Back

End-to-end high-throughput single-cell proteomics via SPRINT and dual-spray LC-MS

Liu, Z.; Dong, W.; Gu, L.; Ge, R.; Zeng, X.; Deng, J.; Zhang, H.; Ye, Z.

2025-11-05 systems biology
10.1101/2025.11.03.686420 bioRxiv
Show abstract

Single-cell proteomics (SCP) enables direct measurement of protein heterogeneity but remains constrained by throughput and limited applicability to primary tissues. Here, we present an integrated workflow developed to address both challenges. We engineered SPRINT, an AI-powered bioprinting platform that prepares more than 10,000 single cells per day, over tenfold faster than existing systems, while maintaining stability and enabling identification of over 6,000 proteins from individual HeLa cells. To expand analytical capacity, we further designed a dual-spray tandem direct injection (TDI) LC system that parallelizes non-analytical steps with peptide separation, doubling MS utilization efficiency and enabling 168 label-free SCP runs per day without sensitivity loss. Together with optimized tissue-dissociation protocols, this integrated workflow enabled creation of the first mouse tissue-derived SCP atlas, profiling >1,000 single cells across six organs. These advances establish SCP as a scalable platform ready for broad biological and biomedical applications.

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.