Background: Understanding the endocytosis process of gold nanoparticles (AuNPs) is important for the drug delivery and photodynamic therapy applications. The endocytosis in living cells is usually studied by fluorescent microscopy. The fluorescent labeling suffers from photobleaching. Besides, quantitative estimation of the cellular uptake is not easy. In this paper, the size-dependent endocytosis of AuNPs was investigated by using plasmonic scattering images without any labeling. Results: The scattering images of AuNPs and the vesicles were mapped by using an optical sectioning microscopy with dark-field illumination. AuNPs have large optical scatterings at 550-600 nm wavelengths due to localized surface plasmon resonances. Using an enhanced contrast between yellow and blue CCD images, AuNPs can be well distinguished from cellular organelles. The tracking of AuNPs coated with aptamers for surface mucin glycoprotein shows that AuNPs attached to extracellular matrix and moved towards center of the cell. Most 75-nm-AuNPs moved to the top of cells, while many 45-nm-AuNPs entered cells through endocytosis and accumulated in endocytic vesicles. The amounts of cellular uptake decreased with the increase of particle size. Conclusions: We quantitatively studied the endocytosis of AuNPs with different sizes in various cancer cells. The plasmonic scattering images confirm the size-dependent endocytosis of AuNPs. The 45-nm-AuNP is better for drug delivery due to its higher uptake rate. On the other hand, large AuNPs are immobilized on the cell membrane. They can be used to reconstruct the cell morphology.

Nanostructure-based sensors are capable of sensitive and label-free detection for biomedical applications. However, plasmonic sensors capable of highly sensitive detection with high-throughput and low-cost fabrication techniques are desirable. We show that capped gold nanoslit arrays made by thermal-embossing nanoimprint method on a polymer film can produce extremely sharp asymmetric resonances for a transverse magnetic-polarized wave. An ultrasmall linewidth is formed due to the enhanced Fano coupling between the cavity resonance mode in nanoslits and surface plasmon resonance mode on periodic metallic surface. With an optimal slit length and width, the full width at half-maximum bandwidth of the Fano mode is only 3.68 nm. The wavelength sensitivity is 926 nm/RIU for 60-nm-width and 1,000-nm-period nanoslits. The figure of merit is up to 252. The obtained value is higher than the theoretically estimated upper limits of the prism-coupling SPR sensors and the previously reported record high figure-of-merit in array sensors. In addition, the structure has an ultrahigh intensity sensitivity up to 48,117%/RIU.

Metallic nanostructure-based surface plasmon sensors are capable of real-time, label-free, and multiplexed detections for chemical and biomedical applications. Recently, the studies of aluminum-based biosensors have attracted a large attention because aluminum is a more cost-effective metal and relatively stable. However, the intrinsic properties of aluminum, having a large imaginary part of the dielectric function and a longer evanescent length, limit its sensing capability. Here we show that capped aluminum nanoslits fabricated on plastic films using hot embossing lithography can provide tailorable Fano resonances. Changing height of nanostructures and deposited metal film thickness modulated the transmission spectrum, which varied from Wood’s anomaly-dominant resonance, asymmetric Fano profile to surface plasmon-dominant resonance. For biolayer detections, the maximum surface sensitivity occurred at the dip of asymmetric Fano profile. The optimal Fano factor was close to −1.3. The wavelength and intensity sensitivities for surface thickness were up to 2.58 nm/nm and 90%/nm, respectively. The limit of detection (LOD) of thickness reached 0.018 nm. We attributed the enhanced surface sensitivity for capped aluminum nanoslits to a reduced evanescent length and sharp slope of the asymmetric Fano profile. The protein-protein interaction experiments verified the high sensitivity of capped nanostructures. The LOD was down to 236 fg/mL.

An optical fiber sensor based on the change of optical confinement in a subwavelength tip is presented. The optical spot is substantially increased when the environmental refractive index (RI) increases from 1.3 to 1.4. By measuring the intensity of low angular spectral components, an intensity sensitivity up to 8000% per RI unit is achieved. The fiber tip sensors take advantage of the small detection volume and real-time responses. We demonstrate the application of the nanofiber sensors for measuring concentrations of acids and evaporation rates of aqueous mixtures.