Modeling & Process Optimization

Computational modeling and optimization are transforming modern biomanufacturing by enabling researchers to better understand, predict, and control complex cellular processes. As biologics become increasingly important in treating diseases ranging from cancer to infectious diseases, there is a growing need for efficient strategies that reduce development costs, accelerate process optimization, and improve product quality. By integrating mechanistic understanding of cellular metabolism with machine learning and advanced optimization techniques, digital biomanufacturing approaches provide a pathway toward more predictive, automated, and data-driven manufacturing platforms capable of producing safer, more affordable, and higher-quality therapeutics.

Our Research in modeling and optimization focuses on developing computational frameworks that describe and predict mammalian cell culture behavior across diverse bioprocess conditions. These efforts combine mechanistic metabolic models, hybrid modeling approaches, machine learning algorithms, and Bayesian optimization techniques to characterize cellular metabolism, optimize media formulations, and improve bioprocess performance. Applications include predicting cell growth and productivity, optimizing culture conditions, improving product quality attributes such as glycosylation, and enabling data-efficient process development. Through the integration of experimental data and computational intelligence, this work supports the development of next-generation digital biomanufacturing systems for therapeutic protein production.

  • Multi-Objective Bayesian Optimization for Data-Efficient Bioprocess Development

    Edward Ma, James Morrissey, Shutong Duan, Ziqi Lu, Sandeep Ranpura, Sneha Arora, Anita Dabek, Chen Liu, Gheorghe Alexandra-Gabriela, Louis K. W. Fong, Maria Snani, Pavle Vrljicak, Deniz Demirhan, Michael Betenbaugh

    February 4, 2026

  • MCBO: Mammalian Cell Bioprocessing Ontology, A Hub-and-Spoke, IOF-Anchored Application Ontology

    Kimberly Robasky, James Morrissey, Markus Riedl, Andreas Dräger, Nicole Borth, Michael J. Betenbaugh, Nathan E. Lewis

    January 5, 2026

  • Comparing Kinetic versus Stoichiometric Priorities in Hybrid Models of CHO Metabolism

    Pratik Khare, Nelson Ndahiro, Stephanie Klaubert, Edward Ma, Tom S. Bertalan, Yannis Kevrekidis, Sarah W. Harcum, Michael J. Betenbaugh

    May 29, 2026

  • Wheels Turning: CHO Cell Modeling Moves into a Digital Biomanufacturing Era

    Sandeep Ranpura, Vishwanathgouda Maralingannavar, Alexandra-Gabriela Gheorghe, Edward Ma, James Morissey, Michael Betenbaugh, Deniz Demirhan

    March 12, 2025

  • Integration of Bayesian Optimization and Solution Thermodynamics to Optimize Media Design for Mammalian Biomanufacturing

    Nelson Ndahiro, Edward Ma, Tom Bertalan, Marc Donohue, Yannis Kevrekidis, Michael Betenbaugh

    August 15, 2025

  • Inferring the Metabolic Objectives of Mammalian Cells via Inverse Modeling of Fluxomics and Metabolomics

    James Morrissey, Mariana Monteiro, Michael Betenbaugh, Cleo Kontoravdi

    September 25, 2025

  • A Community-consensus Reconstruction of Chinese Hamster Metabolism Enables Structural Systems Biology Analyses to Decipher Metabolic Rewiring in Lactate-free CHO Cells

    Pablo Di Giusto, Dong-Hyuk Choi, Athanasios Antonakoudis, Vikash Gokul Duraikannan, Pierrick Craveur, Nicholas Luke Cowie, Tejaswini Ganapathy, Kannan Ramesh, Santiago Benavidez-López, Camila A. Orellana, Natalia E. Jiménez, Leo Alexander Dworkin, James Morrissey, Igor Marin de Mas, Benjamin Strain, Norma A. Valdez-Cruz, Mauricio A. Trujillo-Roldán, Jannis Marzluf, Verónica S. Martínez, Leopold Zehetner, Claudia Altamirano, Ana Maria Vega-Letter, , Bradley Priem, Haoyu Chris Cao, Martin Hold, Edward Ma, Yi Fan Hong, Claudio Angione, Jürgen Zanghellini, Cleo Kontoravdi, Hooman Hefzi, Michael J. Betenbaugh, Lars K. Nielsen, Meyyappan Lakshamanan, Dong-Yup Lee, Anne Richelle, Nathan E. Lewis

    April 17, 2025

  • Modeling Solubilities for Amino Acids in Water as Functions of Temperature and pH

    Tianxin Zhang, Ashwin Dravid, Jayanth Reddy, Lateef Aliyu, Jaeyoung Park, Zibo Wang, Kai-Wen Huang, Jinke Wu, Shuman Liu, Alan Stone, Michael Betenbaugh, Marc Donohue

    December 9, 2024

  • Data-driven and Physics Informed Modeling of Chinese Hamster Ovary (CHO) Cell Bioreactors

    Tianqi Cui, Tom Bertalan, Nelson Ndahiro, Pratik Khare, Michael Betenbaugh, Costas Maranas, Ioannis G. Kevrekidis

    May 4, 2023

  • Computational Predictions of Nutrient Precipitation for Intensified Cell 1 Culture Media via Amino Acid Solution Thermodynamics

    Jayanth Venkatarama Reddy, Nelson Ndahiro, Lateef Aliyu, Ashwin Dravid, Tianxin Xang, Jinke Wu, Michael Betenbaugh, Marc Donohue

    September 8, 2025