Enabling high-throughput biology with flexible open-source automation.

Enabling high-throughput biology with flexible open-source automation.
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通过灵活的开源自动化实现高通量生物学。

DOI:
10.15252/msb.20209942
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发表时间:
2021-03
影响因子:
9.9
通讯作者:
Esvelt KM
Esvelt KM
中科院分区:
生物学1区
文献类型:
--
作者:
Chory EJ;Gretton DW;DeBenedictis EA;Esvelt KM

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我们对复杂生命系统的理解受到我们进行高通量实验的能力的限制。虽然机器人系统已经自动化了许多传统的手动移液方案,但软件的限制已经排除了并行操作,维护和监控数百个实验所需的更先进的操作。在这里,我们介绍了Pyhamilton,一个开源的Python平台,可以执行自定义高通量实验所需的复杂移液模式,例如集合种群动力学模拟。借助集成的酶标仪,我们通过定期进行密度测量来真实的实时调整机器人方法,从而使近500个远程监控的细菌培养物在对数生长期保持数天,无需用户干预。利用这些能力,我们系统地优化生物反应器蛋白质生产,通过一式三份地监测一百种不同连续培养条件的荧光蛋白表达和生长速率,以全面采样碳、氮和磷的适应度景观。我们的研究结果表明,灵活的软件可以增强现有硬件的能力,使新类型和规模的实验成为可能,从而增强从生物制造到基础生物学等领域的能力。开源Python平台使先进的液体处理机器人能够执行各种复杂的高通量实验,这些实验永远无法手动执行。
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. An open‐source Python platform enables advanced liquid handling robots to perform a variety of complex high‐throughput experiments that could never be performed manually.
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