Early and accurate diagnosis of cancer is extremely important to cancer treatment and improving patients’ survival rate. Liquid biopsy is an emerging approach that detects a panel of biomarkers that are available in bodily fluids, and potentially allows noninvasive diagnostics of a broad variety of cancers. Among the most studied biomarkers, microRNAs (miRNAs, single-stranded oligoribonucleotides) are viewed promising candidates, as they function as both oncogenes and tumor suppressors. The dysregulation of miRNAs has been shown to strongly correlate to the proliferation of cancer cells in various types of cancers. Current major approaches for miRNA detection rely heavily on enzymatic reactions that usually introduce biases, demand special instrument, and require long processing time. On the other hand, plasmonic nanoantennas have attracted considerable attentions due to its ultrahigh sensitivity, design flexibility, label-free detection and low instrument cost. However, miRNAs only have relatively small modulation of refractive index near the sensor surface due to their short sequence (~20 bp, or <7 nm in length), and hence usually results in small optical signals that is insufficient to accurate diagnosis.
Here we present a vertically coupled complementary structure, consisting of a nanobar antenna and a perforated nanoslit aperture antenna separated by SiO2 nanopillar. This structure has shown a high sensitivity of 136 nm shift in detecting assembled 1-octadecanethiol in the mid-IR range (ACS Nano, 2017, 11 (8), pp 8034–8046). In our ongoing work, we design nanoantennas at visible and near-IR wavelength range, and optimize its sensitivity through vertical coupling between the nanobar and aperture antennas and horizontal coupling between adjacent nanobar antennas. Our full-wave simulation shows that the captured miRNA on the sensor surface can lead to ~23-30 nm shift upon miRNA hybridization to DNA probes. In our preliminary experiment, we assembled thiolated single-stranded DNA probes to the sensor surface, and demonstrated 13 nm resonance shift upon miR-10b hybridization at 100 pM concentration, which is comparable to the state-of-the-art research (~8.5 nm at same concentration). Currently we are evaluating the detection limit of the miR-10b on our plasmonic nanoantennas and studying the specificity using different probe designs. We expect to update our results at the conference. Our concept of plasmonic nanosensing can be widely extended to more complex structures and used for multiplexed detection, which have broad applications in early, low-cost, and portable cancer diagnosis.