News
LABORATORY PROFILE What's hot in the Manz lab this summer? Andreas Manz is a worried man. As the summer sunlight begins to creep over his desk, he knows that the glass roofs of his labs will soon let in enough light to boost the temperatures, leading to overheated students and technicians. The solution would be to install air conditioning, but although the budgetary means exist from the joint funding by SmithKline Beecham (SKB) and Zeneca of almost $16 million over five years, his building is only halfway through refurbishment. So plans to cool off will have to wait. As the temperature rises, though, so does Manz's enthusiasm for the work he and his team of 19 in the SKB/Zeneca Centre for Analytical Science at Imperial College, London (U.K.), are doing. And although the scale of his enthusiasm is enormous, the scale of their analytical devices is getting smaller. Manz became SKB Professor at Imperial College in November 1995 and brought with him from Ciba-Geigy (now Novartis) vast experience in compressing the scale of analytical equipment to submicroscopic proportions. His work is aided by lecturer Norman Smith, who wheels and deals to get "loan" equipment for the center. "We haven't paid for a single HPLC machine since we arrived," says Manz, "and we have more instruments for capillary electrochromatography in one lab than else in the world." Manz and colleagues, including Zeneca lecturer Andrew de Mello, concentrate their team's efforts on creating tiny channels in glass chips. These channels, they are finding, can be created at just a few micrometers diameter by etching a glass chip and laminat-
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ing it with a second layer of glass. This arrangement allows several thousand CE channels to be squeezed into a couple of square centimeters. Samples of just a few picoliters can be dripped into tiny wells. The potential theoretical plates are 100,000 in a 30-min run for standard GC, says Manz. "We reckon on a million plates in 10 minutes with our techniques, because we spend more time optimizing the miniaturization process in electrochromatography and on the chips." With these tiny sample volumes, Manz achieve separations in a hundredth the time used by conventional instruments but can retain the Scime resolution The chemist's dream would be to couple "lab-on-a-chip" devices or, as Manz prefers, "miniaturized total analysis systems" (u-TAS) to a mass spectrometer and a PC. Just 10,000 or so molecules of separated material could then be analyzed and identified. The ability to scale separation, which Manz perceives as perhaps the most important aspect of analytical science, to levels of picoliters and below could accelerate the development of areas of science such as medical diagnostics, including DNA analysis. Such developments could, for instance, allow analysis of components from just a single blood cell or microbe. Indeed, Manz will soon begin working with Rory Shaw at St Mary's Hospital in London, now part of Imperial College (IC), to accelerate patient assessment following antibiotic treatment for tuberculosis. "It can take several weeks to decide whether a patient is fully clear of infection," says Manz. "We hope to develop u-TAS technology that will allow separation of all microbial DNA from the patient so that the TB genome can be spotted much more readily." He predicts that the thriving field of u-TAS will soon become the technique of choice, allowing researchers—especially in pharmaceuticals—to manipulate minute samples to get the results they need without worrying about sample loss. He suggests that u-TAS might then be extended to environmental monitoring; for instance, tracking algal blooms in waterways and forecasting the data remotely via radio links on the chip. Manz believes u-TAS is not a limited technology, and he is forging links with other departments at IC such as plasma physics and electrical engineering. However, he is less interested in the commer-
Analytical Chemistry News & Features, August 1, 1997
Andreas Manz is thinking small.
cialization of his discoveries than in their creation. "We want to look at the fascinating leads and leave the commercialization to industry and others," he explains. Manz says that they are simply following nature's lead. The optimum scale for chemical reactions seems to be about 1-10 um. Enzymatic manipulation of DNA and neurotransmission takes place on this scale, for instance. "Some insect pheromones even act at the single-molecule level," points out Manz. 'Ten thousand molecules is probably a realistic lower limit for chemists, though!" Manz ponders the idea that industrial processes might be rendered safer and more efficient with u-TAS online monitoring Manz hopes that once academe and industry are routinely using u-TAS, the development of chemical chips will come to the fore in domestic use. "The Japanese are developing a chip that fits in the toilet bowl and analyzes urine for signs of disease," he points out. Similarly, a chip in a saucepan could spot pathogens and increase cooking time accordingly or instead recommend a takeout meal. Since his arrival at IC, Manz has succeeded in doubling die money the center has gained from industry and government sources other than SKB/Zeneca. But, as wiih many other academic analytical chemists, even doubling an initially small pot is simply not enough. As the summer heats up, the chemists will have to keep their cool as they shrink their instruments even without AC. (More information about Manz's work can be found at his Web site: http://www.ch.ic.ac.uk/manz/) David Bradley
