High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage.

In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.

Enhanced Isotopic Ratio Outlier Analysis (IROA) Peak Detection and Identification with Ultra-High Resolution GC-Orbitrap/MS: Potential Application for Investigation of Model Organism Metabolomes.

Identifying non-annotated peaks may have a significant impact on the understanding of biological systems. In silico methodologies have focused on ESI LC/MS/MS for identifying non-annotated MS peaks. In this study, we employed in silico methodology to develop an Isotopic Ratio Outlier Analysis (IROA) workflow using enhanced mass spectrometric data acquired with the ultra-high resolution GC-Orbitrap/MS to determine the identity of non-annotated metabolites. The higher resolution of the GC-Orbitrap/MS, together with its wide dynamic range, resulted in more IROA peak pairs detected, and increased reliability of chemical formulae generation (CFG). IROA uses two different 13C-enriched carbon sources (randomized 95% 12C and 95% 13C) to produce mirror image isotopologue pairs, whose mass difference reveals the carbon chain length (n), which aids in the identification of endogenous metabolites. Accurate m/z, n, and derivatization information are obtained from our GC/MS workflow for unknown metabolite identification, and aids in silico methodologies for identifying isomeric and non-annotated metabolites. We were able to mine more mass spectral information using the same Saccharomyces cerevisiae growth protocol (Qiu et al. Anal. Chem 2016) with the ultra-high resolution GC-Orbitrap/MS, using 10% ammonia in methane as the CI reagent gas. We identified 244 IROA peaks pairs, which significantly increased IROA detection capability compared with our previous report (126 IROA peak pairs using a GC-TOF/MS machine). For 55 selected metabolites identified from matched IROA CI and EI spectra, using the GC-Orbitrap/MS vs. GC-TOF/MS, the average mass deviation for GC-Orbitrap/MS was 1.48 ppm, however, the average mass deviation was 32.2 ppm for the GC-TOF/MS machine. In summary, the higher resolution and wider dynamic range of the GC-Orbitrap/MS enabled more accurate CFG, and the coupling of accurate mass GC/MS IROA methodology with in silico fragmentation has great potential in unknown metabolite identification, with applications for characterizing model organism networks.

Passive sampling for volatile organic compounds in indoor air-controlled laboratory comparison of four sampler types.

Correction for 'Passive sampling for volatile organic compounds in indoor air-controlled laboratory comparison of four sampler types' by Todd McAlary et al., Environ. Sci.: Processes Impacts, 2015, 17, 896-905.

Passive sampling for volatile organic compounds in indoor air-controlled laboratory comparison of four sampler types.

This article describes laboratory testing of four passive diffusive samplers for assessing indoor air concentrations of volatile organic compounds (VOCs), including SKC Ultra II, Radiello®, Waterloo Membrane Sampler (WMS) and Automated Thermal Desorption (ATD) tubes with two different sorbents (Tenax TA and Carbopack B). The testing included 10 VOCs (including chlorinated ethenes, ethanes, and methanes, aromatic and aliphatic hydrocarbons), spanning a range of properties and including some compounds expected to pose challenges (naphthalene, methyl ethyl ketone). Tests were conducted at different temperatures (17 to 30 °C), relative humidities (30 to 90% RH), face velocities (0.014 to 0.41 m s(-1)), concentrations (1 to 100 parts per billion by volume [ppbv]) and sampling durations (1 to 7 days). The results show that all of the passive samplers provided data that met the success criteria (relative percent difference [RPD] ≤ 45% of active sample concentrations and coefficient of variation [COV] ≤ 30%) in the majority of cases, but some compounds were problematic for some samplers. The passive sampler uptake rates depend to varying degrees on the sampler, sorbent, target compounds and environmental conditions, so field calibration is advantageous for the highest levels of data quality.

Quantitative passive soil vapor sampling for VOCs--Part 4: Flow-through cell.

This paper presents a controlled experiment comparing several quantitative passive samplers for monitoring concentrations of volatile organic compound (VOC) vapors in soil gas using a flow-through cell. This application is simpler than conventional active sampling using adsorptive tubes because the flow rate does not need to be precisely measured and controlled, which is advantageous because the permeability of subsurface materials affects the flow rate and the permeability of geologic materials is highly variable. Using passive samplers in a flow-through cell, the flow rate may not need to be known exactly, as long as it is sufficient to purge the cell in a reasonable time and minimize any negative bias attributable to the starvation effect. An experiment was performed in a 500 mL flow-through cell using a two-factor, one-half fraction fractional factorial test design with flow rates of 80, 670 and 930 mL min(-1) and sample durations of 10, 15 and 20 minutes for each of five different passive samplers (passive Automatic Thermal Desorption Tube, Radiello®, SKC Ultra, Waterloo Membrane Sampler™ and 3M™ OVM 3500). A Summa canister was collected coincident with each passive sampler and analyzed by EPA Method TO-15 to provide a baseline for comparison of the passive sampler concentrations. The passive sampler concentrations were within a factor of 2 of the Summa canister concentrations in 32 of 35 cases. Passive samples collected at the low flow rate and short duration showed low concentrations, which is likely attributable to insufficient purging of the cell after sampler placement.

Quantitative passive soil vapor sampling for VOCs--part 2: laboratory experiments.

Controlled laboratory experiments were conducted to demonstrate the use of passive samplers for soil vapor concentration monitoring. Five different passive samplers were studied (Radiello, SKC Ultra, Waterloo Membrane Sampler, ATD tubes and 3M OVM 3500). Ten different volatile organic compounds were used of varying classes (chlorinated ethanes, ethanes, and methanes, aliphatics and aromatics) and physical properties (vapor pressure, solubility and sorption). Samplers were exposed in randomized triplicates to concentrations of 1, 10 and 100 ppmv, with a relative humidity of ∼80%, a temperature of ∼24 °C, and a duration of 30 minutes in a chamber with a face velocity of about 5 cm min(-1). Passive samplers are more commonly used for longer sample durations (e.g., 8 hour workday) and higher face velocities (>600 cm min(-1)), so testing to verify the performance for these conditions was needed. Summa canister samples were collected and analyzed by EPA Method TO-15 to establish a baseline for comparison for all the passive samplers. Low-uptake rate varieties of four of the samplers were also tested at 10 ppmv under two conditions; with 5 cm min(-1) face velocity and stagnant conditions to assess whether low or near-zero face velocities would result in a low bias from the starvation effect. The results indicate that passive samplers can provide concentration measurements with accuracy (mostly within a factor of 2) and precision (RSD < 15%) comparable to conventional Summa canister samples and EPA Method TO-15 analysis. Some compounds are challenging for some passive samplers because of uncertainties in the uptake rates, or challenges with retention or recovery.

Quantitative passive soil vapor sampling for VOCs--part 3: field experiments.

Volatile organic compounds (VOCs) are commonly associated with contaminated land and may pose a risk to human health via subsurface vapor intrusion to indoor air. Soil vapor sampling is commonly used to assess the nature and extent of VOC contamination, but can be complicated because of the wide range of geologic material permeability and moisture content conditions that might be encountered, the wide variety of available sampling and analysis methods, and several potential causes of bias and variability, including leaks of atmospheric air, adsorption-desorption interactions, inconsistent sampling protocols and varying levels of experience among sampling personnel. Passive sampling onto adsorbent materials has been available as an alternative to conventional whole-gas sample collection for decades, but relationships between the mass sorbed with time and the soil vapor concentration have not been quantitatively established and the relative merits of various commercially available passive samplers for soil vapor concentration measurement is unknown. This paper presents the results of field experiments using several different passive samplers under a wide range of conditions. The results show that properly designed and deployed quantitative passive soil vapor samplers can be used to measure soil vapor concentrations with accuracy and precision comparable to conventional active soil vapor sampling (relative concentrations within a factor of 2 and RSD comparable to active sampling) where the uptake rate is low enough to minimize starvation and the exposure duration is not excessive for weakly retained compounds.

Applications of polydimethylsiloxane in analytical chemistry: a review.

Silicones have innumerable applications in many areas of life. Polydimethylsiloxane (PDMS), which belongs to the class of silicones, has been extensively used in the field of analytical chemistry owing to its favourable physicochemical properties. The use of PDMS in analytical chemistry gained importance with its application as a stationary phase in gas chromatographic separations. Since then it has been used in many sample preparation techniques such as solid phase microextraction (SPME), stir bar sorptive extraction (SBSE), thin-film extraction, permeation passive sampling, etc. Further, it is gaining importance in the manufacturing of lab-on-a-chip devices, which have revolutionized bio-analysis. Applications of devices containing PDMS and used in the field of analytical chemistry are reviewed in this paper.

Polydimethylsiloxane-based permeation passive air sampler. Part I: Calibration constants and their relation to retention indices of the analytes.

A simple and cost effective permeation passive sampler equipped with a polydimethylsiloxane (PDMS) membrane was designed for the determination of time-weighted average (TWA) concentrations of volatile organic compounds (VOCs) in air. Permeation passive samplers have significant advantages over diffusive passive samplers, including insensitivity to moisture and high face velocities of air across the surface of the sampler. Calibration constants of the sampler towards 41 analytes belonging to alkane, aromatic hydrocarbon, chlorinated hydrocarbon, ester and alcohol groups were determined. The calibration constants allowed for the determination of the permeability of PDMS towards the selected analytes. They ranged from 0.026 cm² min⁻¹ for 1,1-dichloroethylene to 0.605 cm² min⁻¹ for n-octanol. Further, the mechanism of analyte transport across PDMS membranes allowed for the calibration constants of the sampler to be estimated from the linear temperature programmed retention indices (LTPRI) of the analytes, determined using GC columns coated with pure PDMS stationary phases. Statistical analysis using Student's t test indicated that there was no significant difference at the 95% probability level between the experimentally obtained calibration constants and those estimated using LTPRI for most analyte groups studied. This correlation allows the estimation of the calibration constants of compounds not known to be present at the time of sampler deployment, which makes it possible to determine parameters like total petroleum hydrocarbons in the vapor phase.

Polydimethylsiloxane-based permeation passive air sampler. Part II: Effect of temperature and humidity on the calibration constants.

Polydimethylsiloxane (PDMS) has low permeability towards water vapour and low energy of activation of permeation towards volatile organic compounds (VOCs) when compared to many other polymers. Suitability of the material for use in permeation-type passive air samplers was tested as it theoretically should reduce uptake rate variations due to temperature changes and eliminate or reduce complications arising from sorbent saturation by water vapour. The calibration constants of a simple autosampler vial-based permeation passive sampler equipped with a PDMS membrane (Waterloo Membrane Sampler(®)) were determined for various analytes at different temperatures. From the data, the activation energy of permeation for PDMS towards the analytes was determined. The analytes studied belonged to various classes of compounds with wide ranging polarities, including n-alkanes, aromatic hydrocarbons, esters and alcohols. The results confirmed Arrhenius-type relationship between temperature and calibration constant and the energy of activation of permeation for PDMS ranged from -5kJ/mole for butylbenzene to -17kJ/mole for sec-butylacetate. Calibration constants of the samplers towards n-alkanes and aromatic hydrocarbons determined at humidities between 30% and 91% indicated no statistically significant variations in the uptake rate with changes in humidity for 9 of the 11 analytes studied. The results confirmed the suitability of the sampler for deployment in high humidity areas and under varying temperature conditions.

Passive sampling in environmental analysis.

Since its invention more than three decades ago, passive sampling technology has been widely used for environmental monitoring throughout the world. In many cases, it is the only practical means of determining pollution levels caused by numerous anthropogenic chemicals. Passive sampling technology today is used in various areas ranging from workplace exposure monitoring to global issues of climate change arising due to the presence of various chemicals in the atmosphere. In this review, the present status of the technology and its applications will be discussed along with aspects related to its regulatory acceptance and recent trends.