Rapid Plasma Proteome Profiling via Nanoparticle Protein Corona and Direct Infusion Mass Spectrometry

Noninvasive
detection of protein biomarkers in plasma is crucial
for clinical purposes. Liquid chromatography–mass spectrometry
(LC–MS) is the gold standard technique for plasma proteome
analysis, but despite recent advances, it remains limited by throughput,
cost, and coverage. Here, we introduce a new hybrid method that integrates
direct infusion shotgun proteome analysis (DISPA) with nanoparticle
(NP) protein corona enrichment for high-throughput and efficient plasma
proteomic profiling. We realized over 280 protein identifications
in 1.4 min collection time, which enables a potential throughput of
approximately 1000 samples daily. The identified proteins are involved
in valuable pathways, and 44 of the proteins are FDA-approved biomarkers.
The robustness and quantitative accuracy of this method were evaluated
across multiple NPs and concentrations with a mean coefficient of
variation of 17%. Moreover, different protein corona profiles were
observed among various NPs based on their distinct surface modifications,
and all NP protein profiles exhibited deeper coverage and better quantification
than neat plasma. Our streamlined workflow merges coverage and throughput
with precise quantification, leveraging both DISPA and NP protein
corona enrichment. This underscores the significant potential of DISPA
when paired with NP sample preparation techniques for plasma proteome
studies.