Coated Blade Spray Ion Mobility Spectrometry.

Coated blade spray (CBS) is a microextraction technology with blades that serve as both the extraction device and the electrospray ionization (ESI) emitter. CBS is designed for easy and rapid extraction of analytes in complex matrices as well as ESI directly from the blade. The technology selectively enriches the components of interest on a coated metal blade. The coating consists of a selective polymer. So far, CBS has only been coupled with mass spectrometry but never with ion mobility spectrometry (IMS), where ions are separated and detected based on their ion mobility in a drift gas under the influence of an electric field, while instrumentation is compact and easy to operate so that the advantages of CBS can be particularly well exploited. Therefore, this work focuses on coupling CBS with our previously described ESI-IMS. The ion mobility spectrometer has a drift length of only 75 mm and provides a high resolving power of RP = 100. In this work, preliminary measurements of CBS-IMS are presented. In particular, the detection of benzodiazepines and ketamine in drinks and the pesticide isoproturon in water samples is shown to demonstrate the feasibility of CBS-IMS.

How to Improve the Resolving Power of Compact Electrospray Ionization Ion Mobility Spectrometers.

Every drift tube ion mobility spectrometer (IMS) has an optimum drift voltage to reach maximum resolving power. This optimum depends, among other things, on the temporal and spatial width of the injected ion packet and the pressure within the IMS. A reduction of the spatial width of the injected ion packet leads to improved resolving power, higher peak amplitudes when operating the IMS at optimum resolving power, and thus a better signal-to-noise ratio despite the reduced number of injected ions. Hereby, the performance of electrospray ionization (ESI)-IMS can be considerably improved. By setting the ion shutter opening time to just 5 µs and slightly increasing the pressure, a high resolving power RP > 150 can be achieved with a given drift length of just 75 mm. At such high resolving power, even a mixture of the herbicides isoproturon and chlortoluron having similar ion mobility can be well separated despite short drift length.

Ultra-Fast Ion Mobility Spectrometer for High-Throughput Chromatography.

Fast chromatography systems especially developed for high sample throughput applications require sensitive detectors with a high repetition rate. These high throughput techniques, including various chip-based microfluidic designs, often benefit from detectors providing subsequent separation in another dimension, such as mass spectrometry or ion mobility spectrometry (IMS), giving additional information about the analytes or monitoring reaction kinetics. However, subsequent separation is required at a high repetition rate. Here, we therefore present an ultra-fast drift tube IMS operating at ambient pressure. Short drift times while maintaining high resolving power are reached by several key instrumental design features: short length of the drift tube, resistor network of the drift tube, tristate ion shutter, and improved data acquisition electronics. With these design improvements, even slow ions with a reduced mobility of just 0.94 cm2/(V s) have a drift time below 1.6 ms. Such short drift times allow for a significantly increased repetition rate of 600 Hz compared with previously reported values. To further reduce drift times and thus increase the repetition rate, helium can be used as the drift gas, which allows repetition rates of up to 2 kHz. Finally, these significant improvements enable IMS to be used as a detector following ultra-fast separation including chip-based chromatographic systems or droplet microfluidic applications requiring high repetition rates.

Complex reaction kinetics of a Mannich reaction in droplets under electrospray conditions.

Precise, efficient, and effective control of chemical reaction conditions is a viable measure for the environment-conscious time and energy resource management in modern laboratories and in industry. Parameter changes such as surface enlargement, pH, local reactant accumulation by solvent evaporation and polarization effects, etc., have been shown to greatly affect the reaction rate of a chemical reaction. In electrospray (ES) ionization - a soft ionization method often used for mass spectrometry - all these parameters change constantly and with high dynamics during the nebulization process that generates droplets as the ultimate confined µ-reaction vessels. Therefore, high acceleration factors are reported in literature for a manifold of such µ-droplet reactions. Here, the tri-molecular Mannich reaction was identified as a suitable candidate for studying thermal, electronic, and fluidic manipulation of the ES process to achieve high conversion rates with short reaction times and compare them to the batch reaction. Some of these manipulations were conducted separately to better quantify their individual contributions. Here, the keto-enol-tautomerism of the used ß-diketones, the high proton concentrations, and the longer reaction times in the µ-droplets are presumed to have the greatest impact on these enhancement factors. Experiments were performed to find ES conditions with small initial droplets and long droplet flight times where the highest reaction conversion rates are obtained. A sharp increase in the product peak was found at large distances between the mass spectrometry (MS) inlet and ES source at high voltages. Moreover, different trends were found for the two ketones studied, acetylacetone (AcAc) and 1,3-cyclohexanedione (Cyclo), by changing the temperature of the heated ES source. Finally, high conversion rates were obtained for the combination of formaldehyde (Fal) and piperidine (Pip) with AcAc and Cyclo, respectively, with over 90%. With respect to the batch reaction, this is mainly due to an increase in reaction kinetics as well as a shift in thermodynamics for the µ-droplet reaction environment.

Rebounds of sevoflurane concentration during simulated trigger-free pediatric and adult anesthesia.

BACKGROUND: In trigger-free anesthesia a volatile anesthetic concentration of 5 parts per million (ppm) should not be exceeded. According to European Malignant Hyperthermia Group (EMHG) guideline, this may be achieved by removing the vapor, changing the anesthetic breathing circuit and renewing the soda lime canister followed by flushing with O2 or air for a workstation specific time. Reduction of the fresh gas flow (FGF) or stand-by modes are known to cause rebound effects. In this study, simulated trigger-free pediatric and adult ventilation was carried out on test lungs including ventilation maneuvers commonly used in clinical practice. The goal of this study was to evaluate whether rebounds of sevoflurane develop during trigger-free anesthesia. METHODS: A Dräger® Primus® was contaminated with decreasing concentrations of sevoflurane for 120 min. Then, the machine was prepared for trigger-free anesthesia according to EMHG guideline by changing recommended parts and flushing the breathing circuits using 10 or 18 l⋅min- 1 FGF. The machine was neither switched off after preparation nor was FGF reduced. Simulated trigger-free ventilation was performed with volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) including various ventilation maneuvers like pressure support ventilation (PSV), apnea, decreased lung compliance (DLC), recruitment maneuvers, prolonged expiration and manual ventilation (MV). A high-resolution ion mobility spectrometer with gas chromatographic pre-separation was used to measure sevoflurane in the ventilation gas mixture in a 20 s interval. RESULTS: Immediately after start of simulated anesthesia, there was an initial peak of 11-18 ppm sevoflurane in all experiments. The concentration dropped below 5 ppm after 2-3 min during adult and 4-18 min during pediatric ventilation. Other rebounds of sevoflurane > 5 ppm occurred after apnea, DLC and PSV. MV resulted in a decrease of sevoflurane < 5 ppm within 1 min. CONCLUSION: This study shows that after guideline-compliant preparation for trigger-free ventilation anesthetic machines may develop rebounds of sevoflurane > 5 ppm during typical maneuvers used in clinical practice. The changes in rate and direction of internal gas flow during different ventilation modes and maneuvers are possible explanations. Therefore, manufacturers should provide machine-specific washout protocols or emphasize the use of active charcoal filters (ACF) for trigger-free anesthesia.

Coupling Droplet Microfluidics with Ion Mobility Spectrometry for Monitoring Chemical Conversions at Nanoliter Scale.

We introduce the coupling of droplet microfluidics and ion mobility spectrometry (IMS) to address the challenges of label-free and chemical-specific detection of compounds in individual droplets. In analogy to the established use of mass spectrometry, droplet-IMS coupling can be also achieved via electrospray ionization but with significantly less instrumental effort. Because IMS instruments do not require high-vacuum systems, they are very compact, cost-effective, and robust, making them an ideal candidate as a chemical-specific end-of-line detector for segmented flow experiments. Herein, we demonstrate the successful coupling of droplet microfluidics with a custom-built high-resolution drift tube IMS system for monitoring chemical reactions in nL-sized droplets in an oil phase. The analytes contained in each droplet were assigned according to their characteristic ion mobility with limit of detections down to 200 nM to 1 µM and droplet frequencies ranging from 0.1 to 0.5 Hz. Using a custom sheath flow electrospray interface, we have further achieved the chemical-specific monitoring of a biochemical transformation catalyzed by a few hundred yeast cells, at single droplet level.

Preparation of Dräger Atlan A350 and General Electric Healthcare Carestation 650 anesthesia workstations for malignant hyperthermia susceptible patients.

BACKGROUND: Patients at risk of malignant hyperthermia need trigger-free anesthesia. Therefore, anesthesia machines prepared for safe use in predisposed patients should be free of volatile anesthetics. The washout time depends on the composition of rubber and plastic in the anesthesia machine. Therefore, new anesthesia machines should be evaluated regarding the safe preparation for trigger-free anesthesia. This study investigates wash out procedures of volatile anesthetics for two new anesthetic workstations: Dräger Atlan A350 and General Electric Healthcare (GE) Carestation 650 and compare it with preparation using activated charcoal filters (ACF). METHODS: A Dräger Atlan and a Carestation 650 were contaminated with 4% sevoflurane for 90 min. The machines were decontaminated with method (M1): using ACF, method 2 (M2): a wash out method that included exchange of internal parts, breathing circuits and soda lime canister followed by ventilating a test lung using a preliminary protocol provided by Dräger or method 3 (M3): a universal wash out instruction of GE, method 4 (M4): M3 plus exchange of breathing system and bellows. Decontamination was followed by a simulated trigger-free ventilation. All experiments were repeated with 8% desflurane contaminated machines. Volatile anesthetics were detected with a closed gas loop high-resolution ion mobility spectrometer with gas chromatographic pre-separation attached to the bacterial filter of the breathing circuits. Primary outcome was time until < 5 ppm of volatile anesthetics and total preparation time. RESULTS: Time to < 5 ppm for the Atlan was 17 min (desflurane) and 50 min (sevoflurane), wash out continued for a total of 60 min according to protocol resulting in a total preparation time of 96-122 min. The Carestation needed 66 min (desflurane) and 24 min (sevoflurane) which could be abbreviated to 24 min (desflurane) if breathing system and bellows were changed. Total preparation time was 30-73 min. When using active charcoal filters time to < 5 ppm was 0 min for both machines, and total preparation time < 5 min. CONCLUSION: Both wash out protocols resulted in a significant reduction of trace gas concentrations. However, due to the complexity of the protocols and prolonged total preparation time, feasibility in clinical practice remains questionable. Especially when time is limited preparation of the anesthetic machines using ACF remain superior.

On-Line Coupling of Chip-Electrochromatography and Ion Mobility Spectrometry.

We report the first hyphenation of chip-electrochromatography (ChEC) with ion mobility spectrometry (IMS). This approach combines the separation power of two electrokinetically driven separation techniques, the first in liquid phase and the second in gas phase, with a label-free detection of the analytes. For achieving this, a microfluidic glass chip incorporating a monolithic separation column, a nanofluidic liquid junction for providing post-column electrical contact, and a monolithically integrated electrospray emitter was developed. This device was successfully coupled to a custom-built high-resolution drift tube IMS with shifted potentials. After proof-of-concept studies in which a mixture of five model compounds was analyzed in less than 80 s, this first ChEC-IMS system was applied to a more complex sample, the analysis of herbicides spiked in the wine matrix. The use of ChEC before IMS detection not only facilitated the peak allocation and increased the peak capacity but also enabled analyte quantification. As both, ChEC and IMS work at ambient conditions and are driven by high voltages, no bulky pumping systems are needed, neither for the hydrodynamic pumping of the mobile phase as in high-performance liquid chromatography nor for generating a vacuum system as in mass spectrometry. Accordingly, the approach has great potential as a portable analytical system for field analysis of complex mixtures.

2D in Seconds: Coupling of Chip-HPLC with Ion Mobility Spectrometry.

The online hyphenation of chip-based high-performance liquid chromatography (chip-HPLC) with ion mobility spectrometry (IMS) via fully integrated electrospray emitters is introduced. A custom-built drift tube IMS with shifted potentials was developed in order to keep the IMS orifice electrically grounded, allowing for a robust coupling with chip-HPLC. Proof-of-concept studies with the newly developed analytical setup revealed the suitability of IMS as a promising and powerful detection concept for chip-based separation techniques. Comparison of IMS with fluorescence detection and electrospray ionization-mass spectrometry (ESI-MS) allowed a more detailed characterization of the IMS as a new detection method for chip-HPLC. Moreover, the analysis of a mixture consisting of three isobaric antidepressants demonstrated the performance of chip-HPLC/IMS as a miniaturized two-dimensional separation technique.

Preparation of anaesthesia workstation for trigger-free anaesthesia: An observational laboratory study.

BACKGROUND: Trigger-free anaesthesia is required for patients who are susceptible to malignant hyperthermia. Therefore, all trace of volatile anaesthetics should be removed from anaesthetic machines before induction of anaesthesia. Because the washout procedure is time consuming, activated charcoal filters have been introduced, but never tested under minimal flow conditions. OBJECTIVE: To investigate performance of activated charcoal filters during long duration (24 h) simulated ventilation. DESIGN: A bench study. SETTING: A Primus anaesthesia machine (Dräger) was contaminated with either 4% sevoflurane or 8% desflurane by ventilating a test lung for 90 min. The machine was briefly flushed according to manufacturer instructions, activated charcoal filters were inserted and a test lung was ventilated in a 24 h test. Trace gas concentrations were measured using a closed gas loop high-resolution ion mobility spectrometer with gas chromatographic preseparation. During the experiment reduced fresh gas flows were tested. At the end of each experiment the activated charcoal filters were removed and the machine was set to standby for 10 min to test for residual contamination within the circuit. The activated charcoal filters were reconnected into the circuit to test their ability to continue removing volatile anaesthetics (functional test) from the gas. Control experiments were conducted without activated charcoal filters. MAIN OUTCOME MEASURES: Absolute concentrations of desflurane and sevoflurane. RESULTS: The concentration of volatile anaesthetics dropped to less than 5 ppm (parts per million) following insertion of activated charcoal filters. In the desflurane experiments at least 1 l min FGF was needed to keep the concentration below an acceptable level (<5 ppm): 0.5 l min fresh gas flow was required in sevoflurane experiments. While activated charcoal filters in the sevoflurane tests passed the functional test after 24 h, activated charcoal filters in the desflurane tests failed. CONCLUSION: Activated charcoal filters meet the requirements for trigger-free low flow (1 l min) ventilation over 24 h. Minimal flow (0.5 l min) ventilation may be possible for sevoflurane contaminated machines.

Low anaesthetic waste gas concentrations in postanaesthesia care unit: A prospective observational study.

BACKGROUND: Volatile anaesthetics are a potential hazard during occupational exposure, pregnancy or in individuals with existing disposition to malignant hyperthermia. Anaesthetic waste gas concentration in postanaesthesia care units (PACU) has rarely been investigated. OBJECTIVE(S): The current study aims to assess concentrations of volatile anaesthetics in relation to room size, number of patients and ventilator settings in different PACUs. DESIGN: A prospective observational study. SETTING: Two different PACUs of the Hannover Medical School (Hannover, Germany) were evaluated in this study. The rooms differed in dimensions, patient numbers and room ventilation settings. PATIENTS: During the observation period, sevoflurane anaesthesia was performed in 65 of 140 patients monitored in postanaesthesia unit one and in 42 of 70 patients monitored in postanaesthesia unit two. MAIN OUTCOME MEASURES: Absolute trace gas room concentrations of sevoflurane measured with a compact, closed gas loop high-resolution ion mobility spectrometer. RESULTS: Traces of sevoflurane could be detected in 805 out of 970 samples. Maximum concentrations were 0.96 ±â€Š0.20 ppm in postanaesthesia unit one, 0.82 ±â€Š0.07 ppm in postanaesthesia unit two. Median concentration was 0.12 (0.34) ppm in postanaesthesia unit one and 0.11 (0.28) ppm in postanaesthesia unit two. CONCLUSION: Low trace amounts of sevoflurane were detected in both PACUs equipped with controlled air exchange systems. Occupational exposure limits were not exceeded.

Regarding the Influence of Additives and Additional Plasma-Induced Chemical Ionization on Adduct Formation in ESI/IMS/MS.

Ion mobility spectrometers (IMS) separate ions based on their ion mobility, which depends mainly on collision cross-section, mass, and charge of the ions. However, the performance is often hampered in electrospray ionization (ESI) by the appearance of multiple ion mobility peaks in the spectrum for the same analyte due to clustering and additional sodium adducts. In this work, we investigate the influence of solvents and buffer additives on the detected ion mobility peaks using ESI. Additionally, we investigate the effects of an additional chemical ionization (CI) induced by plasma ionization on the ions formed by electrospray. For this purpose, we coupled our high-resolution IMS with a resolving power of Rp = 100 to a time-of-flight mass spectrometer. Depending on the analyte and the chosen additives, the ionization process can be influenced during the electrospray process. For the herbicide isoproturon, the addition of 5 mM sodium acetate results in the formation of the sodium adduct [M + Na]+, which is reflected in the ion mobility K0 of 1.22 cm2/(V·s). In contrast, the addition of 5 mM ammonium acetate yields the protonated species [M + H]+ and a correspondingly higher K0 of 1.29 cm2/(V·s). In some cases, as with the herbicide pyrimethanil, the addition of sodium acetate can completely suppress ionizations. By carefully choosing the solvent additive for ESI-IMS or additional CI, the formation of different ion mobility peaks can be observed. This can facilitate the assignment of ions to ion mobility peaks using IMS as a compact, stand-alone instrument, e.g., for on-site analysis.