Sensitive and specific detection of biomaterials packaged in exosomes and related extracellular vesicles (EVs) has the potential to revolutionize cancer diagnosis and monitoring. Yet current methods cannot readily distinguish tumor-associated EVs. Surface-enhanced Raman spectroscopy (SERS) represents a promising tool to address current limitations, but are challenging to implement in whole biofluids. Here we outline a simple SERS assay combining nanoparticles with biofluids purified to various extent. We measure variation between clinical samples of head and neck cancer and demonstrate that there is a trade-off between useful molecular information from purified EVs versus the time, cost, and difficulty of isolation procedures.
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