SUMMARY: A theoretical treatment of continuous culture is given, which allows quantitative prediction of the steady-state concentrations of bacteria and substrate in the culture, and how these may be expected to vary with change of medium, concentration and flow-rate. The layout and operation of a small pilot plant for the continuous culture of bacteria are described. This plant has been operated continuously for periods of up to 4 months without breakdown or contamination of the culture. No alterations in the properties of the organisms studied have occurred during such periods of continuous culture. Results are given of a series of experiments on the continuous culture of Aerobacter cloacae in a chemically defined medium, designed to allow quantitative comparison with the results predicted by the theory. The relative advantages of batch and continuous culture as production processes are discussed, and it is concluded that continuous culture may usually be expected to show a five to tenfold increase in output as compared with a batch process.The continuous culture of micro-organisms is a technique of increasing importance in microbiology. The essential feature of this technique is that microbial growth in a continuous culture takes place under steady-state conditions; that is, growth occurs a t a constant rate and in a constant environment. Such factors as pH value, concentrations of nutrients, metabolic products and oxygen, which inevitably change during the ' growth cycle ' of a batch culture, are all maintained constant in a continuous culture; moreover, they may be independently controlled by the experimenter. These features of the continuous culture technique make it a valuable research tool, while it offers many advantages, in the form of more economical production techniques, to the industrial microbiologist. Nevertheless, the technique has so far been comparatively little used. (The review of Novick (1955) lists nearly all the work on the subject that has yet appeared.) The reasons for this relative neglect are, we believe, twofold.The first reason is the lack of a generally accepted theoretical background. Continuous culture presents theoretical problems of an essentially kinetic nature which must be solved before the technique can be intelligently applied.

The theoretical strength of diamond has been calculated for the <100>, <110>, and <111> directions using a first principles approach and is found to be strongly dependent on crystallographic direction. This elastic anisotropy, found at large strains, and particularly the pronounced minimum in cohesion in the <111> direction, is believed to be the reason for the remarkable dominance of the 111 cleavage plane when diamond is fractured. The extra energy required to cleave a crystal on planes other than 111 is discussed with reference to simple surface energy calculations and also the introduction of bond-bending terms.

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SummaryThis paper describes the design and operation of an industrial type culture system for the submerged growth of BHK 21 cells a t a volume of 30 1. Using a modified Eagle's medium and with the culture controlled at pH 7.4 f 0.05 and at a temperature of 35 f 0.25"C., the cells grew from 0.5 X lo6 to about 2.5 X lo6 viable celLs/ml. in 50 hr. a t stirrer speeds of 330 and 460 rpm. The significance of certain aspects of design and operation of a culture system of this type is discussed.

The equipment and operational techniques are described which were found suitable to control pH in the range 6.8-7.8 pH, within 3Z0.03 pH units of the desired value, a t cell concentrations up to a maximum of 2.5 X 106/ml. The results of batch growth of a suspension strain of the BHK cell (clone 13) under conditions of controlled pH are given and the significance of these results is discussed. 147 148 R. C. TELLING AND C. J. STONE 3, METER RECORDER CONTROLLED MAIN