Scientific progress is achieved by new technologies, new discoveries and new ideas, probably in that order. (Sydney Brenner)
Scientific progress is, like it or not, achieved by new technologies. New technologies provide unprecedented capabilities that change our view of nature and lead to new ideas and concepts.
Mass spectrometry, which dramatically evolved and changed over the last two decades, constitutes in our view a technique that has and will fundamentally change the chemical and life sciences offering powerful capabilities driving future scientific progress. These capabilities in order of importance are:
1. Unsurpassed Resolution
A modern high resolution mass spectrometer can resolve several thousand analytes concomitantly and at the current state of art ultra high resolution instruments are able to resolve up to 100 000 analytes in a single spectrum. This resolution is several orders of magnitude higher than any other spectroscopic or separation technique, providing unprecedented insight into the nature and composition of matter. If we assume that a human organism is made up from around 100 000 different chemical entities, this means that at least in theory all human molecules can be analysed at the same time in a single measurement.
2. Structural Information
MS provides two levels of structural information. Firstly high resolution MS data provide information on molecular formulas (elemental composition) and secondly tandem MS provides via fragmentation further structural information on bond connectivities.
3. Coupling to separation techniques
MS instruments can be routinely interfaced with separation devices including HPLC or GC instrument. Additionally further spectrometers can be interfaced providing for each analyte, multi-dimensional specificity and a multitude of structural information via measurement of retention time UV-VIS absorption and MS data.
4. Sensitivity
MS is one of the most sensitive techniques available to chemists with routine sensitivities in the fmol region. Theoretical consideration predict a maximum sensitivity of around 10 ions, which we might see realized within the next decades.
5. Versatility
MS can be used for any type of analyte independent of its size, physical state (gas, solid or liquid) or sensitivity. Modern ionization techniques allow the generation of ions from any analyte imaginable.
6. Speed and Ease of Analysis
MS techniques are relatively easy to use (a few months training is sufficient) are rapid and amenable to high throughput applications.
In our research we use many aspects of modern mass spectrometry to study food, biological systems, environmental samples or synthetic compounds. We try to make the best use out of its unique capabilities and try to identify challenges and find solutions to the challenges to improve the capabilities of this technique to advance scientific progress.
The main challenges in modern mass spectrometry are the following, which we try to address in our research:
1. Interpretation of complex data
As mentioned before, modern high resolution MS is able to routinely provide spectra with tens of thousands of different ions present in a single spectrum. How do we interpret such data? Finding solutions to obtain chemical or biological meaningful information is one of MS most pressing and urgent challenges. We have adopted methods devised in petroleomics to address such complex samples and developed a series of novel data interpretation strategies to extract chemical and biological relevant information from such enormously complex data.
2. Obtaining structural information
We believe that MS is not living up to its full capabilities in chemical structure elucidation. Despite many advances, deriving a full chemical structure from MS data is currently only possible in exceptional circumstances. We believe this can be changed by achieving a better understanding of fragmentation mechanisms and using more sophisticated tandem MS techniques such as energy resolved mass spectrometry. Work in this field will be published soon.
3. Distinction of and unambiguous characterization of isomers
Generally MS is considered to be isomerically blind. Isomers, compounds of identical molecular formula, are generally believed to show if any, only subtle differences in their MS spectra. This is not true. We have shown for a series of regioisomeric compounds (chlorogenic acids, shikimic acid derivatives, carbohydrates) that the use of tandem MS techniques provides a powerful method to distinguish isomeric compounds and even allows a reliable prediction of chemical structure (in most cases even superior to NMR). Current work focuses on extension of these methods and the distinction of stereoisomers by tandem MS.
4. Ion Suppression and Ion Enhancement
If more than one analyte is present in an MS analysis, these analytes compete for ionization, leading to a reduction or enhancement of any number of signals. This effect has been termed ion suppression or enhancement and next to spoiling any quantitation attempts is to the current day poorly understood. Understanding ion enhancement is of utmost importance in complex mixture analysis. If thousands of analytes are present we must know, which ones we can observe and which ones not and what level of quantitative information we can derive from such experiments. We are addressing the problem of ion suppression and have recently shown that such effects can be rationalized on the basis of chemical structure itself.
5. Quantification
For quantification in MS authentic reference materials are required, ideally a set of isotopically labeled and unlabeled reference material (because of ion suppression) to allow thorough quantification of analytes. Would it not be great if quantification could be carried out without such a requirement? Current work is addressing this problem trying to find methods that allow reference free MS quantification.
6. Non-covalent interactions
In MS both non-covalently bound and covalently bound species can be analyzed. In several ongoing projects we try to understand the nature of non-covalent interactions in MS to be able to study both interactions in biological systems.