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

Publication Type:

Article

Authors:

Aditya Garg, Marissa Morales, Aashini Shah, Daniel Kim, Ming Lei, Sahil Patel, Jia Dong, Seleem Badawy, Sangeeta Bhatia, Loza F. Tadesse

Source:

BioRxiv (2025)

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Manuscript (PDF)

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 >103 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 104-fold, enabling ppb level PFP detection in mouse bronchial fluid and establishing a VOC-capturing SERS platform for breath-based diagnostics.