Aufarbeitung (Downstream Processing)

  • Horst Chmiel


Die Produktaufarbeitung - im Englischen Downstream Processing genannt - mit den Schritten Zellabtrennung, Zellaufschluss (wenn das Produkt intrazellulär vorliegt), Produktisolation, Produktkonzentrierung, Produktreinigung und Konfektionierung hat in der Regel einen Anteil, der mehr als die Hälfte der Gesamtproduktionskosten beträgt. Das trifft besonders für Proteinwirkstoffe zu. Ziel muss also die Reduktion der Kosten für die Produktaufarbeitung sein. Hilfe erwartet man sich bei der Optimierung der Produktaufarbeitungs-prozesse von der modellbasierten Hybridprozessentwicklung.


  1. [1]
    Abels Ch, Carstensen F, Wessling M (2013) Membrane processes in biorefinery applications. J Membrane Sci 444:285–317Google Scholar
  2. [2]
    Adamiec J (2008) Drying of microorganisms for food applications. In: Ratti C (Hrsg) Advances in food dehydration, CRC press, Boca Rotan, S. 315–354Google Scholar
  3. [3]
    Ananta E, Volkert M, Knorr D (2005) Cellular injuries and storage stability of spray-dried Lactobacillus rhamnosus GG. Int Dairy J 15(4):399–409Google Scholar
  4. [4]
    Andrieu J, Vessot S (2011) Characterization and control of physical quality factors during freeze-drying of pharmaceuticals in vials. In: Tsotsas E, Mujumdar AS (Hrsg) Modern drying technology, Wiley-VCH, Weinheim, S. 51–90Google Scholar
  5. [5]
    Aruna N, Lali A (2001) Purification of a plant peroxidase using reversibly soluble ion-exchange polymer. Process Biochem 37: 431–437Google Scholar
  6. [6]
    Baker RW (2004) Membrane Technology and Applications. John Wiley & Sons, New YorkGoogle Scholar
  7. [7]
    Balasundaram B, Skill SC, Llewellyn CA (2012) A low energy process fort he recovery of bioproducts from cyanobacteria using a ball mill. Biochem Eng J 69: 48–56Google Scholar
  8. [8]
    Baldwin CV, Robinson CW (1994) Enhanced disruption of candida utilis using enzymatic pretreatment and high pressure homogenization. Biotechnol Bioeng 43: 46–56PubMedGoogle Scholar
  9. [9]
    Bauer B, Gerner FJ, Strathmann H (1988) Development of bipolar membranes. Desalination 68: 279Google Scholar
  10. [10]
    Bauer B, Chmiel H, Menzel Th, Strathmann H, (1991) Biochemical engineering stuttgart: Separation of bioreactor constituents by electrodialysis using bipolar membranes. Gustav Fischer, Stuttgart, S. 38–45Google Scholar
  11. [11]
    Bell, D J, Hoare M, Dunnhill P (1983) Advances in biochemical engineering. Springer-Verlag, Berlin, Vol. 26, S. 1–72Google Scholar
  12. [12]
    Bensch M, Selbach B, Hubbuch J (2007) High throughput screening techniques in downstream processing: Preparation, characterization and optimization of aqueous two-phase systems. Chem Eng Sci 62: 2011–2021Google Scholar
  13. [13]
    Black & Veatch Corporation (2010) White’s handbook of chlorination and alternative disinfectants. John Wiley & Sons, New YorkGoogle Scholar
  14. [14]
    Blume I, Schwerin P, Mulder M, Smolders C (1991) Vapour sorption and permeation properties of poly (dimethylsiloxane) films. J Membrane Sci 2: 61–85Google Scholar
  15. [15]
    Bonazzi C, Dumoulin E (2011) Quality changes in food materials as influenced by drying processes. In: Tsotsas E & Mujumdar AS (Hrsg) Modern drying technology, Wiley-VCH, Weinheim, S. 1–20Google Scholar
  16. [16]
    Bora MM, Borthakur S, Rao PC, Dutta NN (2005) Aqueous two-phase partitioning of cephalosporin antibiotics: effect of solute chemical nature. Sep Purif Technol 45(2):153–156Google Scholar
  17. [17]
    Borsook H, Huffman HM, Liu Y-P (1933) The preparation of crystalline lactic acid. J Biol Chem 102: 449–460Google Scholar
  18. [18]
    Bozoglu F, Ozilgen M, Bakir U (1987) Survival Kinetics of Lactic-Acid Starter Cultures during and after Freeze-Drying. Enzyme Microb Tech 9(9): 531–537Google Scholar
  19. [19]
    Bräutigam S, Dennewald D, Schürmann M, Lutje-Spelberg J, Pitner W-R, Weuster-Botz D (2009) Whole-cell biocatalysis: Evaluationof new hydrphobic ionic liquids for efficient asymmetric reduction of prochiral ketones. Enzyme Microb Tech 45: 310–316Google Scholar
  20. [20]
    Britsch L, Schroeder T, Friedle J (2008) Small scale parallelized biochromatography. GEN 56–57Google Scholar
  21. [21]
    Brookman JSG (1974) Mechanism of cell disintegration in a high pressure homogenizer. Biotechnol Bioeng 16: 371–383Google Scholar
  22. [22]
    Brooks CA, Cramer SM (1992) Steric mass-action ion exchange: Displacement profiles and induced salt gradients. AIChE Journal 38(12):1969–1978Google Scholar
  23. [23]
    Brunner K-H (1988) Sterildesign und -betrieb von Zentrifugalseparatoren. DECHEMA-Monographien Band 113, VCH, WeinheimGoogle Scholar
  24. [24]
    Brunner K-H (1979) Theoretische und experimentelle Untersuchung der Feststoffabscheidung in Tellerseparatoren. Dissertation ErlangenGoogle Scholar
  25. [25]
    Canari R, Eyal AM (2003) Extraction of Carboxylic Acids by Amine-Based Extractants: Apparent Extractant Basicity According to the pH of Half-Neutralization. Ind Eng Chem Res 42: 1285–1292.Google Scholar
  26. [26]
    Carstensen F, Klement T, Büchs J, Melin Th, Wessling M (2013) Continuous production and recovery of itaconic acid in a membrane bioreactor. Bioresource Technol 137: 179–187Google Scholar
  27. [27]
    Chae YK, Jeon W, Cho KS (2002) Rapid and simple method to prepare functional pfu DNA polymerase expressed in Escheridia coli periplasm. J Microbiol Biotech 12: 841–843Google Scholar
  28. [28]
    Chartogne A, Reeuwijk B, Hofte B, Heijden R, Tjaden UR, Greef J (2002) Capillary electrophoretic separations of proteins using carrier ampholytes. J Chrom A 959: 289–298Google Scholar
  29. [29]
    Chayen NE (2005) Methods for separating nucleation and growth in protein crystallisation. Prog Biophys Mol Biol 88: 329–337PubMedGoogle Scholar
  30. [30]
    Cohn EJ. (1932) Naturwissensch 20: 663Google Scholar
  31. [31]
    Cunha T, Aires-Barros R (2002) Large scale extraction of proteins. Mol Biotechnol 20: 29–40PubMedGoogle Scholar
  32. [32]
    Curie JA, Dunnill P, Lilly MD (1972) Release of protein from baker’s yeast by disruption in an industrial agitator mill. Biotechnol Bioeng 14: 725–736Google Scholar
  33. [33]
    Doucha J, Livansky K (2008) Influence of processing parameters on disintegration of chlorella cells in various types of homogenizers. Appl Microbiol Biotechnol 81: 431–440PubMedGoogle Scholar
  34. [34]
    Fonseca, L P and Cabral J M S (2002) Penicillin acylase release from escheridia coli cells by mechanical cell disruption and permeabilization. J Chem Technol Biot 77:159–167Google Scholar
  35. [35]
    Fraud N, Kuczewski M, Zarbis-Papastoitis G, Hirai M (2009) Hydrophobic membrane adsorber for large-scale downstream processing. Bio Pharm Intern. 10: 24–27Google Scholar
  36. [36]
    Frerix A, Muller M, Kula MR, Hubbuch, J (2005) Scalable recovery of plasmid DNA based on aqueous two-phase separation. Biotechnol Appl Bioc 42: 57–66Google Scholar
  37. [37]
    Friedle J (2008) Chromatography media scouting. Euro Biotech News 5-6(7): 41–42Google Scholar
  38. [38]
    Fu N, Chen X D (2011). Towards a maximal cell survival in convective thermal drying processes. Food Res Int 44(5):1127–1149Google Scholar
  39. [39]
    Giovannoni L, Ventani M, Gottschalk U (2009) Antibody purification using membrane adsorbers. Bio Pharm Int 10: 28–32Google Scholar
  40. [40]
    Gogate PR, Pandit AB (2008) Application of cavitational reactors for cell disruption for recovery of intracellular enzymes. J Chem Technol Biot 83:1083–1093Google Scholar
  41. [41]
    Gogate PR, Pandit AB (2011) Cavitation generation and usage without uktrasound: Hydrodynamoic cavitation. In: Theoretical and experimental sonochemestry involving inorganic systems, Springer, HeidelbergGoogle Scholar
  42. [42]
    Gorden J, Zeiner T, Brandenbusch C (2015) Reactive extraction of cis,cis-muconic acid. Fluid Phase Equilibr 393: 78–84Google Scholar
  43. [43]
    Greve A, Kula MR (1991) Recycling of salts in partition protein extraction process. J Chem Technol Biot 50: 27–42Google Scholar
  44. [44]
    Grot W (2011) Fluorinated Ionomers. William Andrew & Elsevier, AmsterdamGoogle Scholar
  45. [45]
    Haimer E (2015) Simulated moving bed chromatography as an alternative capturing tool for bio-based chemicals. ACHEMA, KongressbandGoogle Scholar
  46. [46]
    Hannig K, Wirth H, Meyer B, Zeiller K (1975) Free-Flow electrophoresis I. Theoretical and experimental investigations. Hoppe Seyler's Z Physiol Chem 356: 1209PubMedGoogle Scholar
  47. [47]
    Harris DC (2014) Lehrbuch der quantitaiven Analyse. Springer, HeidelbergGoogle Scholar
  48. [48]
    Harrison RG, Todd P, Rudge SR, Petrides DP (2003) Bioseparation Science and engineering, Oxford University Press, OxfordGoogle Scholar
  49. [49]
    Hebel D, Ürdingen M, Hekmat D, Weuster-Botz D (2013) Development and scale up of high-yield crystallization processes of lysozyme and lipase using additives. Cryst Growth Des 13: 2499–2506Google Scholar
  50. [50]
    Hebel D, Huber S, Stanislawski B, Hekmat D (2013) Stirred batch crystallization of a therapeutic antibody fragment. J Biotechnol 166: 206–211PubMedGoogle Scholar
  51. [51]
    Hekmat D (2015) Large-scale crystallization of proteins for purification and formulation. Bioprocess Biosyst Eng 38: 1209–1231PubMedGoogle Scholar
  52. [52]
    Hekmat D, Breitschwerdt P, Weuster-Botz D (2015) Purification of proteins from impure solutions by preparative crystallization. Biotechnol Lett 37: 1791–1801PubMedGoogle Scholar
  53. [53]
    Hekmat D, Maslak D, Freiherr von Roman M, Breitschwerdt P, Ströhle C, Vogt A, Berensmeier S, Weuster-Botz D (2015b) Non-chromatographic preparative purification of enhanced green fluorescent protein. J Biotechnol 194: 84–90PubMedGoogle Scholar
  54. [54]
    Henzler H-J (2000) Particle stress in bioreactors. Adv Biochem Eng Biotechnol 67: 35–82Google Scholar
  55. [55]
    Hetherington PJ, Follows M, Dunnill P, Lilly MD (1971) Release of protein from baker'syeast by disruption in an industrial homogenizer. Trans Inst Chem Eng 49: 142–148Google Scholar
  56. [56]
    Hilbrig F, Freitag R (2003) Protein purification by affinity precipitation. J Chromat 790: 79–90Google Scholar
  57. [57]
    Hoffstetter-Kuhn S (1989) Untersuchungen zum Scale-up der Free-Flow-Elektrophorese am Beispiel der Anreicherung von Alkoholdehydrogenase aus Saccharomyces cerevisiae. Dissertation SaarbrückenGoogle Scholar
  58. [58]
    Hunter, R J (1981) Zeta potential in colloid science 3. Aufl. Academic Press, SydneyGoogle Scholar
  59. [59]
    Huang C, Xu T, Zhang Y, Xue Y, Chen G (2007) Application of electrodialysis to the production of organic acids: State-of-the-art and recent developments. J Membrane Sci 288: 1–12Google Scholar
  60. [60]
    Hustedt H (1986) Extractive enzyme recovery with simple recycling of phase forming chemicals. Biotechnol Lett 8: 791–796Google Scholar
  61. [61]
    Imamoglu S (2002) Simulated moving bed chromatography (SMB) for applications in bioseparation. Adv Biochem Eng/Biotechn 76: 211–231Google Scholar
  62. [62]
    Issaq HJ, Conrads TP, Janini GM, Veenstra TD (2002) Methods for fractionation, separation and profiling of proteins and peptides. Electrophoresis 23: 3048–3061PubMedGoogle Scholar
  63. [63]
    Johansson G, Kopperschläger G, Albertsson PA (1983) Affinity partitioning of phosphofructokinase from Baker's yeast using polymer-bound cibacron blue F3 G-A. Eur J Biochem 131: 589–594PubMedGoogle Scholar
  64. [64]
    Kaden H (1999) Elektrokinetische Phänomene. Verlag der Sächsichen Akademie der Wissenschaften zu Leipzig, Mathematisch-naturwissenschaftliche Klasse 127(5)Google Scholar
  65. [65]
    Kalyanyur M (2002) Downstream processing in the biotechnology industry. Molec Biotechnol 22: 87–98Google Scholar
  66. [66]
    Kattan O (2013) Membranes in the biobased economy: electrodialysis of amino acids for the production of biochemicals. Dissertation Gildeprint, EnschedeGoogle Scholar
  67. [67]
    Kemperman A et al (2000) Bipolar membrane technology handbook. Twente University Press, TwenteGoogle Scholar
  68. [68]
    Kepka C, Collet E, Roos F, Tjerneld F, Veide A (2005) Two-step recovery process for tryptophan tagged cutinase: interfacing aqueous two-phase extraction and hydrophobic interaction chromatography. J Chrom A 1075(1–2): 33–41Google Scholar
  69. [69]
    Krzyzaniak A, Schuur B, de Haan AB (2014) Equilibrium studies on lactic acid extraction with N, N-didodecylpyridin-4-amine (DDAP) extractant, Chem Eng Sci 109: 236–243Google Scholar
  70. [70]
    Kula MR, Kroner KH, Hustedt H, (1982) Purification of enzymes by Liquid-Liquid extraction. In: Fiechter A (Hrsg) Advances in biochemical engineering/biotechnology, Vol. 24. Springer-Verlag, Berlin, S. 73–118Google Scholar
  71. [71]
    Kula MR, Schütte H (1987) Purification of proteins and the disruption of microbial cells. Biotechnol Progr 3/1: 31–42Google Scholar
  72. [72]
    Kula MR, Schütte H, Vogels C, Frank A (1990) Cell disintegration for the purification of intracellular proteins. Food Biotechnol 4:169–183Google Scholar
  73. [73]
    Kula MR, Selber K (1999) Protein purification, aqueous liquid extraction. In: Flickinger MC, Drew SW (Hrsg) Encyclopedia of bioprocess technology: Fermentation, biocatalysis and bioseparation, John Wiley & Sons, New York, S. 2179–2191Google Scholar
  74. [74]
    Lee CT, Movreale G, Middelberg APJ (2004) Combined infermenter extraction and cross-flow microfiltration for improved inclusion body processing. Biotechn Bioeng 85: 103–113Google Scholar
  75. [75]
    Lee AK, Lewis DM, Ashman PJ (2014) Microalgal cell disruption by hydrodynamic cavitation for the production of biofuels. J Appl Phycol 26(6)Google Scholar
  76. [76]
    Lemmlich R (1972) Adsorptive bubble separation technique. Academic Press, New YorkGoogle Scholar
  77. [77]
    Leslie SB, Israeli E, Lighthart B, et al. (1995). Trehalose and sucrose protect both membranes and proteins in intact bacteria during drying. Appl Environ Microbiol 61(10): 3592–3597PubMedPubMedCentralGoogle Scholar
  78. [78]
    Li X, Stevenson P (2012) Stevenson P (ed.) Foam Engineering, Chapter 14. Wiley-Blackwell, New York, S. 307–330Google Scholar
  79. [79]
    Limon-Lason J, Haare J, Orsborn CB, Doyle DJ, Dunnill P (1983) Experiences with a 20 litre industrial bead mill for the disruption of microorganisms. Enzyme Microb Technol 5: 143–148Google Scholar
  80. [80]
    Lin D-Q, Brixius PJ, Hubbuch JJ, Thömmes J. Kula MR (2003) Biomass/adsorbent electrostatic interactions in expanded bed adsorption: a zeta potential study. Biotechnol Bioeng 83: 149–157PubMedGoogle Scholar
  81. [81]
    Lipnizki F, Hausmann S, Laufenberg G, Field R, Kunz B (2000) Use of pervaporation-bioreactor hybrid process in biotechnology. Chem Eng Technol 23(7): 569–577Google Scholar
  82. [82]
    Lutzer RG, Robinson CW, Glick BR (1994) Two stage process for increasing cell disruption of E.coli for intracellular products recovery. In: Proceedings of the 6th European Congress of Biotechnology, Elsevier Sciences B.V., Amsterdam, S. 111–121Google Scholar
  83. [83]
    Manegold E (1953) Schaum. Straßenbau, Chemie und Technik. Verlagsgesellschaft, HeidelbergGoogle Scholar
  84. [84]
    Maximini A, (2004) Trägergestützte Flüssigkeitsmembranen zur Trennung von Enantiomeren am Beispiel N-geschützter Aminosäurederivate, Dissertation Universität SaarbrückenGoogle Scholar
  85. [85]
    Melin T, Rautenbach R (2007) Membranverfahren. Springer, Berlin HeidelbergGoogle Scholar
  86. [86]
    Mersmann A, Kind M, Stichlmair J (2011) Drying. In: Thermal Separation Technology: Principles, Methods, Process Design, Springer, Heidelberg, S. 561–594Google Scholar
  87. [87]
    Merz J (2012) A contribution to design foam fractionation processes. Dissertation Inversität DortmundGoogle Scholar
  88. [88]
    Middelberg APJ (2000) Microbial cell disruption by high pressure homogenization Methods in Biotechnology, Vol. 9; Downstream Processing of Proteins. In: Dessai MA, (Hrsg) Methods and Protocols, Pub Humana Press Inc., TotowaGoogle Scholar
  89. [89]
    Mölls H, Hörnle R: Wirkungsmechanismus der Naßzerkleinerung in der Rührwerkskugelmühle. Dechema-Monographie 69, Tl. 2: 631–661Google Scholar
  90. [90]
    Morgan CA, Herman N, White PA, et al. (2006) Preservation of micro-organisms by drying; A review. J Microbiol Meth 66(2): 183–193.Google Scholar
  91. [91]
    Muendges J, Stark I, Mohammad S, Górak A, Zeiner T (2015) Single stage aqueous two-phase extraction for monoclonal antibody purification from cell supernatant. Fluid Phase Equilibr 385: 227–236.Google Scholar
  92. [92]
    Nfor B K, Verhaert P, van der Wielen L, Hubbuch J, Ottens M (2009) Rational and systematic protein purification process development: the next generation. Trends Biotechnol 27(12): 673–679PubMedGoogle Scholar
  93. [93]
    Olmstead ILD, Kentish SE, Scales PJ, Martin GJO (2013) Low solvent, low temperature method for extracting biodiesel lipids from concentrated microalgal biomass. Bioresour Technol 148: 615–619PubMedGoogle Scholar
  94. [94]
    Pabby A, Rizvi S, Sastre Requena A et al (2008) Handbook of membrane separations. Chemical, pharmaceutical, food, and biotechnological applications. CRC Press, Boca RatonGoogle Scholar
  95. [95]
    Porada S, Zhao R, van der Wal A, Presser V, Biesheuvel PM (2013) Review on the science and technology of water Desalination by Capacitive Deionization. Prog Mater Sci 58: 1388–1442Google Scholar
  96. [96]
    Prinz A, Koch K, Górak A, Zeiner T (2014). Multi-stage laccase extraction and separation using aqueous two-phase systems: Experiment and model. Process Biochem 49(6): 1020–1031Google Scholar
  97. [97]
    Rautenbach R, Gröschl A (1990) Separation potential of nanofiltrration membranes. Desalination 77: 73–84Google Scholar
  98. [98]
    Reis R, Zydney A (2007) Bioprocess membrane technology. J Membrane Sci 297: 16–50Google Scholar
  99. [99]
    Rodrigues GD, da Silva MdCH, da Silva LHM, Paggioli FJ, Minim LA, Reis Coimbra JSd (2008) Liquid–liquid extraction of metal ions without use of organic solvent. Sep Purif Technol 62: 687–693Google Scholar
  100. [100]
    Sahirgaonkar LZ, Lothe RR, Pandit AB (1998) Comments on the mechanism of microbial cell disruption in high-pressure and high-speed devices. Biotechnol Progr 14(4): 657–660Google Scholar
  101. [101]
    Santivarangkna C, Kulozik U, Foerst P (2007) Alternative drying processes for the industrial preservation of lactic acid starter cultures. Biotechnol Progr 23(2): 302–315Google Scholar
  102. [102]
    Sartor M (2006) Untersuchungen zum Einfluss elektrokinetischer Repulsationseffekte auf die Tiefenfiltration mit partikulären Schüttbetten. Diss. Univ. des Saarlandes, upt-Schriftenreihe, Band 8Google Scholar
  103. [103]
    Sartor M, Kaschek M, Mavrov V, Chmiel H(2008) Untersuchungen zum Einfluss elektrokinetischer Wechselwirkungen auf die Adsorptionsmechanismen bei der Tiefenfiltration. Chem Ing Tech 80(6): 855–859Google Scholar
  104. [104]
    Scheuermann EA (1989) Filtrieren und Separieren: Versuch einer Eingrenzung. Filtr & Separ 2: 260Google Scholar
  105. [105]
    Schlünder, Thurner (1986) Destillation, Absorption and Extraktion. Georg Thieme, StuttgartGoogle Scholar
  106. [106]
    Schmidt S, Wu P, Konstantinov K, Kaiser K, Kauling J, Henzler, H-J und Vogel JH (2003) Kontinuierliche Isolierung von Pharmawirkstoffen mittels annularer Chromatographie. Chem Ing Techn 75: 302–305Google Scholar
  107. [107]
    Schubert H (2003) Handbuch der Mechanischen Verfahrenstechnik. Wiley-VCH, WeinheimGoogle Scholar
  108. [108]
    Schügerl K (2000) Integrated processing of biotechnology products. Biotechn Advanc 18: 581–599Google Scholar
  109. [109]
    Schultze B (1989) Schaumfraktionierung von Biotensiden. Diplomarbeit Stuttgart, StuttgartGoogle Scholar
  110. [110]
    Schustolla D, Ledoux C, Papamichael N, Hustedt H (1989) Reactive (Affinity) Extraction of enzymes from biomass. Ber Bunsenges Phys Chem 93: 971–975Google Scholar
  111. [111]
    Schütte H, Kroner KH, Kula M-R (1983) Experiences with a 20 litre industrial bead mill for the disruption of microorganisms. Enzyme Microb Technol 5: 143–148Google Scholar
  112. [112]
    Schütte H, Kula, M-R (1986) Einsatz von Rührwerkskugelmühlen und Hochdruckhomogenisatoren für den technischen Aufschluß von Mikroorganismen. BTF-Biotech-Forum 3: 68–80Google Scholar
  113. [113]
    Shin YO, Wahnon D, Weber ME, Vera JH (2004) Selective precipitation and recovery of xylanase using surfactant and organic solvent. Biotechnol Bioeng 88: 698–706Google Scholar
  114. [114]
    Smejkal B, Helk B, Rondeau J-M, Anton S, Wilke A, Scheyerer P, Fries J, Hekmat D, Weuster-Botz D (2013) Protein crystallization in stirred systems – scale-up via the maximum local energy dissipation. Biotechnol Bioeng 110: 1956–1963PubMedGoogle Scholar
  115. [115]
    Smejkal B, Agrawal NJ, Helk B, Schulz H, Giffard M, Mechelke M, Ortner F, Heckmeier P, Trout BL, Hekmat D (2013b) Fast and scalable purification of a therapeutic full-length antibody based on process crystallization. Biotechnol Bioeng 110: 2452–2461PubMedGoogle Scholar
  116. [116]
    Spiden EM, Yap BH, Hill DR, Kentis, SE, Scales PJ, Martin GJ (2013) Quantitative evaluation of the ease of rupture of industrially promising microalgae by high pressure homogenization. Bioresour Technol 140: 165–171PubMedGoogle Scholar
  117. [117]
    Stankiewicz A (2003), Reactive separations for process intensification: an industrial perspective. Chem Eng Prog 42: 137–144Google Scholar
  118. [118]
    Stehr N, Schwedes J (1983) Verfahrenstechnische Untersuchungen an einer Rührwerkskugelmühle. Aufbereitungs-Technik 10: 597–604Google Scholar
  119. [119]
    Stieß M (1994) Mechanische Verfahrenstechnik Band 2. Springer, HeidelbergGoogle Scholar
  120. [120]
    Strathmann H, Rapp, H-J, Bauer B, Bell CM (1993) Theoretical and practical aspects of preparing bipolar membranes. Desalination 90: 303–323Google Scholar
  121. [121]
    Strathmann H (2004) Ion-exchange membrane separation processes. Elsevier, AmsterdamGoogle Scholar
  122. [122]
    Susanto A, Knieps-Grunhagen E, von Lieres K, Hubbuch J (2008). High throughput screening for the design and optimization of chromatographic processes: Assessment of model parameter determination from high throughput compatible data. Chem Eng Technol 31(12): 1846–1855Google Scholar
  123. [123]
    Susanto A, Treier K, Knieps-Gruenhagen E, von Lieres, Hubbuch J (2009) High throughput screening for the design and optimization of chromatographic processes: Automated optimization of chromatographic phase systems. Chem Eng Technol 32(1): 140–154Google Scholar
  124. [124]
    Uesugi M, Tsunofuri M, Nagano J, Mizobuchi S (2005) Rotor/stator type homogenizer. Patent US6869212Google Scholar
  125. [125]
    Uhlmann E, Oberschmidt D, Spielvoge, A, Polte M, Herms K, Dumke A (2013) Development of a versatile and continuously operating cell disruption device. Procedia CIRP 5: 119–123Google Scholar
  126. [126]
    van't Land CM (2012) Drying in the process industry. John Wiley & Sons, New YorkGoogle Scholar
  127. [127]
    Vogels G, Kula MR (1992) Combination of enzymatic and/or thermal pretreatment with mechanical cell disintegration. Chem Eng Sci 47: 127–131Google Scholar
  128. [128]
    Voigt I, Puhlfürß P, Richter H, Weyd M, Prehn V (2014) Efficient production integrated separation with ceramic NF membranes. In: Proceeding 15th Aachener Membran Kolloquium, Aachener Verfahrenstechnik, Aachen, S. 175–180. ISBN: 978-3-95886-005-6Google Scholar
  129. [129]
    Wagner H, Blasius E (1989) Praxis der elektrophoretischen Trennverfahren. Springer, HeidelbergGoogle Scholar
  130. [130]
    Wahlund PO, Gustavson PE, Izumrudov VA, Larsson PO, Galaev IY (2004) Precipitation by polycation as capture step in purification of plasmid DNA from a clarified lysate. Biotechnol Bioeng 87: 675–684PubMedGoogle Scholar
  131. [131]
    Waites MJ, Morgan NL, Rockey J S, et al. (2001). Downstream processing. In: Industrial Microbiology: An Introduction Blackwell, Oxford, S. 109–123Google Scholar
  132. [132]
    Wekenborg K, Susanto A, Fredriksen, SS, Schmidt-Traub H (2004) Nichtisokratische SMB-Trennung von Proteinen mittels Ionenaustauschchromatographie. Chem Ing Techn 76: 815–819Google Scholar
  133. [133]
    Weuster-Botz D (2007) Process intenification of whole-cell biocatalysis with ionic liquids. The Chemical Record 7: 334–340PubMedGoogle Scholar
  134. [134]
    Weyd M, Richter H, Puhlfürß P, Voigt I, Hamel Ch, Seidel-Morgenstern A (2008) Transport of binary water-ethanol mixtures through a multilayer hydrophobic zeolite membrane. J Membrane Sci 307: 239–248Google Scholar
  135. [135]
    Weyd M, Richter H, Kühnert, J-K, Voigt I, Tusel E, Brüschke H (2010) Effizeinet Entwässerung von Ethanol durch Zeolithmembranen in Vierkanalgeometrie. Chem Ing Tech 82: 1257–1260Google Scholar
  136. [136]
    Wiendahl M, Schulze Wierling P, Nielsen J, Fomsgaard Christensen D, Krarup J, Staby A, Hubbuch J (2008) High throughput screening for the design and optimization of chromatographic processes – miniaturization, automation and parallelization of breakthrough and elution studies. Chem Eng Technol 31(6): 893–903Google Scholar
  137. [137]
    Willke T, Vorlop K-D (2001) Biotechnological production of itaconic acid. Appl Microbiol Biotechnol 56: 289–295PubMedGoogle Scholar
  138. [138]
    Willson RC (1985) Supercritical fluid extraction. Comprehensive Biotechnology 2: 567–574Google Scholar
  139. [139]
    Wohlgemuth K (2012) Induced Nucleation Processes during Batch Cooling Crystallisation. Dissertation Technische Universität DortmundGoogle Scholar
  140. [140]
    Wyss A, von Stockar V, Marison IW (2004) Production and characterisation of liquid-core capsules made from cross-linked acrylamid copolymers for biotechnological applications. Biotechnol Bioeng 5: 563–572Google Scholar
  141. [141]
    Yap BHJ, Dumsday GJ, Scales PJ, Martin GJO (2014) Energy evaluation of algal cell disruption by high pressure homogenization. Bioresour Technol In pressGoogle Scholar
  142. [142]
    Zhou JX, Solamo F, Hong T, Shearerer M, Tressel T, (2008) Viral Clearance using disposable systems in monoclonal antibody commercial downstream processing. Biotechnol Bioeng 100(3): 488–496PubMedGoogle Scholar

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© Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.MünchenDeutschland

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