Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA.
Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA, 01609, USA.
Sci Rep. 2018 Apr 18;8(1):6217. doi: 10.1038/s41598-018-24504-x.
High-throughput biological and chemical experiments typically use either multiwell plates or microfluidic devices to analyze numerous independent samples in a compact format. Multiwell plates are convenient for screening chemical libraries in static fluid environments, whereas microfluidic devices offer immense flexibility in flow control and dynamics. Interfacing these platforms in a simple and automated way would introduce new high-throughput experimental capabilities, such as compound screens with precise exposure timing. Whereas current approaches to integrate microfluidic devices with multiwell plates remain expensive or technically complicated, we present here a simple open-source robotic system that delivers liquids sequentially through a single connected inlet. We first characterized reliability and performance by automatically delivering 96 dye solutions to a microfluidic device. Next, we measured odor dose-response curves of in vivo neural activity from two sensory neuron types in dozens of living C. elegans in a single experiment. We then identified chemicals that suppressed optogenetically-evoked neural activity, demonstrating a functional screening platform for neural modulation in whole organisms. Lastly, we automated an 85-minute, ten-step cell staining protocol. Together, these examples show that our system can automate various protocols and accelerate experiments by economically bridging two common elements of high-throughput systems: multiwell plates and microfluidics.
高通量生物和化学实验通常使用多孔板或微流控装置以紧凑的格式分析大量独立的样本。多孔板便于在静态流体环境中筛选化学文库,而微流控装置在流量控制和动力学方面具有巨大的灵活性。以简单和自动化的方式将这些平台集成在一起将引入新的高通量实验能力,例如具有精确暴露时间的化合物筛选。尽管当前将微流控装置与多孔板集成的方法仍然昂贵或技术上复杂,但我们在这里提出了一种简单的开源机器人系统,该系统可通过单个连接的入口顺序输送液体。我们首先通过自动将 96 种染料溶液输送到微流控装置来表征可靠性和性能。接下来,我们在单个实验中测量了数十个活体秀丽隐杆线虫中两种感觉神经元类型的体内神经活动的气味剂量反应曲线。然后,我们鉴定出抑制光遗传诱导的神经活动的化学物质,证明了用于整个生物体神经调节的功能筛选平台。最后,我们自动化了一个 85 分钟、十个步骤的细胞染色方案。总之,这些示例表明,我们的系统可以通过经济地桥接高通量系统的两个常见元素(即多孔板和微流控装置)来自动化各种方案并加速实验。