Scanning DIA on the ZenoTOF 8600 system enables ultra-sensitive and quantitative proteomics from single cells to post-translational modifications in a compact platform

Heymann, T.; Oliinyk, D.; Henneberg, L.; Baggio Lorenz, M.; Eikmeier, N.; Thielert, M.; Oeller, M.; Grauvogel, L.; Sitron, C. S.; Loyd, B.; Le Blanc, Y.; Bloomfield, N.; Batruch, I.; Causon, J.; Chelur, A.; Ivosev, G.; Tran, K.; Talamantes, T.; Schneider, B.; Castro-Perez, J.; Mann, M.

doi:10.64898/2026.03.12.711261

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bioRxiv · 10.64898/2026.03.12.711261

Scanning DIA on the ZenoTOF 8600 system enables ultra-sensitive and quantitative proteomics from single cells to post-translational modifications in a compact platform

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Abstract

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 platforms 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 Parkinsons disease cellular model using complementary CID and EAD fragmentation. The instruments compact footprint makes it attractive for settings where both analytical breadth and operational robustness are required.

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Heymann, T., Oliinyk, D., Henneberg, L., Baggio Lorenz, M., Eikmeier, N., Thielert, M., Oeller, M., Grauvogel, L., Sitron, C. S., Loyd, B., Le Blanc, Y., Bloomfield, N., Batruch, I., Causon, J., Chelur, A., Ivosev, G., Tran, K., Talamantes, T., Schneider, B., Castro-Perez, J., Mann, M.. 2026-03-13. Scanning DIA on the ZenoTOF 8600 system enables ultra-sensitive and quantitative proteomics from single cells to post-translational modifications in a compact platform. https://doi.org/10.64898/2026.03.12.711261

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