Novel oscillatory flow reactors for biotechnological applications

Abstract This thesis explores the biotechnological applications of two novel scale-down oscillatory flow reactors (OFRs). A micro-bioreactor (working mostly in batch) and a continuous meso-reactor systems were developed based on a 4.4 mm internal diameter tube with smooth periodic constrictions (SPC), both operating under oscillatory flow mixing (OFM). The first part is dedicated to the flow characterisation in the novel SPC geometry. Flow patterns within SPC geometry were experimentally studied usi

[1]  X. Ni,et al.  Effect of hydrodynamics on mass transfer in a gas–liquid oscillatory baffled column , 2004 .

[2]  J. Higdon,et al.  Oscillatory flow of droplets in capillary tubes. Part 1. Straight tubes , 2000, Journal of Fluid Mechanics.

[3]  X. Ni,et al.  Flow patterns and oil—water dispersion in a 0.38 m diameter oscillatory baffled column , 2000 .

[4]  P. Tabeling,et al.  Chaotic mixing in cross-channel micromixers , 2004, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[5]  Francesco Ballio,et al.  Three-dimensional analysis of the unidirectional oscillatory flow around a circular cylinder at low Keulegan–Carpenter and $\beta$ numbers , 2004, Journal of Fluid Mechanics.

[6]  Cooling of micro spots by oscillatory flows , 2004 .

[7]  Martin Rhodes,et al.  Using pulsed flow to overcome defluidization , 2005 .

[8]  Malcolm R. Mackley.  Process innovation using oscillatory flow within baffled tubes , 1991 .

[9]  Gabriel Wild,et al.  Measuring Techniques in Gas—Liquid and Gas—Liquid—Solid Reactors , 2003 .

[10]  T. Howes,et al.  Simulation of mixing in unsteady flow through a periodically obstructed channel , 1997 .

[11]  Michael Mccoy,et al.  BIOCATALYSIS GROWS FOR DRUG SYNTHESIS: Fine chemicals makers are increasingly using enzymatic methods to make chiral intermediates , 1999 .

[12]  X. Ni,et al.  Experimental flow visualisation in a modified pulsed baffled reactor. , 1997 .

[13]  Manuel J T Carrondo,et al.  Biochemical engineering. , 2004, Current opinion in biotechnology.

[14]  Malcolm R. Mackley,et al.  Experimental observations on flow patterns and energy losses for oscillatory flow in ducts containing sharp edges , 1989 .

[15]  L. Mazzolai,et al.  Tissue Factor Activity Is Upregulated in Human Endothelial Cells Exposed to Oscillatory Shear Stress , 2002, Thrombosis and Haemostasis.

[16]  Adam Harvey,et al.  Oscillatory flow : a technology ready to deliver , 2001 .

[17]  Xiongwei Ni,et al.  Correlation of polymer particle size with droplet size in suspension polymerisation of methylmethacrylate in a batch oscillatory-baffled reactor , 1999 .

[18]  Linda M. Harvey,et al.  Monitoring of Submerged Bioprocesses , 1999 .

[19]  Tony Howes,et al.  On the effect of tracer density on axial dispersion in a batch oscillatory baffled column , 2002 .

[20]  K. Jung.  Continuous production of recombinant interferon-α in Escherichia coli via the derepression of trp promoter using casamino acid , 2006 .

[21]  F. Durst,et al.  Asymmetric flows and instabilities in symmetric ducts with sudden expansions , 1978, Journal of Fluid Mechanics.

[22]  Malcolm R. Mackley,et al.  The mixing and separation of particle suspensions using oscillatory flow in baffled tubes , 1993 .

[23]  O. Käppeli,et al.  Regulation of glucose metabolism in growing yeast cells. , 1981, Advances in microbial physiology.

[24]  X. Ni,et al.  A study of bubble velocity and bubble residence time in a gassed oscillatory baffled column effect of oscillation frequency , 2003 .

[25]  Malcolm R. Mackley,et al.  The simulation of stretch rates for the quantitative prediction and mapping of mixing within a channel flow , 1995 .

[26]  Clive A. Greated,et al.  Experimental Investigation of Bentonite Flocculation in a Batch Oscillatory Baffled Column , 1998 .

[27]  C. A. Greated,et al.  Measurements of velocities of single particles for steady and oscillatory flows in plain and baffled tubes , 1995 .

[28]  A. C. Jealous,et al.  POWER REQUIREMENTS FOR PULSE GENERATION IN PULSE COLUMNS , 1955 .

[29]  Turgut Sarpkaya,et al.  Experimental Determination of the Critical Reynolds Number for Pulsating Poiseuille Flow , 1966 .

[30]  Birth of three-dimensionality in a pulsed jet through a circular orifice , 2003, Journal of Fluid Mechanics.

[31]  H. Brauer.  Growth of fungi and bacteria in the reciprocating jet bioreactor , 1990 .

[32]  Malcolm R. Mackley,et al.  Experimental residence time distribution measurements for unsteady flow in baffled tubes , 1989 .

[33]  R. Greasham,et al.  Chemically defined media for commercial fermentations , 1999, Applied Microbiology and Biotechnology.

[34]  F. Sinada,et al.  Physical and chemical characteristics of the Blue Nile and the White Nile at Khartoum , 1984, Hydrobiologia.

[35]  Cedric Briens,et al.  A new stochastic model and measurement errors in residence time distributions of multiphase reactors , 1995 .

[36]  Yusuf Chisti,et al.  Oxygen transfer and mixing in mechanically agitated airlift bioreactors , 2002 .

[37]  Malcolm R. Mackley,et al.  Process and product innovation , 2003 .

[38]  P. Stonestreet,et al.  Energy dissipation in oscillatory flow within a baffled tube , 1995 .

[39]  Murray Moo-Young,et al.  Comprehensive biotechnology : the principles, applications, and regulations of biotechnology in industry, agriculture, and medicine , 1987 .

[40]  T. Nishimura,et al.  Mass transfer characteristics in a channel with symmetric wavy wall for steady flow. , 1985 .

[41]  Effect of turbulence on Taylor dispersion for oscillatory flows , 2002 .

[42]  F. Sinada,et al.  A quantitative study of the phytoplankton in the Blue and White Niles at Khartoum , 1984, Hydrobiologia.

[43]  Anton P. J. Middelberg,et al.  The influence of mixing on lysozyme renaturation during refolding in an oscillatory flow and a stirred-tank reactor , 2002 .

[44]  Xiongwei Ni,et al.  Parameters affecting fluid dispersion in a continuous oscillatory baffled tube , 2000 .

[45]  Xiongwei Ni,et al.  Computational fluid dynamic modelling of flow patterns in an oscillatory baffled column , 2002 .

[46]  Ian Sobey.  The occurrence of separation in oscillatory flow , 1983 .

[47]  T. Nishimura,et al.  Three-dimensionality of grooved channel flows at intermediate Reynolds numbers , 2001 .

[48]  Malcolm R. Mackley,et al.  Experimental fluid dispersion measurements in periodic baffled tube arrays , 1993 .

[49]  D. Skala,et al.  Mass transfer characteristics in a gas‐liquid reciprocating plate column. I. Liquid phase volumetric mass transfer coefficient , 1988 .

[50]  Malcolm R. Mackley,et al.  On eddy motions near plates and ducts, induced by water waves and periodic flows , 1980, Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences.

[51]  John J. J. Chen,et al.  Effects of an oscillating interface on heat transfer , 1997 .

[52]  Anharmonic analysis of arterial blood pressure and flow pulses. , 2005, Journal of biomechanics.

[53]  Deshusses,et al.  Innovative bioreactors. , 1997, Current opinion in biotechnology.

[54]  M. F. Edwards,et al.  Mixing in the process industries , 1985 .

[55]  J. Howell,et al.  The effect of pulsed flow on ultrafiltration fluxes in a baffled tubular membrane system , 1990 .

[56]  Y. Chisti,et al.  Hydrodynamic Damage to Animal Cells , 2001, Critical reviews in biotechnology.

[57]  M. Cheryan,et al.  Ethanol production in a hollow fiber bioreactor using Saccharomyces cerevisiae , 1984, Applied Microbiology and Biotechnology.

[58]  T. Mullin,et al.  Nonlinear flow phenomena in a symmetric sudden expansion , 1990, Journal of Fluid Mechanics.

[59]  Y. Hirata,et al.  Mixing Performance by Reciprocating Disk in Cylindrical Vessel , 2000 .

[60]  Gary Walsh,et al.  Biopharmaceuticals: recent approvals and likely directions. , 2005, Trends in biotechnology.

[61]  M. Baird,et al.  Power consumption and gas hold-up in a pulsed column , 1967 .

[62]  Xiongwei Ni,et al.  On the determination of axial dispersion coefficient in a batch oscillatory baffled column using laser induced fluorescence , 2003 .

[63]  H. Uehara,et al.  Linear stability analysis of flow in a periodically grooved channel , 2003 .

[64]  The development of asymmetry and period doubling for oscillatory flow in baffled channels , 1996 .

[65]  Hongbing Jian,et al.  An investigation of the effect of viscosity on mixing in an oscillatory baffled column using digital particle image velocimetry and computational fluid dynamics simulation , 2005 .

[66]  M. Shimizu,et al.  Augmented longitudinal diffusion in grooved tubes for oscillatory flow , 2001 .

[67]  T. Hasegawa,et al.  Response of concentrated suspensions under large amplitude oscillatory shear flow , 2005 .

[68]  James J. De Yoreo,et al.  Crystallization of Paracetamol under Oscillatory Flow Mixing Conditions , 2004 .

[69]  Anne Kahru,et al.  The computer-controlled continuous culture of Escherichia coli with smooth change of dilution rate (A-stat) , 1995 .

[70]  J. Fortuin,et al.  Solids holdup and axial dispersion during countercurrent solids-liquid contacting in a pulsed packed column containing structured packing , 1992 .

[71]  Aniruddha B. Pandit,et al.  Enhancement of gas-liquid mass transfer using oscillatory flow in a baffled tube , 1993 .

[72]  John Villadsen,et al.  Modelling of microbial kinetics , 1992 .

[73]  P. Stonestreet,et al.  Evaluation of a novel self‐aerating, oscillating baffle column , 1998 .

[74]  Jochen Büchs,et al.  A Novel Parallel Shaken Bioreactor System for Continuous Operation , 2004, Biotechnology progress.

[75]  D. Skala,et al.  Mass transfer characteristics in a gas–liquid reciprocating plate column. II. Interfacial area , 1988 .

[76]  Adam Harvey,et al.  A Mixing-Based Design Methodology for Continuous Oscillatory Flow Reactors , 2002 .

[77]  J. Büchs,et al.  Characterisation of the gas-liquid mass transfer in shaking bioreactors. , 2001, Biochemical engineering journal.

[78]  William Bains,et al.  Biotechnology from A to Z , 1993 .

[79]  C. Knowles,et al.  Gas transfer characteristics of a novel membrane bioreactor , 1991, Biotechnology and bioengineering.

[80]  J. S. Dennis,et al.  Mixing in Process Vessels Used in Biopharmaceutical Manufacturing , 2000, Biotechnology progress.

[81]  S. S. Sadhal.  Microgravity transport processes in fluid, thermal, biological, and materials sciences , 2002 .

[82]  Cila Herman,et al.  An Experimantal Study of Convective Heat Transfer Enhancement in a Grooved Channel Using Cylindrical Eddy Promoters , 2001 .

[83]  M. Baird,et al.  Scale-up of single phase axial dispersion coefficients in batch and continuous oscillatory baffled tubes , 2001 .

[84]  X. Ni,et al.  A study of velocity and residence time of single bubbles in a gassed oscillatory baffled column: Effect of oscillation amplitude , 2002 .

[85]  D. Cașcaval,et al.  Prediction of oxygen mass transfer coefficients in stirred bioreactors for bacteria, yeasts and fungus broths , 2004 .

[86]  Aaron M. Thomas,et al.  A comparison between the enhanced mass transfer in boundary and pressure driven oscillatory flow , 2002 .

[87]  Malcolm R. Mackley,et al.  Mixing and dispersion in a baffled tube for steady laminar and pulsatile flow , 1991 .

[88]  Tony Howes,et al.  THE SIMULATION OF CHAOTIC MIXING AND DISPERSION FOR PERIODIC FLOWS IN BAFFLED CHANNELS , 1991 .

[89]  Dimitris Drikakis,et al.  Instability in three-dimensional, unsteady, stenotic flows , 2002 .

[90]  R. A. Bajura,et al.  A Numerical Analysis of Pulsating Laminar Flow Through a Pipe Orifice , 1991 .

[91]  Malcolm R. Mackley,et al.  Experimental heat transfer measurements for pulsatile flow in baffled tubes , 1990 .

[92]  M. J. Joyce,et al.  A STUDY OF VELOCITY VECTOR PROFILE AND STRAIN RATE DISTRIBUTION FOR LAMINAR AND OSCILLATORY FLOWS IN A BAFFLED TUBE USING PARTICLE IMAGE VELOCIMETRY , 1995 .

[93]  O. Levenspiel.  Chemical Reaction Engineering , 1972 .

[94]  Adam Harvey,et al.  Operation and Optimization of an Oscillatory Flow Continuous Reactor , 2001 .

[95]  Xiongwei Ni,et al.  An investigation of droplet size and size distribution in methylmethacrylate suspensions in a batch oscillatory-baffled reactor , 1998 .

[96]  C.K. Lee,et al.  Pressure swing reactor for converting suspension of solid substrate p-hydroxyphenylhydantoin by immobilized d-hydantoinase , 1999 .

[97]  M. Baird,et al.  Power dissipation and flow patterns in reciprocating baffle‐plate columns , 1995 .

[98]  Vivek V. Ranade,et al.  Computational Flow Modeling for Chemical Reactor Engineering , 2001 .

[99]  S. Voropayev,et al.  Flow around a short horizontal bottom cylinder under steady and oscillatory flows , 2005 .

[100]  Dirk Weuster-Botz,et al.  Methods and milliliter scale devices for high-throughput bioprocess design , 2005, Bioprocess and biosystems engineering.

[101]  M. Baird,et al.  Characteristics of a countercurrent reciprocating plate bubble column. I. Holdup, pressure drop and bubble diameter , 1988 .

[102]  Y. Hirata,et al.  Characteristics of Laminar Flow Induced by Reciprocating Disk in Cylindrical Vessel , 2001 .

[103]  Takahiro Shibata,et al.  Differential Responses of the Nrf2-Keap1 System to Laminar and Oscillatory Shear Stresses in Endothelial Cells* , 2005, Journal of Biological Chemistry.

[104]  Malcolm R. Mackley,et al.  Chemical reaction in batch pulsatile flow and stirred tank reactors , 1993 .

[105]  Xiongwei Ni,et al.  Gas hold-up and bubble diameters in a gassed oscillatory baffled column , 2001 .

[106]  J Büchs,et al.  Introduction to advantages and problems of shaken cultures. , 2001, Biochemical engineering journal.

[107]  A. Durand,et al.  Laboratory scale bioreactor for solid state processes , 1988 .

[108]  Jonathan I. Betts,et al.  Characterisation and application of a novel stirred miniature bioreactor (MBR) of 18ml working volume for the scale-down of industrially relevant microbial fermentations , 2005 .

[109]  Malcolm R. Mackley,et al.  Heat transfer and associated energy dissipation for oscillatory flow in baffled tubes , 1995 .

[110]  Antonie A. C. M. Beenackers,et al.  Experimental pulse technique for the study of microbial kinetics in continuous culture , 1998 .

[111]  Johannes Tramper,et al.  Multiphase Bioreactor Design , 2007 .

[112]  T. Nishimura,et al.  Influence of imposed oscillatory frequency on mass transfer enhancement of grooved channels for pulsatile flow , 2000 .

[113]  Michael J. Hounslow,et al.  Population balance modelling of droplet coalescence and break-up in an oscillatory baffled reactor , 2004 .

[114]  De-qiang Zhang,et al.  Separation and determination of trace inorganic germanium in β-carboxyethylgermanium sesquioxide by filtration chromatography and hydride generation-graphite furnace atomic absorption spectrometry , 1996 .

[115]  Ingo Klimant,et al.  Integrated optical sensing of dissolved oxygen in microtiter plates: A novel tool for microbial cultivation , 2003, Biotechnology and bioengineering.

[116]  A. Kiener,et al.  Industrial biocatalysis today and tomorrow , 2001, Nature.

[117]  E. Stadlbauer,et al.  Design and operation of pulsed anaerobic digesters , 1990 .

[118]  X. Ni.  A study of fluid dispersion in oscillatory flow through a baffled tube , 1995 .

[119]  Reinaldo Giudici,et al.  Analysis of axial dispersion in an oscillatory-flow continuous reactor , 2003 .

[120]  D. Pritchard,et al.  A study of mass transfer in yeast in a pulsed baffled bioreactor , 1995, Biotechnology and bioengineering.

[121]  R. I. Ristic,et al.  Crystallization by Oscillatory and Conventional Mixing at Constant Power Density (R&D Note) , 2005 .

[122]  D. Schwartz,et al.  DNA Molecules in Microfluidic Oscillatory Flow. , 2005, Macromolecules.

[123]  M. Ralph.  Oscillatory flows in wavy-walled tubes , 1986, Journal of Fluid Mechanics.

[124]  J. Teixeira,et al.  Continuous Primary Beer Fermentation with Brewing Yeast Immobilized on Spent Grains , 2002 .

[125]  Adam Harvey,et al.  Mixing Through Oscillations and Pulsations—A Guide to Achieving Process Enhancements in the Chemical and Process Industries , 2003 .

[126]  Ping Gao,et al.  Photooxidation of a model pollutant in an oscillatory flow reactor with baffles , 2003 .

[127]  Xiongwei Ni,et al.  On the effect of gap size between baffle outer diameter and tube inner diameter on the mixing characteristics in an oscillatory-baffled column , 1999 .

[128]  Malcolm R. Mackley,et al.  A pulsatile flow bioreactor , 1992 .

[129]  Adam Harvey,et al.  Process intensification of biodiesel production using a continuous oscillatory flow reactor , 2003 .

[130]  Xiongwei Ni,et al.  A study of oil-water dispersion in a pulsed baffled reactor , 1996 .

[131]  Xiongwei Ni,et al.  Droplet size distribution in a continuous oscillatory baffled reactor , 2001 .

[132]  H. Gomaa,et al.  Axial mixing in a novel pilot scale gas–liquid reciprocating plate column , 2005 .

[133]  Simulation of concentration dispersion in unsteady deflected flows , 1997 .

[134]  John J. J. Chen,et al.  Local heat transfer for oscillatory flow in the presence of a single baffle within a channel , 1998 .

[135]  D K Robinson,et al.  Metabolic engineering and directed evolution for the production of pharmaceuticals. , 2000, Current opinion in biotechnology.

[136]  M. Barigou,et al.  Vibrational flow of non-Newtonian fluids , 2001 .

[137]  Malcolm R. Mackley,et al.  Residence time distribution enhancement in reactors using oscillatory flow , 1996 .

[138]  Xiongwei Ni,et al.  On the discussion of the dimensionless groups governing oscillatory flow in a baffled tube , 1997 .

[139]  M. Takriff,et al.  Interstage Backmixing in Oscillatory Flow in a Baffled Column , 2002 .

[140]  Malcolm R. Mackley,et al.  Heat transfer performance for batch oscillatory flow mixing , 2002 .

[141]  X. Ni,et al.  On the Effect of Surfactant on Mass Transfer to Water–Glycerol Solutions in a Pulsed Baffled Reactor , 1997 .

[142]  R. Skelton,et al.  The application of oscillatory flow mixing to photocatalytic wet oxidation , 1999 .

[143]  Influence of wall proximity on the lift and drag of a particle in an oscillatory flow , 2005 .

[144]  D. Drikakis.  Bifurcation phenomena in incompressible sudden expansion flows , 1997 .

[145]  John M Woodley,et al.  Accelerated design of bioconversion processes using automated microscale processing techniques. , 2003, Trends in biotechnology.

[146]  Tony Howes,et al.  Experimental axial dispersion for oscillatory flow through a baffled tube , 1990 .

[147]  Nigel J Titchener-Hooker,et al.  A critical assessment of the impact of mixing on dilution refolding , 2006, Biotechnology and bioengineering.

[148]  Aniruddha B. Pandit,et al.  Gas–liquid mass transfer studies with triple impeller system on a laboratory scale bioreactor , 2005 .

[149]  J. Golding,et al.  Recovery and separation of cobalt and nickel in a pulsed sieve-plate extraction column , 1981 .

[150]  P. Gogate,et al.  Survey of measurement techniques for gas–liquid mass transfer coefficient in bioreactors , 1999 .

[151]  Tony Howes,et al.  Polymer product engineering utilising oscillatory baffled reactors , 1999 .

[152]  Clive A. Greated,et al.  On the measurement of strain rate in an oscillatory baffled column using particle image velocimetry , 2000 .

[153]  M. Mackay,et al.  Oscillations flow within tubes containing wall or central baffles , 1991 .

[154]  Xiongwei Ni,et al.  A Systematic Study of the Effect of Geometrical Parameters on Mixing Time in Oscillatory Baffled Columns , 1998 .

[155]  R. Field,et al.  Enhancement of liquid phase adsorption column performance by means of oscillatory flow: an experimental study , 2004 .

[156]  C. Chung,et al.  Oscillatory flow in a cone-and-plate bioreactor. , 2005, Journal of biomechanical engineering.

[157]  Xiongwei Ni,et al.  A comparative study of mass transfer in yeast for a batch pulsed baffled bioreactor and a stirred tank fermenter , 1995 .

[158]  F. Forster,et al.  Oscillatory flow in microchannels Comparison of exact and approximate impedance models with experiments , 2004 .

[159]  Ian Sobey,et al.  The vortex wave membrane bioreactor: hydrodynamics and mass transfer , 1996 .

[160]  I. Sobey.  Observation of waves during oscillatory channel flow , 1985, Journal of Fluid Mechanics.

[161]  A. M. Binnie.  A double-refraction method of detecting turbulence in liquids , 1945 .

[162]  V. Linek,et al.  Critical assessment of gassing‐in methods for measuring kla in fermentors , 1991, Biotechnology and bioengineering.

[163]  R. L. Skelton,et al.  On the Effect of Pulsing Conditions on Reaction Rates in a Pulsed Baffled Tube Photoreactor (PBTPR) , 2000 .

[164]  X. Ni,et al.  Scale-up correlation for mass transfer coefficients in pulsed baffled reactors , 1996 .

[165]  Hongbing Jian,et al.  On modelling turbulent flow in an oscillatory baffled column – RANS model or large‐eddy simulation? , 2002 .

[166]  Xiongwei Ni.  Residence time distribution measurements in a pulsed baffled tube bundle , 1994 .

[167]  R. Skelton,et al.  Photocatalytic mineralisation of methylene blue using buoyant TiO2-coated polystyrene beads , 2000 .

[168]  B J Bellhouse,et al.  A HIGH EFFICIENCY MEMBRANE OXYGENATOR AND PULSATILE PUMPING SYSTEM, AND ITS APPLICATION TO ANIMAL TRIALS , 1973, Transactions - American Society for Artificial Internal Organs.

[169]  R. Field,et al.  Oscillatory flow and axial dispersion in packed beds of spheres , 2005 .

[170]  P. Stonestreet,et al.  Protein refolding in an oscillatory flow reactor , 2004, Biotechnology Letters.