Breath markers for therapeutic radiation.

Radiation dose is important in radiotherapy. Too little, and the treatment is not effective, too much causes radiation toxicity. A biochemical measurement of the effect of radiotherapy would be useful in personalisation of this treatment. This study evaluated changes in exhaled breath volatile organic compounds (VOC) associated with radiotherapy with thermal desorption gas chromatography mass-spectrometry followed by data processing and multivariate statistical analysis. Further the feasibility of adopting gas chromatography ion mobility spectrometry for radiotherapy point-of-care breath was assessed. A total of 62 participants provided 240 end-tidal 1 dm3 breath samples before radiotherapy and at 1, 3, and 6 h post-exposure, that were analysed by thermal-desorption/gas-chromatography/quadrupole mass-spectrometry. Data were registered by retention-index and mass-spectra before multivariate statistical analyses identified candidate markers. A panel of sulfur containing compounds (thio-VOC) were observed to increase in concentration over the 6 h following irradiation. 3-methylthiophene (80 ng.m-3 to 790 ng.m-3) had the lowest abundance while 2-thiophenecarbaldehyde(380 ng.m-3 to 3.85 µg.m-3) the highest; note, exhaled 2-thiophenecarbaldehyde has not been observed previously. The putative tumour metabolite 2,4-dimethyl-1-heptene concentration reduced by an average of 73% over the same time. Statistical scoring based on the signal intensities thio-VOC and 3-methylthiophene appears to reflect individuals' responses to radiation exposure from radiotherapy. The thio-VOC are hypothesised to derive from glutathione and Maillard-based reactions and these are of interest as they are associated with radio-sensitivity. Further studies with continuous monitoring are needed to define the development of the breath biochemistry response to irradiation and to determine the optimum time to monitor breath for radiotherapy markers. Consequently, a single 0.5 cm3 breath-sample gas chromatography-ion mobility approach was evaluated. The calibrated limit of detection for 3-methylthiophene was 10 µg.m-3 with a lower limit of the detector's response estimated to be 210 fg.s-1; the potential for a point-of-care radiation exposure study exists.

Quantitative detection of benzene in toluene- and xylene-rich atmospheres using high-kinetic-energy ion mobility spectrometry (IMS).

One major drawback of ion mobility spectrometry (IMS) is the dependence of the response to a certain analyte on the concentration of water or the presence of other compounds in the sample gas. Especially for low proton affine analytes, e.g., benzene, which often exists in mixtures with other volatile organic compounds, such as toluene and xylene (BTX), a time-consuming preseparation is necessary. In this work, we investigate BTX mixtures using a compact IMS operated at decreased pressure (20 mbar) and high kinetic ion energies (HiKE-IMS). The reduced electric field in both the reaction tube and the drift tube can be independently increased up to 120 Td. Under these conditions, the water cluster distribution of reactant ions is shifted toward smaller clusters independent of the water content in the sample gas. Thus, benzene can be ionized via proton transfer from H3O(+) reactant ions. Also, a formation of benzene ions via charge transfer from NO(+) is possible. Furthermore, the time for interaction between ions and neutrals of different analytes is limited to such an extent that a simultaneous quantification of benzene, toluene, and xylene is possible from low ppbv up to several ppmv concentrations. The mobility resolution of the presented HiKE-IMS varies from R = 65 at high field (90 Td) to R = 73 at lower field (40 Td) in the drift tube, which is sufficient to separate the analyzed compounds. The detection limit for benzene is 29 ppbv (2 s of averaging) with 3700 ppmv water, 12.4 ppmv toluene, and 9 ppmv xylene present in the sample gas. Furthermore, a less-moisture-dependent benzene measurement with a detection limit of 32 ppbv with ca. 21 000 ppmv (90% relative humidity (RH) at 20 °C) water present in the sample gas is possible evaluating the signal from benzene ions formed via charge transfer.

A gated atmospheric pressure drift tube ion mobility spectrometer-time-of-flight mass spectrometer.

Identifying the compounds of an unknown gas mixture by using an ion mobility spectrometer (IMS) is a difficult task, because several ion species can be generated in the ionization process. One method to analyze the occurring peaks in an IMS spectrum is coupling an IMS to a mass spectrometer (MS). In our setup we coupled a (3)H drift tube IMS to a Bruker micrOTOF II. Therefore, the detector plate of the IMS is pierced and a transfer capillary is inserted. The ions are transferred via gas flow and electric fields into the MS. The transmission of the ions through the transfer capillary can be shuttered very precisely by increasing the electric potential of the detector generating a repulsive electric field. Thus, it is possible to transfer single ion clouds of generated IMS spectra into the mass spectrometer where a corresponding mass spectrum is generated. In this work we analyze the positive and negative IMS spectra of single analytes as well as gas mixtures and characterize the occurring ion species.

High kinetic energy ion mobility spectrometer: quantitative analysis of gas mixtures with ion mobility spectrometry.

We present a high kinetic energy ion mobility spectrometer (HiKE-IMS) for quantitative gas analysis. Drift tube and reaction tube can be operated at reduced fields up to 110 Td. At such conditions the distribution of reactant ion water clusters is shifted toward smaller clusters. Due to the resulting presence of bare reactant ions (e.g., H3O(+)) and the kinetic control of the ionization process with decreasing reaction time, unlike conventional IMS, a quantitative detection with ppbv detection limits of low proton affine analytes even in humid gas mixtures containing high proton affine compounds is possible using a direct sample gas inlet. A significantly improved dynamic range compared to conventional IMS is achieved. An incremental change in reduced fields enables the observation of parameters like field dependent ion mobilites or analyte fragmentation. Also, the characteristic of the analyte signal with respect to the reduced reaction field gives insight into the ionization process of the analyte. Thus, HiKE-IMS enables substance identification by ion mobility and additional analytical information that are not observed with conventional IMS. The instrumental effort is similar to conventional desktop IMS with overall dimensions of the drift and reaction tube of 4 cm × 4 cm × 28.5 cm. However, the mobility resolution is limited and between 30 and 40. Because of the moisture independent ionization and the decrease in competing ion-molecule reactions, no preseparation or membrane inlet is necessary when the compounds of interest are distinguishable either by a significant difference in ion mobility or the additional analytical information.

A compact high resolution ion mobility spectrometer for fast trace gas analysis.

Drift tube ion mobility spectrometers (IMS) are widely used for fast trace gas detection in air, but portable compact systems are typically very limited in their resolving power. Decreasing the initial ion packet width improves the resolution, but is generally associated with a reduced signal-to-noise-ratio (SNR) due to the lower number of ions injected into the drift region. In this paper, we present a refined theory of IMS operation which employs a combined approach for the analysis of the ion drift and the subsequent amplification to predict both the resolution and the SNR of the measured ion current peak. This theoretical analysis shows that the SNR is not a function of the initial ion packet width, meaning that compact drift tube IMS with both very high resolution and extremely low limits of detection can be designed. Based on these implications, an optimized combination of a compact drift tube with a length of just 10 cm and a transimpedance amplifier has been constructed with a resolution of 183 measured for the positive reactant ion peak (RIP(+)), which is sufficient to e.g. separate the RIP(+) from the protonated acetone monomer, even though their drift times only differ by a factor of 1.007. Furthermore, the limits of detection (LODs) for acetone are 180 pptv within 1 s of averaging time and 580 pptv within only 100 ms.

Investigation of ion-ion-recombination at atmospheric pressure with a pulsed electron gun.

For future development of simple miniaturized sensors based on pulsed atmospheric pressure ionization as known from ion mobility spectrometry, we investigated the reaction kinetics of ion-ion-recombination to establish selective ion suppression as an easy to apply separation technique for otherwise non-selective ion detectors. Therefore, the recombination rates of different positive ion species, such as protonated water clusters H(+)(H(2)O)(n) (positive reactant ions), acetone, ammonia and dimethyl-methylphosphonate ions, all recombining with negative oxygen clusters O(2)(-)(H(2)O)(n) (negative reactant ions) in a field-free reaction region, are measured and compared. For all experiments, we use a drift tube ion mobility spectrometer equipped with a non-radioactive electron gun for pulsed atmospheric pressure ionization of the analytes. Both, ionization and recombination times are controlled by the duty cycle and repetition rate of the electron emission from the electron gun. Thus, it is possible to investigate the ion loss caused by ion-ion-recombination depending on the recombination time defined as the time delay between the end of the electron emission and the ion injection into the drift tube. Furthermore, the effect of the initial total ion density in the reaction region on the ion-ion-recombination rate is investigated by varying the density of the emitted electrons.