Separation Technologies for Whey Protein Fractionation

Fox PF, Guinee TP, Cogan TM, McSweeney PL (2017) Whey and whey products. In Fundamentals of cheese science, 2nd edn. New York, NY: Springer United States, pp 755–769. https://doi.org/10.1007/978-1-4899-7681-9_22 Ganju S, Gogate PR (2017) A review on approaches for efficient recovery of whey proteins from dairy industry effluents. J Food Eng 215:84–96. https://doi.org/10.1016/j.jfoodeng.2017.07.021 Aguero R, Bringas E, Román SMF, Ortiz I, Ibañez R (2017) Membrane processes for whey proteins separation and purification a review. Curr Org Chem 21(17):1740–1752. https://doi.org/10.2174/1385272820666160927122523 de Wit JN (1998) Nutritional and functional characteristics of whey proteins in food products. J Dairy Sci 81(3):597–608. https://doi.org/10.3168/jds.S0022-0302(98)75613-9 Guo M, Wang G (2016) Whey protein polymerisation and its applications in environmentally safe adhesives. Int J Dairy Technol 69(4):481–488. https://doi.org/10.1111/1471-0307.12303 Korhonen H (1995) Whey as raw material for development of new products for human nutrition and health: A review. NJF-utredning/rapport (Finland) (102):207–219 Madureira AR, Pereira CI, Gomes AM, Pintado ME, Malcata FX (2007) Bovine whey proteins–overview on their main biological properties. Food Res Int 40(10):1197–1211 Ramos OL, Pereira RN, Martins A, Rodrigues R, Fuciños C, Teixeira JA, Pastrana L, Malcata FX, Vicente AA (2017) Design of whey protein nanostructures for incorporation and release of nutraceutical compounds in food. Crit Rev Food Sci Nutr 57(7):1377–1393. https://doi.org/10.1080/10408398.2014.993749 Smithers GW (2008) Whey and whey proteins—from ‘gutter-to-gold.’ Int Dairy J 18(7):695–704. https://doi.org/10.1016/j.idairyj.2008.03.008 Smithers GW (2015) Whey-ing up the options – yesterday, today and tomorrow. Int Dairy J 48:2–14. https://doi.org/10.1016/j.idairyj.2015.01.011 Chen GQ, Talebi S, Gras SL, Weeks M, Kentish SE (2018) A review of salty waste stream management in the Australian dairy industry. J Environ Manag 224:406–413. https://doi.org/10.1016/j.jenvman.2018.07.056 Antonopoulou G, Stamatelatou K, Bebelis S, Lyberatos G (2010) Electricity generation from synthetic substrates and cheese whey using a two chamber microbial fuel cell. Biochem Eng J 50(1–2):10-15. https://doi.org/10.1016/j.bej.2010.02.008 Gannoun H. Khelifi E. Bouallagui H, Touhami Y, Hamdi M (2008) Ecological clarification of cheese whey prior to anaerobic digestion in upflow anaerobic filter. Bioresource Technol. 99(14):6105-6111. https://doi.org/10.1016/j.biortech.2007.12.037 Bylund G, Hellman M (2015) Dairy processing handbook. Tetra Pak Processing Systems, Lund Prazeres A R, Carvalho F, Rivas J (2012). Cheese whey management: A review. J. of Environ. Mgmt, 110(0):48-68. https://doi.org/10.1016/j.jenvman.2012.05.018 Zydney AL (1998) Protein separations using membrane filtration: new opportunities for whey fractionation. Int Dairy J 8(3):243–250. https://doi.org/10.1016/s0958-6946(98)00045-4 Bals A, Kulozik U (2003) Effect of pre-heating on the foaming properties of whey protein isolate using a membrane foaming apparatus. Int Dairy J 13(11):903–908 Lefevre T, Subirade M (2000) Molecular differences in the formation and structure of fine-stranded and particulate β-lactoglobulin gels. Biopolymers 54(7):578–586 Line VLS, Remondetto GE, Subirade M (2005) Cold gelation of β-lactoglobulin oil-in-water emulsions. Food Hydrocolloids 19(2):269–278 Kanekanian A (2005) Dairy technology—principles of milk properties and processes. Int J Dairy Technol 58(4):237–237 Markus CR, Olivier B, Panhuysen GE, Van der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF, de Haan EE (2000) The bovine protein α-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress–. Am J Clin Nutr 71(6):1536–1544 Permyakov EA, Berliner LJ (2000) α-Lactalbumin: structure and function. FEBS Lett 473(3):269–274 Zhang M, Zheng J, Ge K, Zhang H, Fang B, Jiang L, Guo H, Ding Q, Ren F (2014) Glycation of α-lactalbumin with different size saccharides: effect on protein structure and antigenicity. Int Dairy J 34(2):220–228 Lilius E-M, Marnila P (2001) The role of colostral antibodies in prevention of microbial infections. Curr Opin Infect Dis 14(3):295–300 Fox P, McSweeney P (2003) Advanced dairy chemistry. vol. 1, Proteins, 3rd edn. New York, NY: Springer United States. https://doi.org/10.1007/978-1-4419-8602-3 Veerman C, Sagis LM, Heck J, van der Linden E (2003) Mesostructure of fibrillar bovine serum albumin gels. Int J Biol Macromol 31(4–5):139–146 Legrand D, Elass E, Pierce A, Mazurier J (2004) Lactoferrin and host defence: an overview of its immuno-modulating and anti-inflammatory properties. Biometals 17(3):225–229 Van der Strate B, Beljaars L, Molema G, Harmsen M, Meijer D (2001) Antiviral activities of lactoferrin. Antiviral Res 52(3):225–239 Vorland LH (1999) Lactoferrin: a multifunctional glycoprotein. APMIS 107(7–12):971–981 Yoo Y-C, Watanabe S, Watanabe R, Hata K, Shimazaki K-i, Azuma I (1998) Bovine lactoferrin and lactoferricin TM inhibit tumor metastasis in mice. In: Advances in Lactoferrin Research. New York, NY: Springer United States, 1st edn, pp 285–291. https://doi.org/10.1007/978-1-4757-9068-9_35 Kussendrager KD, Van Hooijdonk A (2000) Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications. Br J Nutr 84(S1):19–25 Seifu E, Buys EM, Donkin EF (2005) Significance of the lactoperoxidase system in the dairy industry and its potential applications: a review. Trends Food Sci Technol 16(4):137–154. https://doi.org/10.1016/j.tifs.2004.11.002 Tenovuo J (2002) Clinical applications of antimicrobial host proteins lactoperoxidase, lysozyme and lactoferrin in xerostomia: efficacy and safety. Oral Dis 8(1):23–29 Tsermoula P, Khakimov B, Nielsen JH, Engelsen SB (2021) Whey - the waste-stream that became more valuable than the food product. Trends Food Sci Technol 118:230–241. https://doi.org/10.1016/j.tifs.2021.08.025 Yadav JSS, Yan S, Pilli S, Kumar L, Tyagi RD, Surampalli RY (2015) Cheese whey: a potential resource to transform into bioprotein, functional/nutritional proteins and bioactive peptides. Biotechnol Adv 33(6, Part 1):756–774. https://doi.org/10.1016/j.biotechadv.2015.07.002 El-Sayed MMH, Chase HA (2011) Trends in whey protein fractionation. Biotech Lett 33(8):1501–1511. https://doi.org/10.1007/s10529-011-0594-8 Kamau SM, Cheison SC, Chen W, Liu X-M, Lu R-R (2010) Alpha-lactalbumin: its production technologies and bioactive peptides. Compr Rev Food Sci Food Saf 9(2):197–212. https://doi.org/10.1111/j.1541-4337.2009.00100.x Law BA, Reiter B (1977) The isolation and bacteriostatic properties of lactoferrin from bovine milk whey. J Dairy Res 44(3):595–599. https://doi.org/10.1017/S0022029900020550 Tomita M, Wakabayashi H, Yamauchi K, Teraguchi S, Hayasawa H (2002) Bovine lactoferrin and lactoferricin derived from milk: production and applications. Biochem Cell Biol 80(1):109–112. https://doi.org/10.1139/o01-230 Wakabayashi H, Yamauchi K, Takase M (2006) Lactoferrin research, technology and applications. Int Dairy J 16(11):1241–1251. https://doi.org/10.1016/j.idairyj.2006.06.013 Wang Q, Chen GQ, Kentish SE (2020) Isolation of lactoferrin and immunoglobulins from dairy whey by an electrodialysis with filtration membrane process. Sep Purific Technol 233:115987. https://doi.org/10.1016/j.seppur.2019.115987 Mela I, Aumaitre E, Williamson A-M, Yakubov GE (2010) Charge reversal by salt-induced aggregation in aqueous lactoferrin solutions. Colloids Surf B 78(1):53–60. https://doi.org/10.1016/j.colsurfb.2010.02.011 Pujar NS, Zydney AL (1998) Electrostatic effects on protein partitioning in size-exclusion chromatography and membrane ultrafiltration. J Chromatogr A 796(2):229–238. https://doi.org/10.1016/S0021-9673(97)01003-0 Bennett RM, Bagby GC, Davis J (1981) Calcium-dependent polymerization of lactoferrin. Biochem Biophys Res Commun 101(1):88–95. https://doi.org/10.1016/S0006-291X(81)80014-9 Pintado ME, Malcata FX (2000) Hydrolysis of ovine, caprine and bovine whey proteins by trypsin and pepsin. Bioprocess Eng 23(3):275–282. https://doi.org/10.1007/s004499900167 Guo MR, Fox PF, Flynn A, Kindstedt PS (1995) Susceptibility of beta-lactoglobulin and sodium caseinate to proteolysis by pepsin and trypsin. J Dairy Sci 78(11):2336–2344. https://doi.org/10.3168/jds.S0022-0302(95)76860-6 Konrad G, Kleinschmidt T (2008) A new method for isolation of native α-lactalbumin from sweet whey. Int Dairy J 18(1):47–54. https://doi.org/10.1016/j.idairyj.2007.06.004 Quintieri L, Monaci L, Baruzzi F, Giuffrida MG, de Candia S, Caputo L (2017) Reduction of whey protein concentrate antigenicity by using a combined enzymatic digestion and ultrafiltration approach. J Food Sci Technol 54(7):1910–1916. https://doi.org/10.1007/s13197-017-2625-5 Ha M, El-Din Bekhit A, McConnell M, Carne A (2022) A simple method for enrichment of β-lactoglobulin from bovine milk whey involving selective hydrolysis by two fungal protease preparations. Food Chem 368:130820. https://doi.org/10.1016/j.foodchem.2021.130820 Joyce AM, Brodkorb A, Kelly AL, O’Mahony JA (2017) Separation of the effects of denaturation and aggregation on whey-casein protein interactions during the manufacture of a model infant formula. Dairy Sci Technol 96(6):787–806. https://doi.org/10.1007/s13594-016-0303-4 Baussay K, Bon CL, Nicolai T, Durand D, Busnel J-P (2004) Influence of the ionic strength on the heat-induced aggregation of the globular protein β-lactoglobulin at pH 7. Int J Biol Macromol 34(1):21–28. https://doi.org/10.1016/j.ijbiomac.2003.11.003 Pouzot M, Nicolai T, Visschers RW, Weijers M (2005) X-ray and light scattering study of the structure of large protein aggregates at neutral pH. Food Hydrocolloids 19(2):231–238. https://doi.org/10.1016/j.foodhyd.2004.06.003 Donato L, Schmitt C, Bovetto L, Rouvet M (2009) Mechanism of formation of stable heat-induced β-lactoglobulin microgels. Int Dairy J 19(5):295–306. https://doi.org/10.1016/j.idairyj.2008.11.005 Mutilangi WA, Kilara A (1985) Functional properties of heat denatured whey protein. I. Solubility. Milchwissenschaft (Germany, F.R.) 40(6):338–341 Modler W (2009) Pioneer paper: value-added components derived from whey. Am Dairy Sci Assoc:1–33 Hoffmann MAM, Sala G, Olieman C, de Kruif KG (1997) Molecular mass distributions of heat-induced β-lactoglobulin aggregates. J Agric Food Chem 45(8):2949–2957. https://doi.org/10.1021/jf9700788 Roefs SP, De Kruif KG (1994) A model for the denaturation and aggregation of beta-lactoglobulin. Eur J Biochem 226(3):883–889. https://doi.org/10.1111/j.1432-1033.1994.00883.x Elofsson UM, Dejmek P, Paulsson MA (1996) Heat-induced aggregation of β-lactoglobulin studied by dynamic light scattering. Int Dairy J 6(4):343–357. https://doi.org/10.1016/0958-6946(95)00019-4 Le Bon C, Nicolai T, Durand D (1999) Growth and structure of aggregates of heat-denatured β-lactoglobulin. Int J Food Sci Technol 34(5–6):451–465. https://doi.org/10.1046/j.1365-2621.1999.00310.x Ryan KN, Vardhanabhuti B, Jaramillo DP, van Zanten JH, Coupland JN, Foegeding EA (2012) Stability and mechanism of whey protein soluble aggregates thermally treated with salts. Food Hydrocolloids 27(2):411–420. https://doi.org/10.1016/j.foodhyd.2011.11.006 Mulcahy EM, Mulvihill DM, O’Mahony JA (2016) Physicochemical properties of whey protein conjugated with starch hydrolysis products of different dextrose equivalent values. Int Dairy J 53:20–28. https://doi.org/10.1016/j.idairyj.2015.09.009 Davies TJ, Henstridge SC, Gillham CR, Wilson DI (1997) Investigation of whey protein deposit properties using heat flux sensors. Food Bioprod Process 75(2):106–110. https://doi.org/10.1205/096030897531414 Groves ML, Hipp NJ, McMeekin TL (1951) Effect of pH on the denaturation of β-lactoglobulin and its dodecyl sulfate derivative. J Am Chem Soc 73(6):2790–2793. https://doi.org/10.1021/ja01150a106 Hoffmann MAM, van Mil PJJM (1997) Heat-induced aggregation of β-lactoglobulin: role of the free thiol group and disulfide bonds. J Agric Food Chem 45(8):2942–2948. https://doi.org/10.1021/jf960789q Hoffmann MAM, van Mil PJJM (1999) Heat-induced aggregation of β-lactoglobulin as a function of pH. J Agric Food Chem 47(5):1898–1905. https://doi.org/10.1021/jf980886e Pelegrine DHG, Gasparetto CA (2005) Whey proteins solubility as function of temperature and pH. LWT Food Sci Technol 38(1):77–80. https://doi.org/10.1016/j.lwt.2004.03.013 Toro-Sierra J, Tolkach A, Kulozik U (2013) Fractionation of α-lactalbumin and β-lactoglobulin from whey protein isolate using selective thermal aggregation, an optimized membrane separation procedure and resolubilization techniques at pilot plant scale. Food Bioprocess Technol 6(4):1032–1043. https://doi.org/10.1007/s11947-011-0732-2 Collins KD (1997) Charge density-dependent strength of hydration and biological structure. Biophys J 72(1):65–76. https://doi.org/10.1016/S0006-3495(97)78647-8 Parmar AS, Muschol M (2009) Hydration and hydrodynamic interactions of lysozyme: effects of chaotropic versus kosmotropic ions. Biophys J 97(2):590–598. https://doi.org/10.1016/j.bpj.2009.04.045 Guyomarc’h F, Famelart M-H, Henry G, Gulzar M, Leonil J, Hamon P, Bouhallab S, Croguennec T (2015) Current ways to modify the structure of whey proteins for specific functionalities—a review. Dairy Sci Technol 95(6):795–814. https://doi.org/10.1007/s13594-014-0190-5 de la Fuente MA, Singh H, Hemar Y (2002) Recent advances in the characterisation of heat-induced aggregates and intermediates of whey proteins. Trends Food Sci Technol 13(8):262–274. https://doi.org/10.1016/S0924-2244(02)00133-4 Arakawa T, Timasheff SN (1984) Mechanism of protein salting in and salting out by divalent cation salts: balance between hydration and salt binding. Biochemistry 23(25):5912–5923 Donovan M, Mulvihill D (1987) Thermal denaturation and aggregation of whey proteins. Irish J Food Sci Technol 11(1):87–100. https://www.jstor.org/stable/25558155 Bernal V, Jelen P (1984) Effect of calcium binding on thermal denaturation of bovine α-lactalbumin. J Dairy Sci 67(10):2452–2454. https://doi.org/10.3168/jds.S0022-0302(84)81595-7 De Wit JN, Bronts H (1995) Process for the recovery of α-lactalbumin and β-lactoglobulin from a whey protein product. EP0604684A1 Joyce AM, Kelly AL, O’Mahony JA (2018) Controlling denaturation and aggregation of whey proteins during thermal processing by modifying temperature and calcium concentration. Int J Dairy Technol 71(2):446–453. https://doi.org/10.1111/1471-0307.12507 Calvo MM, Leaver J, Banks JM (1993) Influence of other whey proteins on the heat-induced aggregation of α-lactalbumin. Int Dairy J 3(8):719–727. https://doi.org/10.1016/0958-6946(93)90085-E Chaplin LC, Lyster RLJ (1986) Irreversible heat denaturation of bovine α-lactalbumin. J Dairy Res 53(2):249–258. https://doi.org/10.1017/S0022029900024857 Wijayanti HB, Bansal N, Deeth HC (2014) Stability of whey proteins during thermal processing: a review. Compr Rev Food Sci Food Saf 13(6):1235–1251. https://doi.org/10.1111/1541-4337.12105 Tolkach A, Steinle S, Kulozik U (2005) Optimization of thermal pretreatment conditions for the separation of native α-lactalbumin from whey protein concentrates by means of selective denaturation of β-lactoglobulin. J Food Sci 70(9):E557–E566. https://doi.org/10.1111/j.1365-2621.2005.tb08319.x Montilla A, Casal E, Moreno FJ, Belloque J, Olano A, Corzo N (2007) Isolation of bovine β-lactoglobulin from complexes with chitosan. Int Dairy J 17(5):459–464 Tamaki S, Tomizawa A, Shiba M, Takano M, Imai H (2019) Fractionation method for whey protein, production method for composition including alpha-lactalbumin, and production method for composition including beta-lactoglobulin. US20190124945A1 Muller A, Chaufer B, Merin U, Daufin G (2003) Purification of alpha-lactalbumin from a prepurified acid whey: ultrafiltration or precipitation. Lait 83:439–451 Chen GQ, Leong TSH, Kentish SE, Ashokkumar M, Martin GJO (2019) Chapter 8 - Membrane separations in the dairy industry. In: Galanakis CM (ed) Separation of Functional Molecules in Food by Membrane Technology. London, United Kingdom, Academic Press, Elsevier Science, 1st edn, pp 267–304. https://doi.org/10.1016/B978-0-12-815056-6.00008-5 Ho C-C (2007) Chapter 7 - membranes for bioseparations. In: Yang S-T (ed) Bioprocessing for Value-Added Products from Renewable Resources. Elsevier, Amsterdam, pp 163–183. https://doi.org/10.1016/B978-044452114-9/50008-6 Johnson J, Busch M (2010) Engineering aspects of reverse osmosis module design. Desalin Water Treat 15(1–3):236–248. https://doi.org/10.5004/dwt.2010.1756 Muller A, Daufin G, Chaufer B (1999) Ultrafiltration modes of operation for the separation of α-lactalbumin from acid casein whey. J Membr Sci 153(1):9–21. https://doi.org/10.1016/S0376-7388(98)00218-X Marella C, Muthukumarappan K, Metzger LE (2011) Evaluation of commercially available, wide-pore ultrafiltration membranes for production of α-lactalbumin–enriched whey protein concentrate. J Dairy Sci 94(3):1165–1175. https://doi.org/10.3168/jds.2010-3739 Muller A, Chaufer B, Merin U, Daufin G (2003) Prepurification of lactalbumin with ultrafiltration ceramic membranes from acid casein whey: study of operating conditions. Lait 83:111–129 Espina V, Jaffrin MY, Ding L (2009) Extraction and separation of α-lactalbumin and β-lactoglobulin from skim milk by microfiltration and ultrafiltration at high shear rates: a feasibility study. Sep Sci Technol 44(16):3832–3853. https://doi.org/10.1080/01496390903183238 Bramaud C, Aimar P, Daufin G (1995) Thermal isoelectric precipitation of α-lactalbumin from a whey protein concentrate: influence of protein–calcium complexation. Biotechnol Bioeng 47(2):121–130. https://doi.org/10.1002/bit.260470202 Slack AW, Amundson CH, Hill CG (1986) Production of enriched β-lactoglobulin and α-lactalbumin whey protein fractions. J Food Process Preserv 10(1):19–30. https://doi.org/10.1111/j.1745-4549.1986.tb00002.x Wu C (2003) Whey treatment process for achieving high concentration of α-lactalbumin. US6312755B1 Maubois JL, Pierre A, Fauquant J, Piot M (1987) Industrial fractionation of main whey proteins. Bull Int Dairy Federation J (212):154–159 Pearce R (1983) Thermal separation of [beta]-lactoglobulin and [alpha]-lactalbumin in bovine cheddar cheese whey. Aust J Dairy Technol 38(4):144 Li J, Merrill RK, Wadhwani R (2018) High purity alpha lactalbumin and methods of making. US11206846B2 Uchida Y, Shimatani M, Mitsuhashi T, Koutake M (1996) Process for preparing a fraction having a high content of α-lactalbumin from whey and nutritional compositions containing such fractions. JP2622789B2 Almécija MC, Ibáñez R, Guadix A, Guadix EM (2007) Effect of pH on the fractionation of whey proteins with a ceramic ultrafiltration membrane. J Membr Sci 288(1):28–35. https://doi.org/10.1016/j.memsci.2006.10.021 Tsakali E, Petrotos K, D’Alessandro AG, Mantas C, Tripolitsiotis I, Goulas P, Chatzilazarou A, van Impe JF (2015) Exploring the effect of ultrafiltration/diafiltration processing conditions on the lactoferrin and immunoglobulin g content of feta whey protein concentrates. J Food Process Eng 38(4):363–373. https://doi.org/10.1111/jfpe.12167 Cowan S, Ritchie S (2007) Modified polyethersulfone (PES) ultrafiltration membranes for enhanced filtration of whey proteins. Sep Sci Technol 42(11):2405–2418. https://doi.org/10.1080/01496390701477212 Corbatón-Báguena M-J, Álvarez-Blanco S, Vincent-Vela M-C (2014) Cleaning of ultrafiltration membranes fouled with BSA by means of saline solutions. Sep Purif Technol 125:1–10. https://doi.org/10.1016/j.seppur.2014.01.035 Hashino M, Hirami K, Ishigami T, Ohmukai Y, Maruyama T, Kubota N, Matsuyama H (2011) Effect of kinds of membrane materials on membrane fouling with BSA. J Membr Sci 384(1):157–165. https://doi.org/10.1016/j.memsci.2011.09.015 Kelly ST, Zydney AL (1995) Mechanisms for BSA fouling during microfiltration. J Membr Sci 107(1):115–127. https://doi.org/10.1016/0376-7388(95)00108-O Kuzmenko D, Arkhangelsky E, Belfer S, Freger V, Gitis V (2005) Chemical cleaning of UF membranes fouled by BSA. Desalination 179(1):323–333. https://doi.org/10.1016/j.desal.2004.11.078 Nabe A, Staude E, Belfort G (1997) Surface modification of polysulfone ultrafiltration membranes and fouling by BSA solutions. J Membr Sci 133(1):57–72. https://doi.org/10.1016/S0376-7388(97)00073-2 van Reis R, Brake JM, Charkoudian J, Burns DB, Zydney AL (1999) High-performance tangential flow filtration using charged membranes. J Membr Sci 159(1):133–142. https://doi.org/10.1016/S0376-7388(99)00048-4 Arunkumar A, Etzel MR (2013) Fractionation of α-lactalbumin from β-lactoglobulin using positively charged tangential flow ultrafiltration membranes. Sep Purif Technol 105:121–128. https://doi.org/10.1016/j.seppur.2012.12.018 Arunkumar A, Etzel MR (2014) Fractionation of α-lactalbumin and β-lactoglobulin from bovine milk serum using staged, positively charged, tangential flow ultrafiltration membranes. J Membr Sci 454:488–495. https://doi.org/10.1016/j.memsci.2013.12.040 Arunkumar A, Etzel MR (2015) Negatively charged tangential flow ultrafiltration membranes for whey protein concentration. J Membr Sci 475:340–348. https://doi.org/10.1016/j.memsci.2014.10.049 Greiter M, Novalin S, Wendland M, Kulbe K-D, Fischer J (2004) Electrodialysis versus ion exchange: comparison of the cumulative energy demand by means of two applications. J Membr Sci 233(1):11–19 Kánavová N, Machuca L (2014) A novel method for limiting current calculation in electrodialysis modules. Periodica Polytech Chem Eng 58(2):125 Strathmann H (2010) Electrodialysis, a mature technology with a multitude of new applications. Desalination 264(3):268–288 Xu T, Huang C (2008) Electrodialysis-based separation technologies: a critical review. AIChE J 54(12):3147–3159 Dlask O, Václavíková N, Dolezel M (2016) Insertion of filtration membranes into electrodialysis stack and its impact on process performance. Periodica Polytech Chem Eng 60(3):169 Galier S, Roux-de Balmann H (2004) Study of biomolecules separation in an electrophoretic membrane contactor. J Membr Sci 241(1):79–87. https://doi.org/10.1016/j.memsci.2004.05.007 Chen G, Song W, Qi B, Li J, Ghosh R, Wan Y (2015) Separation of protein mixtures by an integrated electro-ultrafiltration–electrodialysis process. Sep Purif Technol 147:32–43. https://doi.org/10.1016/j.seppur.2015.04.003 Deng H, Chen GQ, Gras SL, Kentish SE (2017) The effect of restriction membranes on mass transfer in an electrodialysis with filtration membrane process. J Membr Sci 526:429–436 Bazinet L, Amiot J, Poulin J-F, Labbé D, Tremblay D (2005) Process and system for separation of organic charged compounds. EP1725323A4 Ogle D, Vigh G, Rylatt D (2003) Multi-port separation apparatus and method. WO2002028516A1 Lawrence N, Kentish S, O’Connor A, Barber A, Stevens G (2008) Microfiltration of skim milk using polymeric membranes for casein concentrate manufacture. Sep Purif Technol 60(3):237–244 Horvath ZS, Corthals GL, Wrigley CW, Margolis J (1994) Multifunctional apparatus for electrokinetic processing of proteins. Electrophoresis 15(1):968–971 Ogle D, Ho A, Gibson T, Rylatt D, Shave E, Lim P, Vigh G (2002) Preparative-scale isoelectric trapping separations using a modified Gradiflow unit. J Chromatogr A 979(1–2):155–161 Ndiaye N, Pouliot Y, Saucier L, Beaulieu L, Bazinet L (2010) Electroseparation of bovine lactoferrin from model and whey solutions. Sep Purif Technol 74(1):93–99. https://doi.org/10.1016/j.seppur.2010.05.011 Bazinet L, Ippersiel D, Mahdavi B (2004) Fractionation of whey proteins by bipolar membrane electroacidification. Innov Food Sci Emerg Technol 5(1):17–25. https://doi.org/10.1016/j.ifset.2003.10.001 Lin Teng Shee F, Angers P, Bazinet L (2005) Relationship between electrical conductivity and demineralization rate during electroacidification of cheddar cheese whey. J Membr Sci 262(1):100–106. https://doi.org/10.1016/j.memsci.2005.03.050 Sarkar B, DasGupta S, De S (2009) Electric field enhanced fractionation of protein mixture using ultrafiltration. J Membr Sci 341(1):11–20. https://doi.org/10.1016/j.memsci.2009.05.020 Song W, Su Y, Chen X, Ding L, Wan Y (2010) Rapid concentration of protein solution by a crossflow electro-ultrafiltration process. Sep Purif Technol 73(2):310–318. https://doi.org/10.1016/j.seppur.2010.04.018 Enevoldsen AD, Hansen EB, Jonsson G (2007) Electro-ultrafiltration of industrial enzyme solutions. J Membr Sci 299(1):28–37. https://doi.org/10.1016/j.memsci.2007.04.021 Zumbusch Pv, Kulcke W, Brunner G (1998) Use of alternating electrical fields as anti-fouling strategy in ultrafiltration of biological suspensions – introduction of a new experimental procedure for crossflow filtration. J Membr Sci 142(1):75–86. https://doi.org/10.1016/S0376-7388(97)00310-4 Oussedik S, Belhocine D, Grib H, Lounici H, Piron DL, Mameri N (2000) Enhanced ultrafiltration of bovine serum albumin with pulsed electric field and fluidized activated alumina. Desalination 127(1):59–68. https://doi.org/10.1016/S0011-9164(99)00192-7 Meyer VR (2005) Chromatography | Principles. In: Worsfold P, Townshend A, Poole C (eds) Encyclopedia of Analytical Science, 2nd edn. Elsevier, Oxford, pp 98–105. https://doi.org/10.1016/B0-12-369397-7/00089-3 Asenjo JA (1990) Separation processes in biotechnology, 1st edn. Boca Raton, United States, CRC Press. https://doi.org/10.1201/9781003066392 Hong P, Koza S, Bouvier ES (2012) A review size-exclusion chromatography for the analysis of protein biotherapeutics and their aggregates. J Liq Chromatogr Relat Technol 35(20):2923–2950 Al-Mashikhi SA, Nakai S (1987) Isolation of bovine immunoglobulins and lactoferrin from whey proteins by gel filtration techniques. J Dairy Sci 70(12):2486–2492. https://doi.org/10.3168/jds.S0022-0302(87)80315-6 Forsum E, Hambraeus L, Siddiqi IH (1974) Large-scale fractionation of whey protein concentrates. J Dairy Sci 57(6):659–664. https://doi.org/10.3168/jds.S0022-0302(74)84943-X Rojas EEG, dos Reis Coimbra JS, Minim LA, Zuniga ADG, Saraiva SH, Minim VPR (2004) Size-exclusion chromatography applied to the purification of whey proteins from the polymeric and saline phases of aqueous two-phase systems. Process Biochem 39(11):1751–1759. https://doi.org/10.1016/j.procbio.2003.07.002 Neyestani TR, Djalali M, Pezeshki M (2003) Isolation of α-lactalbumin, β-lactoglobulin, and bovine serum albumin from cow’s milk using gel filtration and anion-exchange chromatography including evaluation of their antigenicity. Protein Expr Purif 29(2):202–208. https://doi.org/10.1016/S1046-5928(03)00015-9 Gerberding SJ, Byers CH (1998) Preparative ion-exchange chromatography of proteins from dairy whey. J Chromatogr A 808(1–2):141–151. https://doi.org/10.1016/S0021-9673(98)00103-4 Staahlberg J (1994) Electrostatic retention model for ion-exchange chromatography. Anal Chem 66(4):440–449 Abd El-Salam MH, El-Shibiny S (2017) Separation of bioactive whey proteins and peptides. in Ingredients extraction by physicochemical methods in food, (1st ed., pp. 463-494). Academic Press, Elsevier Science, London, United Kingdom. https://doi.org/10.1016/B978-0-12-811521-3.00012-0 Andersson J, Mattiasson B (2006) Simulated moving bed technology with a simplified approach for protein purification: separation of lactoperoxidase and lactoferrin from whey protein concentrate. J Chromatogr A 1107(1):88–95. https://doi.org/10.1016/j.chroma.2005.12.018 Du Q-Y, Lin D-Q, Xiong Z-S, Yao S-J (2013) One-step purification of lactoferrin from crude sweet whey using cation-exchange expanded bed adsorption. Ind Eng Chem Res 52(7):2693–2699. https://doi.org/10.1021/ie302606z Barnfield Frej A-K, Hjorth R, Hammarström Å (1994) Pilot scale recovery of recombinant annexin V from unclarified escherichia coli homogenate using expanded bed adsorption. Biotechnol Bioeng 44(8):922–929. https://doi.org/10.1002/bit.260440808 Outinen M, Tossavainen O, Syväoja EL (1996) Chromatographic fractionation of α-lactalbumin and β-lactoglobulin with polystyrenic strongly basic anion exchange resins. LWT Food Sci Technol 29(4):340–343. https://doi.org/10.1006/fstl.1996.0051 Santos MJ, Teixeira JA, Rodrigues LR (2012) Fractionation of the major whey proteins and isolation of β-lactoglobulin variants by anion exchange chromatography. Sep Purif Technol 90:133–139. https://doi.org/10.1016/j.seppur.2012.02.030 Xu Y, Sleigh R, Hourigan J, Johnson R (2000) Separation of bovine immunoglobulin G and glycomacropeptide from dairy whey. Process Biochem 36(5):393–399. https://doi.org/10.1016/S0032-9592(00)00199-0 Geng XL, Tolkach A, Otte J, Ipsen R (2015) Pilot-scale purification of α-lactalbumin from enriched whey protein concentrate by anion-exchange chromatography and ultrafiltration. Dairy Sci Technol 95(3):353–368. https://doi.org/10.1007/s13594-015-0215-8 Doultani S, Turhan KN, Etzel MR (2004) Fractionation of proteins from whey using cation exchange chromatography. Process Biochem 39(11):1737–1743. https://doi.org/10.1016/j.procbio.2003.07.005 El-Sayed MMH, Chase HA (2010) Purification of the two major proteins from whey concentrate using a cation-exchange selective adsorption process. Biotechnol Prog 26(1):192–199. https://doi.org/10.1002/btpr.316 El-Sayed MMH, Chase HA (2009) Single and two-component cation-exchange adsorption of the two pure major whey proteins. J Chromatogr A 1216(50):8705–8711. https://doi.org/10.1016/j.chroma.2009.02.080 Ye X, Yoshida S, Ng TB (2000) Isolation of lactoperoxidase, lactoferrin, α-lactalbumin, β-lactoglobulin B and β-lactoglobulin A from bovine rennet whey using ion exchange chromatography. Int J Biochem Cell Biol 32(11):1143–1150. https://doi.org/10.1016/S1357-2725(00)00063-7 Dong S, Chen L, Dai B, Johnson W, Ye J, Shen S, Yun J, Yao K, Lin D-Q, Yao S-J (2013) Isolation of immunoglobulin G from bovine milk whey by poly(hydroxyethyl methacrylate)-based anion-exchange cryogel. J Sep Sci 36(15):2387–2393. https://doi.org/10.1002/jssc.201300306 Billakanti JM, Fee CJ (2009) Characterization of cryogel monoliths for extraction of minor proteins from milk by cation exchange. Biotechnol Bioeng 103(6):1155–1163. https://doi.org/10.1002/bit.22344 Pan M, Shen S, Chen L, Dai B, Xu L, Yun J, Yao K, Lin D-Q, Yao S-J (2015) Separation of lactoperoxidase from bovine whey milk by cation exchange composite cryogel embedded macroporous cellulose beads. Sep Purif Technol 147:132–138. https://doi.org/10.1016/j.seppur.2015.04.026 Fee CJ, Chand A (2006) Capture of lactoferrin and lactoperoxidase from raw whole milk by cation exchange chromatography. Sep Purif Technol 48(2):143–149. https://doi.org/10.1016/j.seppur.2005.07.011 Müller E, Vajda J (2016) Routes to improve binding capacities of affinity resins demonstrated for Protein A chromatography. J Chromatogr B 1021:159–168. https://doi.org/10.1016/j.jchromb.2016.01.036 Show PL, Ooi CW, Ling TC (2019) Bioprocess engineering: downstream processing. CRC Press, Boca Raton, United States. https://doi.org/10.1201/9780429466731 Gambero A, Kubota LT, Gushikem Y, Airoldi C, Granjeiro JM, Taga EM, Alcântara EFC (1997) Use of chemically modified silica with β-diketoamine groups for separation of α-lactoalbumin from bovine milk whey by affinity chromatography. J Colloid Interface Sci 185(2):313–316. https://doi.org/10.1006/jcis.1996.4566 Blomkalns AL, Gomez MR (1997) Purification of bovine α-lactalbumin by immobilized metal ion affinity chromatography. Prep Biochem Biotechnol 27(4):219–226. https://doi.org/10.1080/10826069708001280 Gurgel PV, Carbonell RG, Swaisgood HE (2000) Fractionation of whey proteins with a hexapeptide ligand affinity resin. Bioseparation 9(6):385–392. https://doi.org/10.1023/A:1011191818927 Noppe W, Haezebrouck P, Hanssens I, De Cuyper M (1999) A simplified purification procedure of alpha-lactalbumin from milk using Ca(2+)-dependent adsorption in hydrophobic expanded bed chromatography. Bioseparation 8(1–5):153–158 Conrado LdS, Veredas Vd, Nóbrega ES, Santana CC (2005) Concentration of alpha-lactalbumin from cow milk whey through expanded bed adsorption using a hydrophobic resin. Braz J Chem Eng 22:501–509 Wang Q, Swaisgood HE (1993) Characteristics of beta-lactoglobulin binding to the all-trans-retinal moiety covalently immobilized on celite. J Dairy Sci 76(7):1895–1901. https://doi.org/10.3168/jds.S0022-0302(93)77522-0 Vyas HK, Izco JM, Jiménez-Flores R (2002) Scale-up of native β-lactoglobulin affinity separation process. J Dairy Sci 85(7):1639–1645. https://doi.org/10.3168/jds.S0022-0302(02)74236-7 Schlatterer B, Baeker R, Schlatterer K (2004) Improved purification of β-lactoglobulin from acid whey by means of ceramic hydroxyapatite chromatography with sodium fluoride as a displacer. J Chromatogr B 807(2):223–228. https://doi.org/10.1016/j.jchromb.2004.04.013 Puerta Á, Jaulmes A, De Frutos M, Diez-Masa JC, Vidal-Madjar C (2002) Adsorption kinetics of β-lactoglobulin on a polyclonal immunochromatographic support. J Chromatogr A 953(1):17–30. https://doi.org/10.1016/S0021-9673(02)00124-3 Besselink T, Janssen AEM, Boom RM (2015) Isolation of bovine serum albumin from whey using affinity chromatography. Int Dairy J 41:32–37. https://doi.org/10.1016/j.idairyj.2014.09.004 Chen J-P, Wang C-H (1991) Microfiltration affinity purification of lactoferrin and immunoglobulin g from cheese whey. J Food Sci 56(3):701–706. https://doi.org/10.1111/j.1365-2621.1991.tb05360.x Konecny P, Brown RJ, Scouten WH (1994) Chromatographic purification of immunoglobulin G from bovine milk whey. J Chromatogr A 673(1):45–53. https://doi.org/10.1016/0021-9673(94)87056-X Kawakami H, Shinmoto H, Dosako SI, Sogo Y (1987) One-step isolation of lactoferrin using immobilized monoclonal antibodies. J Dairy Sci 70(4):752–759. https://doi.org/10.3168/jds.S0022-0302(87)80070-X Baieli MF, Urtasun N, Miranda MV, Cascone O, Wolman FJ (2014) Isolation of lactoferrin from whey by dye-affinity chromatography with Yellow HE-4R attached to chitosan mini-spheres. Int Dairy J 39(1):53–59. https://doi.org/10.1016/j.idairyj.2014.03.014 Carvalho BMA, Carvalho LM, Silva WF, Minim LA, Soares AM, Carvalho GGP, da Silva SL (2014) Direct capture of lactoferrin from cheese whey on supermacroporous column of polyacrylamide cryogel with copper ions. Food Chem 154:308–314. https://doi.org/10.1016/j.foodchem.2014.01.010 Urtasun N, Baieli MF, Hirsch DB, Martínez-Ceron MC, Cascone O, Wolman FJ (2017) Lactoperoxidase purification from whey by using dye affinity chromatography. Food Bioprod Process 103:58–65. https://doi.org/10.1016/j.fbp.2017.02.011 Atasever A, Ozdemir H, Gulcin I, Irfan Kufrevioglu O (2013) One-step purification of lactoperoxidase from bovine milk by affinity chromatography. Food Chem 136(2):864–870. https://doi.org/10.1016/j.foodchem.2012.08.072 Ben Ounis W, Gauthier SF, Turgeon SL, Roufik S, Pouliot Y (2008) Separation of minor protein components from whey protein isolates by heparin affinity chromatography. Int Dairy J 18(10):1043–1050. https://doi.org/10.1016/j.idairyj.2008.04.004 Du Q-Y, Lin D-Q, Zhang Q-L, Yao S-J (2014) An integrated expanded bed adsorption process for lactoferrin and immunoglobulin G purification from crude sweet whey. J Chromatogr B 947–948:201–207. https://doi.org/10.1016/j.jchromb.2013.12.020 Liu HF, Ma J, Winter C, Bayer R (2010) Recovery and purification process development for monoclonal antibody production. MAbs 2(5):480–499. https://doi.org/10.4161/mabs.2.5.12645 Bhut BV, Christensen KA, Husson SM (2010) Membrane chromatography: protein purification from E. coli lysate using newly designed and commercial anion-exchange stationary phases. J Chromatogr A 1217(30):4946–4957. https://doi.org/10.1016/j.chroma.2010.05.049 Liu HF, McCooey B, Duarte T, Myers DE, Hudson T, Amanullah A, van Reis R, Kelley BD (2011) Exploration of overloaded cation exchange chromatography for monoclonal antibody purification. J Chromatogr A 1218(39):6943–6952. https://doi.org/10.1016/j.chroma.2011.08.008 Muthukumar S, Muralikrishnan T, Mendhe R, Rathore AS (2017) Economic benefits of membrane chromatography versus packed bed column purification of therapeutic proteins expressed in microbial and mammalian hosts. J Chem Technol Biotechnol 92(1):59–68. https://doi.org/10.1002/jctb.5064 Nath A, Zin MM, Molnár MA, Bánvölgyi S, Gáspár I, Vatai G, Koris A (2022) Membrane chromatography and fractionation of proteins from whey—a review. Processes 10(5):1025. https://doi.org/10.3390/pr10051025 Bhattacharjee S, Bhattacharjee C, Datta S (2006) Studies on the fractionation of β-lactoglobulin from casein whey using ultrafiltration and ion-exchange membrane chromatography. J Membr Sci 275(1):141–150. https://doi.org/10.1016/j.memsci.2005.09.013 Girardet J-M, Saulnier F, Linden G, Humbert G (1998) Rapid separation of bovine whey proteins by membrane convective liquid chromatography, perfusion chromatography, continuous bed chromatography, and capillary electrophoresis. Lait 78(4):391–400 Ulber R, Plate K, Weiss T, Demmer W, Buchholz H, Scheper T (2001) Downstream processing of bovine lactoferrin from sweet whey. Acta Biotechnol 21(1):27–34. https://doi.org/10.1002/1521-3846(200102)21:1%3c27::AID-ABIO27%3e3.0.CO;2-W Goodall S, Grandison AS, Jauregi PJ, Price J (2008) Selective separation of the major whey proteins using ion exchange membranes. J Dairy Sci 91(1):1–10. https://doi.org/10.3168/jds.2007-0539 Splitt H, Mackenstedt I, Freitag R (1996) Preparative membrane adsorber chromatography for the isolation of cow milk components. J Chromatogr A 729(1):87–97. https://doi.org/10.1016/0021-9673(95)00937-X Chiu CK, Etzel MR (1997) Fractionation of lactoperoxidase and lactoferrin from bovine whey using a cation exchange membrane. J Food Sci 62(5):996–1000. https://doi.org/10.1111/j.1365-2621.1997.tb15023.x Boi C, Malavasi A, Carbonell RG, Gilleskie G (2020) A direct comparison between membrane adsorber and packed column chromatography performance. J Chromatogr A 1612:460629. https://doi.org/10.1016/j.chroma.2019.460629 Saufi SM, Fee CJ (2011) Recovery of lactoferrin from whey using cross-flow cation exchange mixed matrix membrane chromatography. Sep Purif Technol 77(1):68–75. https://doi.org/10.1016/j.seppur.2010.11.021 Hahn R, Deinhofer K, Machold C, Jungbauer A (2003) Hydrophobic interaction chromatography of proteins: II. Binding capacity, recovery and mass transfer properties. J Chromatogr B 790(1):99–114. https://doi.org/10.1016/S1570-0232(03)00080-1 Harinarayan C, Mueller J, Ljunglöf A, Fahrner R, Van Alstine J, van Reis R (2006) An exclusion mechanism in ion exchange chromatography. Biotechnol Bioeng 95(5):775–787. https://doi.org/10.1002/bit.21080 Wolman FJ, Maglio DG, Grasselli M, Cascone O (2007) One-step lactoferrin purification from bovine whey and colostrum by affinity membrane chromatography. J Membr Sci 288(1):132–138. https://doi.org/10.1016/j.memsci.2006.11.011 Teepakorn C, Fiaty K, Charcosset C (2015) Optimization of lactoferrin and bovine serum albumin separation using ion-exchange membrane chromatography. Sep Purif Technol 151:292–302. https://doi.org/10.1016/j.seppur.2015.07.046 Brand J, Dachmann E, Pichler M, Lotz S, Kulozik U (2016) A novel approach for lysozyme and ovotransferrin fractionation from egg white by radial flow membrane adsorption chromatography: impact of product and process variables. Sep Purif Technol 161:44–52. https://doi.org/10.1016/j.seppur.2016.01.032 Voswinkel L, Kulozik U (2014) Fractionation of all major and minor whey proteins with radial flow membrane adsorption chro-matography at lab and pilot scale. Int Dairy J 39(1):209-214. https://doi.org/10.1016/j.idairyj.2014.06.012 Boi C (2007) Membrane adsorbers as purification tools for monoclonal antibody purification. J Chromatogr B 848(1):19–27. https://doi.org/10.1016/j.jchromb.2006.08.044 Dos Reis Coimbra J, Thömmes J, Kula MR (1994) Continuous separation of whey proteins with aqueous two-phase systems in a Graesser contactor. J Chromatogr A 668(1):85–94. https://doi.org/10.1016/0021-9673(94)80095-2 Freire LAdC, Courtial CGP (2016) Aqueous two-phase systems applied to partition proteins from goat milk whey in-nature. Adv Biosci Biotech 7(9):350–359. https://doi.org/10.4236/abb.2016.79034 Jyh-Ping C (1992) Partitioning and separation of α-lactalbumin and β-lactoglobulin in PEG/potassium phosphate aqueous two-phase systems. J Ferment Bioeng 73(2):140–147. https://doi.org/10.1016/0922-338X(92)90579-J González-Amado M, Tavares APM, Freire MG, Soto A, Rodríguez O (2021) Recovery of lactose and proteins from cheese whey with poly(ethylene)glycol/sulfate aqueous two-phase systems. Sep Purif Technol 255:117686. https://doi.org/10.1016/j.seppur.2020.117686 Heebøll-Nielsen A, Justesen SFL, Thomas ORT (2004) Fractionation of whey proteins with high-capacity superparamagnetic ion-exchangers. J Biotechnol 113(1):247–262. https://doi.org/10.1016/j.jbiotec.2004.06.008 Meyer A, Berensmeier S, Franzreb M (2007) Direct capture of lactoferrin from whey using magnetic micro-ion exchangers in combination with high-gradient magnetic separation. React Funct Polym 67(12):1577–1588. https://doi.org/10.1016/j.reactfunctpolym.2007.07.038 Chen L, Guo C, Guan Y, Liu H (2007) Isolation of lactoferrin from acid whey by magnetic affinity separation. Sep Purif Technol 56(2):168–174. https://doi.org/10.1016/j.seppur.2007.01.019 Lai B-H, Chang C-H, Yeh C-C, Chen D-H (2013) Direct binding of concanvalin A onto iron oxide nanoparticles for fast magnetic selective separation of lactoferrin. Sep Purif Technol 108:83–88. https://doi.org/10.1016/j.seppur.2013.02.020 Nicolás P, Ferreira ML, Lassalle V (2019) Magnetic solid-phase extraction: a nanotechnological strategy for cheese whey protein recovery. J Food Eng 263:380–387. https://doi.org/10.1016/j.jfoodeng.2019.07.020 Prados IM, Barrios-Gumiel A, de la Mata FJ, Marina ML, García MC (2022) Magnetic nanoparticles coated with carboxylate-terminated carbosilane dendrons as a reusable and green approach to extract/purify proteins. Anal Bioanal Chem 414(4):1677–1689. https://doi.org/10.1007/s00216-021-03794-7