{"id":466,"date":"2025-01-28T09:59:30","date_gmt":"2025-01-28T09:59:30","guid":{"rendered":"https:\/\/microfluidics.creative-biolabs.com\/blog\/?p=466"},"modified":"2025-02-18T06:02:41","modified_gmt":"2025-02-18T06:02:41","slug":"uda-seq-universal-droplet-microfluidics-based-combinatorial-indexing","status":"publish","type":"post","link":"https:\/\/microfluidics.creative-biolabs.com\/blog\/uda-seq-universal-droplet-microfluidics-based-combinatorial-indexing\/","title":{"rendered":"UDA-Seq: Universal Droplet Microfluidics-Based Combinatorial Indexing"},"content":{"rendered":"<p>Recently, scientists published a research paper titled &#8220;UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing&#8221; in <em>Nature Methods<\/em>.<\/p>\n<p><img decoding=\"async\" loading=\"lazy\" class=\" wp-image-467 aligncenter\" src=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/1.png\" alt=\"\" width=\"618\" height=\"312\" srcset=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/1.png 837w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/1-300x152.png 300w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/1-768x388.png 768w\" sizes=\"(max-width: 618px) 100vw, 618px\" \/><\/p>\n<p>The research team independently developed a novel single-cell multi-omics sequencing technology called UDA-seq. By optimizing and upgrading the widely used droplet microfluidics platform with a combinatorial indexing approach, they achieved the &#8220;decoupling&#8221; of cell throughput and false singlet rates, overcoming throughput limitations.<\/p>\n<p>UDA-seq is a universal strategy for enhancing throughput, supporting common single-cell multi-omics applications such as RNA and VDJ co-detection, RNA and ATAC co-detection, and RNA and CRISPR perturbation co-detection within the same cell. This study achieved a record-breaking single-channel cell throughput of over 100,000 cells, a 10- to 20-fold improvement over existing technologies, while maintaining compatibility with multimodal analyses. Additionally, the researchers employed genetic diversity combined with bioinformatics to enable label-free single-channel multiplexing of 20 to 40 human samples, significantly reducing per-sample data costs. The study also established a solution for obtaining high-quality, multimodal, single-cell precision data from small frozen blood and biopsy samples on a large scale.<\/p>\n<p><img decoding=\"async\" loading=\"lazy\" class=\"size-large wp-image-468 aligncenter\" src=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/2-863x1024.webp\" alt=\"\" width=\"604\" height=\"717\" srcset=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/2-863x1024.webp 863w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/2-253x300.webp 253w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/2-768x911.webp 768w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/2-1294x1536.webp 1294w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2025\/02\/2-1726x2048.webp 1726w\" sizes=\"(max-width: 604px) 100vw, 604px\" \/><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: 12px;\">The workflow of UDA-seq and its performance across different modalities and samples<\/span><\/p>\n<p>Furthermore, the study applied UDA-seq in three scenarios: aging, disease population cohort studies, and high-throughput CRISPR screening research. For kidney tissues from healthy individuals and patients with various complex kidney diseases, the study constructed a single-cell RNA and ATAC dual-omics atlas. The research overcame the challenges of processing small frozen samples, requiring only one-fifth of a needle-biopsy sample per case. In droplet microfluidics, the team collected 200,000 high-quality dual-modal single-cell data from 35 donors using two-channel reactions. By developing new algorithms, the study identified rare cell types, including podocytes (POD) and endothelial-glomerular cells (EC-GC), associated with proteinuria and kidney injury phenotypes, as well as the regulatory networks and key factors of critical cell subpopulations.<\/p>\n<p>Using UDA-seq, the study constructed a PBMC single-cell transcriptomic and immune receptor sequencing dual-omics atlas for a naturally aging population cohort. With two-channel reactions, 120,000 high-quality single-cell data were collected, revealing aging-related cell subtypes and identifying a new aging-related cell subtype\u2014ITGB1+PREX1+ Naive CD4+ T cells. UDA-seq also demonstrated its compatibility with high-throughput CRISPR screening, analyzing the cellular responses to perturbations of the bromodomain protein gene family in gastric cancer cell lines.<\/p>\n<p>This study breaks through existing technical bottlenecks, enhancing single-cell sequencing throughput while maintaining compatibility with multimodal analyses. It demonstrates reliability and high quality in real-world samples, achieving low-cost and efficient data production. The work developed new algorithms to identify key cell subpopulations, regulatory networks, and critical factors associated with clinical phenotypes, establishing a novel research paradigm for large-scale studies of health and disease cohorts. Additionally, the study upgraded the commonly used droplet microfluidics platform, which holds potential to support data generation for next-generation multimodal virtual cell-based large models.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Reference:<\/strong><\/p>\n<p>Li, Yun et al. \u201cUDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing.\u201d <em>Nature Methods<\/em>, 10.1038\/s41592-024-02586-y. 20 Jan. 2025, doi:10.1038\/s41592-024-02586-y<\/p>\n<p><strong>Related Services:<\/strong><\/p>\n<p><a href=\"https:\/\/microfluidics.creative-biolabs.com\/microfluidic-development-services-for-droplet-generator-and-flow-chemistry.htm\">Microfluidic Development Services for Droplet Generator and Flow Chemistry<\/a><\/p>\n<p><a href=\"https:\/\/microfluidics.creative-biolabs.com\/microfluidic-chip-development-for-cell-solution.htm\">Microfluidic Chip Development Services for Cell<\/a><\/p>\n<p><a href=\"https:\/\/microfluidics.creative-biolabs.com\/single-cell-sequencing.htm\">Single-cell Sequencing Platform<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Recently, scientists published a research paper titled &#8220;UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing&#8221; in Nature Methods. The research team independently developed a novel single-cell multi-omics sequencing technology<a class=\"moretag\" href=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/uda-seq-universal-droplet-microfluidics-based-combinatorial-indexing\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":468,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/466"}],"collection":[{"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/comments?post=466"}],"version-history":[{"count":3,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/466\/revisions"}],"predecessor-version":[{"id":473,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/466\/revisions\/473"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/media\/468"}],"wp:attachment":[{"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/media?parent=466"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/categories?post=466"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/tags?post=466"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}