Fabrication of graphene-based flexible devices utilizing a soft lithographic patterning method.

There has been considerable interest in soft lithographic patterning processing of large scale graphene sheets due to the low cost and simplicity of the patterning process along with the exceptional electrical or physical properties of graphene. These properties include an extremely high carrier mobility and excellent mechanical strength. Recently, a study has reported that single layer graphene grown via chemical vapor deposition (CVD) was patterned and transferred to a target surface by controlling the surface energy of the polydimethylsiloxane (PDMS) stamp. However, applications are limited because of the challenge of CVD-graphene functionalization for devices such as chemical or bio-sensors. In addition, graphene-based layers patterned with a micron scale width on the surface of biocompatible silk fibroin thin films, which are not suitable for conventional CMOS processes such as the patterning or etching of substrates, have yet to be reported. Herein, we developed a soft lithographic patterning process via surface energy modification for advanced graphene-based flexible devices such as transistors or chemical sensors. Using this approach, the surface of a relief-patterned elastomeric stamp was functionalized with hydrophilic dimethylsulfoxide molecules to enhance the surface energy of the stamp and to remove the graphene-based layer from the initial substrate and transfer it to a target surface. As a proof of concept using this soft lithographic patterning technique, we demonstrated a simple and efficient chemical sensor consisting of reduced graphene oxide and a metallic nanoparticle composite. A flexible graphene-based device on a biocompatible silk fibroin substrate, which is attachable to an arbitrary target surface, was also successfully fabricated. Briefly, a soft lithographic patterning process via surface energy modification was developed for advanced graphene-based flexible devices such as transistors or chemical sensors and attachable devices on a biocompatible silk fibroin substrate. Significantly, this soft lithographic patterning technique enables us to demonstrate a simple and efficient chemical sensor based on reduced graphene oxide (rGO), a metallic nanoparticle composite, and an attachable graphene-based device on a silk fibroin thin film.

Comparison of the rabbit pyrogen test and Limulus amoebocyte lysate (LAL) assay for endotoxin in hepatitis B vaccines and the effect of aluminum hydroxide.

The rabbit pyrogen test and Limulus amoebocyte lysate (LAL) assay have been used to detect endotoxins in vaccines, but interactions between the endotoxins and proteins or aluminum hydroxide can interfere with the results. Currently, the rabbit pyrogen test is used to detect endotoxin in hepatitis B (HB) vaccines even though the HB surface protein, the active ingredient, is over-expressed in and purified from eukaryotic cells which lack endotoxin. Therefore, we examined the possibility of replacing the animal tests with the more efficient LAL test. To this end, we determined whether the aluminum hydroxide in the HB vaccines affects the rabbit pyrogen test and the LAL assay. HB vaccines and HB protein solutions spiked with lipopolysaccharide (LPS) produced almost the same dose-dependent temperature rise in rabbits, indicating that the aluminum hydroxide in the HB vaccine does not interfere with the pyrogenic response in rabbit. In contrast, a spike recovery study showed that aluminum hydroxide interfered with the LAL clot and kinetic assays; however, the LAL clot assay was effective at detecting endotoxin without loss of LAL activity after serial dilution of the samples. Furthermore, there was good correlation in the LAL clot assay between the amount of LPS added and the amount recovered. However, both turbidimetric and chromogenic kinetic assays displayed no correlation between the LPS amount added and recovered. Our results suggest that the LAL clot assay is sensitive and reliable when samples are properly prepared, and can be used to replace the rabbit pyrogen test for the detection of endotoxin in HB vaccines.