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Is there any possibility of using the discovery in drug design? Cobbold speculates that pharmacological intervention could be designed to release some of the accumulated adenosine from intact cells. He argues that if all the adenosine released by the ischemic heart has come from lysed cells, they are already irreversibly damaged. Cooper adds, "The point really is that the event of adenosine release appears to signal the end stage of cellular damage, and no amount of biochemical intervention afterwards will save the damaged tissue." There is some hope, though, says Cobbold. "Why not design a drug to promote adenosine efflux from healthy cells, with the aim of improving blood flow, and thereby prevent the cells reaching the point of irreversible injury?" Cooper points out that numerous pharmaceutical and biotechnology companies are currently developing single-cell techniques because they offer such advantages of insight. Indeed, Cooper and his colleagues worked on some aspects of the current research with GlaxoWellcome and Wellcome Trust support. However, there are still problems to face. For instance, the volumes involved are so small that local concentrations might be reached that are well above physiological conditions. He explains that in the present experiments this did not cause difficulties because the experimental time periods short. "The devices we have fabricated are still research tools, but in the future there is a chance of using them in array technologies, for screening compounds [drugs] as cell-based assays," Cooper adds. He also points out that ink-jet technology—of the kind more familiar in computer printers— can be used to dispense the required fluids. "We have just made a 4 x 4 array of these microanalytical devices," he says. Cooper believes the technology could be widely applicable to other cellular systems because the microlithographic techniques used are generic. This could also allow the researchers to reduce the dimensions of the titer vessel even further, making it more suited to smaller cell types (for example, the measurement of the release of the neurotransmitter glutamate from single brain cells). It should also be possible to incorporate more than one sensor into the device so that different analytes might be observed at the same time. David Bradley 244 A
NEWS FROM HPCE '98 Britt EricksonreportsfromOrlando, FL
Swiss go submicron Although several methods exist for surface elemental analysis with submicrometer resolution, molecular analysis on this scale is very difficult to achieve. Renato Zenobi and co-workers at the Swiss Federal Institute of Technology (ETH Zurich) have made it their goal to develop scanning near-field optical microscopy (SNOM) for chemical analysis on a scale of 100 nm or less. SNOM relies on a tapered fiber tip, traditionally made by heating and pulling, which is scanned in very close proximity (< 10 nm) over the sample surface. One practical limitation is the poor optical transmission of SNOM tips. Zenobi's group has developed an alternative way for fabricating such tips, using a chemical etching technique. Their tips are characterized by a large opening angle at the apex, leading to higher optical transmission (up to 0.1%-1%, depending on the aperture size) and a higher damage threshold, while preserving 50-150 nm apertures. Because of their high optical transmission, chemically etched SNOM tips open up new possibilities for analytical chemists, such as fluorescence imaging of biological tissue. For example, ,ctinfilamentsfrom the cytoskeleton have been imaged with better resolution than with state-of-the-art fluorescence microscopy. Fluorescence, however, does not usually give detailed chemical information, so the ETH researchers instead ex-
Quantifying HIV-1 RNA without amplification It's one thing to be able to detect the presence of the HIV-1 virus, known to cause acquired immunodeficiency syndrome (AIDS) in humans, but quantifying the degree of infection is a much different story. Quantitative measurement of the number of HIV-1 copies, referred to as viral load testing, is essential for monitoring the HIV-1 virus. Because more potent antiretroviral drugs are on the market today than ever before, the levels of HIV-1 RNA in infected individuals are often undetectable with currently available techniques. A method that offers improved sensitivity and reproducibility is desirable, particularly for
Analytical Chemistry News & Features, April 1, 1998
All aglow: micrograph of a near-field optical tip with — 100 nm opening.
plored Raman spectroscopy through their SNOMtips(Anall Chem. 1997, 69, 749). They demonstrated surface-enhanced Raman spectroscopy (SERS) with a spatial resolution
