Wolfgang Vautz

Ion mobility spectrometry for food quality and safety

Ion mobility spectrometry is known to be a fast and sensitive technique for the detection of trace substances, and it is increasingly in demand not only for protection against explosives and chemical warfare agents, but also for new applications in medical diagnosis or process control. Generally, a gas phase sample is ionized by help of ultraviolet light, ß-radiation or partial discharges. The ions move in a weak electrical field towards a detector. During their drift they collide with a drift gas flowing in the opposite direction and, therefore, are slowed down depending on their size, shape and charge. As a result, different ions reach the detector at different drift times, which are characteristic for the ions considered. The number of ions reaching the detector are a measure of the concentration of the analyte. The method enables the identification and quantification of analytes with high sensitivity (ng l−1 range). The selectivity can even be increased — as necessary for the analyses of complex mixtures — using pre-separation techniques such as gas chromatography or multi-capillary columns. No pre-concentration of the sample is necessary. Those characteristics of the method are preserved even in air with up to a 100% relative humidity rate. The suitability of the method for application in the field of food quality and safety — including storage, process and quality control as well as the characterization of food stuffs — was investigated in recent years for a number of representative examples, which are summarized in the following, including new studies as well: (1) the detection of metabolites from bacteria for the identification and control of their growth; (2) process control in food production — beer fermentation being an example; (3) the detection of the metabolites of mould for process control during cheese production, for quality control of raw materials or for the control of storage conditions; (4) the quality control of packaging materials during the production of polymeric materials; and (5) the characterization of products — wine being an example. The challenges of such applications were operation in humid air, fast on-line analyses of complex mixtures, high sensitivity — detection limits have to be, for example, in the range of the odour limits — and, in some cases, the necessity of mobile instrumentation. It can be shown that ion mobility spectrometry is optimally capable of fulfilling those challenges for many applications.

Breath analysis—performance and potential of ion mobility spectrometry

Ion mobility spectrometry is a fast and sensitive analytical method for the detection of gas phase analytes in the ppb(v)-ppt(v) range under ambient conditions (pressure and temperature). Ion mobility spectrometers coupled with rapid pre-separation like multi-capillary columns (MCC/IMS) are suitable for the selective characterization of complex and humid mixtures. Recently, MCC/IMS have been applied to analyses of human breath for early diagnosis as well as medication and therapy control. The complete procedure of breath analyses including evaluation and interpretation of the data obtained is demonstrated for the first time on exhaled breath after the consumption of a particular candy as an example. An MCC/IMS equipped with a β-radiation source ((63)Ni) requires 5 to 10 min for a complete analysis of exhaled breath. Retention time and reduced ion mobility of the detected signals are compared to an analyte database for the identification of the related analytes. These findings were successfully validated by gas-chromatographic mass spectroscopy of the headspace of the candy via solid-phase micro-extraction and of breath samples on Tenax adsorption tubes. Furthermore, signal height of particular analyte signals as a measure for their concentration was used to monitor the concentration development with time. This exemplary investigation demonstrates that MCC/IMS is a powerful and rapid non-invasive tool for human breath analyses. The method can be used for medical applications (diagnosis, therapy control, metabolic profiling) as well as for a general determination of the metabolic state of a subject (medication, nutrition, fasting). The demonstrated procedure is independent of whether the analytes detected in breath are caused by nutrition or medication or whether they are metabolite characteristics for a particular disease. Therefore, it can directly be transferred to any relevant peak pattern.

Micro-plasma: a novel ionisation source for ion mobility spectrometry

AbstractIon mobility spectrometry is an analytical method for identification and quantification of gas-phase analytes in the ppbv-pptv range. Traditional ionisation methods suffer from low sensitivity (UV light), lack of long-term stability (partial discharge), or legal restrictions when radioactive sources are used. A miniaturised helium plasma was applied as ionisation source in an ion mobility spectrometer (IMS). Experiments were carried out to compare plasma IMS with β-radiation IMS. It could be demonstrated that the plasma IMS is characterised by higher sensitivity and selectivity than β-radiation ionisation. Plasma IMS is approximately 100 times more sensitive than the β-radiation IMS. Furthermore, variable sensitivity can be achieved by variation of the helium flow and the electric field of the plasma, and variable selectivity can be achieved by changing the electric field of the IMS. The experimental arrangement, optimisation of relevant conditions, and a typical application are presented in detail. FigureMicro-plasma used in ion mobility spectrometry

Detection of characteristic metabolites of Aspergillus fumigatus and Candida species using ion mobility spectrometry - metabolic profiling by volatile organic compounds

Volatile metabolites of Aspergillus fumigatus and Candida species can be detected by gas chromatography/mass spectrometry (GC/MS). A multi‐capillary column – ion mobility spectrometer (MCC‐IMS) was used in this study to assess volatile organic compounds (VOCs) in the headspace above A. fumigatus and the four Candida species Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis in an innovative approach, validated for A. fumigatus and C. albicans by GC/MS analyses. For the detection of VOCs, a special stainless steel measurement chamber for the microbial cultures was used. The gas outlet was either attached to MCC‐IMS or to adsorption tubes (Tenax GR) for GC/MS measurements. Isoamyl alcohol, cyclohexanone, 3‐octanone and phenethylalcohol can be described as discriminating substances by means of GC/MS. With MCC‐IMS, the results for 3‐octanone and phenethylalcohol are concordant and additionally to GC/MS, ethanol and two further compounds (p_0642_1/p_683_1 and p_705_3) can be described. Isoamyl alcohol and cyclohexanone were not properly detectable with MCC‐IMS. The major advantage of the MCC‐IMS system is the feasibility of rapid analysis of complex gas mixtures without pre‐concentration or preparation of samples and regardless of water vapour content in an online setup. Discrimination of fungi on genus level of the investigated germs by volatile metabolic profile and therefore detection of VOC is feasible. However, a further discrimination on species level for Candida species was not possible.

Alignment of retention time obtained from multicapillary column gas chromatography used for VOC analysis with ion mobility spectrometry

Multicapillary column (MCC) ion mobility spectrometers (IMS) are increasingly in demand for medical diagnosis, biological applications and process control. In a MCC-IMS, volatile compounds are differentiated by specific retention time and ion mobility when rapid preseparation techniques are applied, e.g. for the analysis of complex and humid samples. Therefore, high accuracy in the determination of both parameters is required for reliable identification of the signals. The retention time in the MCC is the subject of the present investigation because, for such columns, small deviations in temperature and flow velocity may cause significant changes in retention time. Therefore, a universal correction procedure would be a helpful tool to increase the accuracy of the data obtained from a gas-chromatographic preseparation. Although the effect of the carrier gas flow velocity and temperature on retention time is not linear, it could be demonstrated that a linear alignment can compensate for the changes in retention time due to common minor deviations of both the carrier gas flow velocity and the column temperature around the MCC-IMS standard operation conditions. Therefore, an effective linear alignment procedure for the correction of those deviations has been developed from the analyses of defined gas mixtures under various experimental conditions. This procedure was then applied to data sets generated from real breath analyses obtained in clinical studies using different instruments at different measuring sites for validation. The variation in the retention time of known signals, especially for compounds with higher retention times, was significantly improved. The alignment of the retention time—an indispensable procedure to achieve a more precise identification of analytes—using the proposed method reduces the random error caused by small accidental deviations in column temperature and flow velocity significantly.

Analyses of mouse breath with ion mobility spectrometry: a feasibility study

Exhaled breath can provide comprehensive information about the metabolic state of the subject. Breath analysis carried out during animal experiments promises to increase the information obtained from a particular experiment significantly. This feasibility study should demonstrate the potential of ion mobility spectrometry for animal breath analysis, even for mice. In the framework of the feasibility study, an ion mobility spectrometer coupled with a multicapillary column for rapid preseparation was used to analyze the breath of orotracheally intubated spontaneously breathing mice during anesthesia for the very first time. The sampling procedure was validated successfully. Furthermore, the breath of four mice (2 healthy control mice, 2 with allergic airway inflammation) was analyzed. Twelve peaks were identified directly by comparison with a database. Additional mass spectrometric analyses were carried out for validation and for identification of unknown signals. Significantly different patterns of metabolites were detected in healthy mice compared with asthmatic mice, thus demonstrating the feasibility of analyzing mouse breath with ion mobility spectrometry. However, further investigations including a higher animal number for validation and identification of unknown signals are needed. Nevertheless, the results of the study demonstrate that the method is capable of rapid analyses of the breath of mice, thus significantly increasing the information obtained from each particular animal experiment.

Volatile Organic Compounds in Uremia

Background Although “uremic fetor” has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia. Methods Breath analysis was performed in 28 adults with an eGFR ≥60 ml/min per 1.73 m2, 26 adults with chronic renal failure corresponding to an eGFR of 10–59 ml/min per 1.73 m2, and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry. Results Breath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10–59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis. Conclusion Impairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules.

Detection of Metabolites of Trapped Humans Using Ion Mobility Spectrometry Coupled with Gas Chromatography

For the first time, ion mobility spectrometry coupled with rapid gas chromatography, using multicapillary columns, was applied for the development of a pattern of signs of life for the localization of entrapped victims after disaster events (e.g., earthquake, terroristic attack). During a simulation experiment with entrapped volunteers, 12 human metabolites could be detected in the air of the void with sufficient sensitivity to enable a valid decision on the presence of a living person. Using a basic normalized summation of the measured concentrations, all volunteers involved in the particular experiments could be recognized only few minutes after they entered the simulation void and after less than 3 min of analysis time. An additional independent validation experiment enabled the recognition of a person in a room of ∼25 m(3) after ∼30 min with sufficiently high sensitivity to detect even a person briefly leaving the room. Undoubtedly, additional work must be done on analysis time and weight of the equipment, as well as on validation during real disaster events. However, the enormous potential of the method as a significantly helpful tool for search-and-rescue operations, in addition to trained canines, could be demonstrated.

Linearized equations for the reduced ion mobilities of polar aliphatic organic compounds.

Over the years, ion mobility spectrometry has evolved into a powerful technique for rapid identification of analytes in very complex sample matrixes such as human breath. Every analyte detected has a characteristic ion mobility value (and a retention time when additional preseparation techniques are employed) which is used to identify the peaks in a spectrum either by comparison with reference analytes or by simultaneous mass spectrometric measurements. In this study, the mass-mobility correlations between compounds in three different homologous series are used to predict the mobilities of the other substances in the same series in a medium of synthetic air. The results show a very high accuracy (>99.5%) of the prognosis. The linear trend equations of ion mobilities, as a function of the number of carbon atoms, obtained from the different series were then generalized into one linear equation for the reduced ion mobility for the polar aliphatic compounds and is validated by comparing it with the traditional Mason-Schamp equation. To compare the empirical equation obtained from the prognosis and the Mason-Schamp equation, the collision integral term in the latter was split into two terms to linearize it. The resulting novel ion mobility equation could be the starting step to completely describe the relationship between ion collision integral and the ion mobility for polar aliphatic compounds. The splitting of the collision integral into two terms will also give new inputs to describe the various ion models and the different forces that act on the ions and the neutral gas molecules upon which the collision integral is dependent on. This prognosis method could, furthermore, be extended to all other classes of organic compounds and could serve as a useful tool for identification of unknowns in ion mobility spectra, thereby considerably reducing the time-consuming and costly reference measurements and other coupling techniques that are currently employed.

Comparison of metabolites in exhaled breath and bronchoalveolar lavage fluid samples in a mouse model of asthma.

BACKGROUND A multi-capillary column ion mobility spectrometer (MCC/IMS) was developed to provide a method for the noninvasive diagnosis of lung diseases. The possibility of measuring the exhaled breath of mice was evaluated previously. The aim of the present study was to reveal whether mice affected by airway inflammation can be identified via MCC/IMS. METHODS Ten mice were sensitized and challenged with ovalbumin to induce allergic airway inflammation. The breath and volatile compounds of bronchoalveolar lavage fluid (BALF) were measured by MCC/IMS. Furthermore, histamine, nitric oxide, and arachidonic acid were determined as inflammatory markers in vitro. RESULTS Six volatile molecules were found in the BALF headspace at a significantly higher concentration in mice with airway inflammation compared with healthy animals. The concentration of substances correlated with the numbers of infiltrating eosinophilic granulocytes. However, substances showing a significantly different concentration in the BALF headspace were not found to be different in exhaled breath. Histamine and nitric oxide were identified by MCC/IMS in vitro but not in the BALF headspace or exhaled breath. CONCLUSION Airway inflammation in mice is detectable by the analysis of the BALF headspace via MCC/IMS. Molecules detected in the BALF headspace of asthmatic mice at a higher concentration than in healthy animals may originate from oxidative stress induced by airway inflammation. As already described for humans, we found no correlation between the biomarker concentration in the BALF and the breath of mice. We suggest using the model described here to gain deeper insights into this discrepancy.