STAMP: Single-Cell Transcriptomics Analysis and Multimodal Profiling through Imaging

Abstract We introduce Single-Cell Transcriptomics Analysis and Multimodal Profiling (STAMP), a scalable profiling approach of individual cells. Leveraging transcriptomics and proteomics imaging platforms, STAMP eliminates sequencing costs, to enable single-cell genomics from hundreds to millions of cells at an unprecedented low cost. Stamping cells in suspension onto imaging slides, STAMP supports single-modal (RNA or protein) and multimodal (RNA and protein) profiling and flexible, ultra-high-throughput formats. STAMP allows the analysis of a single or multiple samples within the same experiment, enhancing experimental flexibility, throughput and scale. We tested STAMP with diverse sample types, including peripheral blood mononuclear cells (PBMCs), dissociated cancer cells and differentiated embryonic stem cell cultures, as well as whole cells and nuclei. Combining RNA and protein profiling, we applied immuno-phenotyping of millions of blood cells simultaneously. We also used STAMP to identify ultra-rare cell populations, simulating clinical applications to identify circulating tumor cells (CTCs). Performing in vitro differentiation studies, we further showed its potential for large-scale perturbation studies. Together, STAMP establishes a new standard for cost-effective, scalable single-cell analysis. Without the need for sequencing, STAMP makes high-resolution profiling more affordable and accessible. Designed to meet the needs of research labs, diagnostic cores and pharmaceutical companies, STAMP holds the promise to transform our capacity to map human biology, diagnose diseases and drug discovery. Competing Interest Statement H.H. is co-founder and Chief Scientific Officer of Omniscope, a Scientific Advisory Board member at Nanostring and Mirxes, a consultant for Moderna, and has received honoraria from Genentech. L.G.M. is scientific advisor of Omniscope and ArgenTag.