Experimental and modeling studies of diffusion in immobilized cell systems: A review of recent literature and patents

In summary, the overall behavior of immobilized cells is controlled by the interplay of nutrient and product diffusion and reaction, cell metabolism, cell proliferation, and cell death. These process are intrinsically linked, and evaluation of one process independent of other effects can be difficult. Substantial overlap exists between much of the experimental and computational work done in this field over the past 10 yr but with little cross communication. We hope that the areas of research described here will provide a basis for communication between researchers in disparate fields working on similar problems. The past several years have yielded significant improvements in the development and operation of immobilized cell systems. Possible progress in the near future may develop through the use of new techniques and approaches developed in other research areas. Models and simulations will continue to increase in complexity in proportion to improvements in computer speed, memory, and cost. An increase in simulation sophistication should focus on developing a more thorough understanding of the effect of the accumulation of wastes, deprivation of nutrients, and increased local concentrations of cellular growth factors. Through a combination of experimental and modeling studies, one can thoroughly evaluate the effects of alterations in multiple parameters on the overall productivity of immobilized cell biocatalysts. Possible experimental progress that may impact future use of immobilized cells includes the development of novel polymeric supports that can respond to external stimuli (electrochemical, pH, salt changes); the use of noninvasive monitoring techniques (such as IR microspectroscopy) to directly characterize molecular transport, cellular metabolism, and cell proliferation in situ; and the development of improved methods to deliver precise amounts of nutrients and oxygen, possibly through the use of controlled release methods or the use of techniques to increase substantially the oxygen tension in the culture medium since oxygen is predominantly the most frequent limiting factor.