Current Research

Group members & research projects currently undertaken.

Impression: Lab of...High-Throughput Process Development (Delta, 11/04/2013)

State-of-the-Art Services...

Via Marlin Biopurification, a service centre at TU Delft, we provide professional services on high-throughput screening (HTS), purification process development and characterization.

Hybrid HTPD Explained

Interview Marcel Ottens on HTPD at the BioProcess International Conference, Prague, CZ, 2014

Extended Video Abstract of Nfor, et al, Multi-Dimensional Fractionation and Characterization of Crude Protein Mixtures: Toward Establishment of a Database of Protein Purification Process Development Parameters, Biotechnology & Bioengineering, 109(12), 2012 

Chip Technology

On-chip chromatography and particle & cell handling. Hoon, et all, Programmable v-type valve for cell and particle manipulation in microfluidic devices, Lab Chip, 2016, 16, 305-311, DOI: 10.1039/C5LC01206F

Deshpande, et all, Biofunctionalization and self-interaction chromatography in PDMS microchannels, Biochemical Engineering Journal, 67, 111-119, 2012

Häusler, et all, Microfluidic diffusion coefficient measurements: The optimal H-cell, Chemical Engineering Science, 72, 45-50, 2012 

Dr.ir. Marcel Ottens, PDEng

Professor High Throughput Process Development (HTPD) & Complex Molecules Separation

Delft University of Technology

 

Contact information
Mail address: Department of Biotechnology, van der Maasweg 9, 2629 HZ Delft, The Netherlands
Email address: m.ottens@remove-this.tudelft.nl
Web address: http://www.bt.tudelft.nl/
Office phone: +31 15 278 2151
Fax: +31 15 2782355

The Ottens Lab

The Ottens Lab focuses on the following research fields:

  • Micro bio systems technology and micro fluidics
  • Bioprocess equipment miniaturization,
  • General phase behavior of biomaterials, including crystallization and precipitation,
  • Protein separation, purification and characterization,
  • Fast conceptual bio(pharma)process design (HTPD), and bioprocess integration,
  • Process chromatography of biologicals and nutraceuticals,
  • Continuous bioprocessing (e.g. Simulated Moving Bed technology), 
  • Transport phenomena and bioseparation science.

Research covers both experimental and theoretical grounds - detailed molecular / mesa / macro modeling and experimental data acquisition, verification, etcetera, and applied mainly to the field of biopharmaceuticals and nutraceuticals.

A special interest in our research is the combination of biotechnology/biophysics and micro systems. This combination is useful for studying and quantifying phenomena that determine the behavior of large-scale bioprocesses. But also it allows measuring interaction at the single molecule level, allowing bio molecular information to be retrieved which otherwise would remain impossible to obtain. This field is appropriately named Micro-Bio-Systems Technology (MBST). This combination is for example present in the field of biosensors development and application, which is an important topic in the emerging field of Process Analytical Techniques (PAT) and in diagnostics in the bio-medicinal sciences. It allows for measuring any kind of interactions that play a role in biology, medicine, pharmacology or biotechnology. The development of on-chip technologies for these applications is a main driver.

Small scale screening devices are developed that are used in combination with robotic High Throughput Screening (HTS) and detailed modeling for large scale Process Development for the purification of biologicals: High Throughput Process Development (HTPD).

Process Chromatography (PC), as opposed to analytical chromatography, deals with the separation of mixtures of near-identical bio-molecules on production scale. Since many bio-molecules are pharmaceutical intermediates, high-resolution separation technology such as process chromatography is crucial. The group's research focuses on the rational development of conventional and novel chromatographic systems as well as continuous counter-current chromatography, e.g. Simulated Moving Bed technology.

Teaching and course information

Recent courses taught within the MST and LST tracks at BSc and MSc level

  • Bio-Process Integration (BPI), LM3452, 6 ECTS
  • Bio-Pharmaceutical Technology (BFT), LB1081, 3 ECTS
  • Bio-Systems Engineering (BE), LB2911-cf, 4 ECTS
  • Transport Phenomena in Living Systems (TLS), LB2531, 5 ECTS
  • Advanced Course Downstream Processing (ACDSP), ST6502, 1 ECTS
  • Bio-Separations (BS), BE3191TU, 3 ECTS
  • Practical Biotechnology 2, LB2791-P, 4 ECTS
  • VLAG course Isolation Industrial Proteins, 1 ECTS
  • OSPT MAS course Affinity Chromatography, 1 ECTS
  • PAO Pharmacy QA/QC course, “Quality and Safety for the manufacturing of Biopharmaceuticals – form cell line development to downstream processing and formulation”, 1 ECTS

Publications

Double refereed full papers in scientific journals:

  1.  Hoon Suk Rho, Yoonsun Yang, Hanke AT, Ottens M, Terstappen LWMM, Gardeniers JGE, Programmable V-type Valve for Cell and Particle Manipulation in Microfluidic Devices, Lab Chip, 2016, 16, 305-311, doi: 10.1039/C5LC01206F
  2. Hanke AT, Klijn ME, Verhaert PDEM, van der Wielen LAM, van de Sandt EJAX, Eppink MHM, Ottens M, Prediction of protein retention times in hydrophobic interaction chromatography by robust statistical characterization of their atomic-level surface properties, Biotechnology Progress, 2015, doi: 10.1002/btpr.2219
  3. Hanke AT, Verhaert PDEM, van der Wielen LAM, Eppink, MHM, van de Sandt EJAX, Ottens, M, Fourier transform assisted deconvolution of skewed peaks in complex multi-dimensional chromatograms, J Chromatogr. A, 1394, 54-61, 2015
  4. Kittelmann, J, Ottens, M, Hubbuch, J, Robust high-throughput batch screening method in 384-well format with optical in-line resin quantification, J Chromatogr B, 988, 98-105, 2015
  5. Hanke AT, Ottens M., Purifying biopharmaceuticals: knowledge-based chromatographic process development., Trends Biotechnol., 32(4), 210-220, 2014, doi: 10.1016/j.tibtech.2014.02.001
  6. Glassey J, Ottens M., Editorial: Industrial Biotechnology - technologies and methods for rapid process development, Biotechnol J. 2014 9(6), 711-712, 2014, doi: 10.1002/biot.201400304
  7. Chilamkurthi S, Sevillano DM, Albers LH, Sahoo MR, Verheijen PJ, van der Wielen LA, den Hollander JL, Ottens M., Thermodynamic description of peptide adsorption on mixed-mode resins, J Chromatogr A. 1341, 41-49, 2014, doi: 10.1016/j.chroma.2014.03.031.
  8. Sevillano DM, Jankowiak L, van Gaalen TLT, van der Wielen LAM, Hooshyar N, van der Goot AJ, Ottens M., Mechanism of Isoflavone Adsorption from Okara Extracts onto Food-Grade Resins, Ind. Eng. Chem. Res, 53(39), 15245–15252, 2014, dx.doi.org/10.1021/ie5026419
  9. Sevillano DM, van der Wielen LAM, Hooshyar N, Ottens M, MPP-UNIFAC, A Predictive Activity Coefficient Model for Polyphenols, Fluid Phase Equilibria, 384, 82–88, 2014, doi: 10.1016/j.fluid.2014.10.020
  10. Ottens M, Fee C, Advances in bioseparations for food and bioprocessing, Food and Bioproducts Processing, 92(2), , 99-100, 2014, doi: 10.1016/j.fbp.2014.03.010
  11. Sevillano DM, van der Wielen LAM, Hooshyar N, Ottens M., Resin selection for the separation of caffeine from green tea catechins, Food and Bioproducts Processing, 92 (2), 192–198, 2014, doi: 10.1016/j.fbp.2014.02.002
  12. Sevillano DM, van der Wielen LAM, Trifunovic O, Ottens M, Model Comparison for the Prediction of the Solubility of Green Tea Catechins in Ethanol/Water Mixtures, Ind. Eng. Chem. Res., 52(17), 6039−6048, 2013
  13. Kröner F, Hanke AT, Nfor BK, Pinkse MW, Verhaert PD, Ottens M, Hubbuch J, Analytical characterization of complex, biotechnological feedstocks by pH gradient ion exchange chromatography for purification process development, J Chromatogr A., 1311, 55-64, 2013
  14.  Besselink, T, Liu, M, Ottens, M, van Beckhoven, R, Janssen, AE, Boom, RM, Comparison of activated chromatography resins for protein immobilization, J Sep Sci., 36(7), 1185-91, 2013
  15.  Nfor, BK, Ahamed, T, van Dedem, GWK, Verhaert, PDEM, van der Wielen, LAM, Eppink, MHM, van de Sandt, EJAX, Ottens, M, Model-based rational methodology for protein purification process synthesis, Chemical Engineering Science, 89, 185–195, 2013
  16.  Nfor, BK, Ahamed, T, Pinkse, MWH, van der Wielen, LAM, Verhaert, PDEM, van Dedem, GWK, Eppink, MHM, van de Sandt, EJAX, Ottens, M, Multi-Dimensional Fractionation and Characterization of Crude Protein Mixtures: Toward Establishment of a Database of Protein Purification Process Development Parameters, Biotechnology & Bioengineering, 109(12), 2012
  17.  Nfor, BK, Ripic, J, van der Padt, A, Jacobs, M, Ottens, M, Model-based high-throughput process development for chromatographic whey proteins separation, Biotechnol. J., 7, 1221–1232, 2012
  18.  Li, X, de Roo, G, Burgers, K, Ottens, M, Eppink, MHM, Self-packed filter plates: A good alternative for pre-packed filter plates for developing purification processes for therapeutic proteins, Biotechnol. J., 7, 1269–1276, 2012
  19.  Deshpande, KS, Kuddannaya, S, Staginus, J, Thüne, PC, de Smet, LCPM, ter Horst, JH, van der Wielen, LAM, Ottens, M, Biofunctionalization and self-interaction chromatography in PDMS microchannels, Biochemical Engineering Journal, 67, 111-119, 2012
  20.  López-Garzón, CS, Ottens, M, van der Wielen, LAM, Straathof, AJJ, Direct downstream catalysis: From succinate to its diethyl ester without intermediate acidification, Chemical Engineering Journal, 200–202, 637–644, 2012
  21.  Häusler, E, Domagalski, P, Ottens, M, Bardow, A, Microfluidic diffusion coefficient measurements: The optimal H-cell, Chemical Engineering Science, 72, 45-50, 2012
  22.  Chilamkurthi, S, Willemsen, J.H., van der Wielen, L.A.M., Poiesz, E., Ottens, M., High-throughput determination of adsorption equilibria for chromatographic oligosaccharide separations, J Chromatogr. A, 1239, 22– 34, 2012
  23.  Freydell, EJ, van der Wielen, LAM, Eppink, MHM, and Ottens M., Techno-Economic Evaluation of an Inclusion Body Solubilization and Recombinant Protein Refolding Process, Biotechnology Progress, 27(5), 1315, 2011
  24.  Nfor, BK, Hylkema, NN, Wiedhaup, KR, Verhaert, PDEM, van der Wielen, LAM, Ottens, M. High-throughput protein precipitation and hydrophobic interaction chromatography: Salt effects and thermodynamic interrelation, J Chromatogr. A, 1218, 8958, 2011
  25.  Nfor, BK, Zuluaga, DS, Verheijen, PJT, Verhaert, PDEM, van der Wielen, LAM, and Ottens, M, Model-Based Rational Strategy for Chromatographic Resin Selection, Biotechnology Progress, 27(6), 1629, 2011
  26.  Freydell, EJ, van der Wielen, LAM, Eppink, MHM, and Ottens M., Size-exclusion chromatographic protein refolding: Fundamentals, modeling and operation operation, J Chromtogr. A, 1217(49), 7723-7737, 2010
  27.  Freydell, EJ, van der Wielen, LAM, Eppink, MHM, and Ottens M., Ion-exchange chromatographic protein refolding, J Chromtogr. A, 1217(46), 7265-7274, 2010
  28.  Freydell E.J., Bulsink Y, van Hateren S.H., van der Wielen L.A.M., Eppink M.H.M., Ottens M., Size-exclusion simulated moving bed chromatographic protein refolding, Chemical Engineering Science, 65, 4701–4713, 2010
  29.  B.K. Nfor, M. Noverraz, S. Chilamkurthi, P.D.E.M. Verhaert, L.A.M. van der Wielen, M. Ottens, High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents, J Chromatogr. A., 1217(44), 6829-6850, 2010
  30.  Nfor, BK, Verhaert, PDEM, van der Wielen, LAM, Hubbuch, JJ, Ottens, M, Rational and systematic protein purification process development: the next generation, Trends in Biotechnology, 27(12), 673-679, 2009
  31.  van Leeuwen M, Li X, Krommenhoek EE, van Gulik WM, Gardeniers JGE, Ottens M, van der Wielen LAM, Heijnen JJ, Quantitative determination of glucose transfer between cocurrent, laminar flowing water streams in H-shaped microchannel diffusion in a microchip, Biotechnology Progress,2009, DOI: 10.1002/btpr.271
  32.  Li, X, G. van der Steen, G.W.K . van Dedem, L.A.M. van der Wielen, M. van Leeuwen, W.M. van Gulik, J.J. Heijnen, E.E. Krommenhoek, J.G.E. Gardeniers, A. van den Berg and M. Ottens, Application of direct fluid flow oscillations to improve mixing in micro bioreactors, AICHEJ,55(10), 2725-2736, 2009
  33.  Tashima, AK, M Ottens, LAM Van der Wielen, DE Cyntra, JR. Pauli, P de Alcantara Pesso a Filho, E Alves Miranda, Precipitation of Porcine Insulin With Carbon Dioxide, Biotechnology & Bioengineering, 2009, 103(5), 909-919
  34.  Deshpande, K., T. Ahamed, LAM. van der Wielen J. Horst,P. Jansens and M. Ottens ,The use of Self Interaction Chromatography in stable formulation and crystallization of proteins, Biotechnology Journal, 4(9), 1266-1277, 2009
  35.  Deshpande, K., T. Ahamed, LAM. van der Wielen J. Horst,P. Jansens and M. Ottens, Protein self-interaction chromatography on a microchip, Lab-on-a-chip, 9, 600, 2009
  36.  Woodley JM, Bisschops M, Straathof AJJ, Ottens M, Future directions for in-situ product removal (ISPR), J Chem Technol Biotechnol, 83(2), 121-123, 2008
  37.  Nfor, BK, Ahamed, T, van Dedem, GWK, van der Wielen, LAM, van de Sandt, EJAX, Eppink, MHM and Ottens, M, Design strategies for integrated protein purification processes: challenges, progress and outlook - Review, J Chem Technol Biotechnol, 83(2), 124–132, 2008
  38.  Ahamed, T, Chilamkurthi S, Nfor BK, Verhaert PDEM, van Dedem GWK, van der Wielen LAM, Eppink MHM, van de Sandt EJAX, Ottens, M, Selection of pH-related parameters in ion-exchange chromatography using pH-gradient operations, J Chromtogr. A, 1194(1), 22-29, 2008
  39.  Li, X, G. van der Steen, G.W.K . van Dedem, L.A.M. van der Wielen, M. van Leeuwen, W.M. van Gulik, J.J. Heijnen, E.E. Krommenhoek, J.G.E. Gardeniers, A. van den Berg and M. Ottens, Improving mixing in micro bioreactors, Chem Eng. Sci., 63, 3036-3046, 2008
  40.  Krommenhoek, EE, van Leeuwen, M Gardeniers, JGE, van Gulik, WM, van den Berg, A, Li, X, Ottens, M, van der Wielen, LAM, Heijnen, JJ, Lab-Scale Fermentation Tests of Microchip With Integrated Electrochemical Sensors for pH, Temperature, Dissolved Oxygen and Viable Biomass Concentration, Biotechnol.Bioeng. 99, 2008, 884–892
  41.  Golubovic, M.; van Hateren, S. H.; Ottens, M.; Witkamp, G. J.; van der Wielen, L. A. M. A method for lipase co-precipitation in a biodegradable protein matrix, Biotechnol. Bioeng (2007), 98(6), 1209-1218.
  42.  Ahamed, Tangir; Nfor, Beckley K.; Verhaert, Peter D. E. M.; van Dedem, Gijs W. K.; van der Wielen, Luuk A. M.; Eppink, Michel H. M.; van de Sandt, Emile J. A. X.; Ottens, Marcel. PH-gradient ion-exchange chromatography: An analytical tool for design and optimization of protein separations. J Chromatogr A (2007), 1164(1-2), 181-188.
  43.  Ahamed, Tangir; Esteban, Beatriz N. A.; Ottens, Marcel; van Dedem, Gijs W. K.; van der Wielen, Luuk A. M.; Bisschops, Marc A. T.; Lee, Albert; Pham, Christine; Thoemmes, Joerg. Phase behavior of an intact monoclonal antibody. Biophysical J (2007), 93(2), 610-619. 
  44.  Freydell, Esteban J.; Ottens, Marcel; Eppink, Michel; van Dedem, Gijs; van der Wielen, Luuk. Efficient solubilization of inclusion bodies. Biotechnology J (2007), 2(6), 678-684.
  45.  Horneman, D. A.; Ottens, M.; Keurentjes, J. T. F.; van der Wielen, L. A. M. Surfactant-aided size-exclusion chromatography for the purification of immunoglobulin G, J Chromatogr A  (2007), 1157(1-2), 237-245.
  46.  Krommenhoek, E. E.; Gardeniers, J. G. E.; Bomer, J. G.; Li, X.; Ottens, M.; van Dedem, G. W. K.; Van Leeuwen, M.; Van Gulik, W. M.; Van der Wielen, L. A. M.; Heijnen, J. J.; Van den Berg, A. Integrated Electrochemical Sensor Array for On-Line Monitoring of Yeast Fermentations. Anal Chem (2007), 79(15), 5567-5573.
  47.  Horneman, D. A.; Ottens, M.; van der Wielen, L. A. M.; Keurentjes, J. T. F. Viral clearance using surfactant-aided size-exclusion chromatography. AIChE J (2007), 53(6), 1441-1449.
  48.  Ahamed T, Ottens M, van Dedem GWK, and van der Wielen LAM, Design of self-interaction chromatography as an analytical tool for predicting protein phase behavior (vol 1089, pg 111, 2005), J Chromatogr A, 1115 (1-2): 272-272 2006
  49.  Ottens M, Houwing J, Van Hateren SH, van Baalen T and van der Wielen LAM, Multi-component fractionation in SMB chromatography for the purification of active fractions from protein hydrolysates, Food Bioprod Proc84 (C1): 59-71 2006
  50.  Krommenhoek EE, Gardeniers JGE, Bomer JG, Van den Berg A, Li X, Ottens M, van der Wielen LAM, van Dedem GWK, Van Leeuwen M, van Gulik WM, Heijnen JJ, Monitoring of yeast cell concentration using a micromachined impedance sensor, Sens Act B-Chem, 115 (1): 384-389 2006
  51.  Horneman DA, Ottens M, Keurentjes JTF, van der Wielen LAM, Micellar gradients in size-exclusion simulated moving bed chromatography, J Chromatogr A, 1113 (1-2): 130-139 2006
  52.  Ahamed T, Ottens M, Nfor BK, van Dedem GWK, and van der Wielen LAM, A generalized approach to thermodynamic properties of biomolecules for use in bioseparation process design, Fluid Phase Equil, 241 (1-2): 268-282 2006
  53.  Ferreira, Juliana S.; Straathof, Adrie J. J.; Li, Xiaonan; Ottens, Marcel; Franco, Telma T.; van der Wielen, Luuk A. M. Solution Crystallization Kinetics of 6-Aminopenicillanic Acid, IECR (2006), 45(20), 6740-6744.
  54.  Golubovic, M; van Hateren, SH; Ottens, M; Witkamp GJ, van der Wielen LAM, Novel method for the production of pure glycinin from soybeans, J. Agri. Food Chem., 53 (13): 5265-5269 2005
  55.  Ahamed, T; Ottens, M; van Dedem, GWK; and L.A.M. van der Wielen, Design of self-interaction chromatography as an analytical tool for predicting protein phase behavior, J.Chromatogr. A, 1089 (1-2): 111-124 2005
  56.  E.E. Krommenhoek, J.G.E. Gardeniers, J.G. Bomer, A. Van den Berg, X. Li, M. Ottens, L.A.M. van der Wielen, G.W.K. van Dedem, M. Van Leeuwen, W.M. van Gulik and J.J. Heijnen, Monitoring of yeast cell concentration using a micromachined impedance sensor, Sensors and Actuators B, published online 9 November 2005
  57.  Breil MP, Mollerup JM, Rudolph ESJ, Ottens M, van der Wielen LAM, Densities and solubilities of glycylglycine and glycyl-L-alanine in aqueous electrolyte solutions, Fluid Phase Equil, 215 (2): 221-225, 2004
  58.  Maia MLO, Ottens M, van der Wielen LAM, Exergy analysis of chromatographic separations in a fixed-bed column, IECR, 43 (12): 3183-3193, 2004
  59.  D.A. Horneman, M. Ottens, J.T.F. Keurentjes and L.A.M. van der Wielen, “Surfactant aided size exclusion chromatography”, J Chromatogr B, 807 (1): 39-45, 2004
  60. S choevaart R, Wolbers MW, Golubovic M, Ottens M, Kieboom APG, van Rantwijk F, van der Wielen LAM, Sheldon RA, Preparation, optimization, and structures of cross-linked enzyme aggregates (CLEAs), Biotechnol. Bioeng, 87 (6): 754-762, 2004
  61.  Danielle A. Horneman, Marcel Ottens, Marieke Hoorneman, Luuk A. M. van der Wielen, Martijn Tesson, Reaction and diffusion during demineralization of animal bone, AIChEJ, 50 (11), 2682-2690, 2004
  62.  M. Ottens, B. Lebreton, M. Zomerdijk, M. P. W. M. Rijkers, O. S. L. Bruinsma, and L. A. M van der Wielen, Impurity Effects on the Crystallization Kinetics of Ampicillin, IECR, 43 (24): 7932 – 7938, 2004
  63.  Y. Zhou, M. Ottens, E. Hansen and L.A.M. van der Wielen, Human insulin and desamido human insulin isotherms in ethanol-water reversed phase systems, J Chromatogr A, 1061/2, 143-150, 2004
  64.  Winkelman JGM, Voorwinde OK, Ottens M, Beenackers AACM, Janssen LPBM, Kinetics and chemical equilibrium of the hydration of formaldehyde, Chem Eng. Sci., 57 (19): 4067-4076, 2002
  65.  Ottens M, Lebreton B, Zomerdijk M, Rijkers MPWM., Bruinsma OSL, van der Wielen LAM, Crystallization Kinetics of Ampicillin, IECR: 40 (22): 4821-4827, 2001
  66.  Ottens M, Hoefsloot HCJ, Hamersma PJ, Correlations predicting liquid hold-up and pressure gradient in steady-state (nearly) horizontal co-current gas-liquid pipe flow, Chem Eng Res Des.79: (A5) 581-592, 2001
  67.  Ottens M, Hoefsloot HCJ, Hamersma PJ, Transient gas-liquid flow in horizontal T-junctions, Chem Eng. Sci. 56: (1) 43-55, 2001
  68.  Breil MP, Mollerup JM, Rudolph ESJ, Ottens M, van der Wielen LAM, Determination of the activity coefficients of glycylglycine and glycyl-L-alanine in sodium chloride solutions by an electrochemical cell with ion-selective electrodes: experimental measurements and thermodynamic theory, Fluid Phase Equil.191 (1-2): 127-140, 2001
  69.  Cabatingan LK, Agapay RC, Rakels JLL, Ottens M, van der Wielen LAM, Potential of biosorption for the recovery of chromate in industrial wastewaters, IECR, 40: (10) 2302-2309, 2001
  70.  Rudolph ESJ, Zomerdijk M, Ottens M, van der Wielen LAM, Solubilities and partition coefficients of semi-synthetic antibiotics in water+1-butanol systems, IECR, 40: (1) 398-406, 2001
  71.  Ottens M, Leene G, Beenackers AACM, Cameron N, Sherrington DC, PolyHipe: A new polymeric support for heterogeneous catalytic reactions: Kinetics of hydration of cyclohexene in two- and three-phase systems over a strongly acidic sulfonated PolyHipe, IECR, 39: (2) 259-266, 2000.
  72.  van Berlo M, Ottens M, Luyben KCAM, van der Wielen LAM, Feasible boundaries of aqueous two-phase systems with NH3 and CO2 as recyclable volatile salts, Biotechnol. Bioeng, 70: (1) 65-71, 2000.
  73.  Winkelman JGM, Ottens M, Beenackers AACM, The kinetics of the dehydration of methylene glycol, Chem Eng. Sci. 55: (11) 2065-2071, 2000.
  74.  van Berlo M, Ottens M, Luyben KCAM, van der Wielen LAM, Partitioning behavior of amino acids in aqueous two-phase systems with recyclable volatile salts, J Chromatogr B, 743: (1-2) 317-325, 2000.
  75.  Ottens M, Hoefsloot HCJ, Hamersma PJ, Effect of small branch inclination on gas-liquid flow separation in T junctions, AIChEJ, 45 (3): 465-474, 1999
  76.  Ottens M, Klinkspoor K, Hoefsloot HCJ, Hamersma, PJ, Wave characteristics during cocurrent gas-liquid pipe flow, Exp Therm Fluid Sci., 19 (3): 140-150, 1999.

Patents 

  • Golubovic, M, Ottens, M; Witkamp GJ, van der Wielen LAM, Preparation of a protein aggregate, useful for pharmaceutical applications, comprises acidification of an aqueous solution of the protein, Delft University of Technology.

Patent Number

Publ. Date

Main IPC

WO2005087016-A1

22 Sep 2005

A23J-003/16

NL1025723-C2

16 Sep 2005

A23J-003/28

EP1727436-A1

06 Dec 2006

A23J-003/00A23J-003/16

BR200508853-A

28 Aug 2007

A23J-003/00A23J-003/16

  • Golubovic, M, Ottens, M; Witkamp GJ, van der Wielen LAM, WO2005087016-A1; NL1025723-C2, Preparation of a protein aggregate, useful for pharmaceutical applications, comprises acidification of an aqueous solution of the protein, Delft University of Technology
  • Werkwijze voor de bereiding van een eiwitaggregaat en een farmaceutisch preparaat, M. Golubovic, M. Ottens, G.J. Witkamp and L.A.M. van der Wielen, Dutch Patent Application 1025723 (application date: 15-3-2004)
  • Separation method for bioparticles, D.A. Horneman, M. Ottens, LJP van den Broeke, van Roosmalen, J.T.F. Keurentjes and L.A.M. van der Wielen, European Patent Application 03076960.8 (application date: 23-6-2003)

Books

  • Proceeding of the International Conference on Biopartitioning and Purification, BPP2005, June 20-14, 2005, Editors: T. Ahamed, M. Ottens and L.A.M. van der Wielen, ISBN 90-809691-2-5
  • Ottens, M. PhD Thesis, "Gas-Liquid Flow in Pipes and T-junctions", Oct. 1998, Amsterdam ISBN 90-5651-055-X.

Chapters in books

  • “Protein and Peptide Purification”, Beckley K. Nfor, Esteban Freydell and Marcel Ottens, Chapter 8 in “Biological Drug Products: Development and Strategies”, Editors Wei Wang &, Manmohan Singh, ISBN: 978-1-118-14889-1, November 2013
  • Advances in Process Chromatography, by Marcel Ottens and Sreekanth Chilamkurti, Chapter 4 in Separation, extraction and concentration processes in the food, beverage and nutraceutical industries, Editor: S.S.H. Rizvi, Cornell University, Woodhead Publishing, in preparation, 2010
  • Downstream Processing in Biotechnology, by Marcel Ottens, Johannes A. Wesselingh, Luuk A.M. van der Wielen, Chapter 9 in Basic Biotechnology, edited by Ratledge and Kristiansen, 3rd edition, 2006, Cambridge University Press.
  • Horneman, D.A., Ottens, M., Tesson, M, and van der Wielen, L.A.M., Improving Gelatin Plant Productivity by Modelling the Demineralization Process of Animal Bones, European Symposium on Computer Aided Process Engineering 12, Ed. Grievink and van Schijndel, in Computer-Aided Chemical Engineering, 10, p691, 2002, ISBN: 0-444-51109-1
  • Ottens, M., Straathof, A.J.J. and van der Wielen, L.A.M., Process Technology and Process Integration in the Preparation of Penicillins, In Synthesis of b-lactam antibiotics, ISBN 0-7923-7060-0, edited by Ale Bruggink, Kluwer Academic Publishers, Dordrecht, 2001
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