The synergy of elemental and biomolecular mass spectrometry: new analytical strategies in life sciences

The application of mass spectrometry with soft ionization techniques (ESI, electrospray ionization, and MALDI, matrix-assisted laser desorption ionization) in the life sciences for the detection and identification of biomolecules is already well established, whereas the application of elemental mass spectrometry and in particular inductively coupled plasma mass spectrometry (ICP-MS) for the determination of metals, metalloids and non-metals in biomolecules is rather new and there is some hesitation in accepting this analytical method, although it offers many advantages. Therefore, it is the aim of this tutorial review to highlight new analytical strategies consisting of the combined applications of elemental and molecular mass spectrometric techniques. In fact, elemental and biomolecular mass spectrometric methods are highly complementary: elemental mass spectrometry methods, such as ICP-MS, offer very sensitive element analysis in the trace and ultra-trace concentration range with multielement capability and the excellent and uniform sensitivity is structure-independent and can be used analytically for accurate quanti. cation as well as for fast screening of specific elements even in complex samples. Laser ablation (LA) ICP-MS, as a solid state mass spectrometric technique, allows the direct determination of trace elements in biological and environmental samples and is applied for microlocal analysis with spatial resolution in the mm range. In contrast, molecular weight determination and structural information is completely lost during the ionization step so that these features have to be provided by biomolecular mass spectrometry and in particular by ESI- and MALDI-MS. On the basis of selected examples, it will be shown that only the combination of different elemental and biomolecular mass spectrometric techniques can solve analytical problems in the life sciences and environmental research in a synergistic way where neither technique alone would be successful. This synergy will be demonstrated by selected applications from various areas: food and nutrition, toxicology, clinical and pharmaceutical research, biochemistry and in particular proteomics. Future developments and trends will be discussed concerning instrumental developments of new mass spectrometric techniques providing high sensitivity with lower detection limits for many elements measured quasi-simultaneously so that new analytical information about biological systems can be drawn from isotopic information and the application of stable non-radioactive isotopic tracers. In addition, elemental labels enable the development of new high-throughput screening techniques based on multiplexed biomarkers. Advanced powerful surface mass spectrometric techniques are required for the imaging of elemental and molecular information in order to analyse tissue samples and to develop novel array-based biochips.