Acoustic ejection mass spectrometry empowers ultra-fast protein biomarker quantification

Area of Science:

• Biochemistry
• Analytical Chemistry
• Mass Spectrometry

Background:

• The COVID-19 pandemic revealed critical needs for high-throughput bioanalytical methods.
• Precise protein quantification is essential for understanding health and disease states.
• Existing methods like LC-MS lack the speed required for large-scale screening.

Purpose of the Study:

• To present a quantitative Acoustic Ejection Mass Spectrometry (AEMS) assay for ultra-fast biomarker screening.
• To demonstrate the application of AEMS with peptide immunocapture for protein quantification in plasma and nasopharyngeal swabs.
• To evaluate the speed, reproducibility, and stability of the AEMS assay.

Main Methods:

• Developed a quantitative AEMS assay utilizing peptide immunocapture for analyte enrichment.
• Applied the assay to quantify 10 acute phase response (APR) protein markers in 267 human plasma samples.
• Applied the assay to quantify SARS-CoV-2 nucleocapsid (NCAP) peptides in 145 nasopharyngeal swabs.

Main Results:

• Quantified 10 APR proteins in plasma samples with %CV ranging from 4.2% to 10.5% within 4.8 hours.
• Quantified SARS-CoV-2 NCAP peptides from viral swabs in just 10 minutes.
• Achieved a 15-fold speed improvement compared to traditional LC-MS, with stable performance over 10,000 measurements.

Conclusions:

• The developed AEMS assay offers ultra-high throughput and reproducible quantitative biomarker screening.
• This method is suitable for analyzing very large patient cohorts, enhancing diagnostic capabilities.
• AEMS combined with peptide immunocapture represents a significant advancement in bioanalytical laboratory capacity.