NY, pp. 379-394 (2014).

[2] Pinto A.C., Ades F., de Azambuja E., Piccart-Gebhart M., Trastuzumab for Patients with HER2 Positive Breast Cancer: Delivery, Duration and Combination Therapies, Breast, 22, Supplement 2 S152-S155 (2013).

[3] Alaei Shahmirzadi M.A., Hosseini S.S., Ruan G., Tan N.R., Tailoring PES Nanofiltration Membranes Through Systematic Investigations of Prominent Design, Fabrication and Operational Parameters, RSC Advances, 5: 49080-49097 (2015).

[4] Hosseini S.S., Najari S., Kundu P.K., Tan N.R., Roodashti S.M., Simulation and Sensitivity Analysis of Transport in Asymmetric Hollow Fiber Membrane Permeators for Air Separation, RSC Advances, 5: 86359-86370 (2015).

[5] Çelik S.Ü., Bozkurt A., Hosseini S.S., Alternatives Toward Proton Conductive Anhydrous Membranes for Fuel Cells: Heterocyclic Protogenic Solvents Comprising Polymer Electrolytes, Progress in Polymer Science, 37: 1265-1291 (2012).

[6] Krantz W.B., Greenberg A.R., Kujundzic E., Yeo A., Hosseini S.S., Evapoporometry: A Novel Technique for Determining the Pore-Size Distribution of Membranes, Journal of Membrane Science, 438: 153-166 (2013).

[8] Najari S., Hosseini S.S., Omidkhah M., Tan N.R., Phenomenological Modeling and Analysis of Gas Transport in Polyimide Membranes for Propylene/ Propane Separation, RSC Advances, 5: 47199-47215 (2015).

[9] Hosseini S.S., Roodashti S.M., Kundu P.K., Tan N.R., Transport Properties of Asymmetric Hollow Fiber Membrane Permeators for Practical Applications: Mathematical Modeling For Binary Gas Mixtures Canadian Journal of Chemical Engineering, 93(7): 1275-1287 (2015).

[10] Tamaddondar M., Pahlavanzadeh H., Hosseini S.S., Ruan G., Tan N.R., Self-Assembled Polyelectrolyte Surfactant Nanocomposite Membranes for Pervaporation Separation of MeOH/MTBE, Journal of Membrane Science, 472: 91-101 (2014).

[11] Hosseini S.S., Dehkordi J.A., Kundu P.K., Gas Permeation and Separation in Asymmetric Hollow Fiber Membrane Permeators: Mathematical Modeling, Sensitivity Analysis and Optimization, Korean Journal of Chemical Engineering, 33(11): 3085-3101 (2016).

[12] Xiao Y., Low B.T., Hosseini S.S., Chung T.S., Paul D.R., The Strategies of Molecular Architecture and Modification of Polyimide-Based Membranes for CO2 Removal from Natural Gas—A Review, Progress in Polymer Science, 34: 561-580 (2009).

[13] Hosseini S.S., Najari S., Polymeric Membranes for Gas and Vapor Separations, in: P.M. Visakh, N. Olga (Eds.) “Nanostructured Polymer Membranes, Applications”, Wiley, (2016).

[14] Zeng X., Ruckenstein E., Membrane Chromatography: Preparation and Applications to Protein Separation, Biotechnology Progress, 15: 1003-1019 (1999).

[15] Mayani M., Filipe C.D.M., Ghosh R., Cascade Ultrafiltration Systems—Integrated Processes for Purification and Concentration of Lysozyme, Journal of Membrane Science, 347: 150-158 (2010).

[16] Atasever A., Ozdemir H., Gulcin me., Irfan Kufrevioglu O., One-Step Purification of Lactoperoxidase from Bovine Milk by Affinity Chromatography, Food Chemistry, 136: 864-870 (2013).

[17] Arkell A., Jönsson A.S., Back-Pulsing as a Flux Increasing Method in Microfiltration of Milk, Procedia Engineering, 44: 29-32 (2012).

[18] Ining A.J., Dmitriy V.M., Maria E.G., Protein Permeation Through an Electrically Tunable Membrane, Nanotechnology, 27: 205201 (2016).

[19] Arrutia F., Rubio R., Riera F.A., Production and Membrane Fractionation of Bioactive Peptides from a Whey Protein Concentrate, Journal of Food Engineering, 184: 1-9 (2016).

[20] Yua H., Yu B., Cong H., Peng Q., Yang Z., Luo Y., Chi M., Preparation of Highly Permeable BPPO Microfiltration Membrane with Binary Porous Structures on a Colloidal Crystal Substrate by the Breath Figure Method, Journal of Colloid and Interface Science, 461: 232-238 (2016).

[21] Alele N., Ulbricht M., Membrane-Based Purification of Proteins from Nanoparticle Dispersions: Influences of Membrane Type and Ultrafiltration Conditions, Separation and Purification Technology, 158: 171-182 (2016).

[22] Saxena A., Tripathi B.P., Kumar M., Shahi V.K., Membrane-Based Techniques for the Separation and Purification of Proteins: An Overview, Advances in Colloid and Interface Science, 145: 1-22 (2009).

[23] Metsämuuronen S., Nyström M., Critical Flux in Cross-Flow Ultrafiltration of Protein Solutions, Desalination, 175: 37-47(2005).

[25] Birch J.R., Onakunle Y., Biopharmaceutical Proteins, in: C.M. Smales, D.C. James (Eds.) “Therapeutic Proteins: Methods and Protocols”, Humana Press, Totowa, NJ, pp. 1-16 (2005).

[26] Nathwani A.C., Reiss U.M., Tuddenham E.G.D., Rosales C., Chowdary P., McIntosh J., Della Peruta M., Lheriteau E., Patel N., Raj D., Riddell A., Pie J., Rangarajan S., Bevan D., Recht M., Shen Y.-M., Halka K.G., Basner-Tschakarjan E., Mingozzi F., High K.A., Allay J., Kay M.A., Ng C.Y.C., Zhou J., Cancio M., Morton C.L., Gray J.T., Srivastava D., Nienhuis A.W., Davidoff A.M., Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B, New England Journal of Medicine, 371: 1994-2004 (2014).

[27] Bonnerjea J., Purification of Therapeutic Proteins, in: P. Cutler (Ed.) “Protein Purification Protocols”, Humana Press, Totowa, NJ, pp. 455-462 (2004).

[28] Fouladitajar A., Zokaee Ashtiani F., Rezaei H., Haghmoradi A., Kargari A., Gas Sparging to Enhance Permeate Flux and Reduce Fouling Resistances in Cross Flow Microfiltration, Journal of Industrial and Engineering Chemistry, 20: 624-632 (2014).

[29] Saxena A., Kumar M., Tripathi B.P., Shahi V.K., Organic-Inorganicybrid Charged Membranes for Proteins Separation: Isoelectric Separation of Proteins under Coupled Driving Forces, Separation and Purification Technology, 70: 280-290 (2010).

[30] O'Keeffe M.B., FitzGerald R.J., Antioxidant Effects of Enzymatic Hydrolysates of Whey Protein Concentrate on Cultured Human Endothelial Cells, International Dairy Journal, 36: 128-135 (2014).

[31] Ghribi A.M., Sila A., Przybylski R., Nedjar-Arroume N., Makhlouf me., Blecker C., Attia H., Dhulster P., Bougatef A., Besbes S., Purification and Identification of Novel Antioxidant Peptides from Enzymatic Hydrolysate of Chickpea (Cicer arietinum L.) Protein Concentrate, Journal of Functional Foods, 12: 516-525 (2015).

[32] Raja G., Ultrafiltration-Based Protein Bioseparation, in: “Handbook of Membrane Separations”, CRC Press, pp. 497-511 (2008).

[33] Eppler A., Weigandt M., Schulze S., Hanefeld A., Bunjes H., Comparison of Different Protein Concentration Techniques wthfin Preformulation Development, International journal of pharmaceutics, 421: 120-129 (2011).

[34] Tomic S., Besnard L., Fürst B., Reithmeier R., Wichmann R., Schelling P., Hakemeyer C., Complete Clarification Solution for Processing High Density Cell Culture Harvests, Separation and Purification Technology, 141: 269-275 (2015).

[35] Hahn R., Schulz P.M., Schaupp C., Jungbauer A., Bovine Whey Fractionation Based on Cation-Exchange Chromatography, Journal of Chromatography A, 795: 277-287 (1998).

[36] Goklen K.E., Hatton T.A., Liquid-Liquid Extraction of Low Molecular-Weight Proteins by Selective Solubilization in Reversed Micelles, Separation Science and Technology, 22: 831-841 (1987).

[37] Ersson B., Rydén L., Janson J.-C., Introduction to Protein Purification, in: “Protein Purification”, John Wiley & Sons, Inc., pp. 1-22 (2011).

[38] Lv S.H., Liang Z.H., Zen Y.Y., Fa H.B., Soybean Whey Treatment with an Air Sparging Ultrafiltration System, Advanced Materials Research, 726-731: 2823-2828 (2013).

[39] Walter J.K., Jin Z., Jornitz M.W., Gottschalk U., Membrane Separations, in: “Protein Purification”, John Wiley & Sons, Inc., pp. 279-317 (2011).

[40] Janson J.-C, Jönsson J.Å., Introduction to Chromatography, in: “Protein Purification”, John Wiley & Sons, Inc., pp. 23-50 (2011).

[41] Mehta A., Tse M.L., Fogle J., Len A., Shrestha R., Fontes N., Lebreton B., Wolk B., Van Reis R., Purifying Therapeutic Monoclonal Antibodies, Chemical Engineering Progress, 104: S14-S20 (2008).

[42] Guérin-Dubiard C., Pasco M., Hietanen A., Quiros del Bosque A., Nau F., Croguennec T., Hen egg white Fractionation by Ion-Exchange Chromatography, Journal of Chromatography A, 1090: 58-67 (2005).

[43] Ayyar B.V., Arora S., Murphy C., O’Kennedy R., Affinity Chromatography as a Tool for Antibody Purification, Methods, 56: 116-129 (2012).

[44] Feins M., Sirkar K.K., Novel Internally Staged Ultrafiltration for Protein Purification, Journal of Membrane Science, 248: 137-148 (2005).

[45] Orr V., Scharer J., Moo-Young M., Honeyman C.H., Fenner D., Crossley L., Suen S.-Y., Chou C.P., Simultaneous Clarification of Escherichia coli Culture and Purification of Extracellularly Produced Penicillin G Acylase Using Tangential Flow Filtration and Anion-Exchange Membrane Chromatography (TFF-AEMC), Journal of Chromatography B, 900: 71-78 (2012).

[46] Teepakorn C., Fiaty K., Charcosset C., Optimization of Lactoferrin and Bovine Serum Albumin Separation Using Ion-Exchange Membrane Chromatography, Separation and Purification Technology, 151: 292-302 (2015).

[47] Westermeier R., Electrophoresis in Gels, in: “Protein Purification”, John Wiley & Sons, Inc., pp. 363-377 (2011).

[48] Hosseini S.S., “Membranes and Materials for Separation and Purification of Hydrogen and Natural Gas”, Ph.D. Thesis, Department of Chemical and Biomolecular Engineering, National University of Singapore, (2009).

[49] Hosseini S.S., Bringas E., Tan N.R., Ortiz me., Ghahramani M., Alaei Shahmirzadi M.A., Recent Progress in Development of High Performance Polymeric Membranes and Materials for Metal Plating Wastewater Treatment: A Review, Journal of Water Process Engineering, 9: 78-110 (2016).

[50] Zadhoush A., Hosseini S.S., Mousavi S.M., The Importance and Influence of Rheological Characteristics of Polymer Solutions in Phase Inversion Process and Morphology of Polymeric Membranes, Iranian Journal of Polymer Science and Technology, 28: (2015) 351-371.

[51] Hosseini S.S., Dehkordi J.A., Kundu P.K., Mathematical Modeling and Investigation on the Temperature and Pressure Dependency of Permeation and Membrane Separation Performance for Natural gas Treatment, Chemical Product and Process Modeling, 11, 7-10 (2016).

[52] Shahmirzadi M.A.A., Hosseini S.S., Tan N.R., Enhancing Removal and Recovery of Magnesium from Aqueous Solutions by Using Modified Zeolite and Bentonite and Process Optimization, Korean Journal of Chemical Engineering, 33, 3529-3540 (2016).

[53] Hosseini S.S., Nazif A., Alaei Shahmirzadi M.A., Ortiz me., Fabrication, Tuning and Optimization f Poly (acrilonitryle) Nanofiltration Membranes or Effective Nickel and Chromium Removal from Electroplating Wastewater, Separation and Purification Technology, 187, 46-59 (2017).

[54] Soleimany A., Hosseini S.S., Gallucci F., Recent Progress in Developments of Membrane Materials and Modification Techniques for High Performance Helium Separation and Recovery: A Review, Chemical Engineering and Processing: Process Intensification, 122, 296-318 (2017).

[55] Hosseini S.S., Chung T.S., Polymer Blends and Carbonized Polymer Blends, US Patent 8,623,124, (2014).

[56] Hosseini S.S., Pahlavanzadeh H., Tamadondar M., Dehydration of Organic Compounds Using Poly (vinyl alcohol) Membranes in Pervaporation Process, Iranian Journal of Chemical Engineering, 13, 76-84 (2014).

[57] Alaei Shahmirzadi M.A., Hosseini S.S., Potentials and Challenges of Heavy Metal Recovery and Removal from Zinc and Lead Industrial Waste Streams Using Membrane Technology, Iranian Journal of Chemical Engineering, 13, 91-105 (2015).

[58] Hosseini S.S., Nazif A., Zarrin Ghalam Moghaddam A., Study and Investigation on the Parameters Influencing the Performance of Polymeric Nanofiltration Membranes for Treatment of Chromium and Nickel in Electroplating Wastewater, Iranian Journal of Chemical Engineering, 15, 76-89 (2016).

[59] Jalili Palandi R., Hosseini S.S., Improving the Characteristics and Desalination Performance of Thin Film Composite Reverse Osmosis Membranes by Nanoparticles, Iranian Journal of Chemical Engineering, 15 86-97 (2016).

[60] Hosseini S.S., Aminian Dehkordi J., Najari S., Investigation and Analysis of Concentration Polarization and its Consequences in Modeling the Performance of Polymeric Gas Separation, Iranian Journal of Chemical Engineering, 15, 16-26 (2017).

[61] van Reis R., Zydney A., Bioprocess Membrane Technology, Journal of Membrane Science, 297, 16-50 (2007).

[62] Li Q.Y., Cui Z.F., Pepper D.S., Fractionation of HSA and IgG by Gas Sparged Ultrafiltration, Journal of Membrane Science, 136, 181-190 (1997).

[63] Christy C., Adams G., Kuriyel R., Bolton G., Seilly A., High-Performance Tangential Flow Filtration: A Highly Selective Membrane Separation Process, Desalination, 144: 133-136 (2002).

[64] Li Q., Bi Q.-y., Lin H.-H., Bian L.-X., Wang X.-L., A Novel Ultrafiltration (UF) Membrane with Controllable Selectivity for Protein Separation, Journal of Membrane Science, 427: 155-167 (2013).

[65] Strathmann H., Membranes and Membrane Separation Processes, in: “Ullmann's Encyclopedia of Industrial Chemistry”, Wiley-VCH Verlag GmbH & Co. KGaA, (2000).

[66] Benedetti S., Prudêncio E.S., Nunes G.L., Guizoni K., Fogaça L.A., Petrus J.C.C., Antioxidant Properties of Tofu Whey Concentrate by Freeze Concentration and Nanofiltration Processes, Journal of Food Engineering, 160: 49-55 (2015).

[67] Kwon B., Molek J., Zydney A.L., Ultrafiltration of PEGylated Proteins: Fouling and Concentration Polarization Effects, Journal of Membrane Science, 319: 206-213 (2008).

[68] Hurt E., Barbano D.M., Processing Factors that Influence Casein and Serum Protein Separation by Microfiltration, Journal of Dairy Science, 93:4928-4941 (2010).

[69] Cheang B., Zydney A.L., A Two-Stage Ultrafiltration Process for Fractionation of Whey Protein Isolate, Journal of Membrane Science, 231: 159-167 (2004).

[70] Atra R., Vatai G., Bekassy-Molnar E., Balint A., Investigation of Ultra-and Nanofiltration for Utilization of Whey Protein and Lactose, Journal of Food Engineering, 67: 325-332 (2005).

[71] Smith D.M., “Protein Separation and Characterization Procedures, in: Food Analysis”, Springer US, Boston, MA, pp. 261-281 (2010).

[72] Bet-moushoul E., Mansourpanah Y., Farhadi K., Tabatabaei M., TiO2 Nanocomposite Based Polymeric Membranes: A Review on Performance Improvement for Various Applications in Chemical Engineering Processes, Chemical Engineering Journal, 283: 29-46 (2016).

[74] Biron D.d.S., Bortoluz J., Zeni M., Bergmann C., Santos V.d., Characterization of Mullite Ceramic Membranes and their Application in the Removal Escherichia Coli, Materials Research, 19: 513-519 (2016).

[75] Laorko A., Tongchitpakdee S., You'reavong W., Storage Quality of Pineapple Juice Non-Thermally Pasteurized and Clarified by Microfiltration, Journal of Food Engineering, 116: 554-561 (2013).

[76] Drioli E., Cassano A., Advances in Membrane-Based Concentration in the Food and Beverage Industries: Direct Osmosis and Membrane Contactors, in: S.S.H. Rizvi (Ed.) “Separation, Extraction and Concentration Processes in the Food, Beverage and Nutraceutical Industries”, Woodhead Publishing, pp. 244-283 2013.

[77] Qiu Y., Smith T., Foegeding E., Drake M., The Effect of Microfiltration on Color, Flavor, and Functionality of 80% Whey Protein Concentrate, Journal of Dairy Science, 98: 5862-5873 (2015).

[78] Hernández A., Harte F.M., Isolation of Caseins from Whey Proteins by Microfiltration Modifying the Mineral Balance in Skim Milk, Journal of Dairy Science, 92: 5357-5362 (2009).

[79] Hurt E.E., Adams M.C., Barbano D.M., Microfiltration: Effect of Channel Diameter on Limiting Flux and Serum Protein Removal, Journal of Dairy Science, 98: 3599-3612 (2015).

[80] Adams M.C., “Examination of Methods to Reduce Membrane Fouling During Dairy Microfiltration and Ultrafiltration”, Graduate Thesis, Cornell University, (2012).

[81] van Reis R., Zydney A., Membrane Separations in Biotechnology, Current Opinion in Biotechnology, 12: 208-211 (2001).

[82] Tremblay-Marchand D., Doyen A., Britten M., Pouliot Y., A Process Efficiency Assessment of Serum Protein Removal From Milk Using Ceramic Graded Permeability Microfiltration Membrane, Journal of Dairy Science, 99: 5230-5243 (2016).

[83] Jørgensen C.E., Abrahamsen R.K., Rukke E.-O., Johansen A.-G., Schüller R.B., Skeie S.B., Optimization of Protein Fractionation by Skim Milk Microfiltration: Choice of Ceramic Membrane Pore Size and Filtration Temperature, Journal of Dairy Science, 9: 6164-6179 (2016).

[84] Chen G., Song W., Qi B., Ghosh R., Wan Y., Separation of Human Serum Albumin and Polyethylene Glycol by Electro-Ultrafiltration, Biochemical Engineering Journal, 109: 127-136 (2016).

[85] Luján-Facundo M.J., Mendoza-Roca J.A., Cuartas-Uribe B., Álvarez-Blanco S., Cleaning Efficiency Enhancement by Ultrasounds for Membranes Used in Dairy Industries, Ultrasonics Sonochemistry, 33: 18-25 ((2016)).

[86] Mehta A., Zydney A.L., Permeability and Selectivity Analysis for Ultrafiltration Membranes, Journal of Membrane Science, 249: 245-249 (2005).

[89] Meng H., Cheng Q., Li C., Polyacrylonitrile-Based Zwitterionic Ultrafiltration Membrane with Improved Anti-Protein-Fouling Capacity, Applied Surface Science, 303: 399-405 (2014).

[90] Alventosa-deLara E., Barredo-Damas S., Zuriaga-Agustí E., Alcaina-Miranda, Iborra-Clar, Ultrafiltration Ceramic Membrane Performance During the Treatment of Model Solutions Containing Dye and Salt, Separation and Purification Technology, 129: 96-105 (2014).

[91] Waszak M., Gryta M., The Ultrafiltration Ceramic Membrane Used for Broth Separation in Membrane Bioreactor, Chemical Engineering Journal, (2015).

[93] Walsh C., Thomas R., Kunkel M., The Use of Metallic Ultrafiltration Membranes to Assess Calcium Availability in Vitro, Food Chemistry, 32: 307-317 (1989).

[94] Thomas R., Westfall P., Louvieri Z., Ellis N., Production of Apple Juice by Single Pass Metallic Membrane Ultrafiltration, Journal of Food Science, 51, 559-563 (1986).

[96] Huisman me.H., Prádanos P., Hernández A., The Effect of Protein-Protein and Protein-Membrane Interactions on Membrane Fouling in Ultrafiltration, Journal of Membrane Science, 179: 79-90 (2000).

[97] Kumar M., Lawler J., Preparation and Characterization of Negatively Charged Organic-Inorganic Hybrid Ultrafiltration Membranes for Protein Separation, Separation and Purification Technology, 130: 112-123 (2014).

[98] Demers-Mathieu V., Gauthier S.F., Britten M., Fliss me., Robitaille G., Jean J., Antibacterial Activity of Peptides Extracted from Tryptic Hydrolyzate of Whey Protein by Nanofiltration, International Dairy Journal, 28: 94-101 (2013).

[99] Nyström M., Kaipia L., Luque S., Fouling and Retention of Nanofiltration Membranes, Journal of Membrane Science, 98: 249-262 (1995).

[100] Li H., Shi W., Wang W., Zhu H., The Extraction of Sericin Protein from Silk Reeling Wastewater by Hollow Fiber Nanofiltration Membrane Integrated Process, Separation and Purification Technology, 146: 342-350 (2015).

[101] Cao J., Wang G., Wu S., Zhang W., Liu C., Li H., Li Y., Zhang L., Comparison of Nanofiltration and Evaporation Technologies on the Storage Stability of Milk Protein Concentrates, Dairy Science & Technology, 96: 107-121 (2016).

[102] Bowen W.R., Mukhtar H., Characterisation and Prediction of Separation Performance of Nanofiltration Membranes, Journal of Membrane Science, 112: 263-274 (1996).

[104] Taniguchi M., Kilduff J.E., Belfort G., Low Fouling Synthetic Membranes by UV-Assisted Graft Polymerization: Monomer Selection to Mitigate Fouling by Natural Organic Matter, Journal of Membrane Science, 222: 59-70

[105] Cui Y., Yao Z.-K., Zheng K., Du S.-Y., Zhu B.-K., Zhu L.-P., Du C.-H., Positively-charged Nanofiltration Membrane Formed by Quaternization and Cross-Linking of Blend PVC/P(DMA-co-MMA) Precursors, Journal of Membrane Science, 492: 187-196 (2015).

[106] Das B., Sarkar S., Sarkar A., Bhattacharjee S., Bhattacharjee C., Recovery of Whey Proteins and Lactose from Dairy Waste: A Step Towards Green Waste Management, Process Safety and Environmental Protection, 101: 27-33 (2016).

[107] Thömmes J., Etzel M., Alternatives to Chromatographic Separations, Biotechnology Progress, 23: 42-45 (2007).

[108] Gottschalk U., Bioseparation in Antibody Manufacturing: The Good, The Bad and The Ugly, Biotechnology Progress, 24: 496-503 (2008).

[109] Teeters M., Conrardy S., Thomas B., Root T., Lightfoot E., Adsorptive Membrane Chromatography for Purification of Plasmid DNA, Journal of Chromatography A, 989: 165-173 (2003).

[110] Vicente T., Sousa M.F., Peixoto C., Mota J.P., Alves P.M., Carrondo M.J., Anion-Exchange Membrane Chromatography for Purification of Rotavirus-Like Particles, Journal of Membrane Science, 311: 270-283(2008).

[111] Pereira L.R., Prazeres D.M.F., Mateus M., Hydrophobic Interaction Membrane Chromatography for Plasmid DNA Purification: Design and Optimization, Journal of Separation Science, 33:  1175-1184 (2010).

[112] Madadkar P., Ghosh R., High-Resolution Protein Separation Using a Laterally-Fed Membrane Chromatography Device, Journal of Membrane Science, 499: 126-133 (2016).

[113] Madadkar P., Wu Q., Ghosh R., A Laterally-Fed Membrane Chromatography Module, Journal of Membrane Science, 487: 173-179 (2015).

[114] Brand J., Dachmann E., Pichler M., Lotz S., Kulozik U., A Novel Approach for Lysozyme and Ovotransferrin Fractionation from Egg White by Radial Flow Membrane Adsorption Chromatography: Impact of Product and Process Variables, Separation and Purification Technology, 161: 44-52 (2016).

[115] Ghosh R., Protein Separation Using Membrane Chromatography: Opportunities and Challenges, Journal of Chromatography A, 952: 13-27 (2002).

[116] Orr V., Zhong L., Moo-Young M., Chou C.P., Recent Advances in Bioprocessing Application of Membrane Chromatography, Biotechnology Advances, 31: 450-465 (2013).

[118] Tennikova T.B., Bleha M., Švec F., Almazova T.V., Belenkii B.G., High-Performance Membrane Chromatography of Proteins, a Novel Method of Protein Separation, Journal of Chromatography A, 555: 97-107 (1991).

[119] Sirkar K.K., Membranes, Phase Interfaces, and Separations: Novel Techniques and Membranes—An Overview, Industrial & Engineering Chemistry Research, 47: 5250-5266 (2008).

[120] Huang Y.-T., Huang T.-H., Yang J.-H., Damodar R.A., Identifications and Characterizations of Proteins from Fouled Membrane Surfaces of Different Materials, International Biodeterioration & Biodegradation, 66: 47-52 (2012).

[121] Drews A., Membrane Fouling in Membrane Bioreactors—Characterisation, Contradictions, Cause and Cures, Journal of Membrane Science, 363: 1-28 (2010).

[123] Charcosset C., 2 - Ultrafiltration, in: Charcosset C. (Ed.) “Membrane Processes in Biotechnology and Pharmaceutics”, Elsevier, Amsterdam, pp. 43-99 (2012).

[124] Rodgers V., Sparks R., Reduction of Membrane Fouling in the Ultrafiltration of Binary Protein Mixtures, AIChE Journal, 37: 1517-1528 (1991).

[125] Wenten me., Mechanisms and Control of Fouling n Crossflow Microfiltration, Filtration & Separation, 32: 252-253 (1995).

[126] Arkell A., Vrgoc F., Jönsson A.S., Back-Pulsing as an Energy-Saving Method in the Microfiltration of Milk, International Dairy Journal, 35: 1-5 (2014).

[127] Vera L., González E., Ruigómez me., Gómez J., Delgado S., Influence of Gas Sparging Intermittence on Ultrafiltration Performance of Anaerobic Suspensions, Industrial & Engineering Chemistry Research, 55: 4668-4675 (2016).

[128] Charoenphun N., You'reavong W., Influence of Gas–Liquid Two-Phase Flow on Angiotensin-me Converting Enzyme Inhibitory Peptides Separation by Ultra-Filtration, Journal of the Science of Food and Agriculture, (2016).

[129] Hashemi Shahraki M., Maskooki A., Faezian A., Effect of Soluble and Insoluble Gas Bubbling Methods on Ultrafiltration Fouling Control, Desalination and Water Treatment, 57: 21173-21181 (2016).

[130] Ghosh R., Li Q., Cui Z., Fractionation of BSA and Lysozyme Using Ultrafiltration: Effect of Gas Sparging, AIChE Journal, 44: 61-67 (1998).

[132] Galier S., Roux-de Balmann H., Study of Biomolecules Separation in an Electrophoretic Membrane Contactor, Journal of Membrane Science, 241: 79-87 (2004).

[133] Galier S., Roux-de Balmann H., Electrophoretic Membrane Contactors, Chemical Engineering Research and Design, 83: 268-275 (2005).

[134] Ogle D., Sheehan M., Rumbel B., Gibson T., Rylatt D.B., Design of a New, Twelve-Channel Electrophoretic Apparatus Based on the Gradiflow Technology, Journal of Chromatography A, 989: 65-72 (2003).

[135] Patil N.V., Janssen A.E.M., Boom R.M., Separation of Whey Proteins using Cascaded Ultrafiltration, Separation Science and Technology, 49: 2280-2288 (2014).

[136] Galier S., Balmann H.R.-d., Fractionation of the Two Major Whey Proteins in an Electrophoretic Membrane Contactor, Procedia Engineering, 44: 830-832 (2012).

[137] Susanto H., Arafat H., Janssen E.M.L., Ulbricht M., Ultrafiltration of Polysaccharide–Protein Mixtures: Elucidation of Fouling Mechanisms and Fouling Control by Membrane Surface Modification, Separation and Purification Technology, 63: 558-565 (2008).

[138] Kim K.S., Lee K.H., Cho K., Park C.E., Surface Modification of Polysulfone Ultrafiltration Membrane by Oxygen Plasma Treatment, Journal of Membrane Science, 199: 135-145 (2002).

[139] Lazaridis N., Jekel M., Zouboulis A., Removal of Cr (VI), Mo (VI), and V (V) Ions from Single Metal Aqueous Solutions by Sorption or Nanofiltration, Separation Science and Technology, 38: 2201-2219 (2003).

[141] Park J.Y., Acar M.H., Akthakul A., Kuhlman W., Mayes A.M., Polysulfone-Graft-Poly(ethylene glycol) Graft Copolymers for Surface Modification of Polysulfone Membranes, Biomaterials, 27: 856-865 (2006).

[142] Bengani P., Kou Y., Asatekin A., Zwitterionic Copolymer Self-Assembly for Fouling Resistant, High Flux Membranes with Size-Based Small Molecule Selectivity, Journal of Membrane Science, 493: 755-765 (2015).

[143] Rohani M.M., Zydney A.L., Protein Transport Through Zwitterionic Ultrafiltration Membranes, Journal of Membrane Science, 397–398: 1-8 (2012).

[144] An Q.-F., Sun W.-D., Zhao Q., Ji Y.-L., Gao C.-J., Study on a Novel Nanofiltaration Membrane Prepared by Interfacial Polymerization wif Zwitterionic Amine Monomers, Journal of Membrane Science, 431: 171-179 (2013).

 [145] Wang M., Yuan J., Huang X., Cai X., Li L., Shen J., Grafting of Carboxybetaine Brush onto Cellulose Membranes via Surface-Initiated ARGET-ATRP for Improving Blood Compatibility, Colloids and Surfaces B: Biointerfaces, 103: 52-58 (2013).

[148] Meng H., Cheng Q., Wang H., Li C., Improving Anti-Protein-Fouling Property of Polyacrylonitrile Ultrafiltration Membrane by Grafting Sulfobetaine Zwitterions, Journal of Chemistry, 2014: 1-9 (2014).

[149] Sun Q., Su Y., Ma X., Wang Y., Jiang Z., Improved Antifouling Property of Zwitterionic Ultrafiltration Membrane Composed of Acrylonitrile and Sulfobetaine Copolymer, Journal of Membrane Science, 285: 299-305 (2006).

[150] Liu G., Zhang L., Mao S., Rohani S., Ching C., Lu J., Zwitterionic Chitosan–Silica–PVA Hybrid Ultrafiltration Membranes for Protein Separation, Separation and Purification Technology, 152: 55-63 (2015).

[151] Castrillón S.R.-V., Lu X., Shaffer D.L., Elimelech M., Amine Enrichment and Poly (ethylene glycol) (PEG) Surface Modification of Thin-Film Composite Forward Osmosis Membranes for Organic Fouling Control, Journal of Membrane Science, 450: 331-339 (2014).

[152] Miller D.J., Araujo P.A., Correia P.B., Ramsey M.M., Kruithof J.C., van Loosdrecht M.C., Freeman B.D., Paul D.R., Whiteley M., Vrouwenvelder J.S., Short-Term Adhesion and Long-Term Biofouling Testing of Polydopamine and Poly (ethylene glycol) Surface Modifications of Membranes and Feed Spacers for Biofouling Control, Water Research, 46: 3737-3753 (2012).

[153] McCloskey B.D., Park H.B., Ju H., Rowe B.W., Miller D.J., Freeman B.D., A Bioinspired Fouling-Resistant Surface Modification for Water Purification Membranes, Journal of Membrane Science, 413-414: 82-90 (2012).

[154] Sarkar B., DasGupta S., De S., Electric Field Enhanced Fractionation of Protein Mixture Using Ultrafiltration, Journal of Membrane Science, 341: 11-20 (2009).

[155] Chen G., Song W., Qi B., Li J., Ghosh R., Wan Y., Separation of Protein Mixtures by an Integrated Electro-Ultrafiltration–Electrodialysis Process, Separation and Purification Technology, 147: 32-43 (2015).

[157] Zydney A.L., Continuous Downstream Processing for High Value Biological Products: A Review, Biotechnology and Bioengineering, 113: 465-475 (2015).

[158] Rao S., Ager K., Zydney A.L., High Performance Tangential Flow Filtration Using Charged Affinity Ligands, Separation Science and Technology, 42: 2365-2385 (2007).

[159] Rao S., Zydney A.L., Controlling Protein Transport in Ultrafiltration Using Small Charged Ligands, Biotechnology and Bioengineering, 91: 733-742 (2005).