1. INTRODUCTION

1.1 A microorganism: a microscopic biochemical factory

A single cell is considered as a microscopic biochemical factory. Materials  such   as  carbon, nitrogen, oxygen and others are brought into the cell and converted within the cell via hundreds of reactions to the various constituents of the cell as well as to biochemical products which may be retained or transported back into the environment outside the cell.¹ Metabolic activities inside the cell are regulated at various levels both inside and outside the cell. Moreover, biological activity of the  cell is extremely sensitive to the environment it is exposed to. Because of this multi - level complex regulation, by an engineering point of view, it is of utmost importance to understand the nutritional and environmental factors affecting cell metabolism.

1.2 Bioreactor as a controlled environment for the growth of microorganisms

 An engineer is always interested in consistently producing large quantities of product of interest over long periods of time. The best way to achieve this goal will be to grow the cells in a bioreactor where the cellular activity can be controlled efficiently. The three basic modes of bioreactor operation are batch, fed-batch and continuous. The control issues related to each of these will be discussed in later sections.

1.3 Importance of process control in bioreactors

Development of methods for monitoring and control of commercial bioprocessing including reliable and robust real-time  sensors  has  been  listed  an  outreaching priority for federal investment   in   a   report    published    in    July 95    from    the   Biotechnology   Research Subcommittee (BRS) of the Committee on Fundamental Science of the National Science and Technology   Council. The   optimal    performance    of    the   upstream processing  can  not  be  achieved  without  the knowledge  of  the state of the system and on control  algorithms  that  can  optimize  the process. Controls of bioprocesses is challenging, particularly  in  batch  and  fed-batch  bioreactors,   due   to   high   degree   of  nonlinearity (meaning  that  nonlinear  differential equations are required for mathematical modeling); and  their  potential  for  instability  when  they  involve  high-yield  mutant or recombinant microorganism. These  problems  are  further  complicated  by  the  scarcity of  on-line real -time  sensors  and  realistic  models  that  capture  the  intricate  complexities  of  biological systems.²