Electrochemical Detection of Dopamine Release from Living Neurons Using Graphene Oxide-Incorporated Polypyrrole/Gold Nanocluster Hybrid Nanopattern Arrays.

Stem-cell-based therapeutics have shown immense potential in treating various diseases that are currently incurable. In particular, partial recovery of Parkinson's disease, which occurs due to massive loss or abnormal functionality of dopaminergic (DAnergic) neurons, through the engraftment of stem-cell-derived neurons ex vivo is reported. However, precise assessment of the functionality and maturity of DAnergic neurons is still challenging for their enhanced clinical efficacy. Here, a novel conductive cell cultivation platform, a graphene oxide (GO)-incorporated metallic polymer nanopillar array (GOMPON), that can electrochemically detect dopamine (DA) exocytosis from living DAnergic neurons, is reported. In the cell-free configuration, the linear range is 0.5-100 µm, with a limit of detection of 33.4 nm. Owing to its excellent biocompatibility, a model DAnergic neuron (SH-SY5Y cell) can be cultivated and differentiated on the platform while their DA release can be quantitatively measured in a real-time and nondestructive manner. Finally, it is showed that the functionality of the DAnergic neurons derived from stem cells can be precisely assessed via electrochemical detection of their DA exocytosis. The developed GOMPON is highly promising for a wide range of applications, including real-time monitoring of stem cell differentiation into neuronal lineages, evaluating differentiation protocols, and finding practical stem cell therapies.

Extremely Uniform Graphene Oxide Thin Film as a Universal Platform for One-Step Biomaterial Patterning.

Graphene oxide (GO) has proven to be a highly promising material across various biomedical research avenues, including cancer therapy and stem cell-based regenerative medicine. However, creating a uniform GO coating as a thin layer on desired substrates has been considered challenging owing to the intrinsic variability of the size and shape of GO. Herein, a new method is introduced that enables highly uniform GO thin film (UGTF) fabrication on various biocompatible substrates. By optimizing the composition of the GO suspension and preheating process to the substrates, the "coffee-ring effect" is significantly suppressed. After applying a special postsmoothing process referred to as the low-oxygen concentration and low electrical energy plasma (LOLP) treatment, GO is converted to small fragments with a film thickness of up to several nanometers (≈5.1 nm) and a height variation of only 0.6 nm, based on atomic force microscopy images. The uniform GO thin film can also be generated as periodic micropatterns on glass and polymer substrates, which are effective in one-step micropatterning of both antibodies and mouse melanoma cells (B16-F10). Therefore, it can be concluded that the developed UGTF is useful for various graphene-based biological applications.

A fibronectin-coated gold nanostructure composite for electrochemical detection of effects of curcumin-carrying nanoliposomes on human stomach cancer cells.

Curcumin, which is produced by the medicinal herbaceous plant Curcuma longa, has been widely investigated for use as a potential anticancer drug. In this study, the potential toxicity of curcumin-carrying nanoliposomes (curcumin-NLC) toward human stomach cancer cells (MKN-28) was investigated using a new cell-based electrochemical sensing platform. To satisfy both biocompatibility and electroconductivity of the electrodes, the density of the gold nanostructure and the coating conditions of extracellular matrix proteins (fibronectin and collagen) were optimized. The developed platform enabled the successful adhesion and long-term growth of stomach cancer cells on the chip surface, allowing label-free and real-time monitoring of cell viability in a quantitative manner. According to the electrochemical results, both bare curcumin and curcumin-NLC showed toxicity toward MKN-28 cells in the concentration range of 10-100 µM, which was consistent with the results obtained from a conventional colorimetric method (CCK-8). Remarkably, at a low concentration range (<50 µM), this electrochemical platform determined the decrease in cell viability to be approximately 22.8%, 33.9% and 53.1% in the presence of 10, 30, and 50 µM of curcumin-NLC, respectively, compared with the 1.3%, 18.5%, and 28.1% determined by CCK-8, making it 1.7-2 times more sensitive than the conventional colorimetric assay. Hence, it can be concluded that the newly developed fibronectin-coated electroconductive platform is highly promising as an electrochemical detection tool for the sensitive and precise assessment of the anticancer effects of various food-derived compounds with low toxicity.

Size-selective nanoparticle growth on few-layer graphene films.

We observe that gold atoms deposited by physical vapor deposition onto few-layer graphenes condense upon annealing to form nanoparticles with an average diameter that is determined by the graphene film thickness. The data are well described by a theoretical model in which the electrostatic interactions arising from charge transfer between the graphene and the gold particle limit the size of the growing nanoparticles. The model predicts a nanoparticle size distribution characterized by a mean diameter D that follows a D proportional, variant m(1/3) scaling law where m is the number of carbon layers in the few-layer graphene film.

DNA translocation through graphene nanopores.

We report on DNA translocations through nanopores created in graphene membranes. Devices consist of 1-5 nm thick graphene membranes with electron-beam sculpted nanopores from 5 to 10 nm in diameter. Due to the thin nature of the graphene membranes, we observe larger blocked currents than for traditional solid-state nanopores. However, ionic current noise levels are several orders of magnitude larger than those for silicon nitride nanopores. These fluctuations are reduced with the atomic-layer deposition of 5 nm of titanium dioxide over the device. Unlike traditional solid-state nanopore materials that are insulating, graphene is an excellent electrical conductor. Use of graphene as a membrane material opens the door to a new class of nanopore devices in which electronic sensing and control are performed directly at the pore.

Elimination of Uremic Toxins by Functionalized Graphene-Based Composite Beads for Direct Hemoperfusion.

Conventional absorbents for hemoperfusions suffer from low efficiency and slow absorption with numerous side effects. In this research, we developed cellulose acetate (CA) functionalized graphene oxide (GO) beads (∼1.5-2 mm) that can be used for direct hemoperfusion, aiming at the treatment of kidney dysfunction. The CA-functionalized GO bead facilitates adsorption of toxins with high biocompatibility and high-efficiency of hemoperfusion while maintaining high retention for red blood cell, white blood cells, and platelets. Our in vitro results show that the toxin concentration for creatinine reduced from 0.21 to 0.12 µM (p < 0.005), uric acid from 0.31 to 0.15 mM (p < 0.005), and bilirubin from 0.36 to 0.09 mM (p < 0.005), restoring to normal levels within 2 h. Our in vivo study on rats (Sprague-Dawley, n = 30) showed that the concentration for creatinine reduced from 83.23 to 54.87 µmol L-1 (p < 0.0001) and uric acid from 93.4 to 54.14 µmol L-1 (p < 0.0001), restoring to normal levels within 30 min. Results from molecular dynamics (MD) simulations using free-energy calculations reveal that the presence of CA on GO increases the surface area for adsorption and enhances penetration of toxins in the binding cavities because of the increased electrostatic and van der Waals force (vdW) interactions. These results provide critical insight to fabricate graphene-based beads for hemoperfusion and to have the potential for the treatment of blood-related disease.