An Intelligent Automation Platform for Rapid Bioprocess Design

Abstract

Bioprocess development is very labor intensive, requiring many experiments to characterize each unit operation in the process sequence to achieve product safety and process efficiency. Recent advances in microscale biochemical engineering have led to automated experimentation. A process design workflow is implemented sequentially in which (1) a liquid-handling system performs high-throughput wet lab experiments, (2) standalone analysis devices detect the data, and (3) specific software is used for data analysis and experiment design given the user’s inputs. We report an intelligent automation platform that integrates these three activities to enhance the efficiency of such a workflow. A multiagent intelligent architecture has been developed incorporating agent communication to perform the tasks automatically. The key contribution of this work is the automation of data analysis and experiment design and also the ability to generate scripts to run the experiments automatically, allowing the elimination of human involvement. A first-generation prototype has been established and demonstrated through lysozyme precipitation process design. All procedures in the case study have been fully automated through an intelligent automation platform. The realization of automated data analysis and experiment design, and automated script programming for experimental procedures has the potential to increase lab productivity.

Design of experiments‐based high‐throughput strategy for development and optimization of efficient cell disruption protocols

“…However, human involvement was still needed in most steps, for example, in designing the experimental plan, in programming and initiating the liquid handling unit, in data treatment obtained from the plate reader, as well as in modification the plan of experiments for the next round. Such a strategy is in accordance with previously published automated HT platforms for bioprocess development [18,19]. Further extension of such an automated flow can be envisioned by a full closed-loop system as recently published by Wu and Zhou [18].…”

“…Such a strategy is in accordance with previously published automated HT platforms for bioprocess development . Further extension of such an automated flow can be envisioned by a full closed‐loop system as recently published by Wu and Zhou . Such an “intelligent” system could perform the modification of experimental plans for the next round automatically (e.g., optimization step) based on the results obtained from a previous round (e.g., screening step).…”

Designing a blueprint for next‐generation stem cell bioprocessing development

“…Furthermore, advances in technologies and informatic tools for generating and processing massive biological datasets will require contributions from a myriad of fields from basic research to stem cell bioprocessing. These required contributions include the development of rapid run time or real‐time measurements as well as techniques for data‐based modeling and control of bioprocessing (Kami et al, ; Manzoni et al, ; Wu & Zhou, ). Design of integrated bioprocesses: an integrated approach for the design of entire bioprocesses would recognize the interactions outlined above, and enable new bioprocessing design methods to take these into considerations. Bioprocess engineering fundamentals, including culture design, bioreactor development, and process automation, must be combined with cellular system biology principles to guide the development of next‐generation technologies and tools to produce hPSC‐derived products in a robust, cost‐effective manner (Lei, Jeong, Xiao, & Schaffer, ; Wu & Zhou, ).…”

“…These required contributions include the development of rapid run time or real‐time measurements as well as techniques for data‐based modeling and control of bioprocessing (Kami et al, ; Manzoni et al, ; Wu & Zhou, ). Design of integrated bioprocesses: an integrated approach for the design of entire bioprocesses would recognize the interactions outlined above, and enable new bioprocessing design methods to take these into considerations. Bioprocess engineering fundamentals, including culture design, bioreactor development, and process automation, must be combined with cellular system biology principles to guide the development of next‐generation technologies and tools to produce hPSC‐derived products in a robust, cost‐effective manner (Lei, Jeong, Xiao, & Schaffer, ; Wu & Zhou, ). To fulfill these requirements, bioreactor systems must be designed as components of fully automated bioprocessing systems, or as complete closed‐systems considering flexibility, adaptability, scalability, modifiability, and robustness to enable robust and reproducible bioprocessing for various applications (Kami et al, ; Manzoni et al, ; Olmer et al, ; Wu & Zhou, ).…”

“…Bioprocess engineering fundamentals, including culture design, bioreactor development, and process automation, must be combined with cellular system biology principles to guide the development of next‐generation technologies and tools to produce hPSC‐derived products in a robust, cost‐effective manner (Lei, Jeong, Xiao, & Schaffer, ; Wu & Zhou, ). To fulfill these requirements, bioreactor systems must be designed as components of fully automated bioprocessing systems, or as complete closed‐systems considering flexibility, adaptability, scalability, modifiability, and robustness to enable robust and reproducible bioprocessing for various applications (Kami et al, ; Manzoni et al, ; Olmer et al, ; Wu & Zhou, ). To monitor the biological environments within bioreactors for further research of growth characteristics and to increase product yields, several sensors have been added to bioreactors, which function to control the environmental conditions by enabling the measurement of physical variable parameters (e.g., temperature, shear rate, flow motion, pressure), chemical variables (e.g., pH, pO 2 , nutrients, metabolites), and biological variables (e.g., biomass concentration, cell metabolism; Kami et al, ; Manzoni et al, ).…”