Reimagining plasma biomarker discovery with P2 enrichment workflow

The discovery of plasma biomarkers is crucial for advancing early disease diagnosis, monitoring treatment responses, and tracking disease progression. Plasma proteomics, however, faces substantial analytical challenges due to the vast dynamic range of protein concentrations. The 22 most abundant plasma proteins account for over 99% of the total protein content, effectively masking lower-abundance proteins that may hold critical diagnostic and prognostic value.

Mass spectrometry (MS)-based proteomics has been instrumental in biomarker discovery, but its ability to detect low-abundant proteins is often limited by sample complexity and the dominance of the aforementioned high-abundance proteins. To overcome this challenge, various strategies have been developed, with particle-based enrichment workflows emerging as a promising approach. These workflows leverage nanoparticles or other materials to selectively adsorb and concentrate plasma proteins, forming a “corona” layer around the particles. This not only reduces the dynamic range of the plasma proteome but also enhances the detection of otherwise undetectable analytes, thereby improving the depth and sensitivity of proteomic profiling. Here, we present the P2 enrichment workflow, coupling a single-particle enrichment system to state-of-the-art LC-DIA-MS approach which enables robust, high-throughput and cost-efficient profiling of the plasma proteome.