Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting

Single-cell multiomics can provide comprehensive insights into gene regulatory networks, cellular diversity, and temporal dynamics. While tools for co-profiling the single-cell genome, transcriptome, and epigenome are available, accessing the proteome in parallel is more challenging. To overcome this limitation, we developed nanoSPLITS (nanodroplet SPlitting for Linked-multimodal Investigations of Trace Samples), a platform that enables unbiased measurement of the transcriptome and proteome from same single cells using RNA sequencing and mass spectrometry-based proteomics, respectively. We demonstrated the nanoSPLITS can robustly profile > 5000 genes and > 2000 proteins per single cell, and identify cell-type-specific markers from both modalities. ### Competing Interest Statement J.C.B., J.W.B, and A.S. are employees of Scienion/Cellenion. Battelle Memorial Institute has submitted a U.S. provisional patent application for the design of nanoSPLITS devices and the associated operation methods (Application number: 63/250,011 filed 09/29/2021; Inventors: Ying Zhu, James M Fulcher, Lye Meng Markillie, and Ljiljana Pasa-Tolic; Status of application: Pending). Other authors declare no competing interests.