IBM Research-Zurich, Rüschlikon, Switzerland.
Institute of Neuroinformatics, University of Zurich/ETH Zurich, Zurich, Switzerland.
Nature. 2019 Oct;574(7777):228-232. doi: 10.1038/s41586-019-1635-z. Epub 2019 Oct 9.
Microfluidic systems can deliver portable point-of-care diagnostics without the need for external equipment or specialist operators, by integrating all reagents and manipulations required for a particular assay in one device. A key approach is to deposit picogram quantities of dried reagents in microchannels with micrometre precision using specialized inkjet plotters. This means that reagents can be stored for long periods of time and reconstituted spontaneously when adding a liquid sample. But it is challenging to carry out complex operations using multiple reagents, because shear flow enhances their dispersion and they tend to accumulate at moving liquid fronts, resulting in poor spatiotemporal control over the concentration profile of the reconstituted reagents. One solution is to limit the rate of release of reagents into the liquid. However, this requires the fine-tuning of different reagents, conditions and targeted operations, and cannot readily produce the complex, time-dependent multireagent concentration pulses required for sophisticated on-chip assays. Here we report and characterize a capillary flow phenomenon that we term self-coalescence, which is seen when a confined liquid with a stretched air-liquid interface is forced to 'zip' back onto itself in a microfluidic channel, thereby allowing reagent reconstitution with minimal dispersion. We provide a comprehensive framework that captures the physical underpinning of this effect. We also fabricate scalable, compact and passive microfluidic structures-'self-coalescence modules', or SCMs-that exploit and control this phenomenon in order to dissolve dried reagent deposits in aqueous solutions with precise spatiotemporal control. We show that SCMs can reconstitute multiple reagents so that they either undergo local reactions or are sequentially delivered in a flow of liquid. SCMs are easily fabricated in different materials, readily configured to enable different reagent manipulations, and readily combined with other microfluidic technologies, so should prove useful for assays, diagnostics, high-throughput screening and other technologies requiring efficient preparation and manipulation of small volumes of complex solutions.
微流控系统可以通过在一个设备中集成特定测定所需的所有试剂和操作，实现无需外部设备或专业操作人员的便携式即时诊断。一种关键方法是使用专用喷墨绘图仪以微米级精度将皮克数量的干燥试剂沉积在微通道中。这意味着试剂可以长时间储存，并在添加液体样品时自发重新配制。但是，使用多种试剂进行复杂操作具有挑战性，因为剪切流会增强它们的分散性，并且它们往往会在移动的液体前缘处积累，导致对重新配制试剂的浓度分布的时空控制不佳。一种解决方案是限制试剂向液体中的释放速度。然而，这需要对不同的试剂、条件和目标操作进行微调，并且不能轻易产生复杂的、随时间变化的多试剂浓度脉冲，这些脉冲是用于复杂的芯片上测定所必需的。在这里，我们报告并描述了一种我们称之为自聚结的毛细流动现象，当具有拉伸气液界面的受限液体被迫在微流道中“拉链”回到自身时，就会出现这种现象，从而可以最小化分散地进行试剂重配。我们提供了一个全面的框架，该框架捕获了该效应的物理基础。我们还制造了可扩展、紧凑且无源的微流控结构——自聚结模块或 SCMs——利用并控制这种现象，以便在精确的时空控制下用水溶液溶解干燥的试剂沉积物。我们表明，SCM 可以重新配制多种试剂，以便它们要么在局部发生反应，要么在液体流中依次输送。SCM 可以用不同的材料轻松制造，易于配置以实现不同的试剂操作，并且易于与其他微流控技术结合使用，因此应该对需要有效制备和处理复杂溶液小体积的测定、诊断、高通量筛选和其他技术有用。
