Electron Beam Processing as a Promising Tool to Decontaminate Polymers Containing Brominated Flame Retardants.

Electron Beam (EB) irradiation was utilized to decontaminate model systems of industrial polymers that contain a brominated flame retardant (BFR). Acrylonitrile-butadiene-styrene (ABS) and Polycarbonate (PC) are two types of polymers commonly found in Waste Electrical and Electronic Equipment (WEEE). In this study, these polymers were exposed to EB irradiation to degrade DecaBromoDiphenylEther (DBDE), one of the most toxic BFRs. Fourier-transform infrared spectroscopy analysis demonstrated an 87% degradation rate of DBDE for the ABS-DBDE system and 91% for the PC-DBDE system following an 1800 kGy irradiation dose. Thermal analysis using Differential Scanning Calorimetry revealed the presence of crosslinking in ABS and a minor reduction in the glass transition temperature of PC after EB processing. Polymers exhibited thermal stability after photolysis, as indicated by thermogravimetric analysis. In summary, EB irradiation had no impact on the overall thermal properties of both polymers. High-resolution mass spectrometry analysis has confirmed the debromination of both ABS-DBDE and PC-DBDE systems. Therefore, the results obtained are promising and could offer an alternative approach for removing bromine and other additives from plastic E-waste.

Degradation processes of brominated flame retardants dispersed in high impact polystyrene under UV-visible radiation.

In order to protect human health and the environment, several regulations have been introduced in recent years to reduce or even eliminate the use of some brominated flame retardants (BFRs) due to their toxicity, persistence and bioaccumulation. Dispersions of these BFRs in polymers are widely used for various applications. In this report, four different brominated molecules, decabromodiphenyl ether (DBDE), hexabromocyclododecane (HBCDD), decabromodiphenyl ethane (DBDPE) and tris(tribromophenoxy)triazine (TTBPT), were dispersed in the solid matrix of an industrial polymer, high impact polystyrene (HIPS). The possibility of degradation of these BFRs within HIPS under UV-visible irradiation in ambient air was investigated. The degradation kinetics of DBDE and HBCDD were followed by Fourier transform infrared spectroscopy (FTIR) and high-resolution two-step laser mass spectrometry (L2MS). The thermal properties of the pristine and irradiated polymer matrix were monitored by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), which showed that these properties were globally preserved. Volatile photoproducts from the degradation of DBDE, DBDPE and TTBPT were identified by headspace gas chromatography/mass spectrometry analysis. Under the chosen experimental conditions, BFRs underwent rapid degradation after a few seconds of irradiation, with conversions exceeding 50% for HIPS/DBDE and HIPS/HBCDD systems.

Direct Water-Assisted Laser Desorption/Ionization Mass Spectrometry Lipidomic Analysis and Classification of Formalin-Fixed Paraffin-Embedded Sarcoma Tissues without Dewaxing.

BACKGROUND: Formalin-fixed paraffin-embedded (FFPE) tissue has been the gold standard for routine pathology for general and cancer postoperative diagnostics. Despite robust histopathology, immunohistochemistry, and molecular methods, accurate diagnosis remains difficult for certain cases. Overall, the entire process can be time consuming, labor intensive, and does not reach over 90% diagnostic sensitivity and specificity. There is a growing need in onco-pathology for adjunct novel rapid, accurate, reliable, diagnostically sensitive, and specific methods for high-throughput biomolecular identification. Lipids have long been considered only as building blocks of cell membranes or signaling molecules, but have recently been introduced as central players in cancer. Due to sample processing, which limits their detection, lipid analysis directly from unprocessed FFPE tissues has never been reported. METHODS: We present a proof-of-concept with direct analysis of tissue-lipidomic signatures from FFPE tissues without dewaxing and minimal sample preparation using water-assisted laser desorption ionization mass spectrometry and deep-learning. RESULTS: On a cohort of difficult canine and human sarcoma cases, classification for canine sarcoma subtyping was possible with 99.1% accuracy using "5-fold" and 98.5% using "leave-one-patient out," and 91.2% accuracy for human sarcoma using 5-fold and 73.8% using leave-one-patient out. The developed classification model enabled stratification of blind samples in <5 min and showed >95% probability for discriminating 2 human sarcoma blind samples. CONCLUSION: It is possible to create a rapid diagnostic platform to screen clinical FFPE tissues with minimal sample preparation for molecular pathology.

Real-Time Molecular Diagnosis of Tumors Using Water-Assisted Laser Desorption/Ionization Mass Spectrometry Technology.

Histopathological diagnosis of biopsy samples and margin assessment of surgical specimens are challenging aspects in sarcoma. Using dog patient tissues, we assessed the performance of a recently developed technology for fast ex vivo molecular lipid-based diagnosis of sarcomas. The instrument is based on mass spectrometry (MS) molecular analysis through a laser microprobe operating under ambient conditions using excitation of endogenous water molecules. Classification models based on cancer/normal/necrotic, tumor grade, and subtypes showed a minimum of 97.63% correct classification. Specific markers of normal, cancer, and necrotic regions were identified by tandem MS and validated by MS imaging. Real-time detection capabilities were demonstrated by ex vivo analysis with direct interrogation of classification models.

A real-world, multi-site, observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab.

OBJECTIVES: To assess real-world infusion times for golimumab (GLM-IV) and infliximab (IFX) for rheumatoid arthritis (RA) patients and factors associated with treatment satisfaction. METHODS: An observational study assessed infusion time including: clinic visit duration, RA medication preparation and infusion time, and infusion process time. Satisfaction was assessed by a modified Treatment Satisfaction Questionnaire for Medication (patient) and study-specific questionnaires (patient and clinic personnel). Comparative statistical testing for patient data utilized analysis of variance for continuous measures, and Fisher's exact or Chi-square test for categorical measures. Multivariate analysis was performed for the primary time endpoints and patient satisfaction. RESULTS: One hundred and fifty patients were enrolled from six US sites (72 GLM-IV, 78 IFX). The majority of patients were female (80.0%) and Caucasian (88.7%). GLM-IV required fewer vials per infusion (3.7) compared to IFX (4.9; p = .0001). Clinic visit duration (minutes) was shorter for GLM-IV (65.1) compared to IFX (153.1; p < .0001), as was total infusion time for RA medication (32.8 GLM-IV, 119.5 IFX; p < .0001) and infusion process times (45.8 GLM-IV, 134.1 IFX; p < .0001). Patients treated with GLM-IV reported higher satisfaction ratings with infusion time (p < .0001) and total visit time (p = .0003). Clinic personnel reported higher satisfaction with GLM-IV than IFX specific to medication preparation time, ease of mixing RA medication, frequency of patients requiring pre-medication, and infusion time. LIMITATIONS: Findings may not be representative of care delivery for all RA infusion practices or RA patients. CONCLUSIONS: Shorter overall clinic visit duration, infusion process, and RA medication infusion times were observed for GLM-IV compared to IFX. A shorter duration in infusion time was associated with higher patient and clinic personnel satisfaction ratings.

Remote Atmospheric Pressure Infrared Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry (Remote IR-MALDI MS) of Proteins.

Remote Infrared Matrix-Assisted Laser Desorption/Ionization (Remote IR-MALDI) system using tissue endogenous water as matrix was shown to enable in vivo real-time mass spectrometry analysis with minimal invasiveness. Initially the system was used to detect metabolites and lipids. Here, we demonstrate its capability to detect and analyze peptides and proteins. Very interestingly, the corresponding mass spectra show ESI-like charge state distribution, opening many applications for structural elucidation to be performed in real-time by Top-Down strategy. The charge states show no dependence toward laser wavelength or length of the transfer tube. Indeed, remote analysis can be performed 5 m away from the mass spectrometer without modification of spectra. On the contrary, addition of glycerol to water shift the charge state distributions toward even higher charge states. The desorption/ionization process is very soft, allowing to maintain protein conformation as in ESI. Observation of proteins and similar spectral features on tissue, when protein standards are deposited on raw tissue pieces, could potentially open the way to their direct analysis from biological samples. This also brings interesting features that could contribute to the understanding of IR MALDI ionization mechanism.

In vivo Real-Time Mass Spectrometry for Guided Surgery Application.

Here we describe a new instrument (SpiderMass) designed for in vivo and real-time analysis. In this instrument ion production is performed remotely from the MS instrument and the generated ions are transported in real-time to the MS analyzer. Ion production is promoted by Resonant Infrared Laser Ablation (RIR-LA) based on the highly effective excitation of O-H bonds in water molecules naturally present in most biological samples. The retrieved molecular patterns are specific to the cell phenotypes and benign versus cancer regions of patient biopsies can be easily differentiated. We also demonstrate by analysis of human skin that SpiderMass can be used under in vivo conditions with minimal damage and pain. Furthermore SpiderMass can also be used for real-time drug metabolism and pharmacokinetic (DMPK) analysis or food safety topics. SpiderMass is thus the first MS based system designed for in vivo real-time analysis under minimally invasive conditions.

Substrate-Mediated Laser Ablation under Ambient Conditions for Spatially-Resolved Tissue Proteomics.

Numerous applications of ambient Mass Spectrometry (MS) have been demonstrated over the past decade. They promoted the emergence of various micro-sampling techniques such as Laser Ablation/Droplet Capture (LADC). LADC consists in the ablation of analytes from a surface and their subsequent capture in a solvent droplet which can then be analyzed by MS. LADC is thus generally performed in the UV or IR range, using a wavelength at which analytes or the matrix absorb. In this work, we explore the potential of visible range LADC (532 nm) as a micro-sampling technology for large-scale proteomics analyses. We demonstrate that biomolecule analyses using 532 nm LADC are possible, despite the low absorbance of biomolecules at this wavelength. This is due to the preponderance of an indirect substrate-mediated ablation mechanism at low laser energy which contrasts with the conventional direct ablation driven by sample absorption. Using our custom LADC system and taking advantage of this substrate-mediated ablation mechanism, we were able to perform large-scale proteomic analyses of micro-sampled tissue sections and demonstrated the possible identification of proteins with relevant biological functions. Consequently, the 532 nm LADC technique offers a new tool for biological and clinical applications.

Progress toward the Quantitative Analysis of PAHs Adsorbed on Soot by Laser Desorption/Laser Ionization/Time-of-Flight Mass Spectrometry.

Ex situ analyses of substances extracted from flames provide useful albeit mostly qualitative information on the formation process of soot and on the impact of exhausts on the environment. An experimental setup based on the coupling of laser desorption, laser ionization and time-of-flight mass spectrometry (LD/LI/ToF-MS) is presented in past works as an alternative means to more traditional techniques like gas chromatography (GC) to characterize the polycyclic aromatic hydrocarbons (PAHs) content of soot. In this paper, we go one step further in the understanding of the laser desorption/laser ionization dynamics and propose a combined experimental/simulation approach: we estimate the limit of detection of LD/LI/ToF-MS as low as [0.2, 2.8] fmol per laser pulse and we make quantitative predictions on the concentration of PAHs desorbed from soot. In particular, external calibration with model samples where PAHs are adsorbed on black carbon at known concentrations allows us to link the concentration of PAHs desorbed and detected by photoionization ToF-MS to the concentration of PAHs adsorbed on soot. The comparison of data obtained from the analysis of flame sampled soot with standard commercial GC-MS run in parallel validates the approach and defines limits and potentialities of both techniques.

CO2 capture using semi-clathrates of quaternary ammonium salt: structure change induced by CO2 and N2 enclathration.

Semi-clathrates of tetrabutylammonium bromide (TBAB) are investigated for their potential application in the CO2 capture context based on hydrate technology. The three-phase lines of semi-clathrates of CO2-TBAB-H2O and N2-TBAB-H2O are established simultaneously with their structure using in situ Raman scattering performed at high pressure. The preferred crystal phase obtained at ambient pressure from solutions of 5 and 40 wt % TBAB initial concentrations is shown to change upon enclathration of CO2 or N2, or by applying a higher pressure on the system. Deep in the stability field, metastable hydrate phases are occurring at the onset of the formation and correspond to the ones expected under ambient pressure conditions. Depending on the pressure, they progressively transformed into the most stable ones when approaching equilibrium and dissociation points. Besides, it is shown that a 5 wt % TBAB original solution forms preferentially a mixed structure of both type B and type A at low gas pressure with CO2 as the guest gas. A new structure is spectroscopically characterized at pressures higher than ∼2 MPa CO2. Type A is demonstrated to be stable at 5 wt % initial TBAB concentration with N2 as the guest molecule and pressure between 8 and 12 MPa. These structural data address new insights on the relationship between the hydrophilic-anion and hydrophobic-cation intercalation with a guest gas producing hydrophobic interaction in a distorted water lattice.

On the origin of increased sensitivity and mass resolution using silicon masks in MALDI.

Since its development, MALDI has proved its performance in the analysis of intact biomolecules up to high molecular weights, regardless of their polarity. Sensitivity of MALDI instruments is a key point for breaking the limits of observing biomolecules of lower abundances. Instrumentation is one way to improve sensitivity by increasing ion transmission and using more sensitive detection systems. On the other side, improving MALDI ion production yields would have important outcomes. MALDI ion production is still not well-controlled and, indeed, the amount of ions produced per laser shot with respect to the total volume of desorbed material is very low. This has particular implications for certain applications, such as MALDI MS imaging where laser beam focusing as fine as possible (5-10 µm) is searched in order to reach higher spatial resolution images. However, various studies point out an intrinsic decrease in signal intensity for strong focusing. We have therefore been interested in developing silicon mask systems to decrease an irradiated area by cutting rather than focusing the laser beam and to study the parameters affecting sensitivity using such systems. For this, we systematically examined variation with laser fluence of intensity and spectral resolution in MALDI of standard peptides when using silicon-etched masks of various aperture sizes. These studies demonstrate a simultaneous increase in spectral resolution and signal intensity. Origin of this effect is discussed in the frame of the two-step ionization model. Experimental data in the low fluence range are fitted with an increase of the primary ionization through matrix-silicon edge contact provided by the masks. On the other hand, behavior at higher fluence could be explained by an effect on the secondary ionization via changes in the plume dynamics.

Search for resolution of chiral fluorohalogenomethanes and parity-violation effects at the molecular level.

The first observation of a parity-violation effect in molecules induced by weak interactions is still a dream that requires the synthesis and, eventually, the resolution of the enantiomers of well-chosen simple chiral molecules together with an appropriate experimental set-up for high-resolution spectroscopy. Performing IR spectroscopy on highly enantiomerically enriched samples of bromochlorofluoromethane succeeded in giving an upper limit of 10(-13) for the relative vibrational energy difference between the two enantiomers. These results led us to conceive a new experimental set-up based on a supersonic molecular beam and to work on other chiral molecules, such as chlorofluoroiodomethane. A synthesis of (+/-)-CHCIFI from racemic chlorofluoroiodoacetic acid should, in the near future permit the preparation of optically active samples of this haloform. The development of molecular beam spectroscopy using a two-photon Ramsey-fringes experiment should allow us to reach the precision needed to observe parity violation. These experimental challenges, which stimulate a close collaboration between chemists and physicists, are presented. The success of these projects would open the route to new information on the molecular Hamiltonian, a better knowledge of the electroweak interaction, and a better control of the various chirality-related properties of simple molecules.