Soft Ionization by Chemical Reaction in Transfer

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Soft Ionization by Chemical Reaction in Transfer is a method for ionizing small organic compounds at ambient atmospheric pressure. It is used for ion generation in mass spectrometers (MS).

Contents

The technique is often abbreviated as SICRIT, a trademark of Plasmion GmbH, [1] which commercialized the technique in the 2020s. [2]

Ionization technique

Sicrit ionizes molecules through a technique known as dielectric barrier discharge. This process involves creating an electrical discharge between two electrodes that are separated by a dielectric. The electrodes are a stainless-steel tube placed inside a copper tube, with a thin quartz tube separating them. The sample containing the molecules to be ionized flows through the quartz tube separating the electrodes. A voltage is applied to the electrodes; the resulting electrical discharge ignites a cold plasma which ionizes the sample. [3]

Unlike other ambient ionization methods such as DART, DAPPI or DESI, SICRIT takes place directly in line with the inlet system of the MS and thus in a continuous flow:

Conventional ionization technologies compared to the SICRIT technology Abbildung 1- Vergleich konventionelle Ionisationstechnologien und SICRIT Technologie.png
Conventional ionization technologies compared to the SICRIT technology

Several reaction pathways have been identified that lead to ionization during this process: [4]

Regardless of the specific reaction pathway, almost exclusively protonated species [M+H]+ are generated during ionization.

Since the analytes do not come into direct contact with the plasma during ionization, but rather charge transfer occurs via reactive species and UV radiation, the molecules remain intact and fragmentation is avoided. Consequently, SICRIT is a very "soft" ionization method.

Characteristics

The SICRIT technology decouples sample delivery from the ionization process. Through the flow principle, the sample is directly drawn into the high vacuum behind the MS inlet and ionized on its way into the inlet. The electrode geometry is chosen so that, under the given physical parameters (pressure, ignition voltage, gas constant, see Paschen's law), flexibility regarding the plasma medium is ensured. This allows the generation of stable cold plasma even in ambient air. In the simplest application, ambient air can be directly analyzed.

Ionization in flow enables high ion transmission since ion loss is significantly reduced compared to the most commonly used spraying methods in mass spectrometry (cf. ESI, APCI). Consequently, this leads to an increase in sensitivity compared to these methods.

Ionization in flow also allows for real-time measurement without the need for sample preparation. Simple screening applications, especially for volatile organic compound analysis, can be easily implemented since the usual sample preparation (including crushing, extraction, purification, etc.) becomes obsolete for simple screening applications.

The different reaction pathways in plasma ionization broaden the spectrum of ionizable substances. This means that compared to ionization methods that only allow for single reaction pathways, a wider polarity range of analytes is covered, and nonpolar substances such as hexane can be ionized.

The low fragmentation ionization allows for identification based on the molecular mass as protonated [M+H]+ species. This can be particularly useful in combination with high-resolution mass spectrometers such as time-of-flight mass spectrometers (TOF-MS) or Orbitrap-MS for non-target analysis, where the entire substance spectrum of a sample is captured based on the exact mass of the molecules. [5]

Thus, SICRIT can be used in combination with both liquid chromatography (LC) as well as gas chromatography (GC). This enables the performance of both LC-MS and GC-MS analyses on the same mass spectrometer and the establishment of a unified database for comparing data from these otherwise instrumentally separated separation and detection methods.

Instruments and application

Direct screening

As ambient ionization, SICRIT technology enables direct, real-time gas phase measurement using a mass spectrometer. The sample is positioned directly in front of the SICRIT source without any preparation. One application area is the measurement of aromatic compounds. [6]

Chromatography couplings

The SICRIT ion source allows for coupling with various types of chromatography (GC, HPLC, SFC, etc.) as interface technology to any atmospheric pressure mass spectrometer (LC-MS). The ionization with its characteristics (see above) is not influenced by the coupling, allowing the same ionization method to be used for different chromatography couplings. The ability to couple gas chromatography with a low-fragmentation ionization technique on an LC-MS, for example, can be utilized in the analysis of saturated hydrocarbons. Electron impact ionization commonly used in GC-MS leads to difficult-to-interpret fragmentation spectra, while plasma ionization provides fragmentation-free spectra. [7] Thus, the DBD plasma with its broad ionization range opens up new fields of application possibilities for LC mass spectrometers in residue analysis, such as pesticides, where gas chromatographic separation is the method of choice and plasma ionization achieves very low detection limits. [8]

Chemical imaging

In combination with appropriate sample preparation and instrumentation, the SICRIT ion source can also be used for imaging mass spectrometry. The standard procedure typically involves elaborate sample preparation combined with laser desorption/ionization (e.g., MALDI or atmospheric pressure MALDI), allowing spatial visualization of biomolecules, for example, in tissue sections. [9]

The use of the SICRIT source for additional in-line post-ionization in AP-MALDI experiments can result in significant signal enhancement in the detection of metabolites in biological sample material or enables detection of small (bio)molecules that are not addressable using MALDI alone. [9]

Figure 2: MS Imaging with SICRIT Post-Ionization after AP-MALDI SICRIT-Postionization AP-MALDI Imaging.png
Figure 2: MS Imaging with SICRIT Post-Ionization after AP-MALDI

Furthermore, the SICRIT ion source enables spatially resolved analysis of unprepared samples in laser ablation experiments (cf. Fig. 3). The analytes released by laser bombardment are ionized directly with the SICRIT ion source, and the spatially resolved data are translated into two-dimensional images. This provides information, for example, on the distribution of active ingredients in tablets. [10]

Figure 3: MS Imaging with SICRIT Post-Ionization after High-Resolution Laser Ablation SICRIT Postionization High resolution Laser ablation imaging.png
Figure 3: MS Imaging with SICRIT Post-Ionization after High-Resolution Laser Ablation

Cell analysis

In combination with a flow cytometer, the SICRIT ion source also enables the analysis of individual cells. The separated cell is introduced into the mass spectrometer through the ion source, and the lysate released upon cell rupture is analyzed. More precisely, the molecules contained in the lysate (mostly lipids) are ionized.

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<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">Gas chromatography–mass spectrometry</span> Analytical method

Gas chromatography–mass spectrometry (GC–MS) is an analytical method that combines the features of gas-chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC–MS include drug detection, fire investigation, environmental analysis, explosives investigation, food and flavor analysis, and identification of unknown samples, including that of material samples obtained from planet Mars during probe missions as early as the 1970s. GC–MS can also be used in airport security to detect substances in luggage or on human beings. Additionally, it can identify trace elements in materials that were previously thought to have disintegrated beyond identification. Like liquid chromatography–mass spectrometry, it allows analysis and detection even of tiny amounts of a substance.

<span class="mw-page-title-main">Chemical ionization</span> Technique in mass spectroscopy

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<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">Liquid chromatography–mass spectrometry</span> Analytical chemistry technique

Liquid chromatography–mass spectrometry (LC–MS) is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry (MS). Coupled chromatography – MS systems are popular in chemical analysis because the individual capabilities of each technique are enhanced synergistically. While liquid chromatography separates mixtures with multiple components, mass spectrometry provides spectral information that may help to identify each separated component. MS is not only sensitive, but provides selective detection, relieving the need for complete chromatographic separation. LC–MS is also appropriate for metabolomics because of its good coverage of a wide range of chemicals. This tandem technique can be used to analyze biochemical, organic, and inorganic compounds commonly found in complex samples of environmental and biological origin. Therefore, LC–MS may be applied in a wide range of sectors including biotechnology, environment monitoring, food processing, and pharmaceutical, agrochemical, and cosmetic industries. Since the early 2000s, LC–MS has also begun to be used in clinical applications.

<span class="mw-page-title-main">Atmospheric-pressure chemical ionization</span> Ionization method

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

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

Desorption electrospray ionization (DESI) is an ambient ionization technique that can be coupled to mass spectrometry (MS) for chemical analysis of samples at atmospheric conditions. Coupled ionization sources-MS systems are popular in chemical analysis because the individual capabilities of various sources combined with different MS systems allow for chemical determinations of samples. DESI employs a fast-moving charged solvent stream, at an angle relative to the sample surface, to extract analytes from the surfaces and propel the secondary ions toward the mass analyzer. This tandem technique can be used to analyze forensics analyses, pharmaceuticals, plant tissues, fruits, intact biological tissues, enzyme-substrate complexes, metabolites and polymers. Therefore, DESI-MS may be applied in a wide variety of sectors including food and drug administration, pharmaceuticals, environmental monitoring, and biotechnology.

Sample preparation for mass spectrometry is used for the optimization of a sample for analysis in a mass spectrometer (MS). Each ionization method has certain factors that must be considered for that method to be successful, such as volume, concentration, sample phase, and composition of the analyte solution. Quite possibly the most important consideration in sample preparation is knowing what phase the sample must be in for analysis to be successful. In some cases the analyte itself must be purified before entering the ion source. In other situations, the matrix, or everything in the solution surrounding the analyte, is the most important factor to consider and adjust. Often, sample preparation itself for mass spectrometry can be avoided by coupling mass spectrometry to a chromatography method, or some other form of separation before entering the mass spectrometer. In some cases, the analyte itself must be adjusted so that analysis is possible, such as in protein mass spectrometry, where usually the protein of interest is cleaved into peptides before analysis, either by in-gel digestion or by proteolysis in solution.

<span class="mw-page-title-main">Ion-mobility spectrometry–mass spectrometry</span>

Ion mobility spectrometry–mass spectrometry (IMS-MS) is an analytical chemistry method that separates gas phase ions based on their interaction with a collision gas and their masses. In the first step, the ions are separated according to their mobility through a buffer gas on a millisecond timescale using an ion mobility spectrometer. The separated ions are then introduced into a mass analyzer in a second step where their mass-to-charge ratios can be determined on a microsecond timescale. The effective separation of analytes achieved with this method makes it widely applicable in the analysis of complex samples such as in proteomics and metabolomics.

<span class="mw-page-title-main">Desorption atmospheric pressure photoionization</span>

Desorption atmospheric pressure photoionization (DAPPI) is an ambient ionization technique for mass spectrometry that uses hot solvent vapor for desorption in conjunction with photoionization. Ambient Ionization techniques allow for direct analysis of samples without pretreatment. The direct analysis technique, such as DAPPI, eliminates the extraction steps seen in most nontraditional samples. DAPPI can be used to analyze bulkier samples, such as, tablets, powders, resins, plants, and tissues. The first step of this technique utilizes a jet of hot solvent vapor. The hot jet thermally desorbs the sample from a surface. The vaporized sample is then ionized by the vacuum ultraviolet light and consequently sampled into a mass spectrometer. DAPPI can detect a range of both polar and non-polar compounds, but is most sensitive when analyzing neutral or non-polar compounds. This technique also offers a selective and soft ionization for highly conjugated compounds.

<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">Triple quadrupole mass spectrometer</span> Type of mass spectrometer

A triple quadrupole mass spectrometer (TQMS), is a tandem mass spectrometer consisting of two quadrupole mass analyzers in series, with a (non-mass-resolving) radio frequency (RF)–only quadrupole between them to act as a cell for collision-induced dissociation. This configuration is often abbreviated QqQ, here Q1q2Q3.

Electrostatic spray ionization (ESTASI) is an ambient ionization method for mass spectrometry (MS) analysis of samples located on a flat or porous surface, or inside a microchannel. It was developed in 2011 by Professor Hubert H. Girault’s group at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. In a typical ESTASI process, a droplet of a protic solvent containing analytes is deposited on a sample area of interest which itself is mounted to an insulating substrate. Under this substrate and right below the droplet, an electrode is placed and connected with a pulsed high voltage (HV) to electrostatically charge the droplet during pulsing. When the electrostatic pressure is larger than the surface tension, droplets and ions are sprayed. ESTASI is a contactless process based on capacitive coupling. One advantage of ESTASI is, that the electrode and sample droplet act contact-less avoiding thereby any oxidation or reduction of the sample compounds at the electrode surface, which often happens during standard electrospray ionization (ESI). ESTASI is a powerful new ambient ionization technique that has already found many applications in the detection of different analytes, such as organic molecules, peptides and proteins with molecule weight up to 70 kDa. Furthermore, it was used to couple MS with various separation techniques including capillary electrophoresis and gel isoelectric focusing, and it was successfully applied under atmospheric pressure to the direct analysis of samples with only few preparation steps.

<span class="mw-page-title-main">Atmospheric-pressure photoionization</span> Soft ionization method

Atmospheric pressure photoionization (APPI) is a soft ionization method used in mass spectrometry (MS) usually coupled to liquid chromatography (LC). Molecules are ionized using a vacuum ultraviolet (VUV) light source operating at atmospheric pressure, either by direct absorption followed by electron ejection or through ionization of a dopant molecule that leads to chemical ionization of target molecules. The sample is usually a solvent spray that is vaporized by nebulization and heat. The benefit of APPI is that it ionizes molecules across a broad range of polarity and is particularly useful for ionization of low polarity molecules for which other popular ionization methods such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are less suitable. It is also less prone to ion suppression and matrix effects compared to ESI and APCI and typically has a wide linear dynamic range. The application of APPI with LC/MS is commonly used for analysis of petroleum compounds, pesticides, steroids, and drug metabolites lacking polar functional groups and is being extensively deployed for ambient ionization particularly for explosives detection in security applications.

<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.

<span class="mw-page-title-main">Laser diode thermal desorption</span>

Laser diode thermal desorption (LDTD) is an ionization technique that is coupled to mass spectrometry to analyze samples with atmospheric pressure chemical ionization (APCI). It uses a laser to thermally desorb analytes that are deposited on a stainless steel sheet sample holder, called LazWell. The coupling of LDTD and APCI is considered to be a soft-ionization technique. With LDTD-APCI, it is possible to analyze samples in forensics, pharmaceuticals, environment, food and clinical studies. LDTD is suitable for small molecules between 0 and 1200 Da and some peptides such as cyclosporine.

References

  1. ↑ "EUTM eRegister: 018821175 - SICRIT". European Union Intellectual Property Office . Retrieved 2024-10-13.
  2. ↑ "Agilent Technologies and Plasmion Collaborate". The Column. March 2023. 19 (3): 8. 2023-03-08.
  3. ↑ Thaler, Klemens M.; Gilardi, Lorenza; Weber, Markus; Vohburger, Andreas; Toumasatos, Zisimos; Kontses, Anastasios; Samaras, Zissis; Kalliokoski, Joni; Simonen, Pauli; Timonen, Hilkka; Aurela, Minna; Saarikoski, Sanna; Martikainen, Sampsa; Karjalainen, Panu; Dal Maso, Miikka (2021-08-03). "HELIOS/SICRIT/mass spectrometry for analysis of aerosols in engine exhaust". Aerosol Science and Technology. 55 (8): 886–900. doi:10.1080/02786826.2021.1909699. ISSN   0278-6826.
  4. ↑ Jan-Christoph Wolf, Luzia Gyr, Mario F. Mirabelli, Martin Schaer, Peter Siegenthaler, Renato Zenobi: A Radical-Mediated Pathway for the Formation of [M + H] + in Dielectric Barrier Discharge Ionization. In: Journal of the American Society for Mass Spectrometry. Volume 27, No. 9, September 1, 2016, ISSN 1044-0305, p. 1468–1475, doi:10.1007/s13361-016-1420-2.
  5. ↑ Markus Weber, Jan-Christoph Wolf, Christoph Haisch: Effect of Dopants and Gas-Phase Composition on Ionization Behavior and Efficiency in Dielectric Barrier Discharge Ionization. In: Journal of the American Society for Mass Spectrometry. Volume 34, No. 4, 2023, ISSN 1044-0305, p. 538–549, doi:10.1021/jasms.2c00279.
  6. ↑ Klaus Wutz: Elektronische Nase und der Duft von Kaffee. In: Nachrichten aus der Chemie. Volume 66, No. 10, 2018, ISSN 1439-9598, p. 985–987, doi:10.1002/nadc.20184080389 (nfm-mediashop.de [PDF]).
  7. ↑ Markus Weber, Jan-Christoph Wolf, Christoph Haisch: Gas Chromatography–Atmospheric Pressure Inlet–Mass Spectrometer Utilizing Plasma-Based Soft Ionization for the Analysis of Saturated, Aliphatic Hydrocarbons. In: Journal of the American Society for Mass Spectrometry. Volume 32, No. 7, July 7, 2021, ISSN 1044-0305, p. 1707–1715, doi:10.1021/jasms.0c00476.
  8. ↑ Juan F. Ayala-Cabrera, Lidia Montero, Sven W. Meckelmann, Florian Uteschil, Oliver J. Schmitz: Review on atmospheric pressure ionization sources for gas chromatography-mass spectrometry. Part I: Current ion source developments and improvements in ionization strategies. In: Analytica Chimica Acta. Volume 1238, January 15, 2023, ISSN 0003-2670, p. 340353, doi:10.1016/j.aca.2022.340353.
  9. 1 2 Efstathios A. Elia, Marcel Niehaus, Rory T. Steven, Jan-Christoph Wolf, Josephine Bunch: Atmospheric Pressure MALDI Mass Spectrometry Imaging Using In-Line Plasma Induced Postionization. In: Analytical Chemistry. Volume 92, No. 23, 2020, ISSN 0003-2700, p. 15285–15290, doi:10.1021/acs.analchem.0c03524.
  10. ↑ Sabrina K. I. Funke, Valérie A. Brückel, Markus Weber, Elias Lützen, Jan-Christoph Wolf, Christoph Haisch, Uwe Karst: Plug-and-play laser ablation-mass spectrometry for molecular imaging by means of dielectric barrier discharge ionization. In: Analytica Chimica Acta. Volume 1177, September 8, 2021, ISSN 0003-2670, p. 338770, doi:10.1016/j.aca.2021.338770.
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