Droplet-based microfluidic systems have emerged as powerful alternatives to conventional high throughput screening platforms, due to their operational flexibility, high-throughput nature and ability to efficiently process small fluid volumes. However, the challenges associated with performing bespoke operations on user-defined droplets often limit their utility in screening applications that involve complex workflows. To this end, the marriage of droplet- and valve-based microfluidic technologies offers the prospect of balancing the controllability of droplet manipulations and analytical throughput. In this spirit, we present a microfluidic platform that combines the capabilities of integrated microvalve technology with droplet-based sample compartmentalization to realize a highly adaptable programmable fluid handling functionality. The microfluidic device consists of a programmable formulator linked to an automated droplet generation device and storage array. The formulator leverages multiple inputs coupled to a mixing ring to produce combinatorial solution mixtures, with a peristaltic pump enabling titration of reagents into the ring with picoliter resolution. The platform allows for the execution of user-defined reaction protocols within an array of storage chambers by consecutively merging programmable sequences of pL-volume droplets containing specified reagents. The precision in formulating solutions with small differences in concentration is perfectly suited for the accurate estimation of kinetic parameters. The utility of our platform is showcased through the performance of enzymatic kinetic measurements of beta-galactosidase and horseradish peroxidase with fluorogenic substrates. The presented platform provides for a range of automated manipulations and paves the way for a more diverse range of droplet-based biological experiments.

中文翻译：

---

迈向用于可编程流体处理的基于液滴的主动微流体平台

基于液滴的微流体系统已成为传统高通量筛选平台的强大替代品，因为它们具有操作灵活性、高通量特性和有效处理小体积流体的能力。然而，与对用户定义的液滴执行定制操作相关的挑战通常会限制它们在筛选涉及复杂工作流程的应用程序中的效用。为此，基于液滴和阀的微流体技术的结合提供了平衡液滴操作的可控性和分析通量的前景。本着这种精神，我们提出了一种微流体平台，该平台将集成微阀技术的功能与基于液滴的样品分隔相结合，以实现高度适应性的可编程流体处理功能。微流体装置由连接到自动液滴生成装置和存储阵列的可编程配方器组成。配方设计师利用耦合到混合环的多个输入来产生组合溶液混合物，并使用蠕动泵以皮升分辨率将试剂滴定到环中。该平台允许通过连续合并包含指定试剂的 pL 体积液滴的可编程序列，在一系列存储室中执行用户定义的反应协议。配制浓度差异很小的溶液的精度非常适合动力学参数的准确估计。我们平台的实用性通过使用荧光底物对 β-半乳糖苷酶和辣根过氧化物酶进行酶动力学测量来展示。所呈现的平台提供了一系列自动化操作，并为更多样化的基于液滴的生物实验铺平了道路。