Introduction to special issue

Chemical Detectives

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Science  17 Mar 2006:
Vol. 311, Issue 5767, pp. 1565
DOI: 10.1126/science.311.5767.1565

Like the detective in a murder mystery trying to reconstruct events from a thicket of useful and extraneous information, the analytical chemist often seeks to determine the composition of only a tiny fraction of a complex sample. Classically, the approach has been to perform an initial step of separation into purer components before proceeding to quantification. However, many problems, especially in biology and in earth and atmospheric sciences, benefit from approaches that can minimize sample preparation and skip straight to analysis. In this special issue, we focus on advances in this mode of direct detection.

Mass spectrometry can inherently deal with complex samples because it integrates separation and detection; it is the means of delivering the sample to the vacuum chamber for ionization that often limits applications. Cooks et al. (p. 1566) review recent methods that allow molecules to be skimmed straight off the surface of samples in the open air for mass analysis.

In a similar vein, Wightman (p. 1570) reviews the applications of electrodes whose micrometer dimensions facilitate high-resolution probing of cellular environments with minimal perturbation of the surrounding system. Through electrochemical detection, the concentration gradients that regulate physiological processes can be tracked in real time, even in live animals.

Three Reports highlight further technological advances to improve detection. A promising approach for detecting biomolecules is to decorate microcantilevers with receptors or antibodies and then observe stress-induced changes in cantilever position. Shekhawat et al. (p. 1592) show that a field-effect transistor embedded in the end of the cantilever can provide sufficient sensitivity and is unaffected by the analyte solution. Yu et al. (p. 1600) have developed a method to observe single protein molecules as they are synthesized in live Escherichia coli cells. Low-level expression of yellow fluorescent protein gives bursts of protein molecules from single mRNA transcripts. For spectroscopic detection of more diffuse species, such as atmospheric contaminants, a tradeoff is often made between the spectral width of the probe (for versatility) and the detection resolution (for specificity). Thorpe et al. (p. 1595) have created a broadband version of cavity ringdown spectroscopy that allows rapid high-resolution detection across a 100-nm wavelength range.

In related online features, the Signal Transduction Knowledge Environment (STKE) features two Perspectives. Cognet et al. describe how the movement of surface receptors can be monitored by means of electrophysiological and optical methods. These approaches have allowed the real-time measurement of glutamate receptor surface trafficking in live neurons. Lynch et al. describe how the adsorption of proteins onto nanoparticles may produce aberrant signaling due to conformational changes in the adsorbed proteins.

All great detective stories must come to an end. For scientists, though, these technological advances open the door to an ever-broadening vista of the complexities underlying the natural world.

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