Table 2.

Different separation techniques used in the production of milk bioactives and their commercial potential

Milk bioactive and source	Isolation/separation technique	Reference	Commercial potentiala
α-La
Whey	Isoelectric/thermal precipitation and solubilization	Bramaud et al (1997)43;	Pilot scale
		Tolkach et al (2006)44
Whey	Thermal precipitation + MF+UF	Toro-Sierra et al (2013)45	Pilot scale
Whey protein concentrate	Thermal precipitation+ continuous centrifugation	Haller and Kulozik (2020)46	Commercially feasible
Whey	UF/MF with DF	Cheang and Zydney (2003)47	Industrial scale-up is feasible
Whey	MF with enzymatic hydrolysis	Cheison et al, (2011)49; Konrad and Kleinschmidt (2008)50; Lisak et al (2013)51	Pilot scale
Whey protein concentrate	Anion-exchange chromatography and UF	Geng et al (2015)52	Commercially available
Bovine milk	Gel filtration + anion exchange chromatography	Neyestani et al (2003)53	Small and medium scale
Whey	2-step ion-exchange chromatography	Ye et al (2000)54	Pilot scale
Bovine milk	Salt out/+ anion-exchange chromatography	Mao et al (2017)55	Pilot scale
Cow milk/whey	Cationic-exchange expanded-bed chromatography	Conrado et al (2005)56	Commercially feasible
Skim milk	HHP + UF	Touhami et al (2021)57	Laboratory scale
LF
Bovine milk/whey	Cation exchange chromatography/+ MSP	Liang et al (2011)58; Lu et al (2007)59	Commercially available
Whey	Cation exchange chromatography with modified stationary phases	Hirsch et al(2020)60; Matijašić et al (2020)61; Teepakorn et al (2015)62	Industrial scale-up is feasible
Whey	Electrodialysis with MSP	Brisson et al (2007)63; Ndiaye et al (2010)64; Wang et al (2020)65.	Laboratory scale
Whey	Metal/dye/magnetic affinity chromatography	Baieli et al (2014)66; L. Chen et al (2007)67; Lönnerdal et al (1977)68	Laboratory scale
Whey	Hydrophobic interaction chromatography	Santos et al (2011)69	Laboratory scale
Whey	Cationic exchange expanded bed chromatography/+UF	Maciel et al (2020)70	Laboratory scale
GMP
Whey	Anion exchange chromatography	Nakano et al (2018)71 and (2020)72	Large-scale production
Whey	DF+ anion exchange chromatography + UF	Davis et al (2004)73; Etzel et al (2011)74	Commercially available
Whey	Gel filtration	Takuo et al (2002)75	Laboratory scale
Whey	Affinity chromatography	Baieli et al (2017)76	Laboratory scale
Whey	Hydrophobic interaction chromatography	Silva-Hernandez et al (2002)77	Laboratory scale
Milk	Deproteinization with TCA	Nakano et al (2002)75	Laboratory scale
Whey	Thermal treatment and ethanol precipitation	Berrocal and Neeser (1993)78; Rojas and Torres (2013)79	Industrial scale up is feasible
Whey	Cellulose acetate electrophoresis	Nakano et al (2009)80	Laboratory scale
MFGM
Bovine milk	Fat remover + cream wash +centrifugation+ UF/MF	Hansen et al (2020)81; Le et al (2009)82; Ye et al (2004)83	Laboratory application
Butter milk	MF/+DF (several circles)	Fuller et al (2013)84; Morin et al (2007) 85	Pilot-scale
Butter serum	MF	Rombaut et al (2006)86	Laboratory scale
Whey	UF	Rombaut et al (2007)87	Laboratory scale
Butter milk	Acid/rennet coagulation + DF/MF	Holzmüller et al (2016)88	Pilot scale is feasible
BMO
Whey	Enzymatic digestion of lactose + (graphitized carbon-) SPE	Robinson et al (2018)89; Ward (2009)90	Laboratory scale only
Whey	Enzymatic digestion of lactose + NF/+ DF	Altmann et al (2015)91; Cohen et al (2017)92	Scale-up experiment
Whey	Integrated method: Lactose hydrolysis + fermentation + NF	De Moura Bell et al (2018)93	Pilot scale

^aBased on statements in the referenced articles or in patents.

Abbreviations: α-La, α-lactalbumin; BMO, bovine milk oligosaccharide; DF, diafiltration; GMP, glycomacropeptide; HHP, high hydrostatic pressure; LF, lactoferrin; MF, microfiltration; MFGM, milk fat globule membrane; MSP, membrane separation process; NF, nanofiltration; SPE, solid-phase extraction; TCA, UF, ultrafiltration.