The Future of Miniature Mass Spectrometers and a Path Forward: A Few Thoughts from an Academic Researcher

Feb 01, 2014

Mass spectrometry (MS) serves as a versatile and effective tool in chemical analysis. It provides highly specific molecular information at excellent sensitivity. The emerging miniature MS systems could potentially be used outside analytical laboratories by personnel not trained in analytical chemistry, and thereby the range of applications for MS could also be significantly broadened. This column installment defines the future role of miniature MS systems in specialized analysis, justifies the need for simplification in operation, proposes a development approach involving ambient ionization, and delineates challenges in development and commercialization.

When we mention miniature mass spectrometers, it often brings to mind handheld research prototypes such as the Mini 10 or Mini 11 systems developed at Purdue University (West Lafayette, Indiana) or commercial products that specialize in homeland security applications (1). A marked advance in the same category is the recent development at Purdue of a backpack mass spectrometer that has a sampling probe that can scan ground surfaces for in-field detection of explosives (2). In this column installment, however, we contemplate a different type of miniature mass spectrometry (MS) analysis systems, such as the Mini 12 system (3). Also developed at Purdue, the Mini 12 system weighs 25 kg, is as compact as a desktop computer, and could prove useful in the field of biomedicine as well in the pharmaceutical, chemical, and agrochemical industries. A primary motivation for developing such a system is to enable physicians, nurses, and biologists to analyze samples at their desks, obviating the need to send the samples to an analytical laboratory.

Miniature Mass Spectrometry Analysis System Defined

In the past, the term miniature mass spectrometer has been used for a variety of devices that fall within a broad range of system completeness or self-sustainability. The miniature mass analyzers or vacuum manifold assemblies by themselves have all been called miniature mass spectrometers previously. Finally, complete instrument packages were developed to perform vacuum pumping, ionization, mass analysis, instrument control, and data acquisition. As demonstrated by the Mini 11, a mass spectrometer, even with multistage MS-MS capability, can be made to weigh only 4 kg (4). Such a miniaturized instrument by itself, however, would not be practically useful because it could not perform complete chemical analyses starting from raw samples (1). As for a mobile chemical analysis laboratory, additional equipment for sample preparation and chromatographic separation is always needed and could require more space than the mass spectrometer. Thus, sample preparation before MS analysis must also be done using miniaturized equipment and highly autonomous procedures.

Assuming such miniaturization is feasible at a system level, a biologist doing a preclinical study could almost effortlessly perform routine work such as finding the concentration of a drug metabolite in blood. To do that, he or she would draw about 0.5 μL of blood from a study animal (for example, a mouse), drop the blood onto a paper substrate inside a disposable sample cartridge, push the cartridge into the analysis system, and then wait 60 s for a report of the concentration. With such a small amount of sample required, this type of analysis would be minimally invasive. More importantly, the biologist would not need to program the instrument, telling it what to look for or what to do. Instead, a bar code on the cartridge would be scanned, and a presaved scan function would be automatically loaded and executed. The biologist also would not need to be concerned about the accuracy of measuring a 0.5-μL sample, because he or she would use a precut capillary, taking the blood by capillary action. The biologist could also expect a high degree of precision for the quantitation result because the internal standard (IS) would be precoated on the inside wall of the capillary (5), and the concentration calculated according to the analyte/IS ratio measured and a presaved calibration curve.

A similar system could be used by a nurse performing a blood test to identify a smoker (6), by a physician who must perform therapeutic drug monitoring to prescribe the correct dosage of cancer or immunosuppressive drugs (7), or by a police officer or anxious parent who wants to determine the presence or absence of illicit drugs in urine (8). To do these things, complete systems much smaller than the current systems used in analytical laboratories must be developed. Nevertheless, though we could never overemphasize the importance of a system's operational simplicity, we might indeed overemphasize the importance of its small size. Yet we must avoid doing so. If we can accommodate printers or copiers of various sizes, it might be ok for us to accept MS systems of 50 kg, as long as they can be operated like a printer or copier and fit unobtrusively in our offices.