小型集成化自动移液工作站系统及应用

doi:10.12211/2096-8280.2021-095

摘要/Abstract

摘要：

现代生物技术、合成生物学和化学生物学研究中经常需要处理大量样本，对通量、精准度和时效性有很高要求。手动液体分装、转移和分发等操作不仅给科研人员带来很大工作负荷，还是导致实验误差和效率低下的重要原因。搭建以移液工作站为核心的小型集成化自动移液工作站系统，整合必要的外围设备，并通过软件和人机交互界面协调各个设备运行，可用于完成大量耗费人力的工作，提高工作效率和科研数据质量。本文结合研究团队所搭建的自动移液工作站系统，介绍了集成化移液工作站系统的主要组成，分享其在菌株及培养基评价、酶的定向进化筛选、自动诱导表达及粗酶液制备、酶联免疫吸附筛选、高通量质粒提取等方面的应用，并对集成化移液工作站系统的不足和购置及使用中的注意事项做了简要说明。预计集成化移液工作站系统将在国内高校和科研院所得到越来越普遍的应用，但还需要加大研发投入，从硬件、软件、人才、多学科交叉等多方面入手，共同推动国产实验室自动化设备进步。希望能为科研人员今后设计和添置类似的集成化移液工作站系统提供参考。

关键词: 移液工作站, 合成生物学, 自动化, 集成化

Abstract:

Nowadays experiments in biotechnology, synthetic biology and chemical biology often require handling a lot of samples timely with high throughput and accuracy. Manual operations such as liquid dispensing, transferring and distribution not only impose laborious burdens on researchers, but also lead to experimental errors and low efficiency. Therefore, the small-scale and integrated automation systems have emerged, whereby liquid-handling workstation serves as the core to integrate peripheral equipment and coordinate the operation of all instruments through software and human-machine interface. Such systems can be used to handle a large number of labor-consuming workloads and improve efficiency and data quality. As our laboratory is currently running a small-scale liquid handling system, here we first illustrate the major compositions of the system, and then share the processes used for rapid evaluation of culture media and strains as well as enzyme activities for directed evolution, automatic induction, expression and preparation of crude enzyme samples, automatic enzyme-linked immunosorbent assay-based screening and high-throughput plasmid extraction. We also briefly introduce key factors that may have significant impact on these processes, such as the location of consumables, the details of pipetting, script extension, and workflow planning. We further describe the shortcomings detected during the use of the system, offer suggestions for assembling similar systems with improved performance, and share the precautions that may cause abnormalities. While integrated automated liquid handling systems are expected to become an important part of the automated laboratory in the future in Chinese universities and research institutes, increased R&D investment and personnel training in hardware and software are needed for promoting the development of domestic laboratory automation equipment. Overall, it is a useful reference for other laboratories to design automated workstation systems.

Key words: liquid handling workstation, synthetic biology, automation, integration

中图分类号:

Q816

褚亚东, 赵宗保. 小型集成化自动移液工作站系统及应用[J]. 合成生物学, 2022, 3(1): 195-208.

Yadong CHU, Zongbao ZHAO. Designing and application of small-scale integrated automated liquid handling system[J]. Synthetic Biology Journal, 2022, 3(1): 195-208.

图/表 8

图1 蛋白质定向进化一般流程

Fig. 1 General process for directed evolution with proteins

图2 小型集成化移液工作站系统实例

Fig. 2 Example for a small-scale integrated automated liquid handling system

图3 培养基与菌株快速评价流程

Fig. 3 Process for rapid evaluation of culture media and strains

图4 突变株粗酶活性快速筛选流程

Fig. 4 Process for rapid screening of crude enzyme activity of mutant strains

图5 自动诱导表达制备粗酶液流程

Fig. 5 Process for automatic induction, expression and preparation of crude enzyme samples

图6 自动ELISA初步筛选流程

Fig. 6 Process for automated ELISA screening

图7 高通量质粒提取流程

Fig. 7 Process for high-throughput plasmid extraction

图8 集成移液工作站系统与python脚本协同工作流程

Fig. 8 Schematic diagram for the collaborative work flow between integrated automated liquid handling system and python scripts

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