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Molecular Biotechnology

, Volume 34, Issue 3, pp 355–381 | Cite as

Living with heterogeneities in bioreactors

Understanding the effects of environmental gradients on cells
  • Alvaro R. Lara
  • Enrique Galindo
  • Octavio T. Ramírez
  • Laura A. Palomares
Review

Abstract

The presence of spatial gradients in fundamental culture parameters, such as dissolved gases, pH, concentration of substrates, and shear rate, among others, is an important problem that frequently occurs in large-scale bioreactors. This problem is caused by a deficient mixing that results from limitations inherent to traditional scale-up methods and practical constraints during large-scale bioreactor design and operation. When cultured in a heterogeneous environment, cells are continuously exposed to fluctuating conditions as they travel through the various zones of a bioreactor. Such fluctuations can affect cell metabolism, yields, and quality of the products of interest. In this review, the theoretical analyses that predict the existence of environmental gradients in bioreactors and their experimental confirmation are reviewed. The origins of gradients in common culture parameters and their effects on various organisms of biotechnological importance are discussed. In particular, studies based on the scale-down methodology, a convenient tool for assessing the effect of environmental heterogene ities, are surveyed.

Index Entries

Scale up scale down gradients bioreactors transient 

Nomenclature

C*

Dissolved oxygen concentration at saturation with air

CFD

Computational fluid dynamics

CHO

Chinese hamster ovary

dCO2

Dissolved carbon dioxide

dH2

Dissolved hydrogen

Di

Impeller diameter

DO

Dissolved oxygen concentration

dw

Dry weight

GFP

Green fluorescent protein

HGH

Human growth hormone

kLa

Volumetric oxygen transfer coefficient

N

Impeller rotation speed

PFR

Plug-flow reactor

Po

Power input

Q

Pump rate

SD

Scale-down

SDS

Scale-down system

STR

Stirred-tank reactor

tc

Circulation time

TCA

Tricarboxylic acid

tm

Mixing time

tMT

Characteristic time for mass transfer

tO2u

Characteristic time for oxygen uptake

V

Volume

’

Density

μ

Viscosity

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© Humana Press Inc 2006

Authors and Affiliations

  • Alvaro R. Lara
    • 1
  • Enrique Galindo
    • 2
  • Octavio T. Ramírez
    • 1
  • Laura A. Palomares
    • 1
  1. 1.Departamento de Medicina Molecular y BioprocessosInstituto de Biotecnologia Universidad Nacioral Autónoma de México (UNAM)Cuerravaca, MorelosMéxico
  2. 2.Departamento de Ingeniería Celular y BiocatálisisInstituto de Biotecnologia Universidad Nacioral Autónoma de México (UNAM)Cuerravaca, MorelosMéxico

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