Three-Dimensional Tungsten Disulfide Raman Biosensor for Dopamine Detection.

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) are promising materials for detection of biomolecules due to their large surface-to-volume ratio. However, their poor response to the cellular environment hinders the realization of high-performance 2D TMDC sensors. Here, we present a hierarchical Raman scattering sensor consisting of the WS2 directly grown on an array of three-dimensional (3D) WO3 nanohelixes (NHs) by sulfurization. Both the adsorption of biomolecules and the proliferation of cells are significantly promoted for the 3D WS2/WO3 NH sensor compared to the control sensor with sulfurized WS2 on 2D WO3 film, leading to much enhanced sensitivity to dopamine. In addition, according to the in vitro test using PC12 cells, the 3D WS2/WO3 NH sensor shows a significant increase in hydrophobicity and Raman frequency shift, indicating that both the attachment of cells and the detection of biomolecules are improved.

Hyaluronate-Gold Nanoparticle/Glucose Oxidase Complex for Highly Sensitive Wireless Noninvasive Glucose Sensors.

Noninvasive real-time biosensors to measure glucose levels in the body fluids have been widely investigated for continuous glucose monitoring of diabetic patients. However, they suffered from low sensitivity and reproducibility due to the instability of nanomaterials used for glucose biosensors. Here, we developed a hyaluronate-gold nanoparticle/glucose oxidase (HA-AuNP/GOx) complex and an ultralow-power application-specific integrated circuit chip for noninvasive and robust wireless patch-type glucose sensors. The HA-AuNP/GOx complex was prepared by the facile conjugation of thiolated HA to AuNPs and the following physical binding of GOx. The wireless glucose sensor exhibited slow water evaporation (0.11 µL/min), fast response (5 s), high sensitivity (12.37 µA·dL/mg·cm2) and selectivity, a low detection limit (0.5 mg/dL), and highly stable enzymatic activity (∼14 days). We successfully demonstrated the strong correlation between glucose concentrations measured by a commercially available blood glucometer and the wireless patch-type glucose sensor. Taken together, we could confirm the feasibility of the wireless patch-type robust glucose sensor for noninvasive and continuous diabetic diagnosis.

Electroceutical Residue-Free Graphene Device for Dopamine Monitoring and Neural Stimulation.

The simultaneous neural signal monitoring and stimulation can allow accurate neurotransmitter regulation for patients in various degrees of neural degeneration disorders. Here, we developed a residue-free graphene device as an effective electrical neural interface for dopamine sensing and secretion. We demonstrated the ultrasensitive dopamine sensing of residue-free graphene devices cultured with PC12 cells and the on-demand functional electrical stimulation for electroceutical applications. The doping effect of graphene by the released dopamine from living cells was confirmed from the electrical current change. The dopamine release could be also quantitatively analyzed by ELISA. Then, Ca2+ ion-dependent dopamine release was optically observed by fluorescence microscopy during the stimulation. Taken together, this study confirms the feasibility of graphene surface as a neural interface for electroceutical applications to various central nerve system disorders.

Multimodal Cancer Theranosis Using Hyaluronate-Conjugated Molybdenum Disulfide.

Among various 2D nanomaterials, molybdenum disulfide (MoS2 ) exhibits unique visible photoluminescence with high absorption at the near-infrared (NIR) range. Despite these optical properties, the efforts to use MoS2 nanomaterials for optical imaging and photothermal therapy are hampered by their instability and low intracellular delivery efficiency. Multifunctional MoS2 conjugated with hyaluronate (HA) for cancer theranosis is reported herein. HA facilitates the delivery of MoS2 to tumor cells by the HA-receptor mediated endocytosis. In BALB/c nude mice inoculated with a colorectal cancer cell line of HCT116, HA-MoS2 conjugates appear to be accumulated in the primary tumor at a content more than that in the liver and kidney. The disulfide bonding between MoS2 and thiolated HA seems to degrade in the cytoplasm, releasing MoS2 sheets in stacks and enhancing luminescence efficiency. The HA-MoS2 conjugates are readily detected via photoacoustic imaging as well as upconversion and downconversion fluorescence imaging. With NIR light illumination, HA-MoS2 conjugates enable highly effective photothermal tumor ablation. All these results confirm the promising potential of HA-MoS2 conjugates for cancer theranosis.

Molybdenum Disulfide Surface Modification of Ultrafine-Grained Titanium for Enhanced Cellular Growth and Antibacterial Effect.

The commercially pure Ti (CP Ti) and equal-channel angular pressing (ECAP) processed Ti can contribute to the downsizing of medical devices with their superior mechanical properties and negligible toxicity. However, the ECAP-processed pure Ti has the risk of bacterial infection. Here, the coarse- and ultrafine-grained Ti substrates were surface-modified with molybdenum disulfide (MoS2) to improve the cell proliferation and growth with antibacterial effect for further dental applications. According to in vitro tests using the pre-osteoblast of MC3T3-E1 cell and a bacterial model of Escherichia coli (E. coli), MoS2 nanoflakes coated and ECAP-processed Ti substrates showed a significant increase in surface energy and singlet oxygen generation resulting in improved cell attachment and antibacterial effect. In addition, we confirmed the stability of the surface modified Ti substrates in a physiological solution and an artificial bone. Taken together, MoS2 modified and ECAP-processed Ti substrates might be successfully harnessed for various dental applications.

Superior Pre-Osteoblast Cell Response of Etched Ultrafine-Grained Titanium with a Controlled Crystallographic Orientation.

Ultrafine-grained (UFG) Ti for improved mechanical performance as well as its surface modification enhancing biofunctions has attracted much attention in medical industries. Most of the studies on the surface etching of metallic biomaterials have focused on surface topography and wettability but not crystallographic orientation, i.e., texture, which influences the chemical as well as the physical properties. In this paper, the influences of texture and grain size on roughness, wettability, and pre-osteoblast cell response were investigated in vitro after HF etching treatment. The surface characteristics and cell behaviors of ultrafine, fine, and coarse-grained Ti were examined after the HF etching. The surface roughness during the etching treatment was significantly increased as the orientation angle from the basal pole was increased. The cell adhesion tendency of the rough surface was promoted. The UFG Ti substrate exhibited a higher texture energy state, rougher surface, enhanced hydrophilic wettability, and better cell adhesion and proliferation behaviors after etching than those of the coarse- and fine-grained Ti substrates. These results provide a new route for enhancing both mechanical and biological performances using etching after grain refinement of Ti.

Microneedle biosensor for real-time electrical detection of nitric oxide for in situ cancer diagnosis during endomicroscopy.

A dual-diagnostic system of endom-icroscope and microneedle sensor is developed to demonstrate high-resolution imaging combined with electrical real-time detection of NO released from cancer tissues. The dual-diagnostic system can be a new platform for facile, precise, rapid, and accurate detection of cancers in various biomedical applications.