Signatures of Reaction Mechanisms Encoded in the Vibrational Population Distribution of Small-Molecule Products: Photodissociation of Symmetric-Triazine Using 266 nm Radiation.

We utilize rotationally resolved Chirped-Pulse Fourier Transform millimeter-wave spectroscopy to study photodissociation dynamics of 1,3,5-Triazine (symmetric-Triazine) to form 3 HCN molecules. The state-specific vibrational population distribution (VPD) of the photofragments contains mechanistic details of the reaction. This photodissociation is performed using 266 nm radiation transverse to a seeded supersonic jet. The vibrational cooling inefficiency in the jet preserves the VPD of the photofragments, while rotational cooling enhances the signal of low-J pure-rotational transitions. The multiplexed nature of the spectrometer enables simultaneous sampling of several "vibrational satellites" of the J = 1 ← 0 transition of HCN. Excited state populations along the HCN bend (v2) and CN stretch (v3) modes are observed, which show ≥3.2% vibrational excitation of the photofragments. Observation of an at least bimodal VPD, along the even-v states of v2, implies an asymmetric partitioning of vibrational energy among the HCN photofragments. This suggests a sequential dissociation mechanism of symmetric-Triazine initiated by 266 nm radiation.

Nonlinear rotational spectroscopy reveals many-body interactions in water molecules.

Because of their central importance in chemistry and biology, water molecules have been the subject of decades of intense spectroscopic investigations. Rotational spectroscopy of water vapor has yielded detailed information about the structure and dynamics of isolated water molecules, as well as water dimers and clusters. Nonlinear rotational spectroscopy in the terahertz regime has been developed recently to investigate the rotational dynamics of linear and symmetric-top molecules whose rotational energy levels are regularly spaced. However, it has not been applied to water or other lower-symmetry molecules with irregularly spaced levels. We report the use of recently developed two-dimensional (2D) terahertz rotational spectroscopy to observe high-order rotational coherences and correlations between rotational transitions that were previously unobservable. The results include two-quantum (2Q) peaks at frequencies that are shifted slightly from the sums of distinct rotational transitions on two different molecules. These results directly reveal the presence of previously unseen metastable water complexes with lifetimes of 100 ps or longer. Several such peaks observed at distinct 2Q frequencies indicate that the complexes have multiple preferred bimolecular geometries. Our results demonstrate the sensitivity of rotational correlations measured in 2D terahertz spectroscopy to molecular interactions and complexation in the gas phase.

Long-range model of vibrational autoionization in core-nonpenetrating Rydberg states of NO.

In high orbital angular momentum (ℓ ≥ 3) Rydberg states, the centrifugal barrier hinders the close approach of the Rydberg electron to the ion-core. As a result, these core-nonpenetrating Rydberg states can be well described by a simplified model in which the Rydberg electron is only weakly perturbed by the long-range electric properties (i.e., multipole moments and polarizabilities) of the ion-core. We have used a long-range model to describe the vibrational autoionization dynamics of high-ℓ Rydberg states of nitric oxide (NO). In particular, our model explains the extensive angular momentum exchange between the ion-core and the Rydberg electron that had been previously observed in vibrational autoionization of f (ℓ = 3) Rydberg states. These results shed light on a long-standing mechanistic question around these previous observations and support a direct, vibrational mechanism of autoionization over an indirect, predissociation-mediated mechanism. In addition, our model correctly predicts newly measured total decay rates of g (ℓ = 4) Rydberg states because for ℓ ≥ 4, the non-radiative decay is dominated by autoionization rather than predissociation. We examine the predicted NO+ ion rotational state distributions generated by vibrational autoionization of g states and discuss applications of our model to achieve quantum state selection in the production of molecular ions.

Quantitation of Urinary Acylcarnitines by DMS-MS/MS Uncovers the Effects of Total Body Irradiation in Cancer Patients.

Acylcarnitines have been identified in human and animal metabolomic-profiling studies as urinary markers of radiation exposure, a result which is consistent with their cytoprotective effects and roles in energy metabolism. In the present work, a rapid method for quantitation of the more abundant acylcarnitines in human urine is developed using a valuable set of samples from cancer patients who received total body irradiation (TBI) at Memorial Sloan Kettering Cancer Center. The method uses solid-phase extraction (SPE) processing followed by differential mobility spectrometry (DMS with ethyl acetate modifier) tandem mass spectrometry (ESI-DMS-MS/MS) with deuterated internal standards. The analyzed human urine samples were collected from 38 individual patients at three time points over 24 h during and after the course of radiation treatment, a design allowing each patient to act as their own control and creatinine normalization. Creatinine-normalized concentrations for nine urinary acylcarnitine (acyl-CN) species are reported. Six acyl-CN species were reduced at the 6 h point. Acetylcarnitine (C2:0-CN) and valerylcarnitine (C5:0-CN) showed recovery at 24 h, but none of the other acyl-CN species showed recovery at that point. Levels of three acyl-CN species were not significantly altered by radiation. This rapid quantitative method for clinical samples covers the short- and medium-chain acylcarnitines and has the flexibility to be expanded to cover additional radiation-linked metabolites. The human data presented here indicates the utility of the current approach as a rapid, quantitative technique with potential applications by the medical community, by space research laboratories concerned with radiation exposure, and by disaster response groups.

The Use of DMS-MS for the Quantitative Analysis of Acylcarnitines.

Differential mobility spectrometry (DMS) is capable of separating molecules based on their size and shape. When coupled to mass spectrometry (MS), DMS reduces chemical background and enhances signal-to-noise (S/N) ratio. Flow injection analysis (FIA) is a technique used to introduce samples into the source of the DMS-MS platform. Here we describe the application of FIA-DMS-MS/MS for the analysis of urinary acylcarnitine species. More than 20 acylcarnitine species can be detected and quantified during a single FIA-DMS-MS/MS acquisition.

Quantitation of Cyclosporin A in Cell Culture Media by Differential Mobility Mass Spectrometry (DMS-MS/MS).

Cell permeability is an important factor in determining the bioavailability of therapeutics that is usually measured by cell culture testing. The concentration of pharmaceutical in a medium such as Hank's Balanced Salt Solution with HEPES organic buffer (HBSS-HEPES) is measured at a series of time points, making simplicity and high throughput of the analytical method important characteristics. We report an electrospray differential mobility spectrometry mass spectrometry method (nanoESI-DMS-MS) for the rapid determination of cyclosporin A (CsA, cyclosporine) concentration in such a buffer. DMS technology provides gas phase atmospheric pressure ion filtration for small-molecule bioanalytical methods that suppresses interfering ions and reduces chemical noise, without the use of chromatography. This allows simplified sample preparation, fast calibration curve development, and shortened analysis times. It has also been noted that the DMS prefilter can reduce contamination of the mass spectrometer by salts, thereby extending mass spectrometer system uptime.In the application described here, DMS-MS/MS is applied to cyclosporine A (CsA) in cell medium. Sample preparation is limited to dilution with an ammonium acetate-methanol-water mobile phase and the addition of CsA-d4 internal standard. The isotope ratio data are obtained in DMS-MS MRM mode observing NH3 loss from the ammonium adduct of the two species. A calibration curve with high linearity (R2 = 0.998) is rapidly obtained with nearly zero intercept, while it was found that a liquid chromatography LC-MS method required a preliminary SPE step to obtain a linear calibration curve. The time for data acquisition in the DMS-MS MRM method with flow injection (FIA) or infusion introduction at ESI flow of 400 nL/min is typically 30 s leading to a cycle time of less than 1 min.

Analysis of vibrational autoionization of CaF Rydberg states.

We report calculations of vibrational autoionization rates of CaF Rydberg states, based on the results of a global multi-channel quantum defect theory (MQDT) fit. Our goal is to use intuitive physical models to interpret and extend the results from the MQDT calculations and, in particular, to characterize the physical mechanisms for the interaction between the Rydberg electron and the ion-core. The calculations indicate that, among the six strongly l-mixed core-penetrating (CP) Rydberg series of CaF, the n.36 p^Π Rydberg series has the fastest Δv = 1 vibrational autoionization rate, which is at least four times larger than that for the other CP Rydberg series, in agreement with experimental results. We first demonstrate that the rotational level dependence of the vibrational autoionization rate of the n.36 p^Π series is satisfactorily explained by l-uncoupling interactions, which differ for the positive and negative Kronig symmetry levels. Next, we interpret the relative vibrational autoionization rates of all six CP Rydberg series in the context of a valence-precursor (VP) model. The VP model is a consequence of Mulliken's rule, which states that the innermost lobe of the Rydberg wavefunction remains invariant in both the nodal position and shape for members of the same Rydberg series. The electronic properties of the six VP states, which are the terminus states (lowest-n) of each of the six CP Rydberg series, are further characterized in terms of a ligand-field model, providing insight into the intimate relationship between the Rydberg electron density in the ion-core region and the vibrational autoionization rate.

Differential Mobility Spectrometry-Mass Spectrometry (DMS-MS) in Radiation Biodosimetry: Rapid and High-Throughput Quantitation of Multiple Radiation Biomarkers in Nonhuman Primate Urine.

High-throughput methods to assess radiation exposure are a priority due to concerns that include nuclear power accidents, the spread of nuclear weapon capability, and the risk of terrorist attacks. Metabolomics, the assessment of small molecules in an easily accessible sample, is the most recent method to be applied for the identification of biomarkers of the biological radiation response with a useful dose-response profile. Profiling for biomarker identification is frequently done using an LC-MS platform which has limited throughput due to the time-consuming nature of chromatography. We present here a chromatography-free simplified method for quantitative analysis of seven metabolites in urine with radiation dose-response using urine samples provided from the Pannkuk et al. (2015) study of long-term (7-day) radiation response in nonhuman primates (NHP). The stable isotope dilution (SID) analytical method consists of sample preparation by strong cation exchange-solid phase extraction (SCX-SPE) to remove interferences and concentrate the metabolites of interest, followed by differential mobility spectrometry (DMS) ion filtration to select the ion of interest and reduce chemical background, followed by mass spectrometry (overall SID-SPE-DMS-MS). Since no chromatography is used, calibration curves were prepared rapidly, in under 2 h (including SPE) for six simultaneously analyzed radiation biomarkers. The seventh, creatinine, was measured separately after 2500× dilution. Creatinine plays a dual role, measuring kidney glomerular filtration rate (GFR), and indicating kidney damage at high doses. The current quantitative method using SID-SPE-DMS-MS provides throughput which is 7.5 to 30 times higher than that of LC-MS and provides a path to pre-clinical radiation dose estimation. Graphical Abstract.

Differential mobility spectrometry (DMS) reveals the elevation of urinary acetylcarnitine in non-human primates (NHPs) exposed to radiation.

Acetylcarnitine has been identified as one of several urinary biomarkers indicative of radiation exposure in adult rhesus macaque monkeys (non-human primates, NHPs). Previous work has demonstrated an up-regulated dose-response profile in a balanced male/female NHP cohort. As a contribution toward the development of metabolomics-based radiation biodosimetry in human populations and other applications of acetylcarnitine screening, we have developed a quantitative, high-throughput method for the analysis of acetylcarnitine. We employed the Sciex SelexIon DMS-MS/MS QTRAP 5500 platform coupled to flow injection analysis (FIA), thereby allowing for fast analysis times of less than 0.5 minutes per injection with no chromatographic separation. Ethyl acetate is used as a DMS modifier to reduce matrix chemical background. We have measured NHP urinary acetylcarnitine from the male cohorts that were exposed to the following radiation levels: control, 2, 4, 6, 7, and 10 Gy. Biological variability, along with calibration accuracy of the FIA-DMS-MS/MS method, indicates LOQ of 20 µM, with observed biological levels on the order of 600 µM and control levels near 10 µM. There is an apparent onset of intensified response in the transition from 6 to 10 Gy. The results demonstrate that FIA-DMS-MS/MS is a rapid, quantitative technique that can be utilized for the analysis of urinary biomarker levels for radiation biodosimetry.

Electric potential invariants and ions-in-molecules effective potentials for molecular Rydberg states.

The dependence of multipole moments and polarizabilities on external fields appears in many applications including biomolecular molecular mechanics, optical non-linearity, nanomaterial calculations, and the perturbation of spectroscopic signatures in atomic clocks. Over a wide range of distances, distributed multipole and polarizability potentials can be applied to obtain the variation of atom-centered atoms-in-molecules electric properties like bonding-quenched polarizability. For cylindrically symmetric charge distributions, we examine single-center and atom-centered effective polarization potentials in a non-relativistic approximation for Rydberg states. For ions, the multipole expansion is strongly origin-dependent, but we note that origin-independent invariants can be defined. The several families of invariants correspond to optimized representations differing by origin and number of terms. Among them, a representation at the center of dipole polarizability optimizes the accuracy of the potential with terms through 1/r4. We formulate the single-center expansion in terms of polarization-modified effective multipole moments, defining a form related to the source-multipole expansion of Brink and Satchler. Atom-centered potentials are an origin independent alternative but are limited both by the properties allowed at each center and by the neglected effects like bond polarizability and charge flow. To enable comparisons between single-center effective potentials in Cartesian or spherical form and two-center effective potentials with differing levels of mutual induction between atomic centers, we give analytical expressions for the bond-length and origin-dependence of multipole and polarizability terms projected in the multipole and polarizability expansion of Buckingham. The atom-centered potentials can then be used with experimental data and ab initio calculations to estimate atoms-in-molecules properties. Some results are given for BaF+ and HF showing the utility and limitations of the approach. More detailed results on X 1Σ+ CaF+ are published separately.

Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry.

Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure. Graphical Abstract ᅟ.

Understanding gas phase modifier interactions in rapid analysis by differential mobility-tandem mass spectrometry.

A systematic study involving the use and optimization of gas-phase modifiers in quantitative differential mobility-mass spectrometry (DMS-MS) analysis is presented using nucleoside-adduct biomarkers of DNA damage as an important reference point for analysis in complex matrices. Commonly used polar protic and polar aprotic modifiers have been screened for use against two deoxyguanosine adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak shapes, and product ion signal intensities while optimizing the DMS-MS conditions. The optimized parameters were then applied to rapid quantitation of the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct levels corresponding to less than one modification in 10(6) normal DNA bases were detected using the DMS-MS platform. Based on DMS fundamentals and ab initio thermochemical results, we interpret the complexity of DMS modifier responses in terms of thermal activation and the development of solvent shells. At very high bulk gas temperature, modifier dipole moment may be the most important factor in cluster formation and cluster geometry, but at lower temperatures, multi-neutral clusters are important and less predictable. This work provides a useful protocol for targeted DNA adduct quantitation and a basis for future work on DMS modifier effects.

Differential mobility spectrometry with nanospray ion source as a compact detector for small organics and inorganics.

Electrospray ionization (ESI) is an important tool in chemical and biochemical survey and targeted analysis in many applications. For chemical detection and identification electrospray is usually used with mass spectrometry (MS). However, for screening and monitoring of chemicals of interest in light, low power field-deployable instrumentation, an alternative detection technology with chemical selectivity would be highly useful, especially since small, lightweight, chip-based gas and liquid chromatographic technologies are being developed. Our initial list of applications requiring portable instruments includes chemical surveys on Mars, medical diagnostics based on metabolites in biological samples, and water quality analysis. In this report, we evaluate ESI-Differential Mobility Spectrometry (DMS) as a compact, low-power alternative to MS detection. Use of DMS for chemically-selective detection of ESI suffers in comparison with mass spectrometry because portable MS peak capacity is greater than that of DMS by 10X or more, but the development of light, fast chip chromatography offers compensating resolution. Standalone DMS provides the chemical selectivity familiar from DMS-MS publications, and exploits the sensitivity of ion detection. We find that sub-microliter-per-minute flows and a correctly-designed interface prepare a desolvated ion stream that enables DMS to act as an effective ion filter. Results for a several small organic biomarkers and metabolites, including citric acid, azelaic acid, n-hexanoylglycine, thymidine, and caffeine, as well as compounds such as dinitrotoluene and others, have been characterized and demonstrate selective detection. Water-quality-related halogen-containing anions, fluoride through bromate, contained in liquid samples are also isolated by DMS. A reaction-chamber interface is highlighted as most practical for portable ESI-DMS instrumentation.

Extending the dynamic range of the ion trap by differential mobility filtration.

A miniature, planar, differential ion mobility spectrometer (DMS) was interfaced to an LCQ classic ion trap to conduct selective ion filtration prior to mass analysis in order to extend the dynamic range of the trap. Space charge effects are known to limit the functional ion storage capacity of ion trap mass analyzers and this, in turn, can affect the quality of the mass spectral data generated. This problem is further exacerbated in the analysis of mixtures where the indiscriminate introduction of matrix ions results in premature trap saturation with non-targeted species, thereby reducing the number of parent ions that may be used to conduct MS/MS experiments for quantitation or other diagnostic studies. We show that conducting differential mobility-based separations prior to mass analysis allows the isolation of targeted analytes from electrosprayed mixtures preventing the indiscriminate introduction of matrix ions and premature trap saturation with analytically unrelated species. Coupling these two analytical techniques is shown to enhance the detection of a targeted drug metabolite from a biological matrix. In its capacity as a selective ion filter, the DMS can improve the analytical performance of analyzers such as quadrupole (3D or linear) and ion cyclotron resonance (FT-ICR) ion traps that depend on ion accumulation.

A differential mobility spectrometry/mass spectrometry platform for the rapid detection and quantitation of DNA adduct dG-ABP.

RATIONALE: There is continued interest in exploring new analytical technologies for the detection and quantitation of DNA adducts, biomarkers which provide direct evidence of exposure and genetic damage in cells. With the goal of reducing clean-up steps and improving sample throughput, a Differential Mobility Spectrometry/Mass Spectrometry (DMS/MS) platform has been introduced for adduct analysis. METHODS: A DMS/MS platform has been utilized for the analysis of dG-ABP, the deoxyguanosine adduct of the bladder carcinogen 4-aminobiphenyl (4-ABP). After optimization of the DMS parameters, each sample was analyzed in just 30 s following a simple protein precipitation step of the digested DNA. RESULTS: A detection limit of one modification in 10^6 nucleosides has been achieved using only 2 µg of DNA. A brief comparison (quantitative and qualitative) with liquid chromatography/mass spectrometry is also presented highlighting the advantages of using the DMS/MS method as a high-throughput platform. CONCLUSIONS: The data presented demonstrate the successful application of a DMS/MS/MS platform for the rapid quantitation of DNA adducts using, as a model analyte, the deoxyguanosine adduct of the bladder carcinogen 4-aminobiphenyl.

Chirped-pulse millimeter-wave spectroscopy: spectrum, dynamics, and manipulation of Rydberg-Rydberg transitions.

We apply the chirped-pulse millimeter-wave (CPmmW) technique to transitions between Rydberg states in calcium atoms. The unique feature of Rydberg-Rydberg transitions is that they have enormous electric dipole transition moments (~5 kiloDebye at n* ~ 40, where n* is the effective principal quantum number), so they interact strongly with the mm-wave radiation. After polarization by a mm-wave pulse in the 70-84 GHz frequency region, the excited transitions re-radiate free induction decay (FID) at their resonant frequencies, and the FID is heterodyne-detected by the CPmmW spectrometer. Data collection and averaging are performed in the time domain. The spectral resolution is ~100 kHz. Because of the large transition dipole moments, the available mm-wave power is sufficient to polarize the entire bandwidth of the spectrometer (12 GHz) in each pulse, and high-resolution survey spectra may be collected. Both absorptive and emissive transitions are observed, and they are distinguished by the phase of their FID relative to that of the excitation pulse. With the combination of the large transition dipole moments and direct monitoring of transitions, we observe dynamics, such as transient nutations from the interference of the excitation pulse with the polarization that it induces in the sample. Since the waveform produced by the mm-wave source may be precisely controlled, we can populate states with high angular momentum by a sequence of pulses while recording the results of these manipulations in the time domain. We also probe the superradiant decay of the Rydberg sample using photon echoes. The application of the CPmmW technique to transitions between Rydberg states of molecules is discussed.

Rapid separation and characterization of cocaine and cocaine cutting agents by differential mobility spectrometry-mass spectrometry.

Forensic drug laboratories are inundated with cases requiring time-consuming GC- or LC-based chromatographic separations of submitted samples. High-throughput analytical methods would be of great practical utility within forensic drug analysis. Recently developed ion-mobility-based separation methods combined with mass spectrometry can often be used without chromatography, suppress chemical interferents of similar mass, and operate in seconds. We have evaluated differential mobility spectrometry-mass spectrometry (DMS-MS) for performance on adulterated cocaine mixtures. The DMS interface is only a few centimeters in length, operates in seconds, and can be adapted to any MS system using atmospheric pressure ionization. Drug cutting agents, typical targets such as cocaine, and drug metabolites are rapidly separated by the DMS ion prefilter. Tests demonstrated characterization of complex mixtures, such as isolation of levamisole, an adulterant with alarming side effects, from a 13-component mixture. DMS-MS holds great potential for the analysis of drug samples submitted for forensic analysis.

Development of rapid methodologies for the isolation and quantitation of drug metabolites by differential mobility spectrometry - mass spectrometry.

Clinical and forensic toxicology laboratories are inundated with thousands of samples requiring lengthy chromatographic separations prior to mass spectrometry. Here, we employ differential mobility spectrometry (DMS) interfaced to nano-electrospray ionization-mass spectrometry to provide a rapid ion filtration technique for the separation of ions in gas phase media prior to mass spectral analysis on a DMS-integrated AB SCIEX API 3000 triple-quadrupole mass spectrometer. DMS is efficient at the rapid separation of ions under ambient conditions and provides many advantages when used as an ion filtration technique in tandem with mass spectrometry (MS) and MS/MS. Our studies evaluated DMS-MS/MS as a rapid, quantitative platform for the analysis of drug metabolites isolated from urine samples. In targeted applications, five metabolites of common drugs of abuse were effectively and rapidly separated using isopropanol and ethyl acetate as transport gas modifiers, eliminating the gas chromatography or liquid chromatography-based separations commonly employed in clinical and forensic toxicology laboratories. Calibration curves were prepared for the selected drug metabolites utilizing deuterated internal standards for quantitative purposes. The feasibility of separating and quantitating drug metabolites in a rapid fashion was evaluated by compensation voltage stepping followed by multiple reaction monitoring (MRM) detection. Rapid profiling of clinical and forensic toxicology samples could help to address an urgent need within the scientific community by developing high-throughput analytical methodologies, which could reduce significant case backlogs present within these laboratories.

Chirped-pulse millimeter-wave spectroscopy of Rydberg-Rydberg transitions.

Transitions between Rydberg states of Ca atoms, in a pulsed, supersonic atomic beam, are directly detected by chirped-pulse millimeter-wave spectroscopy. Broadband, high-resolution spectra with accurate relative intensities are recorded instantly. Free induction decay (FID) of atoms, polarized by the chirped pulse, at their Rydberg-Rydberg transition frequencies, is heterodyne detected, averaged in the time domain, and Fourier transformed into the frequency domain. Millimeter-wave transient nutations are observed, and the possibility of FID evolving to superradiance is discussed.

Radiation metabolomics and its potential in biodosimetry.

PURPOSE: Radiation exposure triggers a complex network of molecular and cellular responses that impacts metabolic processes and alters the levels of metabolites. Such metabolites have potential as biomarkers for radiation dosimetry. This review provides an overview of radiation signalling and metabolism, of metabolomic approaches used in the discovery phase, and of instrumentation with the potential to assess radiation injury in the field. APPROACH: Recent developments in fast, high-resolution chromatography and mass spectrometry and new data analysis methods allow the quantitative assessment of thousands of metabolites based on biofluids obtained non-invasively. This complex analysis leads to the discovery-phase identification of groups of metabolites useful for screening and biodosimetry by targeted quantitative measurement. Instrumentation for target analysis can be simpler than that used for discovery, so we examine current technologies based on ion mobility. CONCLUSIONS: Recent published results and ongoing studies examine the complex changes in the levels of many metabolites caused by radiation exposure, and identify groups of small-molecule biomarkers for radiation biodosimetry. Based on results showing separation orthogonal to mass, chemical noise suppression, and high sensitivity, differential mobility mass spectrometry (DMS-MS) ion mobility spectrometry appears highly promising for the development of deployable instrumentation.