Reproducible Plasmonic Nanopyramid Array of Various Metals for Highly Sensitive Refractometric and Surface-Enhanced Raman Biosensing

[Image: see text] Localized surface plasmon resonance (LSPR) biosensors show great potential for practical/commercial use in clinical diagnosis, home healthcare, environmental analysis, and public healthcare. However, two main issues, that is, low refractometric sensitivity and low reproducibility (large-area uniformity and batch-to-batch consistency), hinder the extensive applications of LSPR biosensors. Therefore, plasmonic nanostructures with high sensitivity and excellent reproducibility are desirable for preparing reliable LSPR sensors. Herein, we have fabricated plasmonic nanopyramid arrays (NPAs) for several batches with reproducible morphology and optical properties by elastic soft lithography and metal thermal evaporation. NPAs of various metals (i.e., Al, Au, and Ag) were also prepared by thermal evaporation with the according metals. The transmission spectra of these NPAs showed several narrow LSPR peaks in the visible-infrared wavelength region. The refractometric sensitivities of the LSPR peaks were systematically studied, and high refractometric sensitivities of 774.0, 472.8, and 421.0 nm/RIU were achieved on Al, Au, and Ag NPAs, respectively. To demonstrate the potential of the NPAs for multiplex applications, we first applied this highly sensitive Al NPA biosensor to monitoring the process of proliferation of HeLa cancer cells, in situ and in real time. Then, we demonstrated that the Au NPA was able to identify the absorbed analytes on its surface through the surface-enhanced Raman scattering spectrum. In addition, the finite difference time domain simulations were performed to reveal the electromagnetic field enhancement on NPAs. Because of the properties of high sensitivity and excellent reproducibility of the metal NPA LSPR substrates, as well as the simplicity and cost efficiency of the fabrication method, our proposed work will accelerate the practical use of LSPR sensors.