Enabling high‐throughput biology with flexible open‐source automation

Abstract Our understanding of complex living systems is limited by our capacity to perform experiments in high throughput. While robotic systems have automated many traditional hand‐pipetting protocols, software limitations have precluded more advanced maneuvers required to manipulate, maintain, and...

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Main Authors: Emma J Chory, Dana W Gretton, Erika A DeBenedictis, Kevin M Esvelt
Format: Article
Language:English
Published: Springer Nature 2021-03-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20209942
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author Emma J Chory
Dana W Gretton
Erika A DeBenedictis
Kevin M Esvelt
author_facet Emma J Chory
Dana W Gretton
Erika A DeBenedictis
Kevin M Esvelt
author_sort Emma J Chory
collection DOAJ
description Abstract Our understanding of complex living systems is limited by our capacity to perform experiments in high throughput. While robotic systems have automated many traditional hand‐pipetting protocols, software limitations have precluded more advanced maneuvers required to manipulate, maintain, and monitor hundreds of experiments in parallel. Here, we present Pyhamilton, an open‐source Python platform that can execute complex pipetting patterns required for custom high‐throughput experiments such as the simulation of metapopulation dynamics. With an integrated plate reader, we maintain nearly 500 remotely monitored bacterial cultures in log‐phase growth for days without user intervention by taking regular density measurements to adjust the robotic method in real‐time. Using these capabilities, we systematically optimize bioreactor protein production by monitoring the fluorescent protein expression and growth rates of a hundred different continuous culture conditions in triplicate to comprehensively sample the carbon, nitrogen, and phosphorus fitness landscape. Our results demonstrate that flexible software can empower existing hardware to enable new types and scales of experiments, empowering areas from biomanufacturing to fundamental biology.
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spelling doaj.art-c41ab37745d3457197e8dc00155616302024-10-28T09:22:03ZengSpringer NatureMolecular Systems Biology1744-42922021-03-0117311010.15252/msb.20209942Enabling high‐throughput biology with flexible open‐source automationEmma J Chory0Dana W Gretton1Erika A DeBenedictis2Kevin M Esvelt3Media Laboratory, Massachusetts Institute of TechnologyMedia Laboratory, Massachusetts Institute of TechnologyMedia Laboratory, Massachusetts Institute of TechnologyMedia Laboratory, Massachusetts Institute of TechnologyAbstract Our understanding of complex living systems is limited by our capacity to perform experiments in high throughput. While robotic systems have automated many traditional hand‐pipetting protocols, software limitations have precluded more advanced maneuvers required to manipulate, maintain, and monitor hundreds of experiments in parallel. Here, we present Pyhamilton, an open‐source Python platform that can execute complex pipetting patterns required for custom high‐throughput experiments such as the simulation of metapopulation dynamics. With an integrated plate reader, we maintain nearly 500 remotely monitored bacterial cultures in log‐phase growth for days without user intervention by taking regular density measurements to adjust the robotic method in real‐time. Using these capabilities, we systematically optimize bioreactor protein production by monitoring the fluorescent protein expression and growth rates of a hundred different continuous culture conditions in triplicate to comprehensively sample the carbon, nitrogen, and phosphorus fitness landscape. Our results demonstrate that flexible software can empower existing hardware to enable new types and scales of experiments, empowering areas from biomanufacturing to fundamental biology.https://doi.org/10.15252/msb.20209942bioautomationhigh‐throughput biologyliquid‐handlingroboticssystems biology
spellingShingle Emma J Chory
Dana W Gretton
Erika A DeBenedictis
Kevin M Esvelt
Enabling high‐throughput biology with flexible open‐source automation
Molecular Systems Biology
bioautomation
high‐throughput biology
liquid‐handling
robotics
systems biology
title Enabling high‐throughput biology with flexible open‐source automation
title_full Enabling high‐throughput biology with flexible open‐source automation
title_fullStr Enabling high‐throughput biology with flexible open‐source automation
title_full_unstemmed Enabling high‐throughput biology with flexible open‐source automation
title_short Enabling high‐throughput biology with flexible open‐source automation
title_sort enabling high throughput biology with flexible open source automation
topic bioautomation
high‐throughput biology
liquid‐handling
robotics
systems biology
url https://doi.org/10.15252/msb.20209942
work_keys_str_mv AT emmajchory enablinghighthroughputbiologywithflexibleopensourceautomation
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AT erikaadebenedictis enablinghighthroughputbiologywithflexibleopensourceautomation
AT kevinmesvelt enablinghighthroughputbiologywithflexibleopensourceautomation