@article{vann_layfield_sheppard_2017, title={The application of near-infrared spectroscopy in beer fermentation for online monitoring of critical process parameters and their integration into a novel feedforward control strategy}, volume={123}, ISSN={["2050-0416"]}, DOI={10.1002/jib.440}, abstractNote={Traditional methods used in the analysis of fermentation media suffer from a number of limitations. The search for more rapid and efficient methods has led to the development and application of near-infrared spectroscopy. Near-infrared spectroscopy has been applied successfully in a variety of industrial processes: agricultural, food, chemical and pharmaceutical, generally in the areas of raw material quality control but also including intermediate and finished product testing. The present research explores its potential for online fermentation monitoring of total cell count (TCC), specific gravity (SG), free amino nitrogen (FAN) and percentage alcohol by volume (% v v−1) in a 300 L pilot-scale validation batch. Models that were generated from three calibration batches for each of these constituents exhibited overall favourable standard error of cross validation (SECV) and fit of predicted vs actual cross validated results (SECV, R2): SG (0.00072, 0.995), ethanol (0.17% v v−1, 0.990), FAN (16.5 mg L−1, 0.886) and TCC (1.24 × 106 cells mL−1, 0.640). The data that was most relevant to cell metabolism was determined to be sugar consumption rate, ethanol production rate, yield of ethanol and fermentation lag time. These ‘critical performance parameters’ were incorporated into a novel feed-forward control strategy where yeast pitching rate was modified based on values of the critical performance parameters from the previous batch. Use of this feed-forward strategy demonstrated how brewers can utilize near-infrared monitoring for quality assurance through early detection of shifts in fermentation performance. Copyright © 2017 The Institute of Brewing & Distilling}, number={3}, journal={JOURNAL OF THE INSTITUTE OF BREWING}, author={Vann, Lucas and Layfield, Johnathon B. and Sheppard, John D.}, year={2017}, month={Jul}, pages={347–360} }
 @article{vann_sheppard_2017, title={Use of near-infrared spectroscopy (NIRs) in the biopharmaceutical industry for real-time determination of critical process parameters and integration of advanced feedback control strategies using MIDUS control}, volume={44}, ISSN={["1476-5535"]}, DOI={10.1007/s10295-017-1984-2}, abstractNote={Abstract Control of biopharmaceutical processes is critical to achieve consistent product quality. The most challenging unit operation to control is cell growth in bioreactors due to the exquisitely sensitive and complex nature of the cells that are converting raw materials into new cells and products. Current monitoring capabilities are increasing, however, the main challenge is now becoming the ability to use the data generated in an effective manner. There are a number of contributors to this challenge including integration of different monitoring systems as well as the functionality to perform data analytics in real-time to generate process knowledge and understanding. In addition, there is a lack of ability to easily generate strategies and close the loop to feedback into the process for advanced process control (APC). The current research aims to demonstrate the use of advanced monitoring tools along with data analytics to generate process understanding in an Escherichia coli fermentation process. NIR spectroscopy was used to measure glucose and critical amino acids in real-time to help in determining the root cause of failures associated with different lots of yeast extract. First, scale-down of the process was required to execute a simple design of experiment, followed by scale-up to build NIR models as well as soft sensors for advanced process control. In addition, the research demonstrates the potential for a novel platform technology that enables manufacturers to consistently achieve “goldenbatch” performance through monitoring, integration, data analytics, understanding, strategy design and control (MIDUS control). MIDUS control was employed to increase batch-to-batch consistency in final product titers, decrease the coefficient of variability from 8.49 to 1.16%, predict possible exhaust filter failures and close the loop to prevent their occurrence and avoid lost batches.}, number={12}, journal={JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY}, author={Vann, Lucas and Sheppard, John}, year={2017}, month={Dec}, pages={1589–1603} }
 @article{layfield_vann_sheppard_2014, title={A Novel Method of Inducing and Retaining Cell Cycle Synchronization in Cultures of Saccharomyces cerevisiae}, volume={72}, ISSN={["1943-7854"]}, DOI={10.1094/asbcj-2014-0324-02}, abstractNote={In conventional fermentation, at any one time, individual yeast cells are randomly distributed with respect to the stage of their growth and division cycle. The observed metabolic performance is, therefore, the result of an average of the entire population. In contrast, a synchronous population is characterized by cells that are aligned with respect to their metabolic processes, traversing the cell cycle and dividing mostly in unison. In this study, a novel method for inducing and retaining cell cycle synchronization in yeast cultures (diploid and polyploid-type) was developed using a simple and natural phased expansion method, in which the volume of the culture was increased step-wise at time periods equal to the cell doubling time. Results indicate that this method was effective in producing yeast cultures with a high degree of synchrony, verified by cell counts and fluorescent cytometry. When stored in relatively small volumes at −80°C in glycerol, the cultures maintained their synchrony upon thawing. Experiments were also conducted at the lab-scale to assess the potential use of synchronous cultures in brewing applications. The incorporation of phased seed expansion and periodic feeding of the yeast culture provided increased metabolic uniformity within the population and reduced variability in fermentation performance.}, number={2}, journal={JOURNAL OF THE AMERICAN SOCIETY OF BREWING CHEMISTS}, author={Layfield, J. Blake and Vann, Lucas R. and Sheppard, John D.}, year={2014}, pages={102–109} }