Ion funnel

Last updated December 14, 2023

In mass spectrometry, an ion funnel is a device used to focus a beam of ions using a series of stacked ring electrodes with decreasing inner diameter. A combined radio frequency and fixed electrical potential is applied to the grids.^[1]^[2] In electrospray ionization-mass spectrometry (ESI-MS), ions are created at atmospheric pressure, but are analyzed at subsequently lower pressures. Ions can be lost while they are shuttled from areas of higher to lower pressure due to the transmission process caused by a phenomenon called joule expansion or “free-jet expansion.” These ion clouds expand outward, which limits the amount of ions that reach the detector, so fewer ions are analyzed. The ion funnel refocuses and transmits ions efficiently from those areas of high to low pressure.^[3]

History

The first ion funnel was created in 1997 in the Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratory by the researchers in Richard D. Smith's lab. The ion funnel was implemented to replace the ion transmission-limited skimmer for more efficient ion capture in an ESI source.^[4] Many characteristics of the ion funnel are attributed to the stacked ring ion guide, however, the disks of an ion funnel vary in diameter down its long axis. There is a portion at the base of the ion funnel in which a series of cylindrical ring electrodes have decreasing diameters, which enables the ion cloud entering the ion funnel to be spatially dispersed.^[5] This allows for efficient transfer of the ion cloud through the conductance limiting orifice at the exit as the ion cloud becomes focused to a much smaller radial size. The DC electric field serves to push ions through the funnel. For positive ions, the front plate of the funnel has the most positive DC voltage, and subsequent plates have gradually decreasing DC components, providing added control. RF and DC electric fields are co-applied with a pseudopotential created with alternating RF polarities on adjacent electrodes. This “pseudo-potential” radially confines ions and causes instability in ions with a lower m/z (mass to charge ratio) while ions with a higher m/z are focused to the center of the funnel.^[6] The initial ion funnel design used in the Smith research lab proved inefficient for collecting ions with low m/z . Simulations suggest that decreasing the spacing between the lenses so that they are less than the diameter of the smallest ring electrode could be a plausible solution to this problem.^[7] Another issue with the design is that the funnel is susceptible to noise with fast neutrals and charged droplets at many atmospheric interfaces during the initial vacuum phase. Modifications increase the efficiency and signal to noise ratio of the ion funnel.

Some of the earliest ion funnels struggled to control gas flow as the pressure in the ion vacuum chamber was not uniform due to gas dynamic effects. The pressure at the funnel's exit was estimated to be 2 to 3 times higher than the pressure from the pressure gauge. The higher pressure required greater pumping in downstream vacuum chambers to compensate for the larger injection of gas. The discrepancy between the measured pressure and the pressure at the exit of the funnel was caused by the a sizable portion of the supersonic gas jet from the injector continuing beyond the Mach disk or shock diamond at the beginning of the funnel and continuing through until the end. The most effective resolution is the us of a jet disrupter that consists of a 9 mm diameter brass disk suspended perpendicular to the gas flow in the center of the ion funnel.^[5]

Applications

Mass spectrometry

Ion funnels are frequently used in mass spectroscopy devices to collect ions from an ionization source. Previous devices lacking an ion funnel often lost ions during the transition from ionization source to the detector of the mass spectrometer. This loss was due to the increasing number of collisions undergone by ions with other gas molecules present in the atmosphere. The introduction of the ion funnel greatly reduced the amount of ions lost during experiments by guiding ions towards a desired destination,^[8] and through modification of the number of inlets is also able to increases sensitivity of measurements taken by the mass spectrometer. Multiple inlets allow multiple electrospray emitters, reducing the flow through each individual emitter. This creates many highly efficient electrosprays at low flow rates.^[5] Multiple inlets also improve sensitivity, with a linearly arranged 19 electrospray emitter coupled to 19 inlets operating at 18 Torr giving a nine-fold increase compared to a single inlet.^[5]

Proton transfer reaction chamber

Proton transfer reaction mass spectrometry has traditionally used drift tubes as ion traps. However, radio frequency ion funnels offer an attractive alternative, as they improve compound specific sensitivity significantly. This is due to increasing the effective reaction time and focusing the ions. The same pressure ranges are required for ion funnels and drift tubes, so the technology is not difficult to implement. Ion funnels have been shown to favor transmission of ions with high m/z.^[9]

Breath analysis

Breath analysis is a convenient and non-invasive way to detect chemicals in a bodily system such as alcohol content to determine intoxication, monitor the levels of anesthetics in the body during surgical procedures, and identify performance-enhancing substances in the system of athletes. However, conventional techniques are ineffective at low concentrations. An electrospray ionization interface assisted by an ion funnel used in a linear trap quadrupole Fourier-transform ion cyclotron resonance mass spectrometer was shown to greatly increase sensitivity with high resolution.^[10]

Related Research Articles

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.

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">Electrospray ionization</span> Technique used in mass spectroscopy

Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions using an electrospray in which a high voltage is applied to a liquid to create an aerosol. It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized. ESI is different from other ionization processes since it may produce multiple-charged ions, effectively extending the mass range of the analyser to accommodate the kDa-MDa orders of magnitude observed in proteins and their associated polypeptide fragments.

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.

Atmospheric pressure chemical ionization (APCI) is an ionization method used in mass spectrometry which utilizes gas-phase ion-molecule reactions at atmospheric pressure (10⁵ Pa), commonly coupled with high-performance liquid chromatography (HPLC). APCI is a soft ionization method similar to chemical ionization where primary ions are produced on a solvent spray. The main usage of APCI is for polar and relatively less polar thermally stable compounds with molecular weight less than 1500 Da. The application of APCI with HPLC has gained a large popularity in trace analysis detection such as steroids, pesticides and also in pharmacology for drug metabolites.

In mass spectrometry, direct analysis in real time (DART) is an ion source that produces electronically or vibronically excited-state species from gases such as helium, argon, or nitrogen that ionize atmospheric molecules or dopant molecules. The ions generated from atmospheric or dopant molecules undergo ion-molecule reactions with the sample molecules to produce analyte ions. Analytes with low ionization energy may be ionized directly. The DART ionization process can produce positive or negative ions depending on the potential applied to the exit electrode.

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.

Laser spray ionization refers to one of several methods for creating ions using a laser interacting with a spray of neutral particles or ablating material to create a plume of charged particles. The ions thus formed can be separated by m/z with mass spectrometry. Laser spray is one of several ion sources that can be coupled with liquid chromatography-mass spectrometry for the detection of larger molecules.

Proton-transfer-reaction mass spectrometry (PTR-MS) is an analytical chemistry technique that uses gas phase hydronium reagent ions which are produced in an ion source. PTR-MS is used for online monitoring of volatile organic compounds (VOCs) in ambient air and was developed in 1995 by scientists at the Institut für Ionenphysik at the Leopold-Franzens University in Innsbruck, Austria. A PTR-MS instrument consists of an ion source that is directly connected to a drift tube and an analyzing system. Commercially available PTR-MS instruments have a response time of about 100 ms and reach a detection limit in the single digit pptv or even ppqv region. Established fields of application are environmental research, food and flavor science, biological research, medicine, security, cleanroom monitoring, etc.

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.

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.

Richard Dale Smith is a chemist and a Battelle Fellow and chief scientist within the biological sciences division, as well as the director of proteomics research at the Pacific Northwest National Laboratory (PNNL). Smith is also director of the NIH Proteomics Research Resource for Integrative Biology, an adjunct faculty member in the chemistry departments at Washington State University and the University of Utah, and an affiliate faculty member at the University of Idaho and the Department of Molecular Microbiology & Immunology, Oregon Health & Science University. He is the author or co-author of approximately 1100 peer-reviewed publications and has been awarded 70 US patents.

Structures for lossless ion manipulations (SLIM) are a form of ion optics to which various radio frequency and dc electric potentials can be applied and used to enable a broad range of ion manipulations, such as separations based upon ion mobility spectrometry, reactions, and storage. SLIM was developed by Richard D. Smith and coworkers at Pacific Northwest National Laboratory (PNNL) and are generally fabricated from arrays of electrodes on evenly spaced planar surfaces. In 2017, Erin S. Baker, Sandilya Garimella, Yehia Ibrahim, Richard D. Smith and Ian Webb from the Interactive Omics Group of PNNL received the R&D 100 Award for the development of SLIM.

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">Miniature mass spectrometer</span>

A miniature mass spectrometer (MMS) is a type of mass spectrometer (MS) which has small size and weight and can be understood as a portable or handheld device. Current lab-scale mass spectrometers however, usually weigh hundreds of pounds and can cost on the range from thousands to millions of dollars. One purpose of producing MMS is for in situ analysis. This in situ analysis can lead to much simpler mass spectrometer operation such that non-technical personnel like physicians at the bedside, firefighters in a burning factory, food safety inspectors in a warehouse, or airport security at airport checkpoints, etc. can analyze samples themselves saving the time, effort, and cost of having the sample run by a trained MS technician offsite. Although, reducing the size of MS can lead to a poorer performance of the instrument versus current analytical laboratory standards, MMS is designed to maintain sufficient resolutions, detection limits, accuracy, and especially the capability of automatic operation. These features are necessary for the specific in-situ applications of MMS mentioned above.

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.

Probe electrospray ionization (PESI) is an electrospray-based ambient ionization technique which is coupled with mass spectrometry for sample analysis. Unlike traditional mass spectrometry ion sources which must be maintained in a vacuum, ambient ionization techniques permit sample ionization under ambient conditions, allowing for the high-throughput analysis of samples in their native state, often with minimal or no sample pre-treatment. The PESI ion source simply consists of a needle to which a high voltage is applied following sample pick-up, initiating electrospray directly from the solid needle.

Erin Shammel Baker is an American bioanalytical chemist specializing in developing ion mobility-mass spectrometry hybrid instruments for biological and environmental applications. Baker is an expert in the research of perfluoroalkyl and polyfluoroalkyl substances analysis.

References

↑ Kim, Taeman; Tolmachev, Aleksey V.; Harkewicz, Richard; Prior, David C.; Anderson, Gordon; Udseth, Harold R.; Smith, Richard D.; Bailey, Thomas H.; Rakov, Sergey; Futrell, Jean H. (2000). "Design and Implementation of a New Electrodynamic Ion Funnel". Analytical Chemistry. 72 (10): 2247–2255. doi:10.1021/ac991412x. ISSN 0003-2700. PMID 10845370.
↑ Kelly, Ryan T.; Tolmachev, Aleksey V.; Page, Jason S.; Tang, Keqi; Smith, Richard D. (2009). "The ion funnel: Theory, implementations, and applications". Mass Spectrometry Reviews. 29 (2): 294–312. doi:10.1002/mas.20232. ISSN 0277-7037. PMC 2824015 . PMID 19391099.
↑ "Ion Funnel | Mass Spec Pro". www.massspecpro.com. Retrieved 2018-12-03.
↑ Julian, Ryan R.; Mabbett, Sarah R.; Jarrold, Martin F. (2005-10-01). "Ion Funnels for the Masses: Experiments and Simulations with a Simplified Ion Funnel". Journal of the American Society for Mass Spectrometry. 16 (10): 1708–1712. doi:10.1016/j.jasms.2005.06.012. ISSN 1044-0305. PMID 16095911.
1 2 3 4 Kelly, Ryan T.; Tolmachev, Aleksey V.; Page, Jason S.; Tang, Keqi; Smith, Richard D. (2010). "The Ion Funnel: Theory, Implementations, and Applications". Mass Spectrometry Reviews. 29 (2): 294–312. doi:10.1002/mas.20232. ISSN 0277-7037. PMC 2824015 . PMID 19391099.
↑ Shaffer, Scott A.; Tang, Keqi; Anderson, Gordon A.; Prior, David C.; Udseth, Harold R.; Smith, Richard D. (1997-10-30). "A novel ion funnel for focusing ions at elevated pressure using electrospray ionization mass spectrometry". Rapid Communications in Mass Spectrometry. 11 (16): 1813–1817. doi:10.1002/(sici)1097-0231(19971030)11:16<1813::aid-rcm87>3.0.co;2-d. ISSN 1097-0231.
↑ Shaffer, Scott A.; Prior, David C.; Anderson, Gordon A.; Udseth, Harold R.; Smith, Richard D. (1998-10-29). "An Ion Funnel Interface for Improved Ion Focusing and Sensitivity Using Electrospray Ionization Mass Spectrometry". Analytical Chemistry. 70 (19): 4111–4119. doi:10.1021/ac9802170. ISSN 0003-2700. PMID 9784749.
↑ Smith, Richard D.; Shaffer, Scott A. Method and apparatus for directing ions and other charged particles generated at near atmospheric pressures into a region under vacuum. U.S Patent. US6107628A. June 3, 1998
↑ Brown P, Cristescu S, Mullock S, Reich D, Lamont-Smith C, Harren F (2017). "Implementation and Characterization of an RF Ion Funnel Ion Guide as a Proton Transfer Reaction Chamber" (PDF). International Journal of Mass Spectrometry. 414: 31–38. Bibcode:2017IJMSp.414...31B. doi:10.1016/j.ijms.2017.01.001. hdl: 2066/174572 . S2CID 100259890.
↑ Meier L, Berchtold C, Schmid S, Zenobi R (2012). "High Mass Resolution Breath Analysis using Secondary Electrospray Ionization Mass Spectrometry Assisted by an Ion Funnel". Journal of Mass Spectrometry. 47 (12): 1571–1575. Bibcode:2012JMSp...47.1571M. doi:10.1002/jms.3118. PMID 23280745.

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[KimTolmachev2000-1] Kim, Taeman; Tolmachev, Aleksey V.; Harkewicz, Richard; Prior, David C.; Anderson, Gordon; Udseth, Harold R.; Smith, Richard D.; Bailey, Thomas H.; Rakov, Sergey; Futrell, Jean H. (2000). "Design and Implementation of a New Electrodynamic Ion Funnel". Analytical Chemistry. 72 (10): 2247–2255. doi:10.1021/ac991412x. ISSN 0003-2700. PMID 10845370.

[KellyTolmachev2009-2] Kelly, Ryan T.; Tolmachev, Aleksey V.; Page, Jason S.; Tang, Keqi; Smith, Richard D. (2009). "The ion funnel: Theory, implementations, and applications". Mass Spectrometry Reviews. 29 (2): 294–312. doi:10.1002/mas.20232. ISSN 0277-7037. PMC 2824015 . PMID 19391099.

[3] "Ion Funnel | Mass Spec Pro". www.massspecpro.com. Retrieved 2018-12-03.

[4] Julian, Ryan R.; Mabbett, Sarah R.; Jarrold, Martin F. (2005-10-01). "Ion Funnels for the Masses: Experiments and Simulations with a Simplified Ion Funnel". Journal of the American Society for Mass Spectrometry. 16 (10): 1708–1712. doi:10.1016/j.jasms.2005.06.012. ISSN 1044-0305. PMID 16095911.

[:0-5] 1 2 3 4 Kelly, Ryan T.; Tolmachev, Aleksey V.; Page, Jason S.; Tang, Keqi; Smith, Richard D. (2010). "The Ion Funnel: Theory, Implementations, and Applications". Mass Spectrometry Reviews. 29 (2): 294–312. doi:10.1002/mas.20232. ISSN 0277-7037. PMC 2824015 . PMID 19391099.

[6] Shaffer, Scott A.; Tang, Keqi; Anderson, Gordon A.; Prior, David C.; Udseth, Harold R.; Smith, Richard D. (1997-10-30). "A novel ion funnel for focusing ions at elevated pressure using electrospray ionization mass spectrometry". Rapid Communications in Mass Spectrometry. 11 (16): 1813–1817. doi:10.1002/(sici)1097-0231(19971030)11:16<1813::aid-rcm87>3.0.co;2-d. ISSN 1097-0231.

[7] Shaffer, Scott A.; Prior, David C.; Anderson, Gordon A.; Udseth, Harold R.; Smith, Richard D. (1998-10-29). "An Ion Funnel Interface for Improved Ion Focusing and Sensitivity Using Electrospray Ionization Mass Spectrometry". Analytical Chemistry. 70 (19): 4111–4119. doi:10.1021/ac9802170. ISSN 0003-2700. PMID 9784749.

[8] Smith, Richard D.; Shaffer, Scott A. Method and apparatus for directing ions and other charged particles generated at near atmospheric pressures into a region under vacuum. U.S Patent. US6107628A. June 3, 1998

[9] Brown P, Cristescu S, Mullock S, Reich D, Lamont-Smith C, Harren F (2017). "Implementation and Characterization of an RF Ion Funnel Ion Guide as a Proton Transfer Reaction Chamber" (PDF). International Journal of Mass Spectrometry. 414: 31–38. Bibcode:2017IJMSp.414...31B. doi:10.1016/j.ijms.2017.01.001. hdl: 2066/174572 . S2CID 100259890.

[10] Meier L, Berchtold C, Schmid S, Zenobi R (2012). "High Mass Resolution Breath Analysis using Secondary Electrospray Ionization Mass Spectrometry Assisted by an Ion Funnel". Journal of Mass Spectrometry. 47 (12): 1571–1575. Bibcode:2012JMSp...47.1571M. doi:10.1002/jms.3118. PMID 23280745.

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