R. G. Cooks

Collisions of polyatomic ions with surfaces

Abstract Surface-induced dissociation (SID) of polyatomic ions is reviewed. Instrumentation is described, including hybrid, tandem quadrupole and tandem time-of-flight instruments built especially to study polyatomic ion—surface collision phenomena. In addition, in-line devices that allow SID to be performed on conventional tandem mass spectrometers are noted, as are experiments which utilize ion cyclotron resonance instruments. The extent of energy deposition accompanying surface collisions is characterized and compared with data from gaseous collisions at non-zero scattering angles. The large internal energies available through SID are shown to facilitate structural characterization of molecular ions of polynuclear aromatic hydrocarbons and peptides. Applications to ion strucutre and chemistry are also illustrated. Emphasis is given to competing ion—surface collision phenomena, including charge-changing collisions and ion—surface reactive collisions. These latter processes are shown to provide information on adsorbates and to be thermochemically controlled. When certain projectile ions, especially small fluorocarbons, undergo charge exchange with surface adsorbates, they are released from the surface as ions. The influence of the nature of the surface on these processes and on SID is discussed. Current trends in research on ion—surface collisions are identified.

Membrane introduction Mass Spectrometry: Trends and applications

Recent advances in membrane introduction mass spectrometry (MIMS) are reviewed. On-line monitoring is treated by focusing on critical variables, including the nature and dimensions of the membrane, and the analyte vapor pressure, diffusivity, and solubility in the membrane barrier. Sample introduction by MIMS is applied in (i) on-line monitoring of chemical and biological reactors, (ii) analysis of volatile organic compounds in environmental matrices, including air, water and soil, and (iii) in more fundamental studies, such as measurements of thermochemical properties, reaction mechanisms, and kinetics. New semipermeable membranes are discussed, including those consisting of thin polymers, low vapor pressure liquids, and zeolites. These membranes have been used to monitor polar compounds, selectively differentiate compounds through affinity-binding, and provide isomer differentiation based on molecular size. Measurements at high spatial resolution, for example, using silicone-capped hypodermic needle inlets, are also covered, as is electrically driven sampling through microporous membranes. Other variations on the basic MIMS experiment include analyte preconcentration through cryotrapping (CT-MIMS) or trapping in the membrane (trap-and-release), as well as differential thermal release methods and reverse phase (i.e., organic solvent) MIMS. Method limitations center on semivolatile compounds and complex mixture analysis, and novel solutions are discussed. Semivolatile compounds have been monitored with thermally assisted desorption, ultrathin membranes and derivatization techniques. Taking advantage of the differences in time of membrane permeation, mixtures of structurally similar compounds have been differentiated by using sample modulation techniques and by temperature-programmed desorption from a membrane interface. Selective ionization techniques that increase instrument sensitivity towards polar compounds are also described, and comparisons are made with other direct sampling (nonchromatographic) methods that are useful in mixture analysis.

Classifying Human Brain Tumors by Lipid Imaging with Mass Spectrometry

Brain tissue biopsies are required to histologically diagnose brain tumors, but current approaches are limited by tissue characterization at the time of surgery. Emerging technologies such as mass spectrometry imaging can enable a rapid direct analysis of cancerous tissue based on molecular composition. Here, we illustrate how gliomas can be rapidly classified by desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, multivariate statistical analysis, and machine learning. DESI-MS imaging was carried out on 36 human glioma samples, including oligodendroglioma, astrocytoma, and oligoastrocytoma, all of different histologic grades and varied tumor cell concentration. Gray and white matter from glial tumors were readily discriminated and detailed diagnostic information could be provided. Classifiers for subtype, grade, and concentration features generated with lipidomic data showed high recognition capability with more than 97% cross-validation. Specimen classification in an independent validation set agreed with expert histopathology diagnosis for 79% of tested features. Together, our findings offer proof of concept that intraoperative examination and classification of brain tissue by mass spectrometry can provide surgeons, pathologists, and oncologists with critical and previously unavailable information to rapidly guide surgical resections that can improve management of patients with malignant brain tumors.

Forensic analysis of inks by imaging desorption electrospray ionization (DESI) mass spectrometry

Desorption electrospray ionization mass spectrometry (DESI-MS) is employed in the forensic analysis of documents. Blue ballpoint pen inks applied to ordinary writing paper are examined under ambient conditions without any prior sample preparation. When coupled to an automated moving stage, two-dimensional molecular images are generated. Proof-of-principle experiments include characterization of a simulated forged number and examination of older written records. This application of DESI has advantages over extractive techniques in terms of speed and sample preservation. The effects of the desorbing solvent composition, in this case a mixture of methanol and water, and of flow rate, are evaluated. Results suggest that the solubility of the analyte (dyes Basic Blue 7, Basic Violet 3 and Solvent Blue 26) plays an important role in desorption from the paper surface.

Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors

The main goal of brain tumor surgery is to maximize tumor resection while preserving brain function. However, existing imaging and surgical techniques do not offer the molecular information needed to delineate tumor boundaries. We have developed a system to rapidly analyze and classify brain tumors based on lipid information acquired by desorption electrospray ionization mass spectrometry (DESI-MS). In this study, a classifier was built to discriminate gliomas and meningiomas based on 36 glioma and 19 meningioma samples. The classifier was tested and results were validated for intraoperative use by analyzing and diagnosing tissue sections from 32 surgical specimens obtained from five research subjects who underwent brain tumor resection. The samples analyzed included oligodendroglioma, astrocytoma, and meningioma tumors of different histological grades and tumor cell concentrations. The molecular diagnosis derived from mass-spectrometry imaging corresponded to histopathology diagnosis with very few exceptions. Our work demonstrates that DESI-MS technology has the potential to identify the histology type of brain tumors. It provides information on glioma grade and, most importantly, may help define tumor margins by measuring the tumor cell concentration in a specimen. Results for stereotactically registered samples were correlated to preoperative MRI through neuronavigation, and visualized over segmented 3D MRI tumor volume reconstruction. Our findings demonstrate the potential of ambient mass spectrometry to guide brain tumor surgery by providing rapid diagnosis, and tumor margin assessment in near–real time.

Matrix effects, internal energies and MS/MS spectra of molecular ions sputtered from surfaces

Desorption ionization (DI) involves the transfer of material from a condensed phase to a collision-free environment (ref. 1,2). Tandem mass spectrometry (ref. 3), used with desorption ionization, improves the signal-to-noise ratio for spectra of individual analytes present in complex matrices, provides evidence that fragmentation in DI is typically due to gas phase dissociations of energized but intact molecular ions after they have left the surface, and allows the compositions of desorbed ions to be characterized. A complementary approach to improving analytical performance and obtaining further information on the species and processes of desorption ionization is to be found in the examination of the sample in the presence of matrix materials. Some matrices act as reagents which yield an appropriate ionized form of the analyte (ref. 4), either during or prior to energization of the sample, while others serve to isolate analyte molecules and reduce intermolecular analyte reactions (ref. 5). Particularly complex matrices are those encountered when examining samples directly from chromatographic materials or in their natural state, for example, crude extracts of plant materials. Examples of analyses in these situations are given. Ammonium chloride acts as a valuable matrix material which, even at sample dilutions of 103, can cause an increase in both absolute secondary ion yields and in spectral persistence (ref. 6,7,8). This matrix has beneficial effects in SIMS, FAB and LD mass spectra and has the advantage of being totally transparent except under high flux conditions. It is shown to decrease ion internal energies, presumably by providing a sputtered ion with a shield of solvating molecules which are readily lost as NH3 and HCl, thereby carrying away excess energy. Cluster ions [(NH4)n+1Cln]+ are observed in FAB and shown by MS/MS to undergo ready desolvation. These cluster ions are remarkable for the absence or low intensity of clusters where the total number of anions and cations is a prime number and for the high intensity of clusters which may be made up of regular arrays of atoms, e.g., 3×3×3 or 3×3×5. A qualitative model of desorption ionization, advanced some years ago (ref. 9), accommodates the observations reported here using MS/MS and matrix effects. The chief features of this model are (i) isomerization (loss of identity) of the input energy, (ii) desorption of preformed ions or intact molecules, (iii) ion/molecule reactions such as cationization occurring in the selvedge region, (iv) dissociation of energetic (metastable) ions well-removed from the surface. In most cases just a few types of ionic species are sputtered from the surface and their unimolecular chemistry determines the chief features of the desorption ionization mass spectrum.

Injection of ions into a quadrupole ion trap mass spectrometer

Abstract High quality mass spectra can be recorded by generating ions using electron impact ionization or laser desorption, and injecting them into a Paul type quadrupole ion trap. Injection is accomplished at energies of 10–25 eV. The injected ions lose kinetic energy to the damping gas (helium, neon, argon or xenon) and are thus trapped. The efficiency of trapping is investigated as a function of the radio frequency voltage for ions of several masses. Trapped ions can be studied in the usual ways, including photodissociation, collisionally activated dissociation and ion/molecule reactions.

Kinetic energy effects in mass spectrometry/mass spectrometry using a sector/quadrupole tandem instrument

Abstract Using a new hybrid (magnet/quadrupole) tandem mass spectrometer the effects of ion kinetic energy and target mass upon energy deposition have been investigated. In the range 1–100 eV, the degree of fragmentation is very sensitive to changes in the translational energy of the parent ion. Comparisons with MS/MS spectra recorded for the same ions (protonated 5-indanol, protonated diethylamine) using other instruments show that less significant changes in spectra occur in the kV energy range. Plots of branching ratios for competitive collision-induced dissociation channels against collision energy (1–100 eV) resemble, qualitatively, breakdown curves displaying ion abundances versus internal energy. In addition, comparisons of the effect of collision energy are made with spectral changes resulting from selection of the scattering angle in kV energy collisions. It is evident that translational energy selection is a counterpart, for spectrometers operating at low translational energy, of angle-resolved mass spectrometry.

Ion/surface collisions at functionalized self-assembled monolayer surfaces

Abstract Collisions of polyatomic projectile ions at surfaces which bear a variety of organic functional groups result in the scattering of ions which have incorporated groups picked up from the surface. The reactions observed include abstraction of atoms and groups such as H , F , CH 3 and C 2 H 3 . Dissociative ion/surface reactions are also observed; in these, the initial adduct fragments by loss of radical species such as H or F , or loss of a stable neutral molecule such as H 2 , HCN or HF. The strength of the CF bond is suggested to be the reason why closed-shell ions, such as the phenyl cation, are observed to form fluorine addition products, whereas the corresponding hydrogen atom abstraction process is not observed. Surface-induced dissociation (SID) also shows a strong dependence on the nature of the surface. At one extreme is the fluorinated surface, which is a particularly “hard” surface, being effective at transferring projectile translational energy into internal energy. Metal carbonyl ions serve as thermometer molecules to measure translational to internal energy transfer, and experiments with Cr(CO) + 6 and W(CO) + 6 allowed the distribution of internal energy deposited in the projectile ion to be measured. Under typical conditions, the average energy transferred was some 12–19% of the laboratory energy of the projectile, with the higher value corresponding to the fluorinated surface and the lower value to the hydrocarbon surface. The amount of energy taken up by the target in a typical case was approximately 60% of the projectile laboratory energy. The fluorinated surface is also the most efficient among those studied in the total yield of scattered ions produced relative to the projectile ion current. The carboxylic acid terminated alkanethiol is the least efficient of the surfaces studied, whereas the deuterated, hydroxyl, nitrile and ester-linked ferrocene show intermediate behavior. These results indicate that the fluorinated surface has special value in the SID experiment.

Soft landing of ions as a means of surface modification

Abstract Chemical reactions between low energy mono-, di- and triatomic ions and metal targets lead to products which have been examined using ESCA. The nature, charge state and kinetic energy of the reactant ion all cause changes in the ESCA spectra. Results for the reactions of lead with various sulfur-containing ions (CS2+, CS22+, CS+, S+, S2+) are emphasized. A complex chemistry is involved with the sulfur being present in at least three charge states characteristic of the metal sulfide, elemental or organic sulfur and sulfur in positive oxidation states, respectively.