It's All About Timing

Apr 01, 2006
Volume 21, Issue 4

In "Star Trek," that handy tricorder device provides exactly the analytical result needed to advance the story, and, amazingly, accomplishes this task in just a few seconds of script time. No lengthy sample preparation, no time seemingly spent in analysis, an instantaneous data interpretation, and an irrefutable conclusion. These characteristics, at some level, reflect the desiderata that underlie the development of miniaturized sensor technology in modern analytical chemistry. Modern mass spectrometry (MS) seems far removed from those desiderata, and from that fictional world of instantaneous analysis in the palm of your hand. Our instrumentation seems bulky and complex compared with the compact tricorder. We have developed portable mass spectrometers, dating as far back as 1978 (1,2), but they are targeted to fairly specific and limited applications, and you might not want to carry the batteries for a terrestrial model in your backpack. However, for outer-space applications, at a high cost, mass spectrometers can be made smaller while maintaining extraordinary capabilities. We may look to these devices as the topic of a future column. For now, in a discussion of time and MS, we focus on an Earth-bound laboratory scale. We note that each gas chromatography–mass spectrometry (GC–MS) or liquid chromatography–MS (LC–MS) run typically consumes minutes to tens of minutes. Add time needed for sample preparation, including collection, concentration, transfer, and disposal, as well as collection of data into a presentation format, and it's clear that we might spend time in the holodeck waiting for results with our present-day technology.

But MS itself really takes very little time. Figure 1 presents a slice of time from the very short to the very long (the vertical axis is logarithmic), and places MS time in perspective. The composition in the figure is analogous to that which appeared as a "Mass Perspective" in the February 2006 column (3). The axis crossing is at 1 s; the points to the lower left represent shorter times, and the points to the upper right are longer times. Rather arbitrarily, the length of a GC–MS or LC–MS run is set at 1000 s and is marked on the figure. The average human lifetime also is marked (your lifetime might vary). The solid line to the lower left is the time scale from about 1015 s (length of processes for formation of an ion in electron ionization) to 103 –101 s (time required for instrumental measurement of a single mass spectrum). We provided a laboratory scale of operation in the previous "Mass Perspective" figure. From a time perspective, the laboratory scale represents our ability to measure spectroscopic events at short time scales (say 1012 s) and the ability to integrate data over extended periods of time (extending to perhaps 106 s). Mass spectrometric time is a subset of the 18 order-of-magnitude laboratory scale, except perhaps for the shortest processes of ion formation.

The 1000 s allotted for GC–MS and LC–MS is needed for the separation process (we can consider this a form of sample preparation), and the need to (ideally) present one sample component at a time to the mass spectrometer for analysis. The development of analytical MS–MS provided some early insight into how the separations time barrier could be bypassed, and meaningful information preserved in a complex mixture analysis. More recently, ultrahigh mass accuracy MS, combined with more powerful data processing, is providing another pathway through which meaningful results from a complex information space can be extracted rapidly (4). We consider here MS itself, separate from external separations or sample preparation considerations. To apportion time in MS, we start logically at the point of ion formation and end (rather arbitrarily) at the point of ion detection. Figure 2 is an expanded perspective on mass spectrometric time, arrayed as a timeline, and serves in this discussion as the focal point for related concepts of ion formation and dissociation, and ion analysis by MS. Because the first steps of this timeline focus on ion formation, the unique processes that characterize ion formation in electron ionization, chemical ionization, electrospray ionization (ESI), or matrix-assisted laser desorption ionization (MALDI) will each occur in a different window of time. Here, we use electron ionization (EI) as our model. Descriptions of the timing of other ionization processes are held for a later presentation.

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