Bioseparations Engineering: An overview

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• Bioseparations Engineering An overview
• Bioprocessing manufacture of biological products
  such as biochemicals, pharmaceuticals, foods,
  food additives, nutraceuticals, agrochemicals
• Bioseparations engineering systematic study of
  the scientific and engineering principles
  utilized for the recovery, isolation,
  purification and polishing of biological products
• Bioprocessing
• Reactive bioprocessing, e.g. manufacture of
  penicillin
• Extractive bioprocessing, e.g. manufacture of
  plasma proteins

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Reactive bioprocessing
Bio-separation
Upstream processing
Biological reaction
Biological product
Extractive bioprocessing
Upstream processing
Bio-separation
Biological product
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Cost of bioseparation
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• Nature of bioseparation
• Largely based on chemical separation techniques
• Chemical separation techniques are modified based
  on specific requirements
• Novel separations may be necessary in some cases
• High throughput/productivity
• High selectivity
• Need to satisfy stringent quality requirements
• Need to take into account degradable material
• Low temperature operations
• Multi-technique separation

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• Basis of separation
• Biological products are separated based on one or
  several of the following in combination
• Size, e.g. filtration, membrane separation,
  gel-filtration, centrifugation
• Density, e.g. centrifugation, sedimentation,
  flotation
• Diffusivity, e.g. membrane separation,
  supercritical fluid extraction
• Shape, e.g. centrifugation, filtration,
  sedimentation
• Polarity, e.g. extraction, chromatography,
  adsorption
• Solubility, e.g. extraction, membrane separation,
  precipitation, crystallization
• Electrostatic charge, e.g. adsorption, membrane
  separation
• Mobility, e.g. electrophoresis, membrane
  separation
• Steric hindrance, e.g. filtration
• Volatility e.g. distillation, membrane
  distillation, pervaporation

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• Physical forms separated
• Particle-liquid separation
• Particle-particle separation in liquid medium
• Particle-solute separation in liquid medium
• Solute-solvent separation
• Solute-solute separation in liquid medium
• Liquid-liquid separation

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Bioseparation techniques Low resolution-high
throughput Cell disruption Precipitation Centrifug
ation Liquid-liquid extraction Leaching Filtration
Supercritical fluid extraction Microfiltration Ul
trafiltration Adsorption High resolution-low
throughput Ultracentrifugation Chromatography Affi
nity separation Electrophoresis
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• The RIPP scheme
• Multi-technique separation
• Process design should take into consideration the
  following
• The nature of starting material
• The initial location of the target product
• The volume of process stream
• The relative abundance of the product in the
  starting material
• The susceptibility to degradation of the product
• The desired physical form of the final product
• The quality requirements
• Costing

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Cell culture supernatant
Microfiltration
Filtrate
Precipitation
Ammonium sulfate
Precipitate
Buffer
Solution
Monoclonal antibody purification
Ultrafiltration
Buffer
Ion-exchange chromatography
Buffer
Monoclonal antibody
Ultrafiltration
Gel filtration
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• Current paradigm in the bioseparation
• Replacement of the conventional RIPP scheme by
  using new techniques which can significantly cut
  down the number of steps needed to bioseparation
• Some of these new and emerging techniques are
• Membrane chromatography
• Expanded-bed chromatography
• High-resolution ultrafiltration