The sensitivity and diagnostic accuracy of EUS-FNA for solid pancreatic lesions is strongly correlated with tumor size. Sensitivity and accuracy decrease significantly for tumors that are smaller than 1 cm.

This experiment observed the evolution of metabolite plumes from a human trapped in a simulation of a collapsed building. Ten participants took it in turns over five days to lie in a simulation of a collapsed building and eight of them completed the 6 h protocol while their breath, sweat and skin metabolites were passed through a simulation of a collapsed glass-clad reinforced-concrete building. Safety, welfare and environmental parameters were monitored continuously, and active adsorbent sampling for thermal desorption GC-MS, on-line and embedded CO, CO(2) and O(2) monitoring, aspirating ion mobility spectrometry with integrated semiconductor gas sensors, direct injection GC-ion mobility spectrometry, active sampling thermal desorption GC-differential mobility spectrometry and a prototype remote early detection system for survivor location were used to monitor the evolution of the metabolite plumes that were generated. Oxygen levels within the void simulator were allowed to fall no lower than 19.1% (v). Concurrent levels of carbon dioxide built up to an average level of 1.6% (v) in the breathing zone of the participants. Temperature, humidity, carbon dioxide levels and the physiological measurements were consistent with a reproducible methodology that enabled the metabolite plumes to be sampled and characterized from the different parts of the experiment. Welfare and safety data were satisfactory with pulse rates, blood pressures and oxygenation, all within levels consistent with healthy adults. Up to 12 in-test welfare assessments per participant and a six-week follow-up Stanford Acute Stress Response Questionnaire indicated that the researchers and participants did not experience any adverse effects from their involvement in the study. Preliminary observations confirmed that CO(2), NH(3) and acetone were effective markers for trapped humans, although interactions with water absorbed in building debris needed further study. An unexpected observation from the NH(3) channel was the suppression of NH(3) during those periods when the participants slept, and this will be the subject of further study, as will be the detailed analysis of the casualty detection data obtained from the seven instruments used.

Miniaturized ultra high field asymmetric waveform ion mobility spectrometry (ultra-FAIMS) combined with mass spectrometry (MS) has been applied to the analysis of standard and tryptic peptides, derived from α-1-acid glycoprotein, using electrospray and nanoelectrospray ion sources. Singly and multiply charged peptide ions were separated in the gas phase using ultra-FAIMS and detected by ion trap and time-of-flight MS. The small compensation voltage (CV) window for the transmission of singly charged ions demonstrates the ability of ultra-FAIMS-MS to generate pseudo-peptide mass fingerprints that may be used to simplify spectra and identify proteins by database searching. Multiply charged ions required a higher CV for transmission, and ions with different amino acid sequences may be separated on the basis of their differential ion mobility. A partial separation of conformers was also observed for the doubly charged ion of bradykinin. Selection on the basis of charge state and differential mobility prior to tandem mass spectrometry facilitates peptide and protein identification by allowing precursor ions to be identified with greater selectivity, thus reducing spectral complexity and enhancing MS detection.

A thermal desorption unit has been interfaced to an electrospray ionization-ion mobilitytime-of-flight mass spectrometer. The interface was evaluated using a mixture of six model volatile organic compounds which showed detection limits of <1 ng sample loaded onto a thermal desorption tube packed with Tenax, equivalent to sampled concentrations of 4 μg L-1. Thermal desorption profiles were observed for all of the compounds, and ion mobility-mass spectrometry separations were used to resolve the probe compound responses from each other. The combination of temperature programmed thermal desorption and ion mobility improved the response of selected species against background ions. Analysis of breath samples resulted in the identification of breath metabolites, based on ion mobility and accurate mass measurement using siloxane peaks identified during the analysis as internal lockmasses. IntroductionThe development of electrospray ionization (ESI) by Fenn and co-workers in 19841enabled the routine analysis of macromolecules and revolutionized the role mass spectrometry plays in the analysis of biological samples. It was suggested as early as 19862 that volatile organic compounds (VOCs) could also be ionized and detected with a high degree of sensitivity using ESI. However the first effective demonstration of the application of ESI to VOC analysis was not reported until 1994,3 when an ESI source was interfaced to an ion mobility spectrometer. Hill and co-workers further developed this approach, termed, secondary electrospray ionization (SESI),4 in conjunction with a hybrid ion mobility-quadrupole mass spectrometer, which they used to study a number of illicit 2 drugs. The charged droplets from the electrospray were reacted with the VOCs in a reaction cell placed immediately before the ion mobility drift cell. This work demonstrated that SESI could be used as an effective ionization method for both gas chromatography (GC) and liquid chromatography-mass spectrometry (LC-MS) experiments and that it was also more sensitive than standard electrospray for the analysis of VOCs. SESI was also later used to analyze vapors from explosives with detection limits at the sub-parts per trillion level, further demonstrating the high sensitivity of the approach.5 Recent work has shown that VOCs may be detected down to parts per quadrillion levels using electrospray ionization and that the ESI source parameters can be optimized to give selectivity toward specific ion species.6 Cooks et al. proposed an alternative approach, showed that EESI could be used to follow the concentration of an exhaled breath metabolite (urea) from breath to breath.12 In the same year, Zenobi and co-workers used EESI to look directly at exhaled breath and were able to detect involatile species such as carbohydrates which were present after eating a meal.13 The analysis of breath samples using gas chromatography/ mass spectrometry (GC/MS) has shown that a large number of VOCs may be detected and that VOC profiles in human breath are characterized by a huge degre...

Miniaturized ultra high field asymmetric waveform ion mobility spectrometry (FAIMS) is used for the selective transmission of differential mobility-selected ions prior to in-source collision-induced dissociation (CID) and time-of-flight mass spectrometry (TOFMS) analysis. The FAIMS-in-source collision induced dissociation-TOFMS (FISCID-MS) method requires only minor modification of the ion source region of the mass spectrometer and is shown to significantly enhance analyte detection in complex mixtures. Improved mass measurement accuracy and simplified product ion mass spectra were observed following FAIMS preselection and subsequent in-source CID of ions derived from pharmaceutical excipients, sufficiently close in m/z (17.7 ppm mass difference) that they could not be resolved by TOFMS alone. The FISCID-MS approach is also demonstrated for the qualitative and quantitative analysis of mixtures of peptides with FAIMS used to filter out unrelated precursor ions thereby simplifying the resulting product ion mass spectra. Liquid chromatography combined with FISCID-MS was applied to the analysis of coeluting model peptides and tryptic peptides derived from human plasma proteins, allowing precursor ion selection and CID to yield product ion data suitable for peptide identification via database searching. The potential of FISCID-MS for the quantitative determination of a model peptide spiked into human plasma in the range of 0.45-9.0 μg/mL is demonstrated, showing good reproducibility (%RSD < 14.6%) and linearity (R(2) > 0.99).