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Switching off to drugs A biosensor that closely mimics biological sensory functions has caught the attention of pharmaceutical companies engaged in rapid drug discovery. One year after publishing details of an ion-channel switch (ICS) biosensor {Nature 1997,387, 58083), deals have been closed with two pharmaceutical companies and advanced discussions are underway withfivemore, according to Bruce Cornell of Australia's Cooperative Research Centre for Molecular Engineering and Technology (CMET) The unique feature of the sensor, says Cornell, is that it gives a functional test of the interaction between a potential drug and an artificial cell membrane. Changes of ion flux across the membrane are directly detected as a change in the membrane's electrical conductance. "Our particular strength lies in the fact that we have a tethered artificial biological membrane, so it's convenient and quick to carry out screens mat otherwise would require very complicated patch-clamp experiments," he explains. Converting the concept of an ICS biosensor into a practical device has taken 10 years and involved a team of up to 60 scientists and engineers. The sensors are fabricated with standard self-assembly chemistry, but novel molecular design was required to achieve adequate sensitivity, long-term stability, and reliability. At the heart of die ICS biosensor is a highly insulating synthetic lipid bilayer membrane tethered to a gold substrate with a well-defined ionic reservoir between the membrane and the substrate. Coassembled with the membrane are the elements of the ion-channel switch. Tethered gramicidin ion channels are introduced into the inner layer of the membrane, and BUSINESS
Park Scientific and TopoMetrix become ThermoMicroscopes In the modern version of big fisn—little fish, companies consume each other. Park Scientific, manufacturer of scanningprobe microscopes (SPMs), was acquired in 1997 by ThermoSpectra (a subsidiary of Thermo Instrument Systems). In Octo-
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capture/reporter receptor giving 96 different tests for a single target. Alternatively 96 different molecules can be screened against a single receptor using an array of identical sensors. Although rapid drug discovery is big business, Cornell is also enthusiastic about applying the biosensor in the public health and safety area. Microorganisms and virus particles can be targeted via cell metabolites or membrane proteins, and the ICS biosensor may meet the demand for a fast, sensitive, and simple method of detection. CMET has been working with the Australian Water Technologies Group of Sydney Water for nine months developing tests for waterborne parasites E colt is the target of initial work but the greatest interest lies in detection of Giardia and CrvbtosboSchematic of ICS biosensor in the format used for detecting ridium Monitoring these an analyte with multiple recognition sites. Darasites is based on measuring Giard,a cvst tnd CrvMnsboridium the external solution. Binding of analyte oocyst levels and Cornell sees significant cross links mobile channels and lipidadvantages in use of the ICS biosensor immobilized receptor sites, switching off Not only is biosensor detection faster and the ion current, and reducing the electrical more convenient than the immunofliiores conductance of the membrane. For anacence methods traditionally recommended lytes with a single recognition site, a comby the U.S. Environmental Protection petitive-binding version of the switch is used. A wide range of capture/reporter Agency, but use of a sensor array should ii A. • i-i -c_ s _ i i / \ receptors can be linked via streptavidinallow the viable fraction andJ
