In this paper, a nanobiosensor with surface-enhanced Raman scattering (SERS) capability is introduced for highly sensitive miRNA detection in colorectal cancer. This sensor was designed and fabricated by employing a nanoshielding mechanism from nanopolystyrene beads to resist reactive ion etching and allow anisotropic electrochemical etching, producing high-aspect-ratio, surface-corrugated nanopillars (SiNPs) on a silicon wafer to create extensive hot spots along the nanopillars for improved SERS signals. SERS enhancements were correlated with nanorange roughness, indicating that hot spots along the pillars were the crucial factor to improve the SERS effect. We achieved the detection capability of a trace amount of R6G (10−8 M), and the SERS signal enhancement factor (EF) was close to 1.0 × 107 on surface-corrugated gold SiNPs. miRNA samples were also demonstrated on this sensor with good sensitivity and specificity. The target molecule miR-21-Cy5 was easily monitored through Raman spectrum variation with a PCR-comparable concentration at around 100 pM with clear nucleotide-specific Raman signals, which is also suitable for biomolecule sensing.

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