Conclusions

It is dangerous to predict that all of the essential technical innovations that allow the linkage between chromatography and mass spectrometry are in place. It would be equally foolish to try and identify any combination for which the interface technology has not already been demonstrated, at least in a primitive sense. Certainly one major area of future innovation will be in the continued reduction in the size of the instruments. However, although gas chromato-

graphic and capillary electrophoretic separations on a chip level have been demonstrated, such devices have not swamped the marketplace. There is a realistic laboratory scale for the physical dimensions of instrumentation, and the sizes of a computer keyboard and a computer monitor are quintessential examples of that scale. Further reductions in physical size may be possible, but are not in concordance with human operation. It is not unrealistic to predict that GC-MS units will soon be the size of a PC, and may be moved about and reconfigured as easily. This reduction in physical size by a factor of about two from present day instruments will require clever packaging and insightful engineering, but does not depend on the development of fundamentally new technologies. As long as the analysis of samples occurs in a single instrumental channel (serial analysis), such scale is appropriate.

What would happen if mass spectrometers could be reduced in physical scale to the chip size (xyz dimensions of a few centimetres) and interfaced to some form of miniaturized chromatographic separation? Assuming that the performance of each individual combination was the same, the serial analysis has the potential to become a parallel analysis. The analytical results would be the same no matter which channel of analytical instrumentation is specified. Therefore parallel analysis allows many similar analyses to be run simultaneously, with special data acquisition and processing programs designed to zero identical results (results identical to each other or to a standard result) and highlight differences. Alternatively, adjacent channels of analysis may sample a system in which a variable (temperature, pressure, time, light, reactant concentration) is systematically varied. The possibilities for such miniature analytical instrument arrays are diverse and exciting.

What technological impediments stand between the present and, as an example, miniaturized laser ionization, time-of-flight mass spectrometers? The ions themselves are small, lasers and filaments can be small, and flight tubes are nothing but channels that can be folded into compressed S shapes. Electron multiplier detectors can also be made very small, subject only to space charge effects that limit the entire system. Electrical connections to the outside world are entirely manageable on a micrometre scale. There are two other physical connections to the outside world that have to be managed. The first is the introduction of the sample to the mass spectrometer. Assuming that the sample is eluted from the column, the problem is transformed into loading the sample onto the column. Miniaturized robotic injectors or microfluidics are already available for this task. The second physical connection is the attainment and maintenance of a vacuum. Vacuum pumps are, in general, not amenable to miniaturization, since they must possess the physical means to transport molecules from inside the system to the outside environment. The only restriction is the insistence on maintaining vacuum, with the assumption that many samples will be analysed by the same mass spectrometer. If a miniaturized mass spectrometer has a total evacuated volume of 1 mL (not outside the reasonable scale), then a vacuum reservoir of 100 mL suffices for pumping by virtue of expansion. Essentially the vacuum is a rechargeable resource. Removing of the vacuum hardware as a physical limitation to the size of the mass spectrometer will be a genuine innovation in the field. Hopefully, this same overview written ten years from now will document the applications of new miniaturized chromatography-mass spectrometry systems.

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