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High-throughput small-molecule assays play essential roles in biomedical diagnosis, drug discovery, environmental analysis, and physiological function research. Nanoplasmonics holds a great potential for the label-free detection of small molecules at extremely low concentrations. Here, we report the development of nanoplasmonic paper (NP-paper) for the rapid separation and ultrasensitive detection of mixed small molecules. NP-paper employs nanogap-rich silver nanoislands on cellulose fibers, which were simply fabricated at the wafer level by using low-temperature solid-state dewetting of a thin silver film. The nanoplasmonic detection allows for the scalable quantification and identification of small molecules over broad concentration ranges. Moreover, the combination of chromatographic separation and nanoplasmonic detection allows both the highly sensitive fluorescence detection of mixed small molecules at the attogram level and the label-free detection at the sub-nanogram level based on surface-enhanced Raman scattering. This novel material provides a new diagnostic platform for the high-throughput, low-cost, and label-free screening of mixed small molecules as an alternative to conventional paper chromatography.

Silver nanoislands on cellulose fibers for chromatographic separation and ultrasensitive detection of small molecules