<title>Gated ion channel biosensor: a functioning nanomachine</title>

Abstract

Biosensors combine a biological recognition mechanism with a physical transduction technique. In nature, the transduction mechanism for high sensitivity molecular detection is modulation of cell membrane ionic conductivity, through specific ligand -receptor binding induced switching of ion channels. This effects an inherent signal amplification of 6-8 orders of magnitude, corresponding to the total ion flow arising from the single channel gating event. Here we describe the first reduction of this principle to a practical sensing device, which is a planar impedance element composed of a macroscopically supported synthetic bilayer membrane incorporating ion channels. The membrane and ionic reservoir are covalently attached to an evaporated gold surface. The channels have specific receptor groups attached (usually antibodies) which permit switching of the channels by analyte binding to the receptors. The device may then be made specific for the detection of a very wide range of analytes, including proteins, drugs, hormones, antibodies, DNA, etc., currently in the iO -1012 M range. It also lends itself readily to microelectronic fabrication and signal transduction.By adjusting the surface density of the receptors Ichannel components during fabrication, the optimum sensitivity range of the device may be tuned over several orders of magnitude.

Applications of biological pores in nanomedicine, sensing, and nanoelectronics

“…Binding of these ligands, which can include simple ions (such as Ca 2+ ) or neurotransmitters (such as acetylcholine), to the receptor site of the channel protein causes a transient conformational change that can lead to a physiologically significant, and measurable, change in ion permeability across the membrane [2]. A critical feature of this signaling mechanism is the strong molecular amplification that it entails; binding of a single ligand molecule typically leads to the passage of 10 4 –10 7 ions through the membrane, often resulting in significant changes of the transmembrane potential [169]. Not surprisingly, these channel proteins are particularly appealing for sensing applications since the protein itself possesses not only a recognition element but also the signal transduction and amplification components.…”

Tethered Bilayer Membranes Containing Ionic Reservoirs: Selectivity and Conductance

“…Polar tethering species attach the membrane to the electrode, providing a hydrophilic region between the membrane and the gold surface. This region acts as a reservoir for ions transported across the membrane. ,, The reservoir exists as a gel-like structure, which is permeable to ionic species. The electrical properties of tethered bilayer lipid membranes (tBLM) are very dependent on the properties of this reservoir region.…”

AMBRI biosensor: stabilizing artificial membranes and receptor attachment

“…2 The biosensor can function in a variety of media, including complex matrices such as whole blood, and exhibits detection capabilities below picomolar. 2 The biosensor can function in a variety of media, including complex matrices such as whole blood, and exhibits detection capabilities below picomolar.…”