Paper spray for direct analysis of complex mixtures using mass spectrometry.

A low-temperature plasma (LTP) probe has been developed for ambient desorption ionization. An ac electric field is used to induce a dielectric barrier discharge through use of a specially designed electrode configuration. The low-temperature plasma is extracted from the probe where it interacts directly with the sample being analyzed, desorbing and ionizing surface molecules in the ambient environment. This allows experiments to be performed without damage to the sample or underlying substrate and, in the case of biological analysis on skin surfaces, without electrical shock or perceptible heating. Positive or negative ions are produced from a wide range of chemical compounds in the pure state and as mixtures in the gaseous, solution, or condensed phases, using He, Ar, N2, or ambient air as the discharge gas. Limited fragmentation occurs, although it is greater in the cases of the molecular than the atomic discharge gases. The effectiveness of the LTP probe has been demonstrated by recording characteristi...

Low-temperature plasma probe for ambient desorption ionization.

Paper spray is developed as a direct sampling ionization method for mass spectrometric analysis of complex mixtures. Ions of analyte are generated by applying a high voltage to a paper triangle wetted with a small volume (<10 μL) of solution. Samples can be preloaded onto the paper, added with the wetting solution, or transferred from surfaces using the paper as a wipe. It is demonstrated that paper spray is applicable to the analysis of a wide variety of compounds, including small organic compounds, peptides, and proteins. Procedures are developed for analysis of dried biofluid spots and applied to therapeutic drug monitoring with whole blood samples and to illicit drug detection in raw urine samples. Limits of detection of 50 ng/mL (or 20 pg absolute) are achieved for atenolol in bovine blood. The combination of sample collection from surfaces and paper spray ionization also enables fast chemical screening at high sensitivity, for example 100 pg of heroin distributed on a surface and agrochemicals on fr...

Development, characterization, and application of paper spray ionization.

The emerging field of metabolomics, in which a large number of small-molecule metabolites from body fluids or tissues are detected quantitatively in a single step, promises immense potential for early diagnosis, therapy monitoring and for understanding the pathogenesis of many diseases. Metabolomics methods are mostly focused on the information-rich analytical techniques of NMR spectroscopy and mass spectrometry (MS). Analysis of the data from these high-resolution methods using advanced chemometric approaches provides a powerful platform for translational and clinical research and diagnostic applications. In this review, the current trends and recent advances in NMR- and MS-based metabolomics are described with a focus on the development of advanced NMR and MS methods, improved multivariate statistical data analysis and recent applications in the area of cancer, diabetes, inborn errors of metabolism and cardiovascular diseases.

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Metabolomics-based methods for early disease diagnostics.

Ambient Sampling/Ionization Mass Spectrometry: Applications and Current Trends

Ambient desorption ionization mass spectrometry (MS) allows for the direct analysis of ordinary objects in the open atmosphere of the laboratory or in their natural environment. Analyte desorption usually accompanies the ionization step and these processes are often concerted, multi-step processes. Ambient desorption ionization methods typically require little or no sample preparation, offer a much simplified work flow and deliver unprecedented ease of use to MS analyses. Since the introduction of desorption electrospray ionization (DESI [Z. Takats, J.M. Wiseman, B. Gologan, R.G. Cooks, Science (Washington, D. C.) 306 (2004) 471]) in 2004 and the direct analysis in real time (DART [R.B. Cody, J.A. Laramee, H.D. Durst, Anal. Chem. 77 (2005) 2297]) in 2005, this new field of MS has developed rapidly. Numerous permutations of the various options for analyte desorption and ionization have been demonstrated. Desorption steps, such as momentum transfer, dissolution into ricocheting droplets and thermal desorption, have been combined with ionization steps, including ESI, atmospheric pressure chemical ionization and photo-ionization. The large number of possible combinations of desorption and ionization components that have already been applied is creating a proliferation of techniques and acronyms that is becoming ever more complex. Here, we provide a logical framework for the classification of these related experiments, based on the desorption and ionization processes involved in each.

Ambient desorption ionization mass spectrometry

Extractive electrospray ionization for direct analysis of undiluted urine, milk and other complex mixtures without sample preparation.

A droplet pickup and other mechanisms have been suggested for the ionization of biomolecules like peptides and proteins by desorption electrospray ionization To verify this hypothesis phase Doppler particle analysis was used to study the sizes and velocities of droplets involved in DESI It was found that impacting droplets typically have velocities of 120 m/s and average diameters of 2−4 μm Small differences in sprayer construction influence the operating conditions at which droplets of these dimensions are produced Under these conditions, the kinetic energy per impacting water molecule is less than 06 meV and sputtering through momentum transfer during collisions or ionization by other electronic processes is unlikely Droplets arrive at the surface with velocities well below the speed of sound in common materials, thereby excluding the possibility of ionization by shockwave formation Some droplets appear to roll along the surface, increasing contact time and presumably the amount of material that 

Droplet Dynamics and Ionization Mechanisms in Desorption Electrospray Ionization Mass Spectrometry

Desorption electrospray ionization (DESI) allows the direct analysis of ordinary objects or pre-processed samples under ambient conditions. Among other applications, DESI is used to identify and record spatial distributions of lipids and drug molecules in biological tissue sections. This technique does not require sample preparation other than production of microtome tissue slices and does not involve the use of ionization matrices. This greatly simplifies the procedure and prevents the redistribution of analytes during matrix deposition. Images are obtained by continuously moving the sample relative to the DESI sprayer and the inlet of the mass spectrometer. The timing of the protocol depends on the size of the surface to be analyzed and on the desired resolution. Analysis of organ tissue slices at 250 microm resolution typically takes between 30 min and 2 h.

Ambient molecular imaging by desorption electrospray ionization mass spectrometry

ion. It has also been postulated that compounds can undergo direct Penning ionization with excited plasma species such as helium metastable atoms. Different classes of analytes will preferentially ionize through different mechanisms. For instance, many polar analytes will produce spectra consisting of strictly protonated molecular ions, MH + , indicating they undergo proton-transfer ionization, whereas nonpolar species, such as polycyclic aromatic hydrocarbons (PAHs), yield odd-electron molecular ions, M +· . In addition, sufficiently electronegative molecules, including halogenated or nitrated compounds, preferentially form negative ions through the Page 33 of 61 ACS Paragon Plus Environment Analytical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 34 mechanisms. In general, the observed ions and ionization pathways have been demonstrated to be similar to APCI and atmospheric-pressure photoionization. 163,164 Because these ionization processes rely on the formation of reagent species, differences in ionization with different plasmas can be extrapolated from background reagent-ion spectra. The DART source is an indirect plasma source which also filters any electrons and ions from the stream resulting in mostly lower energy reagent ions such as protonated water clusters, (H2O)nH + , and negative oxygen ions, O2 . 136 It was also shown that the reagent ions from DART could be altered by considerably changing source parameters, such as gas temperature and filter-electrode potentials. 165,166 In comparison, the quasidirect plasmas yield an abundance of higher-energy charge-transfer species, including N2 + , O2 + , and NO3 . 137,138 The higher energy FAPA discharge is capable of producing a significant amount of NO + . 149 The direct plasma methods can be capable of providing even higher energy reagent species, to the point where EI-like fragmentation spectra can

Andre R. Venter

Papers

Ambient desorption ionization mass spectrometry

Extractive electrospray ionization for direct analysis of undiluted urine, milk and other complex mixtures without sample preparation.

Droplet Dynamics and Ionization Mechanisms in Desorption Electrospray Ionization Mass Spectrometry

Ambient molecular imaging by desorption electrospray ionization mass spectrometry

Mechanisms of real-time, proximal sample processing during ambient ionization mass spectrometry.