Scanning DIA on the ZenoTOF 8600 system records a precursor dimension for every fragment at tenfold higher ion flux

Proteomics needs instruments that combine depth with quantitative precision. Here we describe the ZenoTOF 8600 system, a quadrupole time-of-flight instrument that combines triple-quadrupole ion optics with an optical detector, the Zeno trap and electron-activated dissociation. The MS2 ion current increases tenfold over its predecessor, the ZenoTOF 7600+ system. In scanning quadrupole data-independent acquisition (ZT Scan DIA), every fragment records the Q1 profile of its precursor, so wide isolation windows keep their sensitivity while abundant precursors attain the selectivity of a window about ten times narrower. ZT Scan DIA identifies up to 38% more precursors than variable-window DIA and improves quantitative accuracy. The platform quantifies up to 5,200 protein groups in a single HeLa cell, 5,000 from 1 nL of mouse brain tissue, 10,000 in a single run and 5,700 at 500 samples per day, and targeted assays reach 20 amol on column and quantify S129 phosphorylation of -synuclein.