Multiplexed Nanoparticle Protein Corona Enables Accurate and Precise Deep Plasma Proteomics

Area of Science:

• Proteomics
• Biotechnology
• Analytical Chemistry

Background:

• Mass spectrometry (MS) based proteomics faces challenges with dynamic range, limiting deep protein detection.
• The Proteograph Product Suite utilizes multiplexed nanoparticle (NP) protein corona technology to address these limitations.

Purpose of the Study:

• To evaluate the quantitative performance and suitability of the Proteograph Product Suite for large-scale plasma proteomics.
• To assess accuracy, linearity, precision, and lower limit of quantification (LLOQ) across different MS platforms.

Main Methods:

• Multispecies spike-in and dilution experiments were conducted.
• Quantitative performance was assessed using various mass spectrometry (MS) platforms, including Orbitrap Astral and Orbitrap Exploris 480.
• Inter-batch variability was evaluated using data from four distinct nanoparticle (NP) batches.

Main Results:

• The Proteograph XT assay combined with Orbitrap Astral MS identified over 7,000 plasma proteins.
• Proteograph quantified 3.5 times more proteins than the Neat plasma workflow with preserved fold change accuracy.
• High quantitative accuracy was maintained across different proteome backgrounds and showed minimal inter-batch variability (4% increase in protein intensity CV).

Conclusions:

• The Proteograph Product Suite provides enhanced depth and quantitative accuracy for large-scale plasma proteomics.
• This technology enables robust biomarker discovery and biological insights in population-scale studies.