Comprehensive profiling of the human plasma proteome represents an immense opportunity for disease biomarker discovery. However, mass spectrometry-based proteomics has been hindered by limitations in sensitivity, throughput, and the absence of a standardized workflow. To address these challenges, we present the Proteonano HT Assay—a high-throughput, robust, and cost-effective solution for large-scale, deep plasma proteomics. Its modular design incorporates AI-powered nanobinder reagents, which are chemically modified peptides (20–40 AA) that enable the detection of 12,000 human plasma proteins across a 10-log dynamic range. The accompanying fully automated workflow can process up to 500 samples per day.
When integrated with the Evosep One and Orbitrap Astral mass spectrometry systems, the Proteonano HT Assay achieves exceptional performance: minimal sample input (10 µL), ultra-high throughput (500 samples per day), deep proteome coverage (>5,000 protein groups), and excellent reproducibility (CV < 15%). These capabilities establish Proteonano as a key enabling technology for implementing population-scale, MS-based plasma proteomic studies.