Nanoscale secondary ion mass spectrometry

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NanoSIMS (nanoscale secondary ion mass spectrometry) is an analytical instrument manufactured by CAMECA which operates on the principle of secondary ion mass spectrometry. [1] The NanoSIMS is used to acquire nanoscale resolution measurements [2] of the elemental and isotopic composition of a sample. The NanoSIMS is able to create nanoscale maps of elemental or isotopic distribution, parallel acquisition of up to seven masses, isotopic identification, high mass resolution, subparts-per-million sensitivity with spatial resolution down to 50 nm. [3]

Contents

Simplified diagram of a NanoSims50 instrument. NanoSIMS50 instrument diagram.png
Simplified diagram of a NanoSims50 instrument.

The original design of the NanoSIMS instrument was conceived by Georges Slodzian at the University of Paris Sud in France and at the Office National d'Etudes et de Recherches Aérospatiales. [3] There are currently around 50 NanoSIMS instruments worldwide. [4]

How it works

The NanoSIMS uses an ion source to produce a primary beam of ions. These primary ions erode the sample surface and produce atomic collisions, some of these collisions result in the release of secondary ion particles. These ions are transmitted through a mass spectrometer, where the masses are measured and identified. [5] The primary ion beam is rastered across the sample surface and a ‘map’ of the element and isotope distribution is created by counting the number of ions that originated from each pixel with at best a 50 nanometer (nm) resolution, 10-50 times greater than conventional SIMS. [6] [7] This is achieved by positioning the primary probe in close proximity to the sample using a coaxial lens assembly. [7] The primary ion beam impacts the sample surface at 90°, with the secondary ions extracted back through the same lens assembly. This allows for the isotopic composition of individual cells to be distinguished at parts per million (ppm) or parts per billion (ppb) range. The main drawback of this set up is that the primary and secondary ion beams must be of opposite polarity which can limit which elements can be detected simultaneously.

NanoSIMS can detect minute mass differences between ions at the resolution of M/dM > 5000, where M is the nominal mass of the isotope and dM is the mass difference between the isotopes of interest. [8] The high mass resolution capabilities of NanoSIMS allows for different elements and their isotopes to be identified and spatially mapped in the sample, even if very close in mass. The mass spectrometer is capable of multicollection, meaning up to 5 (NanoSIMS 50) or 7 (NanoSIMS 50 L) masses can be simultaneously detected, from hydrogen to uranium, though with limitations. [5] [7] The relatively large number of masses helps eliminate measurement errors as possible changes in instrumental or sample conditions that may occur in between runs are avoided. [8]

The ion beam must either be set to detect negative or positive ions, commonly completed by using a cesium+ or oxygen- beam, respectively. [9] The high mass resolution achievable is particularly relevant to biological applications. For example, nitrogen is one of the most common elements in organisms. However, due to the low electron affinity of the nitrogen atom, the production of secondary ions is rare. Instead, molecules such as CN can be generated and measured. However, due to isotope combinations, such as the isobars 13C14N-, and 12C15N-, nearly identical molecular weights of 27.000 and 27.006 daltons, respectively, will be generated. Unlike other imaging techniques, where 13C14N and 12C15N cannot be independently measured due to nearly identical masses, NanoSIMS can safely distinguish the differences between these molecules allowing isotopic spiking experiments to be conducted. [9]

The physics of NanoSIMS

The magnetic sector mass spectrometer causes a physical separation of ions of a different mass-to-charge ratio. The physical separation of the secondary ions is caused by the Lorentz force when the ions pass through a magnetic field that is perpendicular to the velocity vector of the secondary ions. The Lorentz force states that a particle will experience a force

when it maintains a charge q and travels through an electric field E and magnetic field B with a velocity v. The secondary ions that leave the surface of the sample typically have a kinetic energy of a few electron volts (eV), although a rather small portion have been found to have energy of a few keV. An electrostatic field captures the secondary ions that leave the sample surface; these extracted ions are then transferred to a mass spectrometer. In order to achieve precise isotope measurements, there is a need for high transmission and high mass resolution. High transmission refers to the low loss of secondary ions between the sample surface and the detector, and high mass resolution refers to the ability to efficiently separate the secondary ions (or molecules of interest) from other ions and/or ions of similar mass. Primary ions will collide with the surface at a specific frequency per unit of surface area. The collision that occurs causes atoms to sputter from the sample surface, and of these atoms only a small amount will undergo ionization. These become secondary ions, which are then detected after transfer through the mass spectrometer. Each primary ion generates a number of secondary ions of an isotope that will reach the detector to be counted. The count rate is determined by

where I(iM)is the count rate of the isotope iM of element M. The counting rate of the isotope is dependent on the concentration, XM and the element's isotopic abundance, denoted Ai. Because the primary ion beam determines the secondary ions, Y, that are sputtered, the density of the primary ion beam, db, which is defined as the amount of ions per second per unit of surface area, will affect a portion of the surface area of the sample, S, with an even distribution of the primary ions. Of the sputtered secondary ions, there is only a fraction that will be ionized, Yi. The probability that any ion will be successfully transferred from mass spectrometer to detector is T. The product of Yi and T determines the amount of isotopes that will be ionized, as well as detected, so it is considered the useful yield. [10]

Sample preparation

Sample preparation is one of the most critical steps in NanoSIMS analysis, particularly when analysing biological samples. [11] Specific protocols should be developed for individual experiments in order to best preserve not only the structure of the sample but also the true spatial distribution and abundance of molecules within the sample. As the NanoSIMS operates under ultra high vacuum, the sample must be vacuum compatible (i.e., volatile free), flat, which reduces varying ionization trajectories, and conductive, which can be accomplished by sputter coating with Au, Pt, or C. Biological samples, such as cells or tissue, can be prepared with chemical fixation or cryo-fixation and embedded in a resin before sectioning into thin slices (100 nm - 1μm), and placed on silicon wafers or slides for analysis. [11] Sample preparation for metallographic samples is generally much simpler but a very good metallographic polish is required to achieve a flat, scratch free surface. [4]

Applications

NanoSIMS can capture the spatial variability of isotopic and elemental measurements of sub-micron areas, grains or inclusions from geological, materials science and biological samples. [12] This instrument can characterise nanostructured materials with complex composition that are increasingly important candidates for energy generation and storage.

Geological applications

NanoSIMS has also proved useful in studying cosmochemical issues, where samples of single, micro- or sub-micrometer-sized grains from meteorites as well as microtome sections prepared by the focused ion beam (FIB) technique can be analyzed. NanoSIMS can be combined with transmission electron microscopy (TEM) when using microtome or FIB sections. This combination allows for correlated mineralogical and isotopic studies in situ at a sub-micrometer scale.

It is particularly useful in materials research because of its high sensitivity at high mass resolution, which allow for trace element imaging and quantification. [13]

Biological applications

Initially developed for geochemical and related research, NanoSIMS is now utilized by a wide variety of fields, including biology and microbiology. In biomedical research, [2] NanoSIMS is also referred to as multi-isotope imaging mass spectrometry (MIMS). [14] The 50 nm resolution allows unprecedented resolution of cellular and sub-cellular features (as reference, the model organism E. coli is typically 1,000 to 2,000 nm in diameter). The high resolution that it offers allows intracellular measurement of accumulations and fluxes of molecules containing various stable isotopes. [15] NanoSIMS can be used for pure cultures, co-cultures, and mixed community samples. [8]

The first use of NanoSIMS in biology was by Peteranderl and Lechene in 2004, who used a prototype of NanoSIMS to examine and measure carbon and nitrogen isotopes of eukaryotic cells. This study was the first time that carbon and nitrogen isotope ratios were directly measured at a sub-cellular scale in a biological sample. [16]

Pharmacology applications

The development of NanoSIMS for organo-metallic drugs paved the way for exploring the distribution of biologically active molecules at the subcellular level. Legin et al. [17] combined NanoSIMS with fluorescence confocal laser scanning microscopy to characterize the subcellular distribution of 15N isotopically labeled Pt-bearing cisplatin in human colon cancer cells. Cisplatin appears in the targeted nucleus of the colon cancer cells. 15N and Pt are separated showing subcellular metabolism is in the path of action. The internalization of amiodarone into the lysosomes of macrophages is illustrated in Jiang et al. [18] Thanks to low detection limit, two iodine atoms of 127I in amiodarone molecule enables a label-free imaging by NanoSIMS. Iodine and phosphorus imaging along with plotting the intensity of 127I- vs 31P- indicated a linear relationship between the amount of iodine and phospholipids. These results disclose evidence of amiodarone-induced phospholipidosis.

He et al. [19] visualized the distribution of therapeutic antisense oligonucleotides labelled with bromine (Br-ASO) in some varieties of cultured cells and importantly mouse tissues (heart, kidney, and Liver) using NanoSIMS data combined with back scattered electron microscopy. They demonstrated that phosphorothioate ASOs associate with filopodia and the inner nuclear membrane of cells. They also documented essential cellular and subcellular heterogeneity in ASO distribution in the mouse tissues. Becquart et al. [20] report absolute concentration of Antisense Oligonucleotide therapeutics in human hepatocytes. Their method built upon work in Thomen et al. [21] where they reported the absolute concentration of the prodrug 13C labeled L-dopa.

Materials science applications

The NanoSIMS has been used in many different areas of materials science. [4] It is able to map hydrogen and deuterium at microstructurally relevant scales which is important for studies of hydrogen embrittlement in metals [22] although there are significant challenges associated with accurately detecting hydrogen and deuterium. [23]

Methods commonly coupled with NanoSIMS

Microscopy

Other microscopy techniques are commonly used in tandem with NanoSIMS that allow for multiple types of information to be obtained, such as taxonomic information through fluorescence in situ hybridization (FISH) [24] or identification of additional physiological or microstructural features via transmission electron microscopy (TEM) or scanning electron microscopy (SEM).

Immunogold labeling

Traditional methods that are used to label and identify subcellular features of cells, such as immunogold labeling, can also be used with NanoSIMS analysis. Immunogold labeling uses antibodies to target specific proteins, and subsequently labels the antibodies with gold nano particles. The NanoSIMS instrument can detect the gold particles, providing the location of the labelled proteins at a high scale resolution. Gold-containing or platinum-containing compounds used as anticancer drugs were imaged using NanoSIMS to examine the subcellular distribution in breast cancer and colon cancer cells, respectively. [25] In a separate study, antibody-antigen binding was studied without the need for a fluorescent label to be added to the antibody, allowing for label-free localization and quantitative analysis at a high resolution. [26]

Stable isotope labeling

NanoSIMS analysis of a diatom and bacteria (white arrow) provided with stable isotope labeled N nitrate. In panels a-e, dark blue represents low counts of each isotope, and yellow is high counts. The bacteria, but not the diatom, incorporated the heavy N, as seen in panel c. The natural N to N ratio is 0.04. Any ratio above this indicates the organism incorporated the N nitrate into their organic matter. The natural differences in S abundance between the bacteria and diatom can also be seen (panel d), along with the Si signal of the frustule of the diatom, made of silica (panel e). Panel f is a fluorescence of the same diatom. The red box indicates the same view seen in panels a-e. Each nanoSIMS image is 50 mm by 50 mm. Image provided by the International Geobiology Training Course and Orphan Lab, Caltech. NanoSIMS figure1.jpg
NanoSIMS analysis of a diatom and bacteria (white arrow) provided with stable isotope labeled N nitrate. In panels a-e, dark blue represents low counts of each isotope, and yellow is high counts. The bacteria, but not the diatom, incorporated the heavy N, as seen in panel c. The natural N to N ratio is 0.04. Any ratio above this indicates the organism incorporated the N nitrate into their organic matter. The natural differences in S abundance between the bacteria and diatom can also be seen (panel d), along with the Si signal of the frustule of the diatom, made of silica (panel e). Panel f is a fluorescence of the same diatom. The red box indicates the same view seen in panels a-e. Each nanoSIMS image is 50 μm by 50 μm. Image provided by the International Geobiology Training Course and Orphan Lab, Caltech.

Another common technique typically used in NanoSIMS analysis is stable isotope probing. This method involves the introduction of stable isotopically labelled biologically relevant compounds to organisms for consumption and integration into organic matter. When analyzed via NanoSIMS, the technique is referred to as nanoSIP. [27] NanoSIMS can be used to detect which organisms incorporated which molecules, how much of the labeled molecules was incorporated in a semi-quantitative manner, and where in the cell the incorporation occurred. Previous quantitative analysis techniques at a lower resolution than NanoSIMS of stable isotopically labeled molecules was limited to analyzed bulk material, which did not allow for insights about the contributions of individual cells or subcellular compartments to be made. [28] Additionally, the removal of large foreign molecules (such as antibodies or gold particles) from the experimental setup alleviates concerns that tagged molecules required for other microscopy techniques may have different biochemical responses or properties than normal.

This technique can be used to study nutrient exchange. The mouse gut microbiome was investigated to determine which microbes fed on host-derived compounds. For this, mice were given food enriched in the stable isotopically labelled amino acids and the microbial biomass examined. [29] NanoSIMS allows for the metabolic contributions of individual microbes to be examined. NanoSIMS was used to study and prove for the first time the nitrogen fixing abilities of bacteria and archaea from the deep ocean by supplying 15N nitrogen contain compounds to sediment samples. [30] NanoSIMS can also be used to estimate growth rate of organisms, as the amount of carbon or other substrate accumulated inside the cell allows for estimation of how much biomass is being generated. [31]

Measuring natural isotope abundances in organisms

Organic material naturally contains stable isotopes at different ratios in the environment, which can provide information on the origin of the food source for the organisms. Different types of organic material of food sources has different amounts of stable isotopes, which is reflected in the composition of the organism that eats these food sources. [32] This type of analysis was first used in 2001 in conjunction with FISH to examine syntrophic relationships between anaerobic methane-oxidizing archaea and sulfate reducing bacteria. [33] Isotopes with naturally low abundances may not be able to be detected with this method.

Paleobiology

NanoSIMS can also be used to examine the elemental and isotopic composition of microparticles preserved in the rock record. [6] The types of elements and isotopic ratios can help determine if the material is of biological origin. [8] NanoSIMS was first used in this field of paleobiology in 2005 by Robert et al. [34] In this study, microfossils were found to contain carbon, nitrogen, and sulfur elements arranged as ‘globules’ that were reminiscent of cell walls. The ratio of carbon to nitrogen measured also served as an indicator of biological origin, as the rock surrounding the fossils had very different C to N ratios. [6]

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<span class="mw-page-title-main">Electron microscope</span> Type of microscope with electrons as a source of illumination

An electron microscope is a microscope that uses a beam of electrons as a source of illumination. They use electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing them to produce magnified images or electron diffraction patterns. As the wavelength of an electron can be up to 100,000 times smaller than that of visible light, electron microscopes have a much higher resolution of about 0.1 nm, which compares to about 200 nm for light microscopes. Electron microscope may refer to:

<span class="mw-page-title-main">Mass spectrometry</span> Analytical technique based on determining mass to charge ratio of ions

Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a mass spectrum, a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used in many different fields and is applied to pure samples as well as complex mixtures.

<span class="mw-page-title-main">Ion source</span> Device that creates charged atoms and molecules (ions)

An ion source is a device that creates atomic and molecular ions. Ion sources are used to form ions for mass spectrometers, optical emission spectrometers, particle accelerators, ion implanters and ion engines.

<span class="mw-page-title-main">Electron ionization</span> Ionization technique

Electron ionization is an ionization method in which energetic electrons interact with solid or gas phase atoms or molecules to produce ions. EI was one of the first ionization techniques developed for mass spectrometry. However, this method is still a popular ionization technique. This technique is considered a hard ionization method, since it uses highly energetic electrons to produce ions. This leads to extensive fragmentation, which can be helpful for structure determination of unknown compounds. EI is the most useful for organic compounds which have a molecular weight below 600 amu. Also, several other thermally stable and volatile compounds in solid, liquid and gas states can be detected with the use of this technique when coupled with various separation methods.

<span class="mw-page-title-main">Secondary ion mass spectrometry</span> Surface chemical analysis and imaging method

Secondary-ion mass spectrometry (SIMS) is a technique used to analyze the composition of solid surfaces and thin films by sputtering the surface of the specimen with a focused primary ion beam and collecting and analyzing ejected secondary ions. The mass/charge ratios of these secondary ions are measured with a mass spectrometer to determine the elemental, isotopic, or molecular composition of the surface to a depth of 1 to 2 nm. Due to the large variation in ionization probabilities among elements sputtered from different materials, comparison against well-calibrated standards is necessary to achieve accurate quantitative results. SIMS is the most sensitive surface analysis technique, with elemental detection limits ranging from parts per million to parts per billion.

<span class="mw-page-title-main">Metabolomics</span> Scientific study of chemical processes involving metabolites

Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles. The metabolome represents the complete set of metabolites in a biological cell, tissue, organ, or organism, which are the end products of cellular processes. Messenger RNA (mRNA), gene expression data, and proteomic analyses reveal the set of gene products being produced in the cell, data that represents one aspect of cellular function. Conversely, metabolic profiling can give an instantaneous snapshot of the physiology of that cell, and thus, metabolomics provides a direct "functional readout of the physiological state" of an organism. There are indeed quantifiable correlations between the metabolome and the other cellular ensembles, which can be used to predict metabolite abundances in biological samples from, for example mRNA abundances. One of the ultimate challenges of systems biology is to integrate metabolomics with all other -omics information to provide a better understanding of cellular biology.

<span class="mw-page-title-main">Fluorescence microscope</span> Optical microscope that uses fluorescence and phosphorescence

A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence microscope" refers to any microscope that uses fluorescence to generate an image, whether it is a simple set up like an epifluorescence microscope or a more complicated design such as a confocal microscope, which uses optical sectioning to get better resolution of the fluorescence image.

<span class="mw-page-title-main">Matrix-assisted laser desorption/ionization</span> Ionization technique

In mass spectrometry, matrix-assisted laser desorption/ionization (MALDI) is an ionization technique that uses a laser energy-absorbing matrix to create ions from large molecules with minimal fragmentation. It has been applied to the analysis of biomolecules and various organic molecules, which tend to be fragile and fragment when ionized by more conventional ionization methods. It is similar in character to electrospray ionization (ESI) in that both techniques are relatively soft ways of obtaining ions of large molecules in the gas phase, though MALDI typically produces far fewer multi-charged ions.

<span class="mw-page-title-main">Fast atom bombardment</span>

Fast atom bombardment (FAB) is an ionization technique used in mass spectrometry in which a beam of high energy atoms strikes a surface to create ions. It was developed by Michael Barber at the University of Manchester in 1980. When a beam of high energy ions is used instead of atoms, the method is known as liquid secondary ion mass spectrometry (LSIMS). In FAB and LSIMS, the material to be analyzed is mixed with a non-volatile chemical protection environment, called a matrix, and is bombarded under vacuum with a high energy atomic beam. The atoms are typically from an inert gas such as argon or xenon. Common matrices include glycerol, thioglycerol, 3-nitrobenzyl alcohol (3-NBA), 18-crown-6 ether, 2-nitrophenyloctyl ether, sulfolane, diethanolamine, and triethanolamine. This technique is similar to secondary ion mass spectrometry and plasma desorption mass spectrometry.

<span class="mw-page-title-main">Focused ion beam</span> Device

Focused ion beam, also known as FIB, is a technique used particularly in the semiconductor industry, materials science and increasingly in the biological field for site-specific analysis, deposition, and ablation of materials. A FIB setup is a scientific instrument that resembles a scanning electron microscope (SEM). However, while the SEM uses a focused beam of electrons to image the sample in the chamber, a FIB setup uses a focused beam of ions instead. FIB can also be incorporated in a system with both electron and ion beam columns, allowing the same feature to be investigated using either of the beams. FIB should not be confused with using a beam of focused ions for direct write lithography. These are generally quite different systems where the material is modified by other mechanisms.

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<span class="mw-page-title-main">Desorption electrospray ionization</span>

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Mass spectrometry imaging (MSI) is a technique used in mass spectrometry to visualize the spatial distribution of molecules, as biomarkers, metabolites, peptides or proteins by their molecular masses. After collecting a mass spectrum at one spot, the sample is moved to reach another region, and so on, until the entire sample is scanned. By choosing a peak in the resulting spectra that corresponds to the compound of interest, the MS data is used to map its distribution across the sample. This results in pictures of the spatially resolved distribution of a compound pixel by pixel. Each data set contains a veritable gallery of pictures because any peak in each spectrum can be spatially mapped. Despite the fact that MSI has been generally considered a qualitative method, the signal generated by this technique is proportional to the relative abundance of the analyte. Therefore, quantification is possible, when its challenges are overcome. Although widely used traditional methodologies like radiochemistry and immunohistochemistry achieve the same goal as MSI, they are limited in their abilities to analyze multiple samples at once, and can prove to be lacking if researchers do not have prior knowledge of the samples being studied. Most common ionization technologies in the field of MSI are DESI imaging, MALDI imaging, secondary ion mass spectrometry imaging and Nanoscale SIMS (NanoSIMS).

<span class="mw-page-title-main">Ambient ionization</span>

Ambient ionization is a form of ionization in which ions are formed in an ion source outside the mass spectrometer without sample preparation or separation. Ions can be formed by extraction into charged electrospray droplets, thermally desorbed and ionized by chemical ionization, or laser desorbed or ablated and post-ionized before they enter the mass spectrometer.

<span class="mw-page-title-main">Raman microscope</span> Laser microscope used for Raman spectroscopy

The Raman microscope is a laser-based microscopic device used to perform Raman spectroscopy. The term MOLE is used to refer to the Raman-based microprobe. The technique used is named after C. V. Raman, who discovered the scattering properties in liquids.

<span class="mw-page-title-main">Laser ablation electrospray ionization</span>

Laser ablation electrospray ionization (LAESI) is an ambient ionization method for mass spectrometry that combines laser ablation from a mid-infrared (mid-IR) laser with a secondary electrospray ionization (ESI) process. The mid-IR laser is used to generate gas phase particles which are then ionized through interactions with charged droplets from the ESI source. LAESI was developed in Professor Akos Vertes lab by Peter Nemes in 2007 and it was marketed commercially by Protea Biosciences, Inc until 2017. Fiber-LAESI for single-cell analysis approach was developed by Bindesh Shrestha in Professor Vertes lab in 2009. LAESI is a novel ionization source for mass spectrometry (MS) that has been used to perform MS imaging of plants, tissues, cell pellets, and even single cells. In addition, LAESI has been used to analyze historic documents and untreated biofluids such as urine and blood. The technique of LAESI is performed at atmospheric pressure and therefore overcomes many of the obstacles of traditional MS techniques, including extensive and invasive sample preparation steps and the use of high vacuum. Because molecules and aerosols are ionized by interacting with an electrospray plume, LAESI's ionization mechanism is similar to SESI and EESI techniques.

<span class="mw-page-title-main">Single-cell analysis</span> Testbg biochemical processes and reactions in an individual cell

In the field of cellular biology, single-cell analysis and subcellular analysis is the study of genomics, transcriptomics, proteomics, metabolomics and cell–cell interactions at the single cell level. The concept of single-cell analysis originated in the 1970s. Before the discovery of heterogeneity, single-cell analysis mainly referred to the analysis or manipulation of an individual cell in a bulk population of cells at a particular condition using optical or electronic microscope. To date, due to the heterogeneity seen in both eukaryotic and prokaryotic cell populations, analyzing a single cell makes it possible to discover mechanisms not seen when studying a bulk population of cells. Technologies such as fluorescence-activated cell sorting (FACS) allow the precise isolation of selected single cells from complex samples, while high throughput single cell partitioning technologies, enable the simultaneous molecular analysis of hundreds or thousands of single unsorted cells; this is particularly useful for the analysis of transcriptome variation in genotypically identical cells, allowing the definition of otherwise undetectable cell subtypes. The development of new technologies is increasing our ability to analyze the genome and transcriptome of single cells, as well as to quantify their proteome and metabolome. Mass spectrometry techniques have become important analytical tools for proteomic and metabolomic analysis of single cells. Recent advances have enabled quantifying thousands of protein across hundreds of single cells, and thus make possible new types of analysis. In situ sequencing and fluorescence in situ hybridization (FISH) do not require that cells be isolated and are increasingly being used for analysis of tissues.

<span class="mw-page-title-main">Nanospray desorption electrospray ionization</span> Technique used in mass spectrometry

Nanospray desorption electrospray ionization (nano-DESI) is an ambient pressure ionization technique used in mass spectrometry (MS) for chemical analysis of organic molecules. In this technique, analytes are desorbed into a liquid bridge formed between two capillaries and the sampling surface. Unlike desorption electrospray ionization (DESI), from which nano-DESI is derived, nano-DESI makes use of a secondary capillary, which improves the sampling efficiency.

<span class="mw-page-title-main">Matrix-assisted ionization</span>

In mass spectrometry, matrix-assisted ionization is a low fragmentation (soft) ionization technique which involves the transfer of particles of the analyte and matrix sample from atmospheric pressure (AP) to the heated inlet tube connecting the AP region to the vacuum of the mass analyzer.

References

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