Abstract Single‐cell sequencing has been constrained by the trade‐off among throughput, capture bias, and compatibility with cells of unusual size or morphology. A recent innovative approach, Stereo‐cell, addresses these constraints by coupling high‐density DNA nanoball patterned arrays with planar in situ RNA capture and microscopy‐guided segmentation, thereby eliminating droplet encapsulation while scaling the field of view by chip size. This planar architecture scales from thousands to >10 6 cells per chip, maintains robust RNA in situ capture, and natively integrates multiplex immunofluorescence and oligo‐barcoded antibodies to deliver concurrent transcriptomic and proteomic readouts. This perspective evaluates Stereo‐cell relative to droplet‐ and plate‐based methods across throughput, sensitivity, spatial resolution, and sample versatility, and outlines practical considerations for rare‐cell detection and subcellular transcript localization. By bridging single‐cell and spatial omics in a unified workflow, Stereo‐cell offers a general‐purpose platform to map cellular states, interactions, and subcellular organization at unprecedented scale.
Wang et al. (Thu,) studied this question.