Microfluidic Methods for High-Throughput Biological Screening

Abstract

Often in biology, rare individuals within a population dominate the population’s overall behavior, and we wish to extract those individuals for further analysis. We design a sorting instrument as a flexible platform for the development of novel microfluidic sorting techniques. We demonstrate a microfluidic cell sorter, which screens cells at rates approaching those of commercially-available fluorescence-activated cell sorters. This device incorporates a three-dimensional flow-focusing nozzle with a slanted ceiling groove to enhance the capabilities of a surface acoustic wave (SAW) transducer by harnessing the component of the SAW oriented normal to the plane of the substrate. The device achieves sorting at a rate of 9000 events/s with 54% purity and yields 89% purity, while operating at 1000 events/s; this level of performance approaches that of a FACS operating in its high-purity mode. We also present a rare event sorting technique, which can successfully extract desired droplets from a sample containing nearly a billion droplets. The technique yields pure samples after two rounds. The preliminary round is fast, capable of screening 10 ml of droplets at 100 ml/h, but each sort also captures many other droplets together with the droplet of interest. The second round of sorting enriches the sample to nearly 100% purity, using known designs for high purity drop-by-drop sorting. Thus, we devise a method, which can sort droplets rapidly and achieve high purity of few droplets from samples containing large numbers of droplets. The two disparate approaches to microfluidic sorting use a common platform to create new methods for sorting with biological applications.