High-Resolution Mass Spectrometry

Technology and Nature confront the analytical chemist with a number of extremely challenging processes to unravel, e.g.  because the related spectra (e.g. MS) might be very complex. Interferences are an issue, which, in principle, is a question of mass resolution. Smart sample prep and chromatographic introduction may help to mitigate the issue. However, in many applications the complexity of MS can be only addressed with high (R>10'000) or even ultra-high (R>100'000) mass resolution. A few examples from our research are summarized here.
Strong Mass Interferences of Chlorinated Paraffins
/documents/56094/98188/CP-TOP.jpg/5b808d5c-255b-4afc-8c37-55d33eae4b1c?t=1535682718490

 

Chlorinated paraffins (CPs) are high production volume chemicals. Their analysis is challenging and becomes even more that in presence of CP transformation products. Chlorinated olefins (COs) are expected thermal CP transformation products that are present in technical CP products and in the environment. Thus, a specific analysis of CPs and COs is important. Commonly, CPs are analysed by gas chromatography electron capture negative ionisation mass spectrometry (GC-ECNI-MS). It was shown that GC-ECNI-MS suffers from in-source formation of COs. Further, selected ion monitoring can lead to false quantification of COs as CPs. Alternative methods based on liquid chromatography and soft ionisation techniques can solve the CP/CO problem. Non-interfered CP data is inevitable for CP transformation studies and non-biased degradation kinetics. Data about CP transformation is urgently needed, but respective studies are challenging. Recently, we provided an analytical guide to deal with severe mass interferences of CPs and their transformation products.

Advancing the Capabilities of FT-Orbitrap

High resolution is one of the main benefits for the small molecule analysis provided by Orbitrap FTMS. Direct infusion without on-line separation, on-line separation using liquid chromatography (LC) and gas chromatography (GC), as well as surface imaging are all widely employed sample ionization and introduction approaches for hyphenation with Orbitraps. The limitations may include a moderate throughput (higher resolution means longer ion detection), a certain care being required to provide accurate isotopic abundance ratios, restricted increase of the resolution for achieving isotopic fine structure information and separating isobaric compounds at high mass, and, perhaps most importantly, a sensitivity.

For example, trace level quantitatively-accurate measurements of organic pollutants, for example dioxins in biofluids, are essential for monitoring of the environmental hazards and timely initiating personal preventive care. However, a single measurement of a low concentration sample using GC Orbitrap FTMS may be not sensitive enough to detect the compounds of interests or to accurately quantify their levels. The fundamental nature of FTMS suggests a possible way of increasing the sensitivity of targeted and untargeted analysis for both isolated compounds and those embedded into a complex matrix, by averaging of time-domain unprocessed data (transients) across a number of technical replicates from GC-MS measurements, followed by Fourier transformation. A principal obstacle to realize this approach is the absence of an access to the transient signals from Orbitrap FTMS instruments.

We developed an implementation of a transient-recording capability on the GC Orbitrap FTMS and further method development and application for increasing the sensitivity of the trace level persistent organic pollutant analysis.

Preliminary results demonstrate that a multiplexed GC-MS approach is beneficial for the increased sensitivity and improved accuracy in the quantitative analysis of low abundant dioxins. Furthermore, with an available access to the transients, we were able to significantly increase the overall resolution obtainable from the GC Orbitrap FTMS by recording transients with 2-10 fold extended duration. That proportionally (linearly) increased the maximum achievable resolution in mass spectra. As a result, an isotopic fine structure analysis, which can aid in targeted and untargeted molecular analysis, has been uniquely enabled on the GC Orbitrap FTMS. Comparable advantages have been demonstrated for other applications, including for multiplexed quantitative lipidomics using direct infusion FTMS, LC-MS hyphenation, and imaging of biological tissues.

 

Induction Spectrometry Technology (Patented)

Ultrafast photoelectron and photoion spectroscopy (as well as their combination known as “coincidence spectroscopy”) utilizes detectors based on different electron multipliers such as microchannel plates or single-channel electron multipliers. These detectors have a few important limitations such as fast-signal
distortion (low pass operation), mutually exclusive positive or negative mode, dead time, and requirement of trigger. A high-pass frequency-dispersive (FT) induction detector, based on a hollow-cored toroidal coil, was developed that overcomes the above-mentioned limitations. The frequency-dispersive response and linearity of different configurations were analyzed. It is shown that the response is enhanced for ultrafast electron signals, dependent on construction parameters, thus offering response flexibility by design. Kinetic energy distributions of pseudospark-induced electron pulses are characterized in order to validate the capabilities in real applications.

A compact setup for extreme UV photoionization time-of-flight (TOF) mass spectrometry was realized for the sensitive detection of low and high ionization potential (IP) chemical species, without massive fragmentation typical of hard sources. High IP species, i.e. beyond the ionization limit of the source, are a ected by poor detection limits in state-of-the-art mass spectrometry, which is characterized by large instrument dimensions. Simultaneous validation measurements carried out with a commercial electron impact ionization quadrupole mass lter, were in agreement with the XUV-TOF spectra acquired. The resolution obtained for N2 was at least factor of 2 higher than the one measured with the quadrupole and the mass spectrum, devoid of fragmentation. A self-developed hollow toroidal coil (HCT, patented) induction detector was used for spectrometry on photoion/photoelectron. Kinetic energy distribution of ionized photoelectrons were retrieved, which by cross-correlation gave access to the IP distribution.

/documents/56094/98188/HCT_detector.jpg/63173918-ed85-4df2-8fb7-334f0e61d66d?t=1535902044623
References

Schinkel, L., Lehner, S., Heeb, N. V., Marchand, P., Cariou, R., McNeill, K., & Bogdal, C. (2018). Dealing with strong mass interferences of chlorinated paraffins and their transformation products: an analytical guide. Trends in Analytical Chemistry, 106, 116-124.

Schinkel, L., Lehner, S., Knobloch, M., Lienemann, P., Bogdal, C., McNeill, K., & Heeb, N. V. (2018). Transformation of chlorinated paraffins to olefins during metal work and thermal exposure – Deconvolution of mass spectra and kinetics. Chemosphere, 194, 803-811.

Heeb, N. V., Mazenauer, M., Wyss, S., Geueke, B., Kohler, H. P. E., & Lienemann, P. (2018). Kinetics and stereochemistry of LinB-catalyzed δ-HBCD transformation: comparison of in vitro and in silico results. Chemosphere, 207, 118-129.

 

Schinkel, L., Lehner, S., Heeb, N.V., Lienemann, P., McNeill, K., Bogdal, C., (2017). Deconvolution of mass spectral interferences of chlorinated alkanes and their thermal degradation products: chlorinated alkenes, Analytical chemistry, 89, 5924-5932.

 

Arbelo, Y., & Bleiner, D. (2017). Induction spectrometry using an ultrafast hollow-cored toroidal-coil (HTC) detector. Review of Scientific Instruments, 88(2), 024710

 

Detector supplement device for spectroscopy setup (2015-11-26), Inventors: D. Bleiner, Y. Arbelo-Pena, WO2017089517A1