Highly sensitive detection of exosomes by 3D plasmonic photonic crystal biosensor

Abstract

In this study, two-dimensional (2D), quasi-three-dimensional (3D), and 3D plasmonic photonic crystal (PPC) nanostructures with point-defect cavities were developed and fabricated using direct and reversal nanoimprint lithography. As a result of the hybrid coupling of localized surface plasmon resonance and Fabry–Perot cavity modes, the quasi-3D plasmonic nanoholes showed higher electromagnetic field intensity and sensitivity than the 2D plasmonic nanoholes. Specifically, the sensitivity of the quasi-3D plasmonic nanoholes was 483 nm per refractive index unit (RIU), whereas that of the 2D plasmonic nanoholes was 276 nm RIU⁻¹. In addition, by enhancing electromagnetic field intensity around corners and generating an additional subradiant dark mode, the symmetrical breakage of the quasi-3D plasmonic nanoholes further increased the sensitivity to 946 nm RIU⁻¹. Among all the nanostructures developed in the study, the 3D PPC nanostructures with point-defect cavities showed the highest sensitivity up to 1376 nm RIU⁻¹ and highest figure of merit of 11.6 as the result of the hybrid coupling of plasmonics and photonic crystal modes with multilayered plasmonic nanostructures. The spacing between the 3D PPC nanostructures was comparable with the average size of exosomes derived from fibroblast L cells, which allowed the exosomes to spread around the 3D PPC nanostructures with increased sensing area. This effect further enhanced the detection sensitivity with a large peak shift of 9 nm when using the 3D PPC biosensor to detect exosomes at the concentration of 1 × 10⁴ particles per ml, and the peak shift increased to 102 nm as exosome concentration increased to 1 × 10¹¹ particles per ml.