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Design and Application of Ion-Channel Sensors Based on Biological and Artificial Receptors

Sugawara, M.; Hirano, A.; Buhlmann, P.; Umezawa, Y. Bull. Chem. Soc. Jpn. 2001

Abstract

All cell membranes share a common structural organization, i.e., bilayers of phospholipid with associated membrane proteins, which are responsible for many specialized functions. Some proteins act as receptors that respond to external signals, activating a series of intracellular signaling cascades, and some participate in transporting ions and molecules across the cell membrane.1 All transmembrane and intracellular signaling processes are initiated by the binding of signaling ions and molecules to their receptors in bilayer membranes. Mimicking the principle of such natural sensor systems has been the objective of many recent studies in sensor development.2,3

A variety of new electrochemical sensors have been reported, including ion-channel4-11 or ion-channel mimetic sensors,12-15 active transport membrane electrodes,16-19 ion-channel switch biosensors,20-22 and micro bilayer lipid membrane sensors.4,15 Their responses are based on transmembrane signaling based on changes in membrane permeability6-10,12-15,17,23 or membrane potentials.16,24,25 In addition, advances in the molecular design of receptors and membranes for bio- and biomimetic sensors extended the range of targeted analytes to electroinactive ones; the analytes do not necessarily need to be electroactive. Instead, electrochemically inactive analytes can be detected with these sensors by virtue of their working principles.

A biomimetic sensor whose working principle is similar to transmembrane signaling displayed by ligand-gated ion channels in biological membranes was first reported in 1987.12 The surface of a glassy carbon electrode was coated by means of the Langmuir-Blodgett technique with a thin layer of a synthetic lipid with a phosphate headgroup, and permeation of electroactive marker ions added to the sample solution was regulated by the binding of a stimulus (Ca2+) to the negatively charged lipid. The sensor was called ion-channel sensor because its working principle was similar to the control of transmembrane ion transport by ligand-gated ion channels (Fig. 1). A considerable number of ion-channel sensors have been developed based on various artificial receptors for inorganic ions, organic ions and bioactive substances, as reviewed in the recent articles.14

Although there has been more interest in artificial receptors, biological ion channels like glutamate receptor ion channels in combination with bilayer lipid membranes4-10 and biological material such as DNAs26-28, DNA/enzyme29 and oligonucleotides30 directly attached to the electrode surface have also attracted attention for designing ion-channel sensors. Recently, new modes of ion channel sensors by using the channel former gramicidin linked to a receptor in a supported lipid bilayer membrane or by using gramicidin itself as a molecular signal transducer incorporated in a bilayer membrane have been reported.20-22

In this paper, we highlight different types of ion-channel sensors based on biological and artificial receptors, mostly reported by us, and focus on the working principle and the fundamental aspects, such as sensitivity and selectivity, of these sensors.

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