Quantification! Quantification?
Revolutionizing medical diagnosis via rapid, on-line analysis of exhaled breath is the ambitious long-term goal of Zurich Exhalomics. In the future, a patient should be able to breathe into a high-tech analytical instrument, and from the metabolite pattern detected in the patient’s breath, the doctor (or, perhaps, even some software) should be able to say, for example: “your level of adipicacid is below 1 ppb, this is very good, keep up the regular sports” or “your level of 3-nonenal is elevated, you should have your heart checked out”.
Ppb? This is a concentration unit, parts-per-billion, meaning 1 in 1’000’000’000. This concentration corresponds roughly to a piece of sugar (≈3 g) dissolved in the volume held by a supertanker, in other words very, very little. Metabolites in breath indeed occur in such small concentrations. If one should have limits of levels of metabolites in breath that are healthy, too high or too low, this calls for accurate quantification.
Quantifying such low concentrations poses a considerable challenge. The challenge is not the detection per se, but the comparison with accurate standards. It is impossible to fill a gas bottle with 1 ppb of some material! This is because compounds can stick to the walls of a container, they can undergo chemical reactions, or degrade with time. Moreover, some metabolites are not volatile enough in their natural state. On the other hand, standard gases at concentration levels 1000 times higher (ppm = parts-per-million, 1 in 1’000’000) are possible to prepare and some are even commercially available. One viable solution thus lies in dynamic dilution of such gas standards down to the level of their concentration in exhaled breath.
To be able to really make its way into clinical practice, and also to pass approval by regulatory bodies such as Swissmedic or FDA, it is necessary that the problem of quantification is solved not only for a few, but for many different metabolites that occur in breath. This challenge is currently being addressed by the research groups working on the technological aspects of exhaled breath analysis within Zurich Exhalomics.
