Research

NSERC INDUSTRIAL BIOTECHNOLOGY CHAIR 

The NSERC Industrial Biotechnology Chair is sponsored by the Natural Sciences and Engineering Research Council (NSERC) of Canada and companies of the Apotex Group. The Chair also operates a United Nations-sponsored Microbial Resource Centre (MIRCEN).

• Bioprocess Engineering and Scale-up
• Fermentation and Enzyme Technology
• Animal Cell Culture
• Downstream Bioseparations
• Pharmaceutical Production Facilities
• Environmental Biotechnology

animal cell culture, fermentation technology, enzyme technology,

environmental bioprocessing, biopharmaceuticals, bioseparations

NSERC Industrial Biotechnology Chair NSERC Industrial Biotechnology Chair

Department of Chemical Engineering Department of Chemical Engineering

University of Waterloo University of Waterloo

Waterloo, Ontario Waterloo, Ontario

Canada N2L 3G1 Canada N2L 3G1

Telephone: (519) 888 4567 extension 3919 Telephone: (519) 888 4567 extension 5254

Facsimile: (519) 746 4979 Facsimile: (519) 746 4979

E-mail: mooyoung@cape.uwaterloo.ca
E-mail: ychisti@cape.uwaterloo.ca

Current research is focused on design, characterization and scale-up of bioreactors for applications in microbial fermentations, animal and plant cell culture, and enzymatic biotransformations. Studies include fundamental aspects of aeration and mixing, transport phenomena and kinetics, as well as process development for specific applications (pharmaceuticals, recombinant proteins, foods and feeds). Immobilized and free suspension modes of biocatalysis are also being investigated. Bioreactors up to 1.3 m³ are available for research.

Selected Publications

Bioprocess intensification through bioreactor engineering. Chisti Y and Moo-Young M, Trans Inst. Chem. Eng., 74A: 575–583 (1996).

Split–channel rectangular airlift reactors: Enhancement of performance by geometric modifications. Choi KH, Chisti Y and Moo-Young M, Chem. Eng. Commun., 138: 171–181 (1995).

A new method for the measurement of solids holdup in gas–liquid–solid three–phase systems. Wenge F, Chisti Y and Moo-Young M, Ind. Eng. Chem. Research, 34: 928–935 (1995).

Biochemical engineering in biotechnology. Moo-Young M and Chisti Y, Pure & Appl. Chem., 66(1): 117–136 (1994).

Aeration and mixing in vortex fermenters. Chisti Y and Moo-Young M, J. Chem. Technol. Biotechnol., 58: 331–336 (1993).

Improve the performance of airlift reactors. Chisti Y and Moo-Young M, Chem. Eng. Progress, 89(6): 38–45 (1993).

Airlift bioreactors with packed beds of immobilized biocatalysts: Theoretical evaluation of the liquid circulation performance. Chisti Y and Moo-Young M, Trans. I. Chem. E., 71C: 209–214 (1993).

Airlift reactors: Characteristics, applications and design considerations. Chisti Y and Moo-Young M, Chem. Eng. Commun., 60: 195–242 (1987).

Microbial production of recombinant intracellular and extracellular proteins, enzymes and other primary and secondary metabolites (amino acids, antibiotics) is being investigated. Modelling, optimization, and control of fermentations are areas of major research thrusts. Protein enrichment of low grade carbohydrates to enhanced food-value products is being developed with emphasis on large scale processing (up to 1.3 m³). Applications of enzymes for synthesis, biotransformations, and hydrolytic processing are being examined. Bioreactors for multienzyme reactions are being developed and work on lipase catalyzed synthesis of fragrant compounds is in progress. Processes for hydrolysis of low grade starch and cellulose for direct use in fermentation are being investigated. Methods of immobilization of enzymes are a continuing area of research.

Selected Publications

Plasmid stability in recombinant Saccharomyces cerevisiae. Zhang Z, Moo-Young M and Chisti Y, Biotechnol. Adv., 14: 401–436 (1996).

Fed-batch production of baker's yeast using millet (Pennisetum typhoides) flour hydrolysate as the carbon source. Ejiofor AO, Chisti Y and Moo-Young M, J. Ind. Microbiol., 16: 102–109 (1996).

Bioprocessing with genetically modified and other organisms: Case studies in processing constraints. Moo-Young M, Chisti Y, Zhang Z, Garrido F, Banerjee U and Vlach D, Ann. N. Y. Acad. Sci., 782: 391–401 (1996).

Culture of Saccharomyces cerevisiae on hydrolysed waste cassava starch for production of baking quality yeast. Ejiofor AO, Chisti Y and Moo-Young M, Enzyme Microb. Technol., 18: 519–525 (1996).

Effects of substrate particle size and alkaline pretreatment on protein enrichment by Neurospora sitophila. Banerjee UC, Chisti Y and Moo-Young M, Res. Cons. Recycl., 13: 139–146 (1995).

Fermentation of cellulosic materials to mycoprotein foods. Moo-Young M, Chisti Y and Vlach D, Biotechnol. Adv., 11: 469–479 (1993).

Spectrophotometric determination of mycelial biomass. Banerjee UC, Chisti Y and Moo-Young M, Biotechnol. Tech., 7: 313–316 (1993).

Fermentation technology, bioprocessing, scale-up and manufacture. Chisti Y and Moo-Young M, in Biotechnology: The Science and the Business, (Moses V and Cape RE, editors), Harwood Academic Publishers, New York, 1991, pp. 167-209.

Animal cell culture based processes for production of therapeutic, protective, diagnostic and veterinary proteins are under development. Production of porcine follicle stimulating hormone (FSH), human tissue-type plasminogen activator (tPA), and monoclonal antibodies is being investigated. Cell lines under investigation include recombinant cells, hybridomas, and anchorage-dependent lines. Work is done in a dedicated animal cell culture laboratory.

Selected Publications

Tissue-type plasminogen activator: Characteristics, applications and production technology. Rouf SA, Moo-Young M and Chisti Y, Biotechnol. Adv., 14: 239–266 (1996).

Effects of the hydrodynamic environment and shear protectants on survival of erythrocytes in suspension. Zhang Z, Chisti Y and Moo-Young M, J. Biotechnol., 43: 33–40 (1995).

Hydrodynamic behaviour of animal cell microcarrier suspensions in split–cylinder airlift bioreactors. Ganzeveld KJ, Chisti Y and Moo-Young M, Bioproc. Eng., 12: 239–247 (1995).

Anchorage dependent animal cell culture in packed beds with airlift driven liquid circulation: A theoretical analysis of oxygen transfer and comparison with stirred tank microcarrier culture system. Chisti Y and Moo-Young M, Trans. I. Chem. E., 72C: 92–94 (1994).

Animal cell culture in stirred bioreactors: Observations on scale-up. Chisti Y, Bioproc. Eng., 9: 191–196 (1993).

Considerations for designing bioreactors for shear-sensitive culture. Moo-Young, M and Chisti Y, Biotechnology, 6(11): 1291-1296 (1988).

The bioseparation research program has facilities for pilot-scale chromatography of proteins, disruption of cells for recovering intracellular material, protein precipitation, microfiltration and ultrafiltration, and other more conventional methods of product recovery. Recovery of recombinant proteins from complex mixtures such as those generated by homogenization of microbial cells is a major area of current focus. All steps in a separation sequence are developed concurrently for optimization of the entire recovery train.

Selected Publications

Isolation of a recombinant intracellular b -galactosidase by ammonium sulfate fractionation of cell homogenates. Zhang Z, Chisti Y and Moo-Young M, Bioseparation, 5: 329-337 (1995).

Separation techniques in industrial bioprocessing. Chisti Y and Moo-Young M, I. Chem. E. Symp. Ser., 137: 135–146 (1994).

Disruption of a recombinant yeast for the release of b -galactosidase. Garrido F, Banerjee UC, Chisti Y and Moo-Young M, Bioseparation, 4: 319–328 (1994).

Large scale protein separations: Engineering aspects of chromatography. Chisti Y and Moo-Young M, Biotech. Adv., 8: 699-708 (1990).

Disruption of microbial cells for intracellular products. Chisti Y and Moo-Young M, Enzyme Microb. Technol., 8: 194–204 (1986).

Our industrial pharmaceutical bioprocess expertise includes plant and facility layout; clean–in–place and sterilization–in–place operations; process and plant design for compliance with the US FDA current Good Manufacturing Practices (cGMP) regulations; process and plant validation; production and distribution of clean steam and water–for–injection; and containment and treatment of biohazardous wastes.

Selected Publications

Clean–in–place systems for industrial bioreactors: Design, validation and operation. Chisti Y and Moo-Young M, J. Ind. Microbiol., 13: 201–207 (1994).

Assure bioreactor sterility. Chisti Y, Chem. Eng. Progress, 88 (9): 80-85 (1992).

Build better industrial bioreactors. Chisti Y, Chem. Eng. Progress, 88(1): 55–58 (1992).

Biotransformations of rifamycins: Process possibilities. Banerjee, UC, Saxena, B and Chisti Y, Biotechnol. Adv., 10: 577–595 (1992).

Studies in environmental biotechnology are focused on design of bioprocesses and bioreactors for treatment of recalcitrant organics in soil, gaseous exhausts, and industrial wastewaters. The dynamics of phenol degradation by Pseudomonas putida have recently been elucidated, identifying the distinct patterns of responses that are observed for various loadings of phenol in industrial wastewaters. Studies on bioremediation of hydrocarbon contaminated soils are under way. Attempts are being made to combine physical, chemical and biological remediation schemes into optimized processes for environmental improvement.

Selected Publications

Bioreactor applications in waste treatment. Moo-Young M and Chisti Y, Res. Cons. Recycl., 11: 13–24 (1994).

Airlift bioreactors for treatment of hydrocarbon contaminated wastes. Chisti Y and Moo-Young M, in Better Living Through Biochemical Engineering, Teo WK, Yap MGS and Oh SKW, editors, University of Singapore, Singapore, 1994, pp. 771–776.

Dynamics of phenol degradation by Pseudomonas putida. Allsop PJ, Chisti Y, Moo-Young M and Sullivan GR, Biotechnol. Bioeng., 41: 572–580 (1993).

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