Synthesis of metal nanostructures arrays with large amounts of small nano-gaps on a homogenous macroscale is of significant interest and importance in chemistry, biotechnology, physics, and nanotechnology because of their enhanced properties. However, the fabrication of uncovered nano-gaps with high-density and uniformity is rather difficult due to the complex and multiple synthetic steps. In this research, a facile and low-cost approach is demonstrated for the synthesis of high-density small nano-gaps (about 3.4 nm) between silver nanostructure array patterns (SNAPs) over a large area. Uniform nano-hole patterns were periodically generated over an entire substrate using nano-imprint lithography. Electrochemical reaction at the high over-potential produced multiple silver nanocrystals inside the nano-hole patterns, generating a high-density of small and uncovered nano-gaps. Finally, we fully demonstrate their application in the rapid detection of rhodamine 6G (R6G) molecules by surface-enhanced Raman scattering (SERS) spectroscopy with a very low detection limit (1 fM) as well as excellent signal uniformity (RSD < 8.0% ± 2.5%), indicating an extraordinary capability for single-molecule detection.

Bio-ink properties have been extensively studied for use in the three-dimensional (3D) bio-printing process for tissue engineering applications. In this study, we developed a method to synthesize bio-ink using hyaluronic acid (HA) and sodium alginate (SA) without employing the chemical crosslinking agents of HA to 30% (w/v). Furthermore, we evaluated the properties of the obtained bio-inks to gauge their suitability in bio-printing, primarily focusing on their viscosity, printability, and shrinkage properties. Furthermore, the bio-ink encapsulating the cells (NIH3T3 fibroblast cell line) was characterized using a live/dead assay and WST-1 to assess the biocompatibility. It was inferred from the results that the blended hydrogel was successfully printed for all groups with viscosities of 883 Pa∙s (HA, 0% w/v), 1211 Pa∙s (HA, 10% w/v), and 1525 Pa∙s, (HA, 30% w/v) at a 0.1 s⁻¹ shear rate. Their structures exhibited no significant shrinkage after CaCl₂ crosslinking and maintained their integrity during the culture periods. The relative proliferation rate of the encapsulated cells in the HA/SA blended bio-ink was 70% higher than the SA-only bio-ink after the fourth day. These results suggest that the 3D printable HA/SA hydrogel could be used as the bio-ink for tissue engineering applications.

The noninvasive early detection of biomarkers for Alzheimer’s disease (AD) is essential for the development of specific treatment strategies. This paper proposes an advanced method for fabricating highly ordered and flexible nanopillar-based electrochemical biosensors by the combination of soft/photolithography and metal evaporation. The nanopillar array (NPA) exhibits high surface area containing 1500 nm height and 500 nm diameter with 3:1 ratio. In regard with physical properties of polyurethane (PU) substrate, the developed NPA is sustainable and durable to external pressure such as bending and twisting. To manipulate the NPA surface to biocompatible, the gold was uniformly deposited on the PU substrate. The thiol chemistry which is stably modified on the gold surface as a form of self-assembled monolayer was employed for fabricating the NPA as a biocompatible chip by covalently immobilize the antibodies. The proposed nanopillar-based immunoelectrochemical biosensor exhibited good and stable electrochemical performance in β-amyloid (Aβ) detection. Moreover, we successfully confirmed the performance of the as-developed sensor using the artificial injection of Aβ in human tear, with sensitivity of 0.14 ng/mL and high reproducibility (as a standard deviation below 10%). Our findings show that the developed nanopillar-based sensor exhibits reliable electrochemical characteristics and prove its potential for application as a biosensor platform for testing at the point of care.