INTRODUCTIONThe current food industry as a whole, and dairyindustry in particular, fits in the 5th technologicalparadigm, which is based on biotechnology with relics ofthe 4th (electricity) and the 3d (mechanics) technologicalparadigms [1]. The 6th technological paradigm willsupposedly originate from the current 5th paradigm in2025 [1–5]. The possible start date corresponds withDecree No. 350 issued by the President of the RussianFederation on July 21, 2016. The Decree is entitled ‘Onthe Administration of State Science and TechnologyPolicy for the Development of Agriculture’. It defines2025 as the year by which raw milk production will haveincreased by 40%. The provisions were further specifiedin the Presidential Decree ‘On the national goals andstrategic objectives of the development of the RussianFederation for the period up to 2024’ (May 7, 2018).According to Paragraph 7, almost all sectors of Russianeconomy are to transform to the principles of the bestavailable technologies (BAT) by 2024.Dairy production is an essential component ofthe food industry of the historically established agroindustrialsector, i.e. the milk production – dairyproducts – sales chain. For the new technologicalparadigm to take power in the current Russian dairyindustry, it needs an upgrade [6, 7]. The prospectiveupgrade is directly related to ensuring food security andindependence of the country and its regions [8].STUDY OBJECTS AND METHODSThe research featured the paradigm of dairy rawmaterials, which was tested in the dairy industry on theCopyright © 2019, Khramtsov et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 InternationalLicense (http://creativecommons.org/licenses/by/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix,transform, and build upon the material for any purpose, even commercially, provided the original work is properly cited and states its license.Foods and Raw Materials, 2019, vol. 7, no. 2E-ISSN 2310-9599ISSN 2308-4057292Khramtsov A.G. et al. Foods and Raw Materials, 2019, vol. 7, no. 2, pp. 291–300level of Technological Platform formation. The systemanalysis involved the convergence methodology withelements of the cognitive approach as developed by theRussian Academy of Sciences [4].Table 1 shows a comparative analysis of raw milkcomposition, cream excluded, which resulted frommechanical and biotechnological processing.Skimmed, or rather low-fat, milk and buttermilk areprotein-carbohydrate raw materials and have 50% ofsolids. Whey is a carbohydrate raw material with 70%of solids. Proteins, lipids (milk fat), and carbohydrates(lactose) are the main and most valuable constituentsof the secondary dairy raw materials. In addition tothe main constituents, skimmed milk, buttermilk,and whey also contain mineral salts, non-proteinnitrogenous compounds, vitamins, enzymes, hormones,immune bodies, organic acids, etc. It means that almostall components of milk solids can be utilised, evenbiologically synthesized water with its memory andfullerenes-kenotrons.Table 2 provides data on the degree of transition ofdairy constituents into dairy protein-carbohydrate rawmaterials, or secondary dairy raw materials, as definedby the Technological Regulations.Skimmed milk and buttermilk contain almost theentire protein, carbohydrate, and mineral complexof milk and up to 15% of milk fat. Whey containscarbohydrate complex, proteins, and mineral salts. Thesedata should be taken into account during identification,examination, and industrial processing of secondarydairy raw materials.Table 3 shows the sizes of the structures of the mainconstituents of dairy raw material.Dairy raw materials contain all types of structuralsystems: ions, molecules, colloids, suspensions, andemulsions.In the Russian Federation, the annual processingvolume of dairy raw materials is 30–33 million tons. Itmeans that secondary raw materials are estimated as20 million tons, which is a huge reserve and availableresources for the industrial upgrade. This especiallyconcerns new-generation functional products branded byProf. Petrovsky as ‘minimum of calories – maximum ofbiological value’ [9].A long-term systematic analysis allowed the teamof the North Caucasus Federal University (federalscientific school ‘Living Systems’ No.7510.2010.4) tooffer a scheme that can help the domestic diary industryto adapt safely to the new technological paradigm.The scheme takes into account various factors, such aslimited traditional dairy resources (< 50%), Russia’saccession to the WTO, and the globalisation of theworld dairy market. The generalised scheme has ninefundamental principles, or blocks, and was publishedin [10]. The principles cover the whole range of dairyproduction from dairy raw materials to the problemsof the international dairy industry, including theorganisation of alternative off-season productions. Thispaper introduces the concept of the second principle,which involves the scaling of innovative, sustainablebiological nanomembrane ‘high-tech’ technologies forindustrial processing of dairy raw materials with thecomplete production cycle [11, 12].RESULTS AND DISCUSSIONLogistically, dairy industry should implement a zerowasteproduction scheme that observes the followingprinciple: waste milk is nothing but unused reserves [13].It was 30–50 years ago that the so-called recyclingplants appeared in the global dairy industry. Theyplayed a positive economic and social role: they broughtin profit, gave workers two days-off, and protected theenvironment. For example, all large cheese-makingTable 1 Content of the main constituents in dairy rawmaterials, g/100 gConstituents WholemilkSkimmedmilkButtermilk MilkwheyMilk fat 3.7 0.05 0.5 0.2Proteins 3.3 3.3 3.3 0.9Lactose 4.8 4.8 4.7 4.8Mineral salts 0.7 0.7 0.7 0.6Solids 12.5 8.8 9.1 6.5Table 2 Degree of transition of the main dairy constituentsinto the secondary dairy raw materialsMilk constituents(100%)Degree of transition, %SkimmedmilkButtermilk MilkwheyMilk fat 1.4 14.0 5.5Total protein, including 99.6 99.4 24.3Casein 99.5 99.5 22.5Whey proteins 99.8 99.6 95.0Lactose 99.5 99.4 96.0Mineral salts 99.8 99.6 98.0Solids 70.4 72.8 52.0Table 3 Dispersed composition of dairy clustersMilk constituents Size of themolecule orparticle, nmVolume of themolecule orparticle, %Water 0.1–0.2 90.10Fat 200–10000 4.20Casein 40–300 2.30α-Lactoglobulin 5–20 0.30Β-Lactoglobulin 25–50 0.08Milk sugar (lactose) 1.0–1.5 3.02Mineral salts 0.1–1.0 0.10BAS 0.1–100.0 0.01293Khramtsov A.G. et al. Foods and Raw Materials, 2019, vol. 7, no. 2, pp. 291–300factories are to have skimmed milk and whey dryingstations. According to the new approach to this problem,dairy constituents are to be obtained from the originalmilk. Raw materials of plant and animal origin areto be combined to produce such functional products(bioproducts) as pro-, pre-, and synbiotics. In addition,a significant amount of secondary dairy raw materials(milk protein-carbohydrate raw materials) enters the socalledtechnological cycle. As a result, the industry losesa great deal of skimmed milk, low-fat milk, buttermilk,and especially milk whey, which is responsible for halfof the solids of the original raw material, while pollutingwater sources [14].To update the dairy industry by implementingmodern innovations, the dairy technology platformhas to be revised with subsequent access to the newtechnological paradigm [1, 15, 16]. In the nearestfuture, the industry will have to comprehend andimplement the large-scale high-tech options. Accordingto Metz [11, 17, 18], the 5th technological paradigm willinclude food nanotechnology [19] with biomembraneand baromembrane processes aimed at the clustersof dairy constituents with the use of information andcommunication technologies. The European EconomicCommunity set up the first European Institute for FoodIndustry (EU-IFP) (http://www.hightecheurope.com).It has three branches: Biotechnology (BIOTECH),Nanotechnology (NANOTECH), and Information andCommunication Technology (ICTECH) [20].On the industrial level, the innovative priorities oftechnological upgrade have the following principles.Epistemologically, all dairy raw materials – wholeand skimmed (low-fat) milk, cream, buttermilk, andwhey – are constantly renewable resources. Therefore,the food obtained from them can be viewed upon asobjects of rapidly developing nanotechnology. Hence,their constituents at the molecular level should beconsidered as naturally synthesized clusters of simple(molecules, atoms) or complex (micelles, aggregates,particles) compounds [20]. The cluster structure ofthe main components of dairy raw materials createsprerequisites for directional and controlled modelling,i.e. bio-technology in the 5th technological paradigm andpicotechnology in the 6th.Similarly, from the point of view of the natureformedbiotechnological system, all components ofdairy raw materials can be considered as naturalclusters – lipids (fat), nitrogen (proteins), carbohydrates(lactose), minerals (salt), biologically active substances,and water. As an idealised model of agricultural rawmaterial, milk is extremely complex. Its chemicalcomposition includes more than 2000 constituents and100000 molecular structures. In addition, dairyarchitectonics is also extremely complex: it includessuspension, emulsion, and solution. Finally, milkpossesses unusual physicochemical, osmophoric,structural-mechanical, bio-thermodynamic, and othercharacteristics.Milk as a biotechnological system provides newbornmammals with nutrients and can serve as a basisfor next-generation high-grade foods. According toits physical and chemical properties, its active acidityand osmotic pressure are close to the nutriciology ofmammals. Thus, it can be of practical importance thatproteins, milk sugar, and mineral salts increase thedensity of dairy raw materials, while milk fat reduces it.As a biotechnological system, dairy raw materialsillustrate the opinion voiced by the great Russianphysiologist and Nobel Prize winner Pavlov: ‘milk is anamazing food prepared by nature itself.’ Structurally,this is a heterogeneous system in the form of a solutionintended for direct (oral) use. It has a sufficiently highcontent of solids, particles (milk fat in the form ofsuspension or emulsion), colloids (proteins and mineralcompounds), and a molecular solution (lactose, mineralsalts, and BAS). Milks obtained from sheep, goats,mares, camels, and buffalos differ from cow’s milkas a complex biotechnological system. This should beconsidered in industrial processing. The same applies totheir secondary dairy raw materials, e.g. skimmed milk,buttermilk, and whey [23].In 2007, we introduced the concept, or doctrine, ofnano-, bio-, membrane, and biomembrane technologiesto implement this principle. The concept was publishedin food industry journals and tested at food industryseminars and international summits in 2008, 2009, 2011,2015, and 2016. Apparently, it can serve as an alternativebasis for the industry upgrade [24].The fundamental paradigm of nano-food technologyin the dairy business can be confirmed by the processesof synthesis of lactose derivatives [25, 26]. For instance,the biological nanotechnology of lactose hydrolysisproduces two monoses from lactose disaccharide(1 nm), i.e. glucose and galactose with a size of0.5 nm. This solves the problem of milk intolerance.The Stavropolsky Dairy Plant (Stavropol, Russia) usedthis unique procedure to obtain marketable low-lactosemilk under the Healthy City programme. The globallyfamous synthesis of lactulose at the proton level, whichis pure nanotechnology, is the pride of the industry andhas proved to be extremely profitable [27]. Lactuloseis known to be the best prebiotic, a bifidobacteriapromoter, and an ideal natural laxative. A research in itsproduction and implementation was awarded the Prizeof the Russian Federation Government on Science andTechnology in 2002.The last decade has seen a fundamentally newdirection of dairy nanotechnology: whey proteins aremicroparticulated into nanotubes that imitate the flavourof milk fat [28]. The industry has already mastered thelogistics for the formation of microgranules (nanotubes)of whey proteins from the so-called ‘albumin milk’.Such products are well known abroad under theSimplesse brand [23]. This innovation has also beenimplemented in Russia [12, 29].294Khramtsov A.G. et al. Foods and Raw Materials, 2019, vol. 7, no. 2, pp. 291–300Biotechnology of dairy products is historicallyassociated with pure cultures of microorganisms in theform of starter cultures and enzymatic catalysis that areused to obtain such fermented milk products as sourcream, cheese, cottage cheese, and dairy beverages.High-biotech solutions have a long history in thedomestic industry. Sour cream is known as traditional‘Russian cream’; sour clotted milk is a Russianbiocenosis; kefir is traditionally favoured by thecentenarians from the Caucasus; yogurts, or ‘dairyferments’ were introduced by the famous Russian NobelPrize winner Mechnikov as part of lactotherapy, etc.Such elements of superbiotechnologies as enzymaticcatalysis and microbial synthesis have long been partof centuries-old cheese-making procedures. Uniquebiotechnologies of dairy industry are as sophisticatedas the finest surgical operations and require the samedisinfection measures. Some of them can be adaptedto obtain starter cultures in controlled fermentationprocedures for silage making, sauerkraut production,meat industry, as well as in medicine and veterinary.According to Luff, the ‘life code’ that nature andbionanotechnology give to industrially processed wheyprovides people with immune protection against manydiseases, including various flu strain [23, 30]. As formilk lactose, Canadian veterinarian De Lookk called itthe ‘saviour of mankind’ because it can prevent and treatsalmonellosis [31].One of the most promising biotech solutions inthe dairy industry is the production of derivatives ofthe nitrogen-containing milk complex, namely caseinand whey proteins. It deserves special consideration.It involves two separation methods: hydrolysisand proteolysis. Casein hydrolysis is well-studiedand globally implemented, e.g. in pharmacy. Itsbiotechnology is based on the proteolysis of caseinsin cheese, which determines the type and qualityof products. The hydrolysis of whey proteins is ofparticular importance in the biomedical aspect sinceit is used in infant formulae, as well as in dietary andtherapeutic nutrition.The amino acid composition of whey proteins isbelieved to be closest to human muscle tissue [32]. Theyexceed all other animal and vegetable proteins accordingto the content of essential amino acids and branchedchainamino acids (BCAA), e.g. valine, leucine, andisoleucine. According to the FAO/WHO, the biologicalvalue of albumin and globulin, which are the mainwhey proteins, exceeds the ideal 100 cu ascribed toeggs. It amounts to 104 cu, which is twice as high asthe biological value of wheat. This corresponds withthe traditional Russian proverb that bread and milk arethe best food. The digestibility of whey proteins is 98%,which is extremely high. Table 4 illustrates the data onthe content of some essential amino acids according tothe scale used by the FAO/WHO and their presence inwhey proteins.Numerous peptides and amino acids are extremelyimportant for human health, especially those naturalpolypeptide chains that can be found in dairy rawmaterials. They can also be obtained artificially fromcasein fractions and polypeptide chains of wheyproteins. For instance, exomorphins are naturalpainkillers. They regulate the general endocrineprofile of mammals and produce a soothing effecton cubs. As for β-casomorphins, they are excellentimmunomodulators. ‘Dairy peptides’ increase thephagocytic activity of certain gastrointestinal bacteria,thus ensuring resistance to infectious diseases. Forexample, the Institute of Biophysics (Siberian Branchof the Russian Academy of Sciences) has synthesizedlactoptin, an analogue of breast milk low molecularweight peptide. It possesses antitumor and antimetastaticproperties and is absolutely safe [33]. Angiogenin(Milkang) is beneficial for blood vessels and healswounds and burns [34]. Unfortunately, the issue remainslargely understudied.The process is extremely complex, and its resultscan be implemented in various ways. One can mentionthe studies of phenylketonuria performed at theKemerovo Institute of Technology (University) [35]. Theproprietary technology of obtaining biologically activepeptides from milk proteins has been implemented onan industrial scale in England. The Molvest company(Voronezh, Russia) has started to produce dairy productswith reduced antigenicity using the controlled hydrolysisof β-globulin into peptides. The technology wasdeveloped by the combined efforts of A. Bach ResearchInstitute, the Russian Academy of Sciences, theInterindustry Scientific Center of the Siberian ResearchInstitute of Mining Geomechanics and Surveyingand the Voronezh State University of EngineeringTechnologies [36].Baromembrane technology makes it possible toseparate high molecular weight polydisperse liquidsystems, as shown in Fig. 1. It has been adapted todairy raw materials, especially ultrafiltration andelectrodialysis [37, 38].Figure 2 shows installations that use baromembranemethods of molecular sieve separation of whey.Table 4 Content of essential amino acidsAmino acids Content, g/100 g of proteinFAO/WHOscaleWhey proteinsIsoleucine 4. 0 6.2Leucine 7.0 12.3Lysine 5.5 9.1Methionine + Cystine 3.5 5.7Phenylalanine + Tyrosine 6.0 8.2Threonine 4.0 5.2Tryptophan 1.0 2.2Valine 5.0 8.7295Khramtsov A.G. et al. Foods and Raw Materials, 2019, vol. 7, no. 2, pp. 291–300Figure 1 Diagrams of baromembrane separation ofconstituents of dairy raw materials: RO – reverse osmosis,NF – nanofiltration, UF – ultrafiltration, MF – microfiltrationFigure 2 Baromembrane installations for molecular sieve filtration of wheyMembrane processPressure, atmParticle size, μm0.0001 0.001 0.01 0.1 1.0 10FONFUFSalts MFLactoseWheyproteinsCaseinFatBacteriaMicrofiltration UltrafiltrationNanofiltration Reverse osmosisThe illustrations demonstrate the achievementsand prospective scaling of the industry. As forelectroflotation, sorption, desorption, and ion exchange,they are still under research and are undergoingexperimental testing.Electrodialysis desalting of whey produces up to100000 tons annually and increases by 30% each year.Such a large-scale production has made it possible toreduce the export of solids, which were purchased fromas far away as Argentina. Now it is a full sub-industryof dairy production. To demonstrate the process, Figure3 shows the scheme of electrodialysis and devices ofdomestic production.Biomembrane technology. There has been aseries of long-term case studies performed by Prof.Molochnikov’s team. The studies were conductedby the joint efforts of the Institute of OrganoelementCompounds (Moscow) and a number of medicalinstitutions, such as the Institute of Aviation and SpaceMedicine (Moscow), Ministry of Defence, Instituteof Nutrition (USSR Academy of Medical Sciences),All-Union Scientific Cancer Centre (Moscow).The researches have made it possible to review andfundamentally change the approaches to raw milkprocessing and the composition and quality of dairyproducts [39–42].The studies employed the biomembrane technology:an aqueous solution of a polysaccharide, e.g. pectin,is introduced into milk raw materials, i.e. natural orcondensed skimmed milk, reconstituted milk powder,or buttermilk. Milk casein is thermodynamicallyincompatible with polysaccharide. As a result, casein296Khramtsov A.G. et al. Foods and Raw Materials, 2019, vol. 7, no. 2, pp. 291–300containing dairy raw materials spontaneously split intotwo liquid fractions – natural casein concentrate (NCC)and a whey-polysaccharide fraction (WPF). After that,the two liquid raw materials are separated by gravityor centrifuged. They are easily combined with theremaining dairy raw materials. The initial raw materialscan be processed, and no by-products are formed,which corresponds with the principles of zero-wastetechnology with a closed zero-discharge production.Figure 4 illustrates a hypothetical simulation modelof the interaction between the liquid membrane (a polysaccharidesolution, e.g. pectin) and the main milkconstituents. The system’s stability is modelledaccording to the DLVO theory (Derjaguin + Landau +Verwey + Overbeek) [43].In general, basic researches in academic institutionsand programme-targeted studies conducted by industryresearch institutes on the issue of biomembranetechnology with the Bio-Ton dairy product line giveevery reason to revise the existing principles ofproduction in the dairy industry. This can serve as abasis for the 6th technological paradigm in accordancewith the principles of the system approach [44]. The6th technological paradigm presupposes sono- and(a) (b)Figure 3 Schematic diagram of whey demineralisation (a) and a module of Istok electrodialysis installation (b)(a) (b) (c)Figure 4 Hypothetical model of the interaction between the liquid membrane and the milk constituents (a); formation of associatesof the first level casein micelles (b)$ and the interaction energy curve according to the DLVO theory (c)Liquid membrane phaseFunctional groupLinearmacromolecules3D structureElectrostaticsOsmosisH-OHColloidalphaseMolecularsolution phaseHydrationCaseinIonexchangeLactoseWhey Saltsproteins Low-fat milk rawmaterialDehydrationPolysaccharideLiquidmembraneMicelleCan(PO4)mclusterHydratationshellAttraction RepulsionEnergy barrierHUU min maxPrimary wellSecondary wellMembrane pair297Khramtsov A.G. et al. Foods and Raw Materials, 2019, vol. 7, no. 2, pp. 291–300picotechnologies with a full automation under asepticconditions, i.e. unmanned technologies.The abovementioned data make it possible toimagine the complexity of the problems and theirsolutions based on modern genomics, proteomics(peptidomics), lipidomics, and genetic engineering.Their practical implementation in the form ofnano-, bio-, membrane, and biomembrane technologiescan shape a fundamentally new dairy science –LactoOmics [7, 45–48]. The issue has to be consideredseparately on the principles of cognitive approach andconvergence methodology within the framework of thenew technological paradigm [49].The concept was adapted for milk whey, whichwas named ‘universal agricultural raw material’ byProf. Lipatov [50]. The research team was representedby members of the Scientific and Educational Centre‘Membrane BioTechnologies’ and the engineeringBioCentre of the North Caucasus Federal University,which belong to the scientific school No.7510.2010.4.The proposed concept of bionomembrane technologiesfully complies with the principles of the 5th technologicalparadigm with its high-tech (1985–2025) and createsreal prerequisites for the 6th technological paradigm(2025–2080). The latter will employ picotechnologyand elements of artificial intelligence (neural networks)to produce food and fodders of the new generation. Theconcept is outlined in a manual for the new generation ofindustry professionals [51].CONCLUSIONOn the eve of the 6th technological paradigm andthe BAT principles, the dairy industry as we know ithas to be upgraded [52, 53]. The upgrade will requiretremendous efforts. The principles of LactoOmics listedin [55] have to be implemented in practice [54]. Only thefundamental principles of food technology will makeit possible to avoid the tragedies of such manufacturedfamines as Holodomor [56–60]. Now that Russia hasjoined the WTO, the globalisation of the world dairymarket requires an adequate response.CONFLICT OF INTERESTThe authors declare that the authenticity of the issuemakes any conflict of interests impossible. The researchresults were only published in the Bulletin of theRussian Academy of Sciences, which was mentioned inthe text.ACKNOWLEDGEMENTSThe authors express their deepest gratitude toAcademician of the Russian Academy of Sciences I.F.Gorlov and Professor A.Yu. Prosekov for theirencouragement and advice.FUNDINGThe research topic ‘High-tech production oflactose in pharmaceutical and food industries’ wasdeveloped together with JSC Stavropolsky Dairy Plant(AO Molochny Kombinat Stavropolskiy) and financedby the Ministry of Education and Science of the RussianFederation, agreement No. 03.G25.31.0241.