Electric-Field Enhanced Molecule Detection in Suspension on Assembled Plasmonic Arrays by Raman Spectroscopy

In the last decade, the technique of SERS has been intensively studied due to its great potentials for label-free and multiplex detection of biomolecules [1–3], pollutants [4,5], and chemical warfare agents [6–8]. When light interacts with noble metal NPs with very narrow junctions, the conduction-band electrons in the NP can collectively oscillate and generate localized surface plasmon. As a result, substantially enhanced electric fields are created in the vicinity or junctions of the NPs, which are also called hot spots. If the analyte molecules are in the hot spots, their Raman signals can be dramatically increased by 108–1012 times [9], which is sufficient for detecting single molecules of various species [10,11]. Previously, different types of SERS substrates were fabricated including metals with roughened surfaces [12,13], nanowires [14,15], metal NPs [16,17], sharp tips [18,19], and core/shell nanospheres [20,21]. However, most SERS detections were carried out by drying analyte solutions on the SERS substrates to force molecules to get into hotspots before the detection. The employed drying methods can be different among individual research groups. Quantitative comparison of these results should be conducted carefully. Given the same employed equipmental conditions, it is highly desirable to directly detect molecules in suspension to accurately evaluate the performances of different SERS substrates, which will also have pivotal implications for SERS biosensing in microfluidics. However, when directly detecting from solutions, we found that with the same SERS substrate, the lowest detection limit of molecules at the same experimental and equipmental conditions, such as Rhodamine 6G (R-6G) and Nile blue, commonly used SERS probes, can be higher by a few orders of magnitudes compared to that from samples with dried molecule probes [11,22]. Therefore, it is of great interest to investigate new mechanisms to detect biochemicals directly from solutions with high sensitivity. Electrokinetic phenomena due to AC and direct current electric fields applied on designed microelectrodes have generated immense interest in manipulation of NPs, live cells, and even biomolecules [23]. Recently, it was applied on prepatterned plasmonic substrates, such as Au nanoholes [24], microneedles [25], nanopillars [26], and nanospheres [27,28] to focus analyte molecules to the hotspots before optical detection. Nevertheless, most previous efforts either require complex lithography for fabricating SERS-active entities [25–27] or could not precisely control the sizes/junctions of plasmonic particles for high reproducible detection when electric fields are applied [27]. In this work, we report electric-field enhanced molecule detection from an innovative type of SERS-active nanocapsule structures. The nanocapsules can be bottom-up synthesized in a large scale, dynamically assembled into ordered arrays, and offer a large number of hotspots with controlled sizes owing to the unique design of the structures. With optimized AC frequencies, voltages, and structure of the microelectrodes, biomolecules, including those having low molecular weights such as Nile blue, can be effectively concentrated on the surface of the nanocapsules. The Raman signal of Nile blue can be improved by 34.4 ± 3.1% after applying the electric field for a few minutes. This work could inspire the next generation microfluidic based Raman sensing devices.