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Design of an Automated Reagent-Dispensing System for Reaction Screening and Validation with DNA-Tagged Substrates.
ACS Combinatorial Science Pub Date : 2020-02-27 , DOI: 10.1021/acscombsci.9b00207
Jens Bobers 1 , Mateja Klika Škopić 2 , Robin Dinter 1 , Piriyanth Sakthithasan 1 , Laura Neukirch 2 , Christian Gramse 3 , Ralf Weberskirch 3 , Andreas Brunschweiger 2 , Norbert Kockmann 1
Affiliation  

Laboratory automation strategies have vast potential for accelerating discovery processes. They enable higher efficiency and throughput for time-consuming screening procedures and reduce error-prone manual steps. Automating repetitive procedures can for instance support chemists in optimizing chemical reactions. Particularly, the technology of DNA-encoded libraries (DELs) may benefit from automation techniques, since translation of chemical reactions to DNA-tagged reactants often requires screening of multiple reaction parameters and evaluation of large numbers of reactants. Here, we describe a portable, automated system for reagent dispensing that was designed from open source materials. The system was validated by performing amide coupling of carboxylic acids to DNA-linked amine and a micelle-mediated Povarov reaction to DNA-tagged hexahydropyrroloquinolines. The latter reaction required accurate pipetting of multiple components including different solvents and a surface-active reagent. Analysis of reactions demonstrated that the robotic system achieved high accuracy comparable to experimentation by an experienced chemist with the potential of higher throughput.

中文翻译:

设计用于DNA标记底物的反应筛选和验证的自动试剂分配系统。

实验室自动化策略具有加速发现过程的巨大潜力。它们为费时的筛选过程提供了更高的效率和通量,并减少了容易出错的手动步骤。自动化重复程序可以例如支持化学家优化化学反应。特别地,DNA编码文库(DEL)的技术可能会受益于自动化技术,因为将化学反应翻译成带有DNA标签的反应物通常需要筛选多个反应参数并评估大量反应物。在这里,我们描述了一种由开源材料设计的便携式自动试剂分配系统。该系统通过羧酸与DNA连接的胺的酰胺偶联以及胶束介导的Povarov反应与DNA标记的六氢吡咯并喹啉进行了验证。后一反应需要精确移液多种组分,包括不同的溶剂和表面活性剂。反应分析表明,与经验丰富的化学家进行的实验相比,该机器人系统具有较高的准确性,并且具有更高的通量潜力。
更新日期:2020-02-28
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