Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platform

One goal of synthetic biology is to provide well-characterised biological parts that behave predictably in genetic assemblies. To achieve this, each part must be characterised in a time-resolved manner under relevant conditions. Robotic platforms can be used to automate this task and provide suffici...

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Main Authors: Jan Benedict Spannenkrebs, Aron Eiermann, Thomas Zoll, Silke Hackenschmidt, Johannes Kabisch
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Bioengineering and Biotechnology
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Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2024.1528224/full
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author Jan Benedict Spannenkrebs
Aron Eiermann
Thomas Zoll
Silke Hackenschmidt
Johannes Kabisch
Johannes Kabisch
Johannes Kabisch
author_facet Jan Benedict Spannenkrebs
Aron Eiermann
Thomas Zoll
Silke Hackenschmidt
Johannes Kabisch
Johannes Kabisch
Johannes Kabisch
author_sort Jan Benedict Spannenkrebs
collection DOAJ
description One goal of synthetic biology is to provide well-characterised biological parts that behave predictably in genetic assemblies. To achieve this, each part must be characterised in a time-resolved manner under relevant conditions. Robotic platforms can be used to automate this task and provide sufficiently large and reproducible data sets including provenance. Although robotics can significantly speed up the data collection process, the collation and analysis of the resulting data, needed to reprogram and refine workflows for future iterations, is often a manual process. As a result, even in times of rapidly advancing artificial intelligence, the common design-build-test-learn (DBTL) cycle is still not circular without human intervention. To move towards fully automated DBTL cycles, we developed a software framework to enable a robotic platform to autonomously adjust test parameters. This interdisciplinary work between computer science and biology thus transforms a static robotic platform into a dynamic one. The software framework includes software components such as an importer that retrieves measurement data from the platform’s devices and writes it to a database. This is followed by an optimizer that selects the next measurement points based on a balance between exploration and exploitation. The platform is shown to be able to automatically and autonomously optimize the inducer concentration for a Bacillus subtilis system and the combination of inducer and feed release for a Escherichia coli system. As a target product the readily measurable green fluorescent reporter protein (GFP) is produced over multiple, consecutive iterations of testing. An evaluation of chosen (learning) algorithms for single and dual factor optimization was performed. In this article, we share the lessons learned from the development, implementation and execution of this automated design-build-test-learn cycles on a robotic platform.
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spelling doaj-art-4a77814313e544aea3fe0ad9058b550d2025-01-22T09:15:04ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-01-011210.3389/fbioe.2024.15282241528224Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platformJan Benedict Spannenkrebs0Aron Eiermann1Thomas Zoll2Silke Hackenschmidt3Johannes Kabisch4Johannes Kabisch5Johannes Kabisch6Institute for Biotechnology and Food Science, NTNU, Trondheim, NorwayProteineer GmbH, Neu-Isenburg, GermanyComputer-Aided Synthetic Biology, TU Darmstadt, Darmstadt, GermanyComputer-Aided Synthetic Biology, TU Darmstadt, Darmstadt, GermanyInstitute for Biotechnology and Food Science, NTNU, Trondheim, NorwayProteineer GmbH, Neu-Isenburg, GermanyComputer-Aided Synthetic Biology, TU Darmstadt, Darmstadt, GermanyOne goal of synthetic biology is to provide well-characterised biological parts that behave predictably in genetic assemblies. To achieve this, each part must be characterised in a time-resolved manner under relevant conditions. Robotic platforms can be used to automate this task and provide sufficiently large and reproducible data sets including provenance. Although robotics can significantly speed up the data collection process, the collation and analysis of the resulting data, needed to reprogram and refine workflows for future iterations, is often a manual process. As a result, even in times of rapidly advancing artificial intelligence, the common design-build-test-learn (DBTL) cycle is still not circular without human intervention. To move towards fully automated DBTL cycles, we developed a software framework to enable a robotic platform to autonomously adjust test parameters. This interdisciplinary work between computer science and biology thus transforms a static robotic platform into a dynamic one. The software framework includes software components such as an importer that retrieves measurement data from the platform’s devices and writes it to a database. This is followed by an optimizer that selects the next measurement points based on a balance between exploration and exploitation. The platform is shown to be able to automatically and autonomously optimize the inducer concentration for a Bacillus subtilis system and the combination of inducer and feed release for a Escherichia coli system. As a target product the readily measurable green fluorescent reporter protein (GFP) is produced over multiple, consecutive iterations of testing. An evaluation of chosen (learning) algorithms for single and dual factor optimization was performed. In this article, we share the lessons learned from the development, implementation and execution of this automated design-build-test-learn cycles on a robotic platform.https://www.frontiersin.org/articles/10.3389/fbioe.2024.1528224/fullautomationsynthetic biologydesign-build-test-learn (DBTL) cycleautonomous systemlearning algorithm
spellingShingle Jan Benedict Spannenkrebs
Aron Eiermann
Thomas Zoll
Silke Hackenschmidt
Johannes Kabisch
Johannes Kabisch
Johannes Kabisch
Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platform
Frontiers in Bioengineering and Biotechnology
automation
synthetic biology
design-build-test-learn (DBTL) cycle
autonomous system
learning algorithm
title Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platform
title_full Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platform
title_fullStr Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platform
title_full_unstemmed Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platform
title_short Closing the loop: establishing an autonomous test-learn cycle to optimize induction of bacterial systems using a robotic platform
title_sort closing the loop establishing an autonomous test learn cycle to optimize induction of bacterial systems using a robotic platform
topic automation
synthetic biology
design-build-test-learn (DBTL) cycle
autonomous system
learning algorithm
url https://www.frontiersin.org/articles/10.3389/fbioe.2024.1528224/full
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