# Enhanced sensitivity and scalability with a Chip-Tip workflow enables deep single-cell proteomics

“Enhanced sensitivity and scalability with a Chip-Tip workflow enables deep single-cell proteomics” (2025), by Zilu Ye et al. Chemistry research paper. Original abstract below, unchanged. A free PDF is available.

- Authors: Zilu Ye, Pierre Sabatier, Leander van der Hoeven, Maico Y. Lechner, Teeradon Phlairaharn, Ulises H. Guzmán, Zhen Liu, Haoran Huang, Min Huang, Xiangjun Li et al.
- Published: January 16, 2025
- Field: Chemistry
- DOI: https://doi.org/10.1038/s41592-024-02558-2
- Free PDF: https://www.nature.com/articles/s41592-024-02558-2.pdf

## Abstract

Single-cell proteomics (SCP) promises to revolutionize biomedicine by providing an unparalleled view of the proteome in individual cells. Here, we present a high-sensitivity SCP workflow named Chip-Tip, identifying >5,000 proteins in individual HeLa cells. It also facilitated direct detection of post-translational modifications in single cells, making the need for specific post-translational modification-enrichment unnecessary. Our study demonstrates the feasibility of processing up to 120 label-free SCP samples per day. An optimized tissue dissociation buffer enabled effective single-cell disaggregation of drug-treated cancer cell spheroids, refining overall SCP analysis. Analyzing nondirected human-induced pluripotent stem cell differentiation, we consistently quantified stem cell markers OCT4 and SOX2 in human-induced pluripotent stem cells and lineage markers such as GATA4 (endoderm), HAND1 (mesoderm) and MAP2 (ectoderm) in different embryoid body cells. Our workflow sets a benchmark in SCP for sensitivity and throughput, with broad applications in basic biology and biomedicine for identification of cell type-specific markers and therapeutic targets.

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