SIMS-TOF Instruments

FIGURE 5.2 Dependence of the quasimolecular ion yield on molecular weight for a series of peptides bombarded with Cf fission fragments and with 8-keV Cs ions. (Reprinted with permission from reference 7). 

---

While few SIMS-TOF instruments have been developed for the analysis of large biological molecules, the development of ion microprobes capable of focusing an ion... 

The quantification capability is normally limited by the detector and/or the ion source. The MCP that is often utilized in TOF instruments cannot fully handle the ion currents that are produced in MALDI and are often saturated to some extent. With other ion sources, such as SIMS, the detection system is less strained so the detector is less limiting. Instead the ion source will limit the quality in quantification. Magnetic sectors and also qudmpoles are more often utilized when quantification is important. 

Analysis of surface chemical structure requires use of the static SIMS technique to ensure that the major portion of the surface should not be affected by secondary ion emission. Time-of-flight SIMS (ToF SIMS) is the most widely used static SIMS technique. As its name indicates, ToF SIMS uses the ToF mass analyzer to measure mz l of secondary ions. ToF SIMS is a stand-alone instrument, not incorporated into or attached to other SIMS instruments as for dynamic SIMS. A typical structure is illustrated in Figure 8.13. 

ToF systems are well suited to the pulsed nature of SIMS and MALDI measurements, and combine many characteristics that are advantageous to imaging experiments. High detection efficiency, parallel detection, and a wide m/z detection range have made them ubiquitous for MALDI and SIMS-MSI. Recent improvements in measurement speed have particularly benefited MSI experiments. Modem commercially available MALDI-ToF instruments are equipped with solid-state lasers that allow acquisitions at up to 2 kHz. Such speed is a prerequisite for the development of higher spatial resolution analysis and three-dimensional imaging or for the analysis of large animal/ patient series of tissues. 

Recent reviews [264,265] show the possibilities of these different techniques of soft ionization, with various analyzers to separate the high-mass ions in particular, with a time-of-flight, it has been possible to transmit ions of m/z 12651 ( 10) [266]. Recently, resolution of TOF instruments has been improved [267], enabling the determination of metastable transitions. The FAB [268], SIMS [269] and laser desorption [270] techniques are consistent with MS/MS methodology. 

Alignment of the postionizing laser as close as possible to the sample surface improves G d). Depending on the selected ionization scheme, irradiation is achieved with one or more lasers simultaneously. The delay between the primary ion and laser pulses must match the time needed for the neutrals to reach the ionization volume. Hence, adjustment of this parameter is critical to maximize the density of neutrals in the ionization volume. The laser pulse duration of typically 1-20 ns is selected to optimize both ionization probability and mass resolution. The spread on velocity and direction of the neutrals motivates application of relatively long pulses. As a result, the mass resolution in SALI experiments is lower than that for the SIMS mode with the same TOF instrument. 

Kratos Prism ToF-SIMS spectrometer (Manchester, UK) or similarly designed static SIMS imaging instrument. 

On the other hand, ions produced in a continuous beam must be formed into pulses by an appropriate device, so an additional complication is introduced. Examples are electron ionization, secondary-ion mass spectrometry (SIMS), and most recently electrospray ionization (ESI). As mentioned above, the earliest commercial TOF instruments used electron-impact ionization, and the difficulty in producing short ion bursts with this method was mainly responsible for their limitations in mass resolution. However, new technology has enabled dramatically improved performance for continuous sources, particularly ESI, and TOF has been gaining popularity for such sources as well. 

---