Three-dimensional hierarchical plasmonic nano-architecture enhanced surface-enhanced Raman scattering immunosensor for cancer biomarker detection in blood plasma

Abstract

A three-dimensional (3D) hierarchical plasmonic nano-architecture has been designed for a sensitive surface-enhanced Raman scattering (SERS) immunosensor for protein biomarker detection. The capture antibody molecules are immobilized on a plasmonic gold triangle nanoarray pattern. On the other hand, the detection antibody molecules are linked to the gold nanostar@Raman reporter@silica sandwich nanoparticles. When protein biomarkers are present, the sandwich nanoparticles are captured over the gold triangle nanoarray, forming a confined 3D plasmonic field, leading to the enhanced electromagnetic field in intensity and in 3D space. As a result, the Raman reporter molecules are exposed to a high density of "hot spots", which amplifies the Raman signal remarkably, improving the sensitivity of the SERS immunosensor. This SERS immunosensor exhibits a wide linear range (0.1 pg/mL to 10 ng/mL) and a low limit of detection (7 fg/mL) toward human immunoglobulin G protein in the buffer solution. This biosensor has been successfully used for detection of the vascular endothelial growth factor in the human blood plasma from clinical breast cancer patient samples.

Figure 1

TEM images of (a) the Au sphere@MGITC@SiO₂ sandwich nanoparticles and (b) the Au star@MGITC@SiO₂ sandwich nanoparticles, (c) SEM image of the Au triangle nano-array, and (d) UV-visible absorption spectra of the Au sphere@MGITC@SiO₂ sandwich nanoparticles and the Au star@MGITC@SiO₂ sandwich nanoparticles

Figure 2

Schematic illustration of conjugation of (a) the SERS probe (sandwich nanoparticle) to the detection antibody, and (b) the Au triangle nano-array chip to the capture antibody; (c) Schematic illustration of the operating principle of SERS immuno-sensor for biomarker detection. The structure of VEGF biomarker is created by PyMOL with a four-digit code: 1VPF.

Figure 3

SERS spectra of the Au star@MGITC@SiO₂ sandwich nanoparticle coupled to the Au triangle nano-array chip in various concentrations of IgG in the PBS buffer solution (0.1 pg/mL, 0.5 pg/mL, 1.0 pg/mL, 5.0 pg/mL, 10 pg/mL, 50 pg/mL, 0.1 ng/mL, 0.5 ng/mL, 1.0 ng/mL, 10 ng/mL, 100 ng/mL, 500 ng/mL and 1.0 μg/mL).

Figure 4

(a) Plots of SERS peak intensity at 1578 cm⁻¹ as a function of the logarithmic concentration of IgG, and (b) the linear range of (a). (■) the Au sphere coupled on the Au film, ( ) the Au spheres coupled on the Au triangle nano-array, and ( ) the Au stars coupled on the Au triangle nano-array.

Figure 5

(a) SERS spectra of the Au star@MGITC@SiO₂ sandwich nanoparticle/Au triangle nano-array immuno-sensor, which responded to various concentrations of VEGF biomarker in blood plasma, and (b) the plot of the intensity of SERS peak at 1578 cm⁻¹ as a function of the logarithmic concentration of VEGF in blood plasma