New Statistical Algorithms for the Analysis of Mass - FU Berlin, FB MI ...

3.2. INTRODUCTION TO MALDI TOF MS 29
Or, in other words, the more exact the machine can determine the time an ion
travels from the moment of its ionization until it hits the detector, the higher
the resolution is. Analyzing the equations from the previous section we see
that many factors contribute to an ions flight time, including:
1. initial states of the ions (prior to acceleration), such as velocity (v0),
position (s0) and time of formation (t0)
2. non-ideal vacuum that introduces particle collisions (affects uD)
3. non-ideal acceleration or drift regions, which affect uD and UD
4. fragmentation of ions, either in acceleration or drift region (affects at
least uD)
The factors that limit the resolution mostly are the distribution of the ions
initial states. These result in slightly blurred spectra (see the Lego example).
Other Types of MS
In this thesis we mainly use data from MALDI MS machines since most of
the recent publications in clinical setting are using this kind of technology.
However, besides MALDI there are other types of MS technology that are
briefly described in the following paragraphs.
SELDI Surface-enhanced laser desorption/ionization (SELDI) is another
common ionization method in mass spectrometry that is used for the analysis
of protein mixtures (Tang et al., 2004). Opposed to MALDI, the protein
mixture is spotted on a surface with a chemical. Such a surface (e.g. CM10,
a weak-positive ion exchange, or IMAC30, a metal-binding surface) specifically
binds some proteins from the sample while the others are removed by
washing. After washing - as in MALDI - the matrix is applied to the surface
and crystallizes with the sample peptides. Thus, the SELDI surface acts as a
separation step. Surfaces can also be built with antibodies or DNA.
SELDI technology was developed by T. W. Hutchens in 1993 (Hutchens
and Yip, 1993) and commercialized by Ciphergen Biosystems in 1997 as the
ProteinChip system. It is now produced and marketed by Bio-Rad Laboratories.
ESI Electrospray ionization (ESI) (Fenn et al., 1989) is another technique
to produce ions and rewarded with the Nobel Prize in Chemistry to J.B. Fenn
in 2002. It is especially well suited to ionize large macromolecules because it
overcomes the propensity of these molecules to fragment during ionization.
In electrospray ionization, a liquid containing the sample is pushed through
a very small, charged capillary (Fenn et al., 1990). The sample is dissolved in a
large amount of solvent and is already ionized. Because like charges repel, the
liquid pushes itself out of the capillary and forms an aerosol consisting of small
droplets. As the solvent evaporates, the sample molecules are forced closer
together, which causes repellence thus breaking up the droplets. Resulting
ions are then accelerated and fly to the detector as in the SELDI or MALDI
case. Opposed to the MALDI ionization process ESI produces also multiplycharged
ions such as [M+2H] 2+ .