Mass Spectrometer Miniaturization

A brief history of mass spectrometer miniaturization is given in Chapter 13. Developments for the miniaturization of MS instrumentation have been especially driven until now by a few fields of application that require on-site analysis and portable analysis instruments. However, novel fields of analysis would much benefit from fully integrated and portable analysis tools as we already discussed in Section 1.2.3. 

A second important application of miniaturized mass spectrometers which is currently growing rapidly in the USA is homeland safety and the prevention of civil (bio)terrorism. For such purposes, the miniaturized mass spectrometer can also include a system for wireless data transmission for remote site sensing.49 

More recently, handheld mass spectrometers have also been successfully used for the study of ion/molecule reactions50 as well as for biological analysis, and the detection of peptides, oligonucleotides and biological spores.51 

Recent achievements in the miniaturization of MS instrumentation gave rise to the first instruments with characteristic dimensions in the micrometer range52 54 as in the case of microsystems dedicated to analysis and chemical processing. Such achievements should lead in the near future to the development of a fully integrated setup including the steps of both sample preparation and detection. 

---

Henry, C.M., The incredible shrinking mass spectrometer miniaturization is on track to take MS into space and the doctor s office. Anal. Chem. 1999, 71, 264A-268A. 

A multipoint ion collector (also called the detector) consists of a large number of miniature electron multiplier elements assembled, or constructed, side by side over a plane. A multipoint collector can be an array, which detects a dispersed beam of ions simultaneously over a range of m/z values and is frequently used with a sector-type mass spectrometer. Alternatively, a microchannel plate collector detects all ions of one m/z value. When combined with a TOP analyzer, the microchannel plate affords an almost instantaneous mass spectrum. Because of their construction and operation, microchannel plate detectors are cheaper to fit and maintain. Multipoint detectors are particularly useful for situations in which ionization occurs within a very short space of time, as with some ionization sources, or in which only trace quantities of any substance are available. For such fleeting availability of ions, only multipoint collectors can measure a whole spectrum or part of a spectrum satisfactorily in the short time available. 

English, R. D. Warscheid, B. Fenselau, C. Cotter, R. J. Bacillus spore identification via proteolytic peptide mapping with a miniaturized MALDITOF mass spectrometer Anal. Chem. 2003, 75, 6886-6893. 

The properties of an ideal mass analyzer are well described, [2] but despite the tremendous improvements made, still no mass analyzer is perfect. To reach a deeper insight into the evolution of mass spectrometers the articles by Beynon, [3] Habfast and Aulinger, [4,5] Brunnee [6,7], Chapman et al. [8] and McLuckey [9] are recommended for further reading. In recent years, miniature mass analyzers have gained interest for in situ analysis, [10] e.g., in environmental [11] or biochemical applications, [12] for process monitoring, for detection of chemical warfare agents, for extraterrestrial applications, [13] and to improve Space Shuttle safety prior to launch. [14]... 

Dawson, P.H. Whetten, N.R. Miniature Mass Spectrometer. Anal. Chem. 1970, 42, 103A-108A. 

Tabert, A. M., Griep-Raming, J., Guymon, A. J., and Cooks, R. G. (2003). High-throughput miniature cylindrical ion trap array mass spectrometer. Anal. Chem. 75, 5656—5664. 

The two main types of mass spectrometers used for analysis and detection of explosives are the quadrupole and the ion trap. These two types of mass analyzers are relatively small, when compared with magnetic sector instruments. They can be miniaturized to make mobile detectors weighing less than 15 kg. 

Fig. 2. 13 Negative ionization APCI mass spectra of the GPC spin column eluates of 20 pM 1 7jS-estradiol (MW 272 Da, Kj 1 nM) titrated with a variety of ER concentrations (1.25, 2.5, 5.0, 10.0, 20.0 pM). A miniature P6 CPC spin column was used with 10-pL samples, of which 2 pL was injected into the APCI TOP mass spectrometer under low flow...

Since the development of HPLC as a separation technique, considerable effort has been spent on the design and improvement of suitable detectors. The detector is perhaps the second-most important component of an HPLC system, after the column that performs the actual separation it would be pointless to perform any separation without some means of identifying the separated components. To this end, a number of analytical techniques have been employed to examine either samples taken from a fraction collector or the column effluent itself. Although many different physical principles have been examined for their potential as chromatography detectors, only four main types of detectors have obtained almost universal application, namely, ultraviolet (UV) absorbance, refractive index (RI), fluorescence, and conductivity detectors. Today, these detectors are used in about 80% of all separations. Newer varieties of detector such as the laser-induced fluorescence (LIE), electrochemical (EC), evaporative light scattering (ELS), and mass spectrometer (MS) detectors have been developed to meet the demands set by either specialized analyses or by miniaturization. 

Activities for miniaturizing mass spectrometers (e.g., microplasma on chip or insertion of diode lasers in RIMS), for constructing cheaper and more compact instrumentation with the same performance or improved properties compared to existing instruments are required as the next generation mass spectrometers. The introduction of microwave induced plasmas or of p,-torches to reduce Ar gas consumption involves developments in this future direction. 

Even the lawn format still does not represent the final limit of miniaturization. The one well/one catalyst or one bead/one catalyst strategy, where catalyst identity is spatially coded, can be replaced by in situ synthesis combined with mass spectrometry [48]. The advantage of this strategy is the use of a mass spectrometer for the synthesis, reaction and analysis. The described electrospray ionization procedure helps to avoid the cleavage of chemical bonds, which would falsify the results. The synthesis step does not have to deliver clean and isolated products. Instead, after synthesis, the reactants are first separated by a quadrupole. In a second step, they are further reacted in an octapole and the reaction products are finally isolated in a second quadrupole and analyzed. Figure 3.15 describes the screening process in detail [49],... 

The aspects considered for a reliable evaluation of the performance of the miniaturized mass spectrometer are repeatability, resolution, and detection limit. Over the last years, these parameters could be improved by theoretical analyses and validated with successive chip generations [34, 35],... 

However, during the last 10 years, several groups have developed miniature and mobile mass spectrometers. Although these instruments were built for environmental applications, detection of chemical and biological weapons, and space exploration, most of them can easily be converted to detection of explosives. 

A handheld miniaturized mass spectrometer based on the RIT geometry was built [20], It size is 13.5 inches (length) x 8.5 inches (width) x 7.5 inches (height) and weighs 10 kg, with a power consumption of less than 75 W. 

A miniaturized mass spectrometer with APCI was built [21], The analyzer was a monopole with 54 mm rod length and 2 mm radius. A two-stage differentially pumping system and sampling nozzle of 80p,m enabled an inlet gas flow rate of 1 ml/s. The ion current generated by the corona discharge was 0.01-10 p,A. 

A miniature cylindrical ion trap mass spectrometer with APCI and ESI capabilities was developed [22], The system includes a three-stage, differentially pumped vacuum system and can be interfaced to many types of atmospheric pressure ionization sources. 

Issues of size, portability, and power requirements have been addressed during the last years, and miniature and mobile mass spectrometers have been developed, based on a variety of mass analyzers. Also, different ionization techniques, such as ESI and DESI, have been applied for the detection of explosives. 

At present, EOID s have been implemented on several experimental mass spectrometers beyond the ones described above (1) a miniaturized (4.5" focal plane) Mattauch-Herzog type mass spectrometer with a mass range of 25-500 and resolution 1/500, which has been built (Perkin-Elmer Corp., Pomona, California) for JPL as a prototype for future space and/or clinical applications and (2) an ultra-miniature (2" focal plane) Mattauch-Herzog type mass spectrometer for outer-space use. Additional uses of the EOID are presently in the planning and/or design stages. 

---