Technical Evaluation of Plasma Proteomics Technologies

In this head-to-head comparison, researchers benchmarked six plasma-proteomics workflows — unenriched (Neat), acid depletion, a PreOmics ENRICHplus kit, a magnetic-particle “Mag-Net” method, a nanoparticle-based Seer Proteograph^® XT workflow, and an affinity-based Olink Explore HT assay — to assess their ability to deeply profile the human plasma proteome. 

Starting from identical plasma samples and running 618 LC-MS/MS assays plus 93 Olink assays, the authors evaluated each method for proteomic depth, reproducibility, linearity (spike-in recovery), tolerance to lipid interference, and limits of detection/quantification. 

The nanoparticle-based Seer Proteograph XT delivered by far the most comprehensive coverage, detecting ~4,500 proteins — substantially outperforming all other MS-based workflows (which ranged ~600–2,200 proteins) and the Olink platform (~2,600 proteins). 

It also yielded the greatest number of quantifiable proteins above detection thresholds (LOD ~4,407; LOQ ~2,696) and showed robust reproducibility and resistance to lipid interference. 

These findings show that modern plasma proteomics platforms — particularly nanoparticle-enabled workflows like the Seer Proteograph XT Assay— can dramatically expand the detectable plasma proteome compared with traditional depletion or enrichment approaches. For researchers aiming at biomarker discovery or large-scale plasma profiling, the data underscore the importance of choosing a workflow that balances depth, quantifiability, and reproducibility depending on the study’s aims.