Towards Breath Based Diagnostics via Water-mediated Capture of Synthetic Breath Biomarkers in SERS-active Plasmonic Nanogaps

TL;DR

This study develops a water-mediated SERS platform with nanogaps to detect synthetic breath biomarkers at 10 ppb, enabling portable, sensitive breath diagnostics for health monitoring.

Contribution

It introduces a novel water-mediated trapping mechanism in nanogaps that significantly enhances SERS detection sensitivity for low-concentration VOCs.

Findings

Achieved 10 ppb detection of synthetic breath biomarkers.

Enhanced SERS sensitivity by 10,000 times through water-mediated adsorption.

Demonstrated detection in mouse bronchial fluid.

Abstract

Volatile organic compounds (VOCs) are valuable health indicators, with synthetic breath biomarkers offering rapid and disease specific diagnostics. However, their <100 ppb level exhalation requires mass spectrometry, limiting clinical integration. Surface-enhanced Raman spectroscopy (SERS) offers a portable, cost-effective alternative. Yet, detecting synthetic breath biomarkers, with inherently low Raman cross-sections, at <100 ppb remains challenging. We demonstrate SERS detection down to clinically relevant 10 ppb via water-mediated trapping in hydroxylated nanoporous silica-coated plasmonic nanogaps, using pentafluoropropylamine (PFP) as a representative synthetic breath biomarker. Uniform nanogaps, with >1000 times electric field enhancement, were generated between a gold film and gold-silica core-shell nanoparticle assemblies using electric field-driven evaporation. Oxygen plasma treatment hydroxylated the silica, enabling water-mediated hydrogen bonding that strengthened PFP adsorption, confirmed by density functional theory. This mechanism improved SERS sensitivity by 10000 fold, enabling ppb level PFP detection in mouse bronchial fluid and establishing a VOC capturing SERS platform for breath-based diagnostics.