The ability to look at multiple isotopes simultaneously was critical for assessing isotope ratios and normalizing one tracer isotope with respect to another; this is useful, for example, for distinguishing the isotope label from the endogenous atoms. The previous generation of instruments measured only one isotope at a time. Lechene's innovative vision and Slodzian's technical wizardry led to the development of multi-isotope imaging mass spectrometry (MIMS) (see 'The bottom line' box for a summary of the technology). "Lechene was uniquely placed to make this development," notes John Vickerman of Manchester University, UK. "He is deeply immersed in the life-sciences community and has a long-standing interest in SIMS instrumental developments. Slodzian is an ion physicist of enormous skill and reputation who has been responsible for the ion-optical design of a number of extremely successful SIMS instruments. The new instrument that Slodzian developed has the spatial resolving power of an electron microscope with the added capability of detailed differentiation of chemical constituents."

Lechene's demanding requirements were important because he was keen to do experiments using the ¹⁵N isotope. ¹⁵N had been used for the pioneering experiments of Schoenheimer [4], to demonstrate protein turnover, and by Meselson and Stahl [5], to confirm the semiconservative nature of DNA replication. The problem is that nitrogen atoms hardly ionize and must therefore be examined as cyanide (CN^-) ions. Lechene needed a system that could distinguish between the different isobars, such as ¹²C¹⁵N^- (mass 27) and ¹³C¹⁴N^- (also mass 27) and other similar atomic clusters. Slodzian's instruments enabled both high spatial resolution and the high mass resolution necessary for separating isobars at high secondary-ion transmissions.

"The most significant feature of this technique is that it opens up a whole new world of imaging; we haven't yet imagined all that we can do with it," says Peter Gillespie from the Oregon Health & Science University in Portland, USA. He agrees with Amos that the technology represents an imaging revolution. "The novelty of the technique means it will take some time for the details to be absorbed, [but it] sets a spectacular new standard for spatial resolution and detection of stable and radioactive compounds in cells." Vickerman is also enthusiastic about the applications: "This study is important in that it demonstrates across a range of demanding applications that SIMS can deliver unique information, inaccessible by other means."

But Vickerman adds a cautionary note about how widely MIMS technology will be applied in the future. "It is clear that the technique has great potential in medicine and biology, but there are two issues that have to be overcome: the conservative approach of much of the potential user community and the cost of the equipment." Gillespie agrees "Once commercial instruments are available, will they be affordable and easy enough to use that we will do many experiments with them? Or will they be like electron microscopes, where the expense of the instruments and the difficulty in operation means that relatively few people use them well?"

"It may take a long time (EM took a long time), but I am convinced that in 10–15 years this will be an easily accessible technique, with routine instruments in many departments of biological research," responds Lechene. A machine based on Slodzian's prototype is already sold by a French company called Cameca Inc., and Lechene notes that there are over a dozen around the world. At a cost of two million dollars they are beyond the budget of most laboratories. But Lechene is keen to point out that more and more mass spectrometry machines are being purchased. "After all, it's just the price of five electron microscopes, but it does so much more!"