Fast Sensing of Hydrogen Cyanide (HCN) Vapors Using a Hand-Held Ion Mobility Spectrometer with Nonradioactive Ionization Source.

Sensitive real-time detection of vapors produced by toxic industrial chemicals (TICs) always represents a stringent priority. Hydrogen cyanide (HCN) is definitely a TIC, being widely used in various industries and as an insecticide; it is a reactive, very flammable, and highly toxic compound that affects the central nervous system, cardiovascular system, eyes, nose, throat, and also has systemic effects. Moreover, HCN is considered a blood chemical warfare agent. This study was focused toward quick detection and quantification of HCN in air using time-of-flight ion mobility spectrometry (ToF IMS). Results obtained clearly indicate that IMS can rapidly detect HCN at sub-ppmv levels in air. Ion mobility spectrometric response was obtained in the negative ion mode and presented one single distinct product ion, at reduced ion mobility K0 of 2.38 cm2 V-1 s-1. Our study demonstrated that by using a miniaturized commercial IMS system with nonradioactive ionization source model LCD-3.2E (Smiths Detection Ltd., London, UK), one can easily measure HCN at concentrations of 0.1 ppmv (0.11 mg m-3) in negative ion mode, which is far below the OSHA PEL-TWA value of 10 ppmv. Measurement range was from 0.1 to 10 ppmv and the estimated limit of detection LoD was ca. 20 ppbv (0.02 mg m-3).

Hunting for Toxic Industrial Chemicals: Real-Time Detection of Carbon Disulfide Traces by Means of Ion Mobility Spectrometry.

Sensitive real-time detection of vapors produced by toxic industrial chemicals (TICs) represents a stringent priority nowadays. Carbon disulfide (CS2) is such a chemical, being widely used in manufacturing synthetic textile fibers and as a solvent. CS2 is simultaneously a very reactive, highly flammable, irritant, corrosive, and highly toxic compound, affecting the central nervous system, cardiovascular system, eyes, kidneys, liver, skin, and reproductive system. This study was directed towards quick detection and quantification of CS2 in air, using time-of-flight ion mobility spectrometry (IMS); photoionization detection (PID) was also used as confirmatory technique. Results obtained indicated that IMS can detect CS2 at trace levels in air. The ion mobility spectrometric response was in the negative ion mode and presented one product ion, at a reduced ion mobility (K0) of 2.25 cm2 V-1 s-1. Our study demonstrated that by using a portable, commercial IMS system (model Mini IMS, I.U.T. GmbH Berlin Germany) one can easily measure CS2 at concentrations of 0.1 ppmv (0.3 mg m-3) in the negative ion mode, which is below the lowest threshold value of 1 ppmv given for industrial hygiene. A limit of detection (LOD) of ca. 30 ppbv (0.1 mg m-3) was also estimated.

Volatile Organic Compounds in Exhaled Breath as Fingerprints of Lung Cancer, Asthma and COPD.

Lung cancer, chronic obstructive pulmonary disease (COPD) and asthma are inflammatory diseases that have risen worldwide, posing a major public health issue, encompassing not only physical and psychological morbidity and mortality, but also incurring significant societal costs. The leading cause of death worldwide by cancer is that of the lung, which, in large part, is a result of the disease often not being detected until a late stage. Although COPD and asthma are conditions with considerably lower mortality, they are extremely distressful to people and involve high healthcare overheads. Moreover, for these diseases, diagnostic methods are not only costly but are also invasive, thereby adding to people's stress. It has been appreciated for many decades that the analysis of trace volatile organic compounds (VOCs) in exhaled breath could potentially provide cheaper, rapid, and non-invasive screening procedures to diagnose and monitor the above diseases of the lung. However, after decades of research associated with breath biomarker discovery, no breath VOC tests are clinically available. Reasons for this include the little consensus as to which breath volatiles (or pattern of volatiles) can be used to discriminate people with lung diseases, and our limited understanding of the biological origin of the identified VOCs. Lung disease diagnosis using breath VOCs is challenging. Nevertheless, the numerous studies of breath volatiles and lung disease provide guidance as to what volatiles need further investigation for use in differential diagnosis, highlight the urgent need for non-invasive clinical breath tests, illustrate the way forward for future studies, and provide significant guidance to achieve the goal of developing non-invasive diagnostic tests for lung disease. This review provides an overview of these issues from evaluating key studies that have been undertaken in the years 2010-2019, in order to present objective and comprehensive updated information that presents the progress that has been made in this field. The potential of this approach is highlighted, while strengths, weaknesses, opportunities, and threats are discussed. This review will be of interest to chemists, biologists, medical doctors and researchers involved in the development of analytical instruments for breath diagnosis.

Sensing Precursors of Illegal Drugs-Rapid Detection of Acetic Anhydride Vapors at Trace Levels Using Photoionization Detection and Ion Mobility Spectrometry.

Sensitive real-time detection of vapors produced by the precursors, reagents and solvents used in the illegal drugs manufacture represents a priority nowadays. Acetic anhydride (AA) is the key chemical used as acetylation agent in producing the illegal drugs heroin and methaqualone. This study was directed towards quick detection and quantification of AA in air, using two fast and very sensitive analytical techniques: photoionization detection (PID) and ion mobility spectrometry (IMS). Results obtained indicated that both PID and IMS can sense AA at ultra-trace levels in air, but while PID produces a non-selective response, IMS offers richer information. Ion mobility spectrometric response in the positive ion mode presented one product ion, at reduced ion mobility K0 of 1.89 cm2 V-1 s-1 (almost overlapped with positive reactant ion peak), while in the negative ion mode two well separated product ions, with K0 of 1.90 and 1.71 cm2 V-1 s-1, were noticed. Our study showed that by using a portable, commercial IMS system (model Mini IMS, I.U.T. GmbH Berlin) AA can be easily measured at concentrations of 0.05 ppmv (0.2 mg m-3) in negative ion mode. Best selectivity and sensitivity of the IMS response were therefore achieved in the negative operation mode.

An Optimistic Vision of Future: Diagnosis of Bacterial Infections by Sensing Their Associated Volatile Organic Compounds.

Simple tests using sniff analysis that have the ability of diagnosing and rapidly distinguishing between infections due to different bacteria are urgently required by medical community worldwide. Professionals interested in this topic wish for these tests to be simultaneously cheap, fast, easily applicable, non-invasive, robust, reliable, and sensitive. Current analytical instrumentation has already the ability for performing real time (minutes or a few dozens of minutes) analysis of volatile bacterial biomarkers (the VOCs emitted by bacteria). Although many articles are available, a review displaying an objective evaluation of the current status in the field is still needed. This review tries to present an overview regarding the bacterial biomarkers released from in vitro cultivation of various bacterial strains and also from different biological matrices investigated, over the last 10 years. We have described results of relevant studies, which used modern analytical techniques to evaluate specific biomarker profiles associated with bacterial infections. Our purpose was to present a comprehensive view of available possibilities for detection of emitted bacterial VOCs from different matrices. We intend that this review to be of general interest for both medical doctors and for all researchers preoccupied with bacterial infectious diseases and their rapid diagnosis using analytical instrumentation.

Sensors' array of aspiration ion mobility spectrometer as a tool for bacteria discrimination.

The possibility of achieving bacterial discrimination using a miniaturized aspiration ion mobility spectrometer model ChemPro-100i (Environics Oy) has been tested by interrogating the headspace air samples above in vitro bacterial cultures of three species - Escherichia coli, Bacillus subtilis and Staphylococcus aureus, respectively. The ChemPro-100i highly integrated seven sensor array, composed of one a-IMS cell, three MOS (metal oxide sensors), one FET (field effect transistor) sensor and two SC (semiconductor) sensors, provided enough analytical information to discriminate between the three bacterial species. Statistical data processing using either principal component analysis (PCA) or partial least squares discriminant analysis (PLS-DA) was accomplished. We concluded that although the data from the aspiration-type ion mobility sensor, with its 16 ion detectors, is absolutely sufficient to discriminate between various bacteria using their volatile compounds' chemical profile, the other six sensors deliver additional, valuable information.

Temporal influence of different antibiotics onto the inhibition of Escherichia coli bacterium grown in different media.

Escherichia coli (E. coli) is a Gram-negative bacterium commonly found in the lower intestine of warm-blooded organisms, including humans. Although the majority of the strains are considerably harmless, some serotypes are pathogenic, frequently causing diarrhea and other illnesses outside the intestinal tract. The standard antidote against bacteria is the use of antibiotics. Depending on their type, the antibiotics have various mechanisms of action on bacteria. Moreover, in case of in-vitro cultivation of bacteria, the used growth media plays a crucial role, since it influences bacterial inhibition as well. In the present study, we emphasize the importance of cultivability in bacterial inhibition under the treatment with five different antibiotics belonging to different classes. Consequently, E. coli was cultivated in three different growth media: trypcase soy broth (TSB), Mueller Hinton (MH), and minimal salts (M9) enriched with glucose, respectively. MALDI-TOF MS (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) analyses, that were used for fast characterization of changes that occur in ribosomal protein profiles, revealed differentiation and similarities between investigated cases, while flow cytometry (FCM) tests better explained the given changes that occurred in the analyzed samples after 3, 24 and 48 h of experimental campaign.

GC-MS application in determination of volatile profiles emitted by infected and uninfected human tissue.

Volatile organic compounds (VOCs) released into the headspace air over human tissues infected with different bacteria were investigated in this work. The above-mentioned VOCs result both from bacterial metabolic processes (pathogen-specific signals) and from the matrix (tissue samples themselves). The objective of this study was to investigate whether one could reliably identify various microorganism strains that exist inside infected tissue samples by direct monitoring of the headspace atmosphere above their cultures. Headspace samples were directly interrogated using a GC-MS system, which produced distinct profiles for samples contaminated with single bacterial strains or with multiple strains (mixed infections). Principal component analysis (PCA) and predictive analysis based on receiver operating characteristics curves (ROC) were the statistical procedures utilized for differentiating between infected and uninfected samples, while network analysis and heat-mapping were used to highlight the connections between emitted volatiles and infectious pathogens. By using ROC curves, obtained results demonstrated that the area under the ROC (95% probability interval) was 0.86 in case of infected samples and 0.48 for uninfected samples. On the other hand, PCA highlighted separation between components coming from infected and uninfected patients, where 67% of variance was described from the first 2 principal components. The biomarker chemicals documented from this work, as well as the developed methodology may ultimately be applied to identify bacterial infections by analyzing exhaled breath.

Mass spectrometric techniques for the analysis of volatile organic compounds emitted from bacteria.

Bacteria are the main cause of many human diseases. Typical bacterial identification methods, for example culture-based, serological and genetic methods, are time-consuming, delaying the potential for an early and accurate diagnosis and the appropriate subsequent treatment. Nevertheless, there is a stringent need for in situ tests that are rapid, noninvasive and sensitive, which will greatly facilitate timely treatment of the patients. This review article presents volatile organic metabolites emitted from various micro-organism strains responsible for common bacterial infections in humans. Additionally, the manuscript shows the application of different analytical techniques for fast bacterial identification. Details of these techniques are given, which focuses on their advantages and drawbacks in using for volatile organic components analysis.

Discrimination of bacteria by rapid sensing their metabolic volatiles using an aspiration-type ion mobility spectrometer (a-IMS) and gas chromatography-mass spectrometry GC-MS.

The objective of our study was to investigate whether one may quickly and reliably discriminate different microorganism strains by direct monitoring of the headspace atmosphere above their cultures. Headspace samples above a series of in vitro bacterial cultures were directly interrogated using an aspiration type ion mobility spectrometer (a-IMS), which produced distinct profiles ("fingerprints") of ion currents generated simultaneously by the detectors present inside the ion mobility cell. Data processing and analysis using principal component analysis showed net differences in the responses produced by volatiles emitted by various bacterial strains. Fingerprint assignments were conferred on the basis of product ion mobilities; ions of differing size and mass were deflected in a different degree upon their introduction of a transverse electric field, impacting finally on a series of capacitors (denominated as detectors, or channels) placed in a manner analogous to sensor arrays. Three microorganism strains were investigated - Escherichia coli, Bacillus subtilis and Staphylococcus aureus; all strains possess a relatively low pathogenic character. Samples of air with a 5 cm3 volume from the headspace above the bacterial cultures in agar growth medium were collected using a gas-tight chromatographic syringe and injected inside the closed-loop pneumatic circuit of the breadboard a-IMS instrument model ChemPro-100i (Environics Oy, Finland), at a distance of about 1 cm from the ionization source. The resulting chemical fingerprints were produced within two seconds from the moment of injection. The sampling protocol involved to taking three replicate samples from each of 10 different cultures for a specific strain, during a total period of 72 h after the initial incubation - at 24, 48 and 72 h, respectively. Principal component analysis (PCA) was used to discriminate between the IMS fingerprints. PCA was found to successfully discriminate between bacteria at three levels in the experimental campaign: 1) between blank samples from growth medium and samples from bacterial cultures, 2) between samples from different bacterial strains, and 3) between time evolutions of headspace samples from the same bacterial strain over the 3-day sampling period. Consistent classification between growth medium samples and growth medium inoculated with bacteria was observed in both positive and negative detection/ionization modes. In parallel, headspace air samples of 1 dm3 were collected from each bacterial culture and loaded onto Tenax™-Carbograph desorption tubes, using a custom built sampling unit based on a portable sampling pump. One sample was taken for each of 10 different cultures of a strain, at 24, 48 and 72 h after the initial incubation. These adsorption tubes were subsequently analyzed using thermal desorption - gas chromatography - mass spectrometry (TD-GC-MS). This second dataset was intended to produce a qualitative analysis of the volatiles present in the headspace above the bacterial cultures.

The effect of growth medium on an Escherichia coli pathway mirrored into GC/MS profiles.

Escherichia coli (E. coli) is a Gram-negative coliform bacterium that is commonly found in the lower intestine of warm-blooded organisms. Most of the strains are harmless but some serotypes are pathogenic, meaning they can cause illness, either diarrhea or illness outside the intestinal tract. The aim of this work is to assess which components are generated for the purpose of E. coli target analysis. In this study, we intend to emphasize the importance of cultivability and to prove that growth media plays a crucial role in bacteria growth. To do this, E. coli was cultivated in three different growth mediums: (a) trypcase soy broth (TSB), (b) Mueller Hinton (MH), and (c) minimal salts (M9) enriched with glucose, respectively. Solid phase micro extraction was used as a sampling method, followed by gas chromatography-mass spectrometry for subsequent analysis. The relevant microbial volatile organic compounds (MVOCs) released in the headspace over the cultures of the E. coli bacteria and the afferent metabolic processes that occur in order to generate these compounds are presented in this work. The characteristic volatile compounds found in E. coli strain emissions were indole, phenylethyl alcohol and a series of esters when it was grown in TSB. Different pyrazines were found (pyrazine, 2-ethyl-3,5-dimethyl-, pyrazine, 2,5-dimethyl- and pyrazine, trimethyl-) when it was cultivated in MH. Long-chain alcohols such as 2-pentadecanol, 9-tetradecen-1-ol and 11-hexadecenol occurred in M9. Dimethyl disulfide, dimethyl trisulfide and a consistent number of alcohols and ketones were observed for E. coli cultivated in all three growth mediums. The occurrence and biosynthesis of these MVOCs clearly denote that the growth media used plays a crucial role in bacterial cultivation. The biomarker chemicals documented from this work may ultimately be used to identify bacterial infections by analyzing exhaled breath.

Control of dopants/modifiers in differential mobility spectrometry using a piezoelectric injector.

A piezoelectric injector has been interfaced to a differential mobility spectrometer to enable fast and reversible control of dopant/transport-gas modifier levels within the reaction region of the instrument. Operating at 1 Hz with optimised bipolar waveforms for the piezoelectric injector and gas flows within the injector, steady-state 2-butanol mass fluxes of 21 to 1230 ng min(-1) and 1-bromohexane mass fluxes of 149 to 2644 ng min(-1) were delivered to the differential mobility cell. Control of split-flow and transport-gas flow rates enabled rapid and flexible control of the dopant concentrations. The system was consistently reproducible with a relative standard deviation (RSD) of 7.9% at every mass- flux level studied. Stable responses were achieved between 3 to 5 s following a change in the control levels and no significant hysteresis effects were observed. In the positive mode it was possible to control the extent of formation protonated monomer and proton bound cluster ions, tentatively assigned to{C(4)H(9)OH(H(2)O)(n)H}(+) and {(C(4)H(9)OH)(2)(H(2)O)(n)H}(+) and similar control was possible in the negative mode where the concentration relationship for the formation of bromide clusters indicated the presence of multiple ionisation mechanisms. A dopant formulation for the simultaneous control of ions in both the positive and negative modes was demonstrated by the injection of a 50%/50% v/v solution of 2-butanol/1-bromohexane with mass fluxes of 2-butanol in the mixture of between 11 and 1161 ng min(-1) and between 13 and 1325 ng min(-1) for 1-bromohexane.

Characterisation of the phosgene response of a membrane inlet 63Ni ion mobility spectrometer.

A membrane inlet 63Ni ion mobility spectrometer interfaced to a quadrupole mass spectrometer with permeation, exponential dilution approaches and syringe-based systems were used to characterise the ion mobility spectrometry (IMS) response to phosgene in dry air (water concentration less than 16.5 mg m(-3)). Phosgene produced a principle product ion in the negative mode with a reduced mobility of 2.16 cm2 V(-1) s(-1), with an unresolved artefact at higher concentrations having a reduced mobility of 2.32 cm2 V(-1) s(-1). The limit of detection of the system with a membrane inlet fitted was estimated to be less than 1 mg m(-3), with an upper limit to the dynamic range of 32 mg m(-3). Mass spectrometric data indicated the existence of [(H2O)nCl]-, [(H2O)nCl2]-; [(H2O)n(O2)Cl]-; [(H2O)n(O)Cl]-; and, [(H2O)n(CO2)Cl]-. The existence of two possible mechanisms for product ion formation is proposed: dissociative electron capture, as well as hydrolysis followed by electron capture. The effect of water contamination of the drying media within the ion mobility spectrometer was also investigated, and the effects were similar to those observed previously with studies on chlorine. Reduced mobility of the product ions was observed to decrease with increasing water contamination of the drying media used within the instrument, while limits of detection increased slightly to less than 2.4 mg m(-3), with no significant effect on dynamic ranges of response or resolution. Preliminary results also indicated a positive mode response for phosgene, albeit at significantly higher concentrations to those observed in the negative mode.