Three Dimensional Multiple Layers Localized Surface Plasmon Resonance Biosensor with High Sensitivity and Multiple Resonance Modes

具備多種共振模式的高性能三維多層局域表面等離激元共振生物傳感器

Student thesis: Doctoral Thesis

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Award date14 Nov 2018

Abstract

Localized surface plasmon resonance (LSPR) biosensors have been broadly used for fast, label-free, miniaturized, and highly sensitive biomolecular detection. Localized surface plasmons (SPs) are collective oscillation of free electrons in the surface of metal nanostructures and they are extremely sensitive to biomolecular binding due to the changing effective refractive index (RI) in the surrounding area. To improve the performance of LSPR biosensors, most researchers focus on studying two dimensional plasmonic nanostructures, such as dots, holes, rings, split rings, and asymmetrical nanostructures. However, three dimensional (3D) multiple-layer LSPR biosensors with high sensitivity and multiple resonance modes remain unexplored. In this thesis, quasi 3D, 3D multiple-layer, and 3D plasmonic photonic crystal (PPC) biosensors were designed and fabricated with high sensitivity to detect cancer cells, DNA hybridization, and exosomes.

Quasi 3D plasmonic biosensor with gold (Au) nanosquares on top of SU-8 nanopillars and Au nanoholes at the bottom had a high sensitivity of 496 nm/RI unit (RIU) due to the hybrid coupling of LSPR and Fabry–Perot cavity modes. Quasi 3D nanostructures were fabricated by nanoimprint lithography (NIL) and their plasmonic resonance peak wavelength and sensitivity were tuned by varying the Au thickness. Three cancer cells including lung cancer A549 cells, retinal pigment epithelial (RPE) cells, and breast cancer MCF-7 cells with different cell areas were detected and distinguished by the quasi 3D plasmonic biosensor. Using 20 μl A549 cells, cell concentration ranging from 5×102 to 1×107 cells/ml was detected. An 18 nm resonance peak shift was observed for detecting 5×102 cells/ml A549 cells using this quasi 3D plasmonic biosensor. The peak shifts of 20μl MCF-7 and RPE cells at 5×102 cells/ml were as large as 40 and 51 nm, respectively, due to their larger cell size.

Compared with quasi 3D plasmonic biosensor, 3D multiple-layer plasmonic biosensor showed higher electromagnetic field intensity, longer plasmon decay length, and larger plasmon sensing area due to the hybrid coupling of three different plasmonic layers with Au nanosquares on top of SU-8 nanopillars, Au asymmetrical nanostructures in the middle, and Au asymmetrical nanoholes at the bottom. The 3D multiple-layer plasmonic biosensor was fabricated by reversal NIL, and its resonance peak wavelength and sensitivity were tuned by varying the offset between the top and bottom SU-8 nanopillars. High sensitivities of 382 and 442 nm/RIU were observed for resonance peaks at 581 and 805 nm, respectively. These peaks were located in the region of 450−1100 nm. As the peak signals will not be absorbed by the cell culture medium in this region, the biosensors could be used for live cancer cell detection. Polydimethylsiloxane-based microfluidic channels integrated with 3D multiple-layer plasmonic biosensor was utilized to detect a small sample volume of 2 μl of live lung cancer A549 cells at a concentration range of 5×103 to 5×105 cells/ml. The 3D multiple-layer plasmonic biosensor also showed high sensitivity detection range of 10-14 to 10-7 M for complementary target DNA hybridization.

A novel 3D PPC biosensor was proposed to further improve the performance of 3D plasmonic biosensors. The 3D PPC biosensor showed the highest sensitivity up to 1376 nm/RIU and the highest figure of merit of 11.6 due to the hybrid coupling of plasmonics and photonic crystal cavity modes. A large resonance peak shift of 9 nm was observed for the detection of exosomes with concentration of 1×104 particles/ml using the 3D PPC biosensor, and the peak shift increased to 102 nm with exosome concentration of 1×1011 particles/ml.