Scanning DIA on the ZenoTOF 8600 system enables ultra-sensitive and quantitative proteomics from single cells to post-translational modifications in a compact platform
Mass spectrometry-based proteomics increasingly demands platforms that combine quantitative rigor with the discovery capabilities of accurate mass systems. Here we present the ZenoTOF 8600 system, a compact mass spectrometry system that integrates enhanced ion capture and transmission optics with an optical detection system, Zeno trap-enhanced MS/MS, electron-activated dissociation, and scanning quadrupole data-independent acquisition (ZT Scan DIA). We show that ZT Scan DIA outperforms conventional variable-window DIA (Zeno SWATH DIA) in both identifications and quantitative reproducibility, and demonstrate the platform's versatility across proteomics applications: thousands of protein groups from bulk samples at up to 500 samples per day, single-cell proteomics yielding up to 4,700 proteins, accurate ratio recovery in mixed-species quantitative benchmarks, low-attomole targeted quantitation, and detection of disease-relevant phosphorylation in a Parkinson's disease cellular model using complementary CID and EAD fragmentation. The instrument's compact footprint makes it attractive for settings where both analytical breadth and operational robustness are required. ### Competing Interest Statement B.L., Y.L.B., N. B., I.B., J.C., A.C., G.I., K.T., T.T., B.S., and J.C.-P. are employees of SCIEX. M.M. is an indirect investor in Evosep Biosystems. The remaining authors declare no competing interests.
biorxiv.org