New small-scale, low-cost bioreactors provide researchers with exquisite control of environmental parameters of microbial cultures over long durations, allowing them to perform sophisticated, high-quality quantitative experiments that are particularly useful in systems biology, synthetic biology and bioengineering. However, existing setups are limited in their automated measurement capabilities, primarily because sensitive and specific measurements require bulky, expensive, stand-alone instruments. Here, we present ReacSight, a generic and flexible strategy to enhance bioreactor arrays for automated measurements and reactive experiment control. On the hardware side, ReacSight leverages a pipetting robot for sample collection, handling and loading. On the software side, ReacSight provides a versatile instrument control architecture and a generic event system for reactive experiment control. ReacSight is ideally suited to integrate open-source, open-hardware components but can also accommodate closed-source, GUI-only components (e.g. cytometers). We use ReacSight to assemble a platform for cytometry-based characterization and reactive optogenetic control of parallel yeast continuous cultures. Using a dedicated bioreactor array, we showcase its capabilities on three applications. First, we achieve parallel real-time control of gene expression with light in different bioreactors. Second, we explore the impact of nutrient scarcity on fitness and cellular stress using well-controlled, high-information content competition assays. Third, we exploit nutrient scarcity to achieve dynamic control over the composition of a two-strain consortium. To illustrate the genericity of ReacSight, we also assemble an equivalent platform using the optogenetic-ready, open-hardware and commercially available Chi.Bio bioreactors.

中文翻译：

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使用 ReacSight 增强生物反应器阵列的自动化测量和反应控制

新型小规模、低成本的生物反应器为研究人员提供了长时间对微生物培养物环境参数的精确控制，使他们能够进行复杂、高质量的定量实验，这些实验在系统生物学、合成生物学和生物工程中特别有用。然而，现有设置的自动测量功能受到限制，主要是因为敏感和特定的测量需要笨重、昂贵的独立仪器。在这里，我们展示了 ReacSight，这是一种通用且灵活的策略，用于增强生物反应器阵列以进行自动测量和反应实验控制。在硬件方面，ReacSight 利用移液机器人进行样本收集、处理和加载。在软件方面，ReacSight 提供了一个通用的仪器控制架构和一个用于反应实验控制的通用事件系统。ReacSight 非常适合集成开源、开放硬件组件，但也可以容纳闭源、仅限 GUI 的组件（例如细胞仪）。我们使用 ReacSight 组装了一个平台，用于对平行酵母连续培养物进行基于细胞计数的表征和反应性光遗传学控制。使用专用的生物反应器阵列，我们展示了其在三个应用中的能力。首先，我们在不同的生物反应器中用光实现了基因表达的并行实时控制。其次，我们使用控制良好、信息含量高的竞争分析来探索营养缺乏对健康和细胞压力的影响。第三，我们利用营养稀缺来实现对两株菌群组成的动态控制。为了说明 ReacSight 的通用性，我们还使用光遗传学就绪、开放硬件和市售的 Chi.Bio 生物反应器组装了一个等效平台。