Stochastic sensing with protein pores

Biosensors are required in a wide variety of applications for which existin g technologies are inadequate. Recently, sensor elements with favorable pro perties have been made by engineering transmembrane protein pores. Analyte molecules modulate the ionic current passing through the engineered pores u nder a transmembrane potential. Stochastic sensing, which uses currents fro m single pores, is an especially attractive prospect. This approach yields both the concentration and identity of an analyte, the latter from its dist inctive current signature. In one example, the bacterial pore-forming prote in staphylococcal alpha-hemolysin (alpha HL) has been altered to permit the detection of divalent metal cations by using mutagenesis to place a cation binding site within the conductive pathway. In a second example. the hemol ysin pore has been modified with cyclodextrins, which act as non-covalent m olecular adapters, to allow the detection of a variety of small organic mol ecules. The great promise and wide applicability of stochastic sensing warr ants efforts aimed at the development of a practicable device.