Engineering Multiplexed Synthetic Breath Biomarkers as Diagnostic Probes

Area of Science:

• Biomarker Discovery
• Chemical Biology
• Non-invasive Diagnostics

Background:

• Breath biopsy offers rapid, non-invasive disease detection via exhaled chemical signatures.
• Clinical translation is hindered by challenges in detecting endogenous biomarkers in breath.
• Synthetic biomarkers can amplify disease signals but require suitable volatile reporters for breath analysis.

Purpose of the Study:

• To engineer multiplexed breath biomarkers coupling aberrant protease activities to exogenous volatile reporters.
• To develop a platform for sensitive and specific detection of disease-specific biomarkers in exhaled breath.
• To enable rapid, point-of-care diagnostics for various medical conditions.

Main Methods:

• Designed novel intramolecular reactions utilizing protease-mediated aminolysis to release unique volatile reporters.
• Validated the approach in mouse models for influenza and lung cancer.
• Combined multiplexed reporter signals with machine learning algorithms for data analysis.

Main Results:

• Demonstrated successful coupling of protease activity to unique volatile reporters detectable in breath.
• Achieved sensitive and specific detection in controlled inflammatory (influenza) and disease (lung cancer) models.
• Showcased the ability to track tumor progression, monitor treatment response, and detect relapse within 30 minutes.

Conclusions:

• Engineered multiplexed breath biomarkers represent a significant advancement for breath biopsy.
• This platform enables the detection of diverse disease states through protease activity.
• The technology holds promise for rapid, point-of-care diagnostics across a spectrum of diseases.