Biosensors are molecular sensors that combine a biological recognition mechanism with a physical transduction technique. They provide a new class of inexpensive, portable instrument that permit sophisticated analytical measurements to be undertaken rapidly at decentralized locations. However, the adoption of biosensors for practical applications other than the measurement of blood glucose is currently limited by the expense, insensitivity and inflexibility of the available transduction methods. Here we describe the development of a biosensing technique in which the conductance of a population of molecular ion channels is switched by the recognition event. The approach mimics biological sensory functions and can be used with most types of receptor, including antibodies and nucleotides. The technique is very flexible and even in its simplest form it is sensitive to picomolar concentrations of proteins. The sensor is essentially an impedance element whose dimensions can readily be reduced to become an integral component of a microelectronic circuit. It may be used in a wide range of applications and in complex media, including blood. These uses might include cell typing, the detection of large proteins, viruses, antibodies, DNA, electrolytes, drugs, pesticides and other low-molecular-weight compounds.

Using novel synthetic lipids, a tethered bilayer membrane (tBLM) was formed onto a gold electrode such that a well-defined ionic reservoir exists between the gold surface and the bilayer membrane. Self-assembled monolayers of reservoir-forming lipids were first adsorbed onto the gold surface using gold−sulfur interactions, followed by the formation of the tBLM using the self-assembly properties of phosphatidylcholine-based lipids in aqueous solution. The properties of the tBLM were investigated by impedance spectroscopy. The capacitance of the tBLM indicated the formation of bilayer membranes of comparable thickness to solvent-free black (or bilayer) lipid membranes (BLM). The ionic sealing ability was comparable to those of classical BLMs. The function of the ionic reservoir was investigated using the potassium-specific ionophore valinomycin. Increasing the size of the reservoir by increasing the length of the hydrophilic region of the reservoir lipid or laterally spacing the reservoir lipid results in an improved ionic reservoir. Imposition of a dc bias voltage during the measurement of the impedance spectrum affected the conductivity of the tBLM. The conductivity and specificity of the valinomycin were comparable to those seen in a classical BLM.

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