Microfabricated Si Chips Containing Human Ether-a-Go-Go-Related Gene Channels As a Platform for Drug Safety Screenings

Monday, 6 October 2014: 17:10
Sunrise, 2nd Floor, Galactic Ballroom 8 (Moon Palace Resort)
A. Hirano-Iwata, Y. Ishinari (Graduate School of Biomedical Engineering, Tohoku University), Y. Kimura, and M. Niwano (Laboratory for Nanoelectronics and Spintronics, Research Institute of Electrical Communication, Tohoku University)
Reconstitution of ion channel proteins in artificial bilayer lipid membranes (BLMs) provides an excellent system for drug screenings. However, the mechanical fragility of BLMs prevents them from being widely used. Recently, we have succeeded in the formation of mechanically stable BLMs by preparing membranes in microapertures fabricated in silicon (Si) chips (1). The key feature for BLM stabilization is probably the tapered shape of the aperture edge, which allows reducing the stress on the bilayer at the aperture edge. In this presentation, we report on an application of this stable BLM device to measure ion currents of human ether-a-go-go-related gene (hERG) channels (2), which have been found to be related to serious arrhythmic side effects following drug treatment. Microapertures (diameter: 20-60 micrometer) were fabricated in a silicon nitride (Si3N4) layer on a Si chip. The surface of the Si chip was coated with thermal oxide and Teflon-AF. After the chip was treated with a silane-coupling reagent, artificial BLMs were prepared in the microapertures by folding up two phospholipid monolayers in the apertures. Owing to the use of SiO2/Teflon dielectric layer, the current noise level of the BLM was reduced, and clear single-channel events with conductance of 11 ± 1.2 pS were observed for hERG channels. This conductance value is similar to a reported one (12 pS) by the patch-clamp method. The channel current was completely blocked by E-4031, a specific blocker for hERG, and astemizole, an antihistamine that has been withdrawn due to its side effect on hERG channels. Thus the sensitivity of the hERG channels to typical drugs was retained in the Si chips. The BLM with incorporated hERG channels was stable for 65 h and tolerant to repetitive solution exchanges. The next step is to extend this stable BLM device to a multisite array format. The realization of an ion channel array will open a variety of applications, including high-throughput drug screening procedures that can be a complement to the patch-clamp method.


  1. A. Hirano-Iwata, K. Aoto, A. Oshima, T. Taira, R. Yamaguchi, Y. Kimura, M. Niwano, Langmuir, 26, 1949–1952 (2010).
  2. A. Oshima, A. Hirano-Iwata, H. Mozumi, Y. Ishinari, Y. Kimura, and M. Niwano, Anal. Chem., 85, 4363-4369 (2013).