Continuous Microbial Culture Instrumentation Control

Extensible Software Framework for Continuous Microbial Culture Instrumentation Control

PI Dr. Ahmad Khalil (2022 Schmidt Polymath, Boston University)

Continuous culture is a powerful experimental method in which cells are continuously maintained in specific growth conditions, enabling the study of cellular evolution in response to environmental selection pressures. When coupled with DNA sequencing, continuous culture has recently given researchers the ability to understand how genetics and evolution influence each other to ultimately shape cellular behavior in complex environments. This approach has been instrumental in studying various biological phenomena subject to evolution, such as antibiotic resistance, microbial communities, and gene regulation. Continuous culture is now being used in many engineering applications, such as biomanufacturing and protein engineering, demonstrating its broad utility in biotechnology and biomedical research.

Despite its proven value, continuous culture is operationally difficult to implement and often constrains experimental design due to the lack of low-cost, scalable, and flexible solutions. To address these limitations, the Khalil Lab at Boston University developed eVOLVER, a high-throughput, automated, continuous culture platform. With eVOLVER, researchers can precisely tune environmental growth conditions across an array of 16 bioreactors and program real-time, feedback-driven, culturing routines. As a modular, open-source platform, eVOLVER allows researchers to integrate new hardware & software components to adapt eVOLVER for experiment-specific needs and unlock novel, experimental methods in evolutionary biology.

While the reference design of the system supports a small number of operating modes and provides adequate extensibility of the hardware platform (for example adding color LEDs for optogenetic applications), it remains difficult for users to integrate such hardware additions into experimental control and calibration at the control software layer, and typically involves forking and directly modifying core eVOLVER code. This onerous situation is exacerbated when considering new hardware and integration with a multitude of possible UI web applications, where the complexity of integration tends to be higher than backend systems code.

Through the Virtual Institute for Scientific Software at Schmidt Futures, the Khalil Lab is working with the Scientific Software Engineering Center at JHU to revamp eVOLVER’s codebase. The goal of this collaboration is to create a software framework that enables the creation of customizable interfaces to readily setup, visualize, and analyze user-specific experiments and workflows. This work will make eVOLVER accessible to a wider range of users and further the project’s mission of democratizing continuous culture.