NOVAsort for error-free droplet microfluidics

• Published in: Nature communications 2024-11, Vol.15 (1), p.9444-13, Article 9444
• Main Authors: Zhang, Han, Gupte, Rohit, Li, Yuwen, Huang, Can, Guzman, Adrian R., Han, Jeong Jae, Jung, Haemin, Sabnis, Rushant, de Figueiredo, Paul, Han, Arum
• Format: Article
• Language: English
• Subjects: 49/47; 49/62; 631/1647/2163; 631/1647/277; 639/166/985; 639/166/987; Accuracy; Design; Droplets; Electric fields; Electrodes; Engineering; Fluorescence; High-throughput screening; High-Throughput Screening Assays - instrumentation; High-Throughput Screening Assays - methods; Humanities and Social Sciences; Humans; Microfluidic Analytical Techniques - instrumentation; Microfluidic Analytical Techniques - methods; Microfluidics; Microfluidics - instrumentation; Microfluidics - methods; multidisciplinary; Science; Science (multidisciplinary); Screening; Single-Cell Analysis - instrumentation; Single-Cell Analysis - methods
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52932-z

High-throughput screening techniques are pivotal to unlocking the mysteries of biology. Yet, the promise of droplet microfluidics in enabling single-cell resolution, ultra-high-throughput screening remains largely unfulfilled. Droplet sorting errors caused by polydisperse droplet sizes that are often inevitable in multi-step assays have severely limited the effectiveness and utility of this technique, especially when screening large libraries. Even a relatively low 1% sorting error results in 10,000 false calls in a 1,000,000 droplet screen, imposing an unreasonably large burden on downstream validation. Here, we present NOVAsort (Next-generation Opto-Volume-based Accurate droplet sorter), a device capable of discerning droplets based on both size and fluorescence intensity. With a 1000- and 10,000-fold reduction in false positives and false negatives, respectively. NOVAsort addresses the challenges of conventional droplet sorting approaches and sets standards for accuracy and throughput in droplet microfluidic assays. Droplet microfluidic tools with single-cell resolution and high-throughput screening capacities remain scarce. Here, the authors propose NOVAsort, a next-generation droplet sorter that can discern droplets based on both size and fluorescence, which can overcome common problems with conventional sorters.