The laser flow microfluorometer (FMF) can determine the amounts of certain components in single cells at sample rates of several thousand cells per second. This technique has been employed to characterize Bacillus subtilis populations in batch fermentations with different inocula. Protein and distributions obtained by FMF analyses at different times during the batch have been decomposed using an optimized fit of summed subpopulation distributions. The results of these decomposition calculations, some of which have been approximately confirmed by independent microscopic observations, indicate cells relative numbers of single rods, cell chains, spores, and swollen rounded cells change dramatically during the entire fermentation including the stationary phase. The dynamics of these subpopulations may be related to secondary metabolite production.

After expressing the response of a bilinear dynamical system in terms of a Volterra series, the filtering properties of the system are characterized in the frequency domain. The zero harmonic component of the output of a closed-loop system comprised of the bilinear system and a static relay non-linear element is approximated using basic second-order Volterra kernels. This allows estimation of bilinear system parameters based upon measurements of the average value of the closed-loop system output.

Batch cultivation provides a continuous sequence of different environments useful for studying responses of cell cycle controls. Flow cytometry measurements have been made of the frequency functions for protein, RNA, and DNA at different times during batch growth of the fission yeast Schizosaccharomyces pombe. The mean cellular protein and RNA contents and their variances tend to increase with increasing population specific growth rates. Analysis of the mid-exponential phase DNA frequency function data indicates that DNA synthesis occupies 12% of the total cell cycle time and is completed at the same time as cell separation. Coordination of DNA synthesis and cell separation is less precise when population growth rate is low in late lag and early stationary phases.

Calculations of the distribution of states in cell populations grown in well-mixed, isothermal batch and continuous flow reactors are presented. By restricting the analysis to a class of bacteria for which cell division control may be modeled using overlapping timers, analytical results are obtained for many cell population characteristics in terms of the growth rate history. This required growth rate trajectory is evaluated using a separate overall reactor model. The simulation results conform qualitatively to available experimental data and suggest new experiments for further testing of the single-cell model.

The fission yeast Schizosaccharomyces pombe was grown in glucose-limited medium in a steady-state continuous flow reactor. Changes in mean cell protein and RNA contents with growth rate are consistent with earlier observations under different conditions. Flow microfluorometry measurements of the frequency functions of DNA at different dilution rates show changes in coordination of DNA synthesis and cell separation. Shifting from batch growth to small dilution rates results in unusual cell aggregation which leads to multiple steady states at identical operating conditions.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTModification of Consecutive-Competitive Reaction Selectivity by Periodic OperationC. K. Lee and James E. BaileyCite this: Ind. Eng. Chem. Process Des. Dev. 1980, 19, 1, 160–166Publication Date (Print):January 1, 1980Publication History Published online1 May 2002Published inissue 1 January 1980https://pubs.acs.org/doi/10.1021/i260073a028https://doi.org/10.1021/i260073a028research-articleACS PublicationsRequest reuse permissionsArticle Views278Altmetric-Citations43LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts

Biochemical reactors provide a fascinating assortment of new challenges to the reaction engineer. These arise because of the characteristics of the reactants, catalysts, and the reaction networks involved. Especially important are genetic controls of cell metabolism and structure/function/activity relationships in enzyme catalysis. Several examples are discussed which illustrate the implications of these and other biological fundamentals in biochemical reaction analysis and design.

AbstractExperimental studies of diethyl adipate saponification in a CSTR show that forced cycling of feed composition produces significant yield increases in intermediate product relative to the optimal steady state operation, while forced temperature cycling has much less effect. Related experiments provide useful transient heat transfer data for this system. Reaction kinetics have been determined in water and in a 50% (v/v) isopropanol solvent.

Intentional periodic manipulation of the inputs to a chemical reactor can in some cases improve the amount of product and its composition. A variational method for analyzing the effects of single and multivariable periodic forcing functions on process performance is presented in this work and illustrated in several examples. While the method discussed here is not theoretically justified for large-amplitude input variations, comparisons of analytical results obtained with the method and simulation results for large-amplitude reactor cycling show good qualitative agreement. The approximate analytical method provides a reasonable initial estimate of the structure of an advantageous periodic control.

A single-cell model for a bacterium which considers both cell mass and cellular DNA content is formulated based on the Cooper-Helmstetter and Donachie hypotheses. Analysis of this model under transient growth conditions results in bounds for the domain of possible cell masses and in relationships among cell mass, DNA content, and DNA configuration valid at each time t. These results for time t are dependent upon the growth-rate history over the previous L time units, where L is independent of growth rate. Based upon the single-cell analysis, the characteristics of a population of such cells are determined. Included in these results, which apply for a general initial distribution of states, are the frequency functions for cell mass and cellular DNA content. The transient behavior of these functions is illustrated for a growth-rate shift experiment.

Biotechnology and BioengineeringVolume 22, Issue 2 p. 457-462 Communications to the EditorFree Access Flow microfluorometry measurements of multicomponent cell composition during batch bacterial growth Jila Fazel-Madilessi, Jila Fazel-Madilessi Department of Chemical Engineering, University of Houston Houston, Texas 77004Search for more papers by this authorJ. E. Bailey, Corresponding Author J. E. Bailey Department of Chemical Engineering, University of Houston Houston, Texas 77004Department of Chemical Engineering, University of Houston Houston, Texas 77004Search for more papers by this authorD. N. McQuitty, D. N. McQuitty Department of Biology, University of Houston Houston, Texas 77004Search for more papers by this author Jila Fazel-Madilessi, Jila Fazel-Madilessi Department of Chemical Engineering, University of Houston Houston, Texas 77004Search for more papers by this authorJ. E. Bailey, Corresponding Author J. E. Bailey Department of Chemical Engineering, University of Houston Houston, Texas 77004Department of Chemical Engineering, University of Houston Houston, Texas 77004Search for more papers by this authorD. N. McQuitty, D. N. McQuitty Department of Biology, University of Houston Houston, Texas 77004Search for more papers by this author First published: February 1980 https://doi.org/10.1002/bit.260220216Citations: 16AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 P. K. Horan and L. L. Wheeless, Jr., Science, 198, 149 (1977). 2 M. Stohr, H. Eipel, K. Goerttler, and M. Vogt-Schaden, Histochemistry, 51, 305 (1977). 3 J. E. Bailey and J. C. Allred, Eng. Technol. Dig., 4, 80 (1975). 4 A. S. Paau, J. R. Cowles, and J. A. Oro, Can J. Microbiol., 23, 1165 (1977). 5 J. E. Bailey, J. Fazel-Madjlessi, D. N. McQuitty, L. Y. Lee, J. C. Allred, and J. A. Oro, Science, 198, 1175 (1977). 6 K.-J. Hutter, C. Boose, H. Oldiges, and C.-C. Eneis, Chem. Mikrobiol. Technol. Lebensm., 4, 101 (1975). 7 M. L. Slater, S. O. Sharrow, and J. J. Gart, Proc. Nat. Acad. Sci (U.S.A.), 74, 3850 (1977). 8 M. F. Gilbert, D. N. McQuitty, and J. E. Bailey, Apply. Env. Microbiol., 36, 615 (1978). 9 K.-J. Hutter and H. E. Eipel, FEMS Microbiol. Lett., 3, 35 (1978). 10 J. E. Bailey, J. Fazel-Madjlessi, D. N. McQuitty, L. Y. Lee, and J. A. Oro, AIChE J., 24, 561 (1978). 11 K.-J. Hutter and H. E. Eipel, Eur. J. Appl. Microbiol. Biotechnol., 6, 223 (1979). 12 J. Fazel-Madjlessi and J. E. Bailey, Biotechnol. Bioeng., 21, 1995 (1979). 13 H. A. Crissman, P. F. Mullaney, and J. A. Steinkamp, in Methods in Cell Biology, D. Prescott, Ed. (Academic, New York, 1975), Vol IX, p. 179. Citing Literature Volume22, Issue2February 1980Pages 457-462 ReferencesRelatedInformation

Abstract Earlier computational studies of optimal periodic operation of wastewater treatment plants are extended to include comparisons with classical control performance and to consider a structured sludge kinetics model. For two quite different examples, periodic control reduces effluent BOD and/or its variability relative to conventional control. Furthermore, the optimal periodic control for structured sludge kinetics can be substantially different from the Monod/decay sludge kinetics result, illustrating the importance of accurate identification of sludge kinetics for optimizing activated sludge process performance.

Based upon its superior catalytic activity for H2O2 decomposition, a bituminous coal-based activated carbon was selected for investigations of pretreatment and enzyme immobilization methods. Pretreatments considered include acid washing, exposure to strong oxidizing agents, contact with concentrated peroxide solutions, nitration and amination, isothiocyanate derivatization, silanization, and stearic acid coating. Effects of these pretreatments on morphology and trace-metal content of the carbon pellets have been studied using scanning electron microscopy and dispersive analysis of x rays. Immobilization of glucoamylase by adsorption, glutaraldehyde crosslinking, and covalent attachment to carbon activated by water-soluble diimide or diazotization have been examined. These different enzyme-carbon catalysts have been characterized by their enzyme loading, enzyme activity, catalytic activity for H2O2 decomposition, or combinations of these measures of performance.

Periodic control of a general class of dynamic systems involving state and control dependent time delays is considered. Variational analyses yield a necessary condition for optimality and a sufficient condition for proper periodicity. The latter result is applied to analyse a single input-single output example.

Application of relay feedback controllers to maintain process states near unstable steady states is extended to a second order system, the CSTR with an irreversible, exothermic reaction. The control scheme is successful provided the bandwith (the reactor temperature deviation which causes relay switching) is not chosen too large relative to the drive levels (the deviation in coolant temperature caused by relay switching). In this context Tsypkin's analytical methods for approximate solution of this and higher order problems are elaborated and tested. Tsypkin's technique proves superior to Describing Function analysis in accuracy and in bounds on the maximum permissible bandwidth.

By means of flow microfluorometry, the protein and nucleic acid contents of individual bacterial cells may be measured at the rate of several thousand cells per second. Accumulation of such information over a few minutes yields the composition distribution of the microbial population. These distributions have been determined at different times during batch growth of Bacillus subtilis , and the results indicate that the variance of cell composition decreases as the population passes through the exponential into the stationary phase. The relative abundance of endospores and vegetative cells as well as the protein distributions of these subpopulations may be readily determined from flow microfluorometry data. Experimental access to such details of microbial population dynamics should foster improved understanding of cell growth, spore germination, and spore formation kinetics.

Nonlinear chemical process systems which are periodically forced do not necessarily have unique, stable periodic responses with the same period as the input, although such behavior has been widely assumed previously. Theory for the as symptotic case of very fast forced cycling indicates that systems which possess multiple steady-states or self-oscillations under unforced conditions may exhibit unusual dynamic phenomena under forced periodic operation. Simulations of a periodically forced CSTR reveal several jumps in forced system qualitative behavior as the forcing frequency is altered. Among the pathological responses obtained for the CSTR example are multiple stable forced states, subharmonic oscillations, and almost periodic outputs.

The influence of chemical oscillations on membrane transport systems with mobile carriers is investigated. If dynamic asymmetry occurs so that conditions on only one side of the membrane oscillate, a type of active transport can occur. For example, permeant can be transported from region 1 where its time-average concentration is low to region 2 where time-average permeant concentration is higher when the latter concentration oscillates. No additional driving force beyond dynamic asymmetry is necessary for such active transport to occur. Fluctuations in any quantity which influences the boundary carrier-permeant complex concentration in a nonlinear fashion can alter the behavior of the membrane transport system.

Process performance is sometimes best at an unstable steady state. Following a new control philosophy, stable operation near an unstable steady state can be realized using a relay with hysteresis as a feedback controller. Properly designed, this control scheme produces a stable, small amplitude oscillation in the neighborhood of the desired state. Approximate solutions for such oscillations can be obtained by Tsypkin's method or Describing Function analysis. Comparisons of these solutions with exact simulation results for an example reveal that replacing the relay with the describing function is a major source of error in the approximate analysis.