Interfacial Profiling of MicroRNAs at Patterned Nanogaps for an Integrated Microfluidic-SERS Liquid Biopsy

A versatile microfluidic-SERS barcoding system is developed for sensitive and multiplexed imaging of circulating microRNAs through interfacial probing of encoded nanorod aggregates at diverse patterned nanogaps. The use of a single-layer, vertically oriented nanorod array creates a plasmonic coupling-based electromagnetic field with enormously enhanced Raman outputs. The introduction of the herringbone micromixer with circulated microflow sampling accelerates the hybridization and capture of nanorod aggregates on the plasmonic substrate. The method is able to achieve ideal sensitivities at subfemtomolar levels for four miRNAs, with multiplexed assay capability for an integrated liquid biopsy. The on-chip digital profiling of serum miRNAs in mapping and barcoding formats enable both clear discrimination of untreated cancer patients from the healthy cohort and precise classification of tumor stages, metastatic conditions, and subtypes, with an overall accuracy of 94%. The SERS-based microfluidic barcoding system therefore holds great promise in early cancer screening, diagnosis, and prognosis.