Visualization Materials Using Silicon-Based Optical Nanodisks (ViSiON) for Enhanced NIR Imaging in Ophthalmology.

ViSiON (visualization materials composed of silicon-based optical nanodisks) is presented, which offers a unique optical combination of near-infrared (NIR) optical properties and biodegradability. Initially, numerical simulations are conducted to calculate the total extinction and scattering effects of ViSiON by the diameter-to-thickness ratio, predicting precise control over its scattering properties in the NIR region. A top-down patterning technique is employed to synthesize ViSiON with accurate diameter and thickness control. ViSiON with a 50 nm thickness exhibits scattering properties over 400 times higher than that of 30 nm, rendering it suitable as a contrast agent for optical coherence tomography (OCT), especially in ophthalmic applications. Furthermore, ViSiON possesses inherent biodegradability in media, with ≈95% degradation occurring after 48 h, and the degradation rate can be finely tuned based on the quantity of protein coating applied to the surface. Subsequently, the OCT imaging capability is validated even within vessels smaller than 300 µm, simulating retinal vasculature using a retinal phantom. Then, using an ex ovo chick embryo model, it is demonstrated that ViSiON enhances the strength of protein membranes by 6.17 times, thereby presenting the potential for ViSiON as an OCT imaging probe capable of diagnosing retinal diseases.

Discrimination of single nucleotide mismatches using a scalable, flexible, and transparent three-dimensional nanostructure-based plasmonic miRNA sensor with high sensitivity.

Localized surface plasmon resonance (LSPR) biosensors have attracted much interest due to their capacity for multiplexing, miniaturization, and high performance, which offers the potential for their integration into lab-on-a-chip platforms for point-of-care (POC) diagnostics. The need for microRNA (miRNA)-sensing platforms is particularly urgent because miRNAs are key regulators and biomarkers in numerous pathological processes and diseases. Unfortunately, however, development of such miRNA-sensing platforms has not yet been achieved. In order to realize the detection of these important biomarkers, there has been an increasing demand for POC-sensing platforms that enable label-free quantification with low sample consumption, good sensitivity, real-time responsiveness, and high throughput. Here, we developed a highly specific, sensitive LSPR miRNA-sensing platform on a flexible, scalable plasmonic nanostructure to enable single-base mismatch discrimination and attomole detection of miRNAs in clinically relevant samples. The hairpin probe contained a locked nucleic acid (LNA) that enabled the discrimination of single base mismatches based on differences in melting temperatures of perfectly matched or single base mismatched miRNAs when they formed base pairs with probes. In addition, through hybridization induced signal amplification based on precipitate formation on the gold surface through the enzyme reaction, we observed a dramatic LSPR peak shift, which enabled attomole detection. Additionally, our LSPR miRNA sensor enabled the detection of miR-200a-3p in total RNA extracts from primary cancer cell lines without purification or labeling of the miRNA. This label-free and highly specific miRNA sensing platform may have applications in POC cancer diagnostics without the need for gene amplification.

Highly robust, uniform and ultra-sensitive surface-enhanced Raman scattering substrates for microRNA detection fabricated by using silver nanostructures grown in gold nanobowls.

Highly sensitive and reproducible surface enhanced Raman spectroscopy (SERS) requires not only a nanometer-level structural control, but also superb uniformity across the SERS substrate for practical imaging and sensing applications. However, in the past, increased reproducibility of the SERS signal was incompatible with increased SERS sensitivity. This work presents multiple silver nanocrystals inside periodically arrayed gold nanobowls (SGBs) via an electrochemical reaction at an overpotential of -3.0 V (vs. Ag/AgCl). The gaps between the silver nanocrystals serve as hot spots for SERS enhancement, and the evenly distributed gold nanobowls lead to a high device-to-device signal uniformity. The SGBs on the large sample surface exhibit an excellent SERS enhancement factor of up to 4.80 × 109, with excellent signal uniformity (RSD < 8.0 ± 2.5%). Furthermore, the SGBs can detect specific microRNA (miR-34a), which plays a widely acknowledged role as biomarkers in diagnosis and treatment of diseases. Although the small size and low abundance of miR-34a in total RNA samples hinder their detection, by utilizing the advantages of SGBs in SERS sensing, reliable and direct detection of human gastric cancer cells has been successfully accomplished.

Intraocular application of gold nanodisks optically tuned for optical coherence tomography: inhibitory effect on retinal neovascularization without unbearable toxicity.

Bare gold nanospheres have been shown to have anti-angiogenic effects but are optically unfavorable because their resonant wavelength lies in the visible spectrum. Here, we design gold nanodisks with a higher scattering capability than gold nanorods and with a resonant wavelength at near-infrared region - the area where the source of light utilized by optical coherence tomography (OCT) lies. With a physical synthesis system, we then fabricate 160-nm-sized gold nanodisks exhibiting resonant wavelength at 830 nm. The synthesized nanoparticles were successfully visualized in in vivo OCT at concentrations as low as 1 pM. After demonstrating their binding ability to vascular endothelial growth factor (VEGF), we show that they suppress VEGF-induced migration of endothelial cells. Finally, we demonstrate that intravitreally injected gold nanodisks attenuate neovascularization of oxygen-induced retinopathy in mice, in a dose dependent manner, such that they are cleared from the vitreous within 2 weeks without histologic or electrophysiologic toxicity.