Abstract
Single-cell RNA sequencing has emerged as a powerful tool for characterizing cells, but not all phenotypes of interest can be observed through changes in gene expression. Linking sequencing with optical analysis has provided insight into the molecular basis of cellular function, but current approaches have limited throughput. Here, we present a high-throughput platform for linked optical and gene expression profiling of single cells. We demonstrate accurate fluorescence and gene expression measurements on thousands of cells in a single experiment. We use the platform to characterize DNA and RNA changes through the cell cycle and correlate antibody fluorescence with gene expression. The platform’s ability to isolate rare cell subsets and perform multiple measurements, including fluorescence and sequencing-based analysis, holds potential for scalable multi-modal single-cell analysis.
Highlights
Cellular processes, such as replication, migration, and differentiation, are tightly controlled by signaling and gene regulatory networks [1,2,3]
Our single-cell analysis platform is based on Printed Droplet Microfluidics (PDM) [28, 29], an approach that allows cells to be optically scanned and dispensed to custom nanoliter well plates (Fig. 1a)
To perform linked optical and scRNA-seq analysis, we record the fluorescence of a cell while confined to a droplet, dispense the cell and droplet to the nanoplate at defined locations
Summary
Cellular processes, such as replication, migration, and differentiation, are tightly controlled by signaling and gene regulatory networks [1,2,3]. Results and discussion Our single-cell analysis platform is based on Printed Droplet Microfluidics (PDM) [28, 29], an approach that allows cells to be optically scanned and dispensed to custom nanoliter well plates (nanoplates) (Fig. 1a). To perform linked optical and scRNA-seq analysis, we record the fluorescence of a cell while confined to a droplet, dispense the cell and droplet to the nanoplate at defined locations.
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