Conventional biomolecular detection methods are time consuming, requiring several processing stages before the target molecule is identified. Label-free sensing methods provide an immediately measurable change in the property of a platform on binding, and so are quicker, easier to use, and more versatile.

Fig. 1: A ligand (streptavidin) binding to a functionalised lipid vesicle (FLV) trapped in a nanowell.Copyright 2008 Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.

Membranes formed by lipids provide a potentially attractive biomimetic sensing platform for direct electrochemical detection of ligand-receptor interactions. However, creating practical sensors from planar lipid membranes is difficult because lipids can easily form multilayers rather than uniform bilayers, and the membranes are fluid which causes clustering of receptor molecules, which consequently reduces sensitivity.

Kahp Suh and colleagues at Seoul National University, Korea, in collaboration with Tomoji Kawai of Osaka University, Japan have addressed these problems by fabricating a high sensitivity biomolecular detection device from arrays of lipid bilayers, that were self-assembled into hollow nanoscale spheres known as liposomes.

The scientists deposited a polyethylene glycol solution onto a gold electrode and used a nano-molding technique to produce arrays of nanowells, having approximately 750,000 per electrode. The liposomes were prepared using an extrusion technique. The self-assembled lipid walls also contained three other molecules: one was a bioreceptor; the second enabled the attachment of the liposome to the gold electrode substrate; and the third mediated electron transfer to the electrode. The nanowells had sloping walls and depths of 70 nm, enabling deposition of a single liposome per well.

When the desired ligand was introduced to the liposome array platform, it bound to the receptor in the lipid bilayer and blocked the transfer of electrons from the liposome to the gold substrate; this reaction resulted in a drop in current density as measured by square wave voltammetry. The group used the change in current density to identify the presence of streptavidin and leptin using streptavidin-biotin interactions and also (in the latter case) antibody-antigen binding.

This new approach could be useful for a variety of biological assays. “We are now trying to develop a multi-channel platform to detect several biological binding events at the same time,” says Suh.