首页|合成生物学表型测试生物反应器及其装备化研究进展

合成生物学表型测试生物反应器及其装备化研究进展

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合成生物学经过多年的发展,形成了典型的细胞工厂创制"设计-构建-测试-学习"(design-build-test-learn,DBTL)循环,成为支撑面向加速生物制造发展的智慧生物育种的重要方法.其中,测试环节是对前期所设计与构建的生物体系进行表型测试,以提供大量数据用于后续的学习和迭代升级.测试阶段的通量主要依赖于细胞自身或其培养测试所使用的生物反应器及其装备,是整个DBTL流程的限速步骤.本文系统综述了合成生物学表型测试所开发的面向不同通量的生物反应器及装备,从单细胞检测和筛选及不同尺度生物反应器包括皮纳升级生物反应器、微升级生物反应器、毫升级生物反应器和升级生物反应器等,系统地介绍了各自的特点和应用场景.同时,指出了现有生物反应器及其装备的应用潜力、面临的挑战与发展趋势,为合成生物学表型测试技术研究提供重要参考.
Progress in bioreactors and instruments for phenotype testing with synthetic biology research
Over the past years,synthetic biology has seen significant development,establishing a typical"Design-Build-Test-Learn(DBTL)"cycle for engineering cell factories.This cycle has been becoming an enabling methodology for smart breeding to accelerate the development of biomanufacturing.In the DBTL cycle,the testing step primarily aims to evaluate the phenotypes of constructed cell factories,which can provide a large amount of data for further learning and iterative optimization.Due to the complexity of cellular metabolic networks and regulatory mechanisms,as well as the complicated associations between genotypes and phenotypes,the design and construction of cell factories have traditionally involved long-term and labor-intensive iterative experiments.In synthetic biology,the construction of cell factories with designed synthetic pathways is often combined with random mutation and evolution to build up a large screening library,which always requires a high throughput and efficient technology and equipment in the testing step.The testing step is the rate-limiting process in the entire DBTL cycle,and its efficiency is largely dependent on chassis cells themselves,as well as the throughput of bioreactors and instruments needed for their phenotype testing.Here,this review article focuses on an overview of bioreactors and instruments with different throughput scales used for the phenotype testing in synthetic biology.We introduce their characteristics and application scenarios,including single-cell detecting and screening technology as well as pico-,nano-,micro-,milli-,and liter-scale bioreactors.Moreover,this article also points out the application potential of existing phenotype testing bioreactors and instruments,and illustrates how they can be selected for specific research purposes.Finally,the challenges and perspectives for phenotype testing bioreactors and instruments are summarized,which hopefully provides a reference for a wide range of synthetic biology researchers to properly select and use phenotype testing instruments.

synthetic biologyhigh throughput screeningdroplet microfluidicsbioreactormicro-well platemicro-tube bioreactor

郭肖杰、剪兴金、王立言、张翀、邢新会

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清华大学化学工程系,生物化工研究所,北京 100084

工业生物催化教育部重点实验室,北京 100084

清华大学无锡应用技术研究院生物育种中心,无锡 214000

清华大学合成与系统生物学中心,北京 100084

清华大学深圳国际研究生院生物医药与健康工程研究院,深圳 518055

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合成生物学 高通量筛选 液滴微流控 生物反应器 微孔板 微型管式生物反应器

国家重点研发计划国家自然科学基金重大仪器专项深圳市可持续发展专项

2018YFA090150021627812KCXFZ20201221173207022

2024

合成生物学

合成生物学

CSTPCD北大核心
ISSN:
年,卷(期):2024.5(1)
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