US20110183431A1 - Mass analysis system with low pressure differential mobility spectrometer - Google Patents

Mass analysis system with low pressure differential mobility spectrometer Download PDF

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US20110183431A1
US20110183431A1 US13/016,257 US201113016257A US2011183431A1 US 20110183431 A1 US20110183431 A1 US 20110183431A1 US 201113016257 A US201113016257 A US 201113016257A US 2011183431 A1 US2011183431 A1 US 2011183431A1
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ions
region
ion
dms
pressure
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Thomas R. Covey
Bradley B. Schneider
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MDS Analytical Technologies Canada
Applied Biosystems Canada Ltd
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MDS Analytical Technologies Canada
Applied Biosystems Canada Ltd
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Assigned to MDS ANALYTICAL TECHNOLOGIES, A BUSINESS UNIT OF MDS INC., APPLIED BIOSYSTEMS (CANADA) LIMITED reassignment MDS ANALYTICAL TECHNOLOGIES, A BUSINESS UNIT OF MDS INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: COVEY, THOMAS R., SCHNEIDER, BRADLEY B.
Publication of US20110183431A1 publication Critical patent/US20110183431A1/en
Priority to US13/693,837 priority patent/US9305762B2/en
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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/26—Mass spectrometers or separator tubes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
    • G01N27/622—Ion mobility spectrometry
    • G01N27/624—Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS]
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Definitions

  • a Differential Mobility Spectrometer also referred to as a Field Asymmetric Waveform Ion Mobility Spectrometer (FAIMS) or Field Ion Spectrometer (FIS) typically performs gas phase ion sample separation and analysis.
  • DMS Differential Mobility Spectrometer
  • FIMS Field Asymmetric Waveform Ion Mobility Spectrometer
  • FIS Field Ion Spectrometer
  • MS mass spectrometer
  • DMS-based analyzers By interfacing a DMS with an MS, numerous areas of sample analysis, including proteomics, peptide/protein conformation, pharmacokinetic, and metabolism analysis have been enhanced. In addition to pharmaceutical and biotech applications, DMS-based analyzers have been used for trace level explosives detection and petroleum monitoring.
  • a DMS like an ion mobility spectrometer (IMS) is considered an ion mobility based analyzer because the DMS separates and analyzes ions based on the mobility characteristics of the ions.
  • IMS ion mobility spectrometer
  • ions are pulsed into and pass through a drift tube while being subjected to a constant electric field.
  • the ions interact with a drift gas in the drift tube and the interactions affect the time it takes for the sample ions to pass through the drift tube, e.g., the time-of-flight (TOF).
  • TOF time-of-flight
  • a DMS is similar to an IMS in that the ions are separated in a drift gas.
  • the DMS uses an asymmetric electric field waveform that is applied between at least two parallel electrodes through which the ions pass, typically, in a continuous manner.
  • the electric field waveform typically has a high field duration at one polarity and then a low field duration at an opposite polarity. The duration of the high field and low field portions are applied such that the net voltage being applied to the DMS filter electrodes is zero.
  • FIG. 1A shows a plot 100 of the time-varying, RF, and/or asymmetric high and low voltage waveform 101 (e.g., Vrf) that can be applied to generate an asymmetric electric field.
  • FIG. 1B shows a diagram of a DMS filter 102 where the path of an ion M ⁇ is subjected to an asymmetric electric field resulting from the asymmetric voltage waveform 101 .
  • the ion's mobility in the asymmetric electric field indicates a net movement 103 towards the bottom electrode plate of the DMS filter 102 .
  • This example shows that, in a DMS, an ion's mobility is not constant under the influence of the low electric field compared to the high electric field.
  • a compensation voltage is applied to the filter electrodes to maintain a safe trajectory 104 for the ion through the DMS filter 102 without striking one of the filter electrodes.
  • the ions are passed between the two filter electrodes by either being pushed through with a pressurized gas flow upstream of the filter electrodes or pulled through by a pump downstream from the filter electrodes.
  • ions are typically separated in a gas at pressures sufficient to enable collisions between sample ions and neutral drift gas molecules.
  • an ion's cross sectional area can effect the ion's mobility through the drift gas.
  • an ion's mobility is not constant under the influence of a low electric field compared to a high electric field. This difference in mobility may be related to clustering/de-clustering reactions taking place as an ion experiences the weak and strong electric fields.
  • An ion typically experiences clustering with neutral molecules in the drift gas during the weak field portion of the waveform, resulting in an increased cross sectional area.
  • the cluster may be dissociated, reducing the ion's cross sectional area.
  • differences between high and low field mobility behavior may be due to different collision dynamics due to changes that occur in ion translational energy.
  • the integration of a DMS with a MS can provide added selectivity that can be used for purposes such as chemical noise reduction and elimination of isobaric interferences.
  • This general reduction of the chemical background can provide improvements in the detection limit (defined for example as 3 ⁇ /slope of the calibration curve) for various assays.
  • One of the key factors limiting general applicability of DMS technology with MS analysis is the reduction in instrument sensitivity that is observed upon installation of the DMS.
  • a tandem DMS device advantageously includes first and second DMS filters that utilize separation mechanisms based on two different separation models.
  • a cell including the first DMS
  • a second cell including the second DMS
  • a vacuum where declustering to the bare ion is done efficiently.
  • Separation at about atmosphere is done according to a “clusterization model” which derives it's specificity from the differences in the chemical interactions of an ion and its immediate surroundings. For instance, Hydrogen bonding, Vanderwaals forces, steric hindrance, where all of these actions come into play in the clusterization model.
  • modifiers e.g., dopants
  • the tandem device creates dry ions with energetic collisions in, for example, a free jet expansion by accelerating the clusters into a background gas. Because there is a substantially greater mean free path under the vacuum, as compared to atmosphere to accelerate and collide ions, declustering can be done most efficiently in or near the free jet gas expansion.
  • the declustered ions are then separated in the second vacuum DMS according to a “hard sphere collision model”. This mechanism is based upon a more “physical” process where the ion mobility is related to the interaction and scattering of ions during collisions with the inert background gas molecules. Ion mobility based separation using the combination of both models advantageously provides orthogonal separation mechanisms that substantially enhance ion analysis with respect to conventional techniques.
  • a mass analysis system includes a low pressure dissociation region, a low pressure DMS that filters sample ions, and a mass spectrometer that receives some or all of the selected portion of the sample ions.
  • the dissociation region may include, without limitation, a collision region, a fragmentation region, an expansion region, a desolvation region, radiation region, high temperature region, and/or the like.
  • the dissociation region may utilize a laser, radiation source, collision gas source, thermal source, gas expansion mechanism, and the like to effect the dissociation process.
  • the DMS includes at least a pair of filter electrodes defining an ion flow path where the filter electrodes generate an electric field for passing through a selected portion of the sample ions based on their ion mobility characteristics.
  • the DMS can include a plurality of filter electrode pairs.
  • the DMS also includes a voltage source that provides RF and DC voltages to at least one of the filter electrodes to generate the electric field.
  • the DMS further includes an ion inlet that receives sample ions that have passed through the low pressure collision region and an ion outlet that outputs the selected portion of the sample ions.
  • the low pressure dissociation region is configured to accelerate the sample ions and collide the sample ions with a collision gas.
  • the low pressure dissociation region may be configured to perform at least one of declustering and fragmenting the sample ions.
  • the pressure of the DMS and/or a portion of the low pressure dissociation region may be set at less than about atmospheric pressure.
  • the pressure of the DMS and/or portion of the low pressure dissociation region may be set at about 50 to about 760 Torr.
  • the pressure of the DMS and/or a portion of the low pressure dissociation region may be set at less than about 100 Torr.
  • the DMS operates from about 200 to about 500 Torr. In certain configurations, the DMS operates at about 200 Torr.
  • the DMS can operate at less than about 50 Torr, less than about 25 Torr, less than about 15 Torr, less than about 5 Torr, less than about 3 Torr, and less than about 1 Torr.
  • the DMS may be operated at about 2-4 Torr.
  • the pressure of the ion flow path in the DMS is substantially the same as the pressure of a portion of the low pressure dissociation region.
  • the mass analysis system includes at least one ion guide located in at least the low pressure dissociation region or an intermediate region between the low pressure DMS and the low pressure dissociation region.
  • the ion guide may include at least one ion focusing element.
  • the ion focusing element may include an RF rod, RF ring, RF lens, DC lens, DC ring, deflector plate, and/or grid.
  • the low pressure dissociation region may be configured to receive a flow of the sample ions from an ion source.
  • the ion source may include a second DMS that operates at substantially atmospheric pressure or above.
  • the low pressure dissociation region may be configured to accelerate ions within a free jet expansion.
  • a housing substantially encloses the low pressure DMS and the low pressure dissociation region.
  • the housing may include a housing or vacuum inlet for receiving sample ions.
  • the housing may also include a housing outlet, in communication with an outlet of the low pressure DMS, for outputting a portion of selected sample ions into the mass spectrometer.
  • the ion guide located in the low pressure dissociation region can be removed, and the low pressure DMS can comprise four electrodes.
  • the mass spectrometer includes at least one ion optics element that receives the selected portion of the sample ions via the housing outlet.
  • the mass spectrometer may include a mass analyzer in communication with at least one ion optics element.
  • an insulating material is in communication with and/or supports at least one of the DMS filter electrodes.
  • the mass analysis system includes one or more heated regions that are configured to perform i) declustering ions, ii) desolvating ions, iii) accelerating the reclustering of ions with reagents, and/or iv) shifting the clustering equilibrium for ions with dopant or reagents.
  • a sample analysis system in another aspect, includes a first pressure region that operates at a pressure of about atmospheric pressure or greater.
  • the first pressure region includes a first DMS filter that receives sample ions from an ion source and passes through a first set of selected sample ions.
  • the system also includes a second pressure region, in communication with the first pressure region, that operates at less than about atmospheric pressure.
  • the second pressure region includes a dissociation and/or collision region where the first set of selected sample ions are accelerated and collided with a collision gas to desolvate and/or fragment the sample ions.
  • the second pressure region also includes a second DMS filter that passes through a second set of selected sample ions based on their ion mobility characteristics.
  • the system includes a third pressure region, in communication with the second pressure region, that operates at less than about 1 Torr.
  • the third pressure region may include an ion optics element that receives the second set of selected sample ions.
  • the system includes a fourth pressure region, in communication with the third pressure region, that operates at less than about 10 ⁇ 4 torr and includes a mass analyzer.
  • a vacuum drag is established from a lower pressure region to a higher pressure region to facilitate the transport of ions. For instance, a vacuum drag may be utilized to pull ions into and/or through the first and/or second DMS, or through other components of the ion analyzer.
  • an ion analysis system comprises an ion inlet and a first low pressure region maintained at a pressure in the range of about 50 to about 760 Torr including a first dissociation region and a differential mobility spectrometer. Second and third low pressure regions maintained at less than about 50 Torr and less than about 1 Torr, respectively, with RF ion guides for directing ions to a fourth low pressure region comprising a mass analyzer.
  • an ion analyzer in a further aspect, includes an ion source, a flow of ions from the ion source, a reaction region that introduces at least one chemical modifier to the flow of ions, and a first DMS, operating substantially at atmospheric pressure, that receives the flow of ions from the reaction region and performs a first mobility based filter operation on the flow of ions.
  • the analyzer also includes a declustering region, operating at less than atmospheric pressure, that receives the flow of ions from the first DMS.
  • the analyzer further includes a second DMS, operating at less than atmospheric pressure, that receives the flow of ions from the declustering region and performs a second mobility based filter operation on the flow of ions.
  • the ion analyzer may advantageously employ an orthogonal separation approach where the first DMS, operating at about atmospheric pressure, performs ion mobility based separations based on the clusterization model, while the second DMS, operating at less than atmospheric pressure, performs ion mobility based separations based on the hard or rigid sphere collision model. Further details regarding these separation models are provided later herein.
  • the ion analyzer includes a mass spectrometer that receives the flow of ions from the second DMS.
  • the mass spectrometer includes a mass analyzer.
  • the ion analyzer may include at least one heated region configured to perform at least one of i) declustering ions, ii) desolvating ions, iii) accelerating the reclustering of ions with reagents, and iv) shifting the clustering equilibrium for ions with dopant or reagents.
  • an ion analysis system includes an ion source, a flow of ions from the ion source, a first means for modifying a first portion of ions from the flow of ions to provide a specific ⁇ -function for each of the ion species associated with the first portion of ions, a first DMS configured to receive the first portion of ions, conduct a differential mobility separation, and output a second portion of ions, a second means for modifying the second portion of ions to alter the ⁇ function associated with the second portion of ions, and a second DMS configured to receive the second portion of ions, conduct a differential mobility separation, and output a third portion of ions.
  • the means for modifying may include a reaction region, clustering region, dissociation region, and/or declustering region.
  • FIG. 1A shows a plot of a time-varying and/or asymmetric high and low voltage waveform that may be applied to generate an asymmetric electric field in a differential mobility spectrometer (DMS);
  • DMS differential mobility spectrometer
  • FIG. 1B shows a diagram of a DMS filter where the path of an ion M
  • FIG. 2 shows a diagram of a mass analysis system with a vacuum chamber including a DMS and collision region according to an illustrative embodiment of the invention
  • FIG. 3 is a flow diagram of a process for analyzing ions using the system of FIG. 2 according to an illustrative embodiment of the invention
  • FIG. 4 shows a diagram of a mass analysis system as in FIG. 2 with an ion guide according to an illustrative embodiment of the invention
  • FIG. 5A shows a diagram of a mass analysis system as in FIG. 4 with an atmospheric pressure DMS pre-filter according to an illustrative embodiment of the invention
  • FIG. 5B shows a diagram of a mass analysis system as in FIG. 5A but without an RF ion guide, and a DMS comprising four electrodes according to an illustrative embodiment of the invention
  • FIG. 6 shows a diagram of a mass analysis system as in FIG. 5A with a clustering and/or reaction region prior to the atmospheric pressure DMS according to an illustrative embodiment of the invention
  • FIG. 7A includes plots of normalized ion intensity peaks in a DMS without reagent modifiers at various Vrf settings;
  • FIG. 7B includes plots of normalized ion intensity peaks in a DMS with reagent modifiers introduced at various Vrf settings;
  • FIG. 8 shows a diagram of dopant introduction system via a mixing chamber according to an illustrative embodiment of the invention
  • FIG. 9 shows a diagram of an alternative dopant introduction system according to an illustrative embodiment of the invention.
  • FIG. 10 shows a diagram of a mass analysis system as in FIG. 6 with a turbulent heated region according to an illustrative embodiment of the invention.
  • FIG. 11 is a graph including plots of normalized ion intensity vs. compensation voltage when the inlet to the atmospheric pressure DMS is heated and not heated respectively;
  • FIG. 12 is a graph of the of alpha behavior for type A, B, and C ion mobility behavior
  • FIG. 13 is a graph showing the dramatic changes that occur in the alpha function for a sample of norfentanyl with inert transport gases and the inclusion of a clustering modifier.
  • FIGS. 14A-C includes a series of graphs showing alpha function data for 36 compounds under different conditions.
  • a common problem with electrospray ionization sources is that they typically produce heterogeneous ion clusters that can adversely affect the resolution of ion analyzer systems. Clustering of ions and neutral gas phase molecules typically results from ionization at atmospheric pressure. Ions generated during the electrospray process are a combination of bare molecular ions and ions clustered or contained in small droplets of the electrospray solvent. The relative proportion of ions, ion-clusters, and charged droplets is highly dependent on the degree to which the charged nebulized liquid is desolvated.
  • a mobility based analyzer such as a DMS
  • an electrospray ionization source the extent of the production of these heterogeneous cluster ion populations is related to mobile phase introduction flow rate.
  • the mobile phase flow rates extend into the hundreds of microlitres per minute range, a large proportion of the ions produced by the ion evaporation process are created as clusters and small droplets of widely varying composition.
  • Cluster ion populations formed in this way are highly heterogeneous and different from the relatively homogeneous cluster ion populations formed in the gas phase during the interaction of an ion with the background transport gas.
  • a particular ion can exist in a wide variety of different clustered states covering a broad distribution of molecular weights and chemical compositions. This occurs whether or not high desolvation temperatures are used to evaporate the pneumatically nebulized electrospray, although the problem is exacerbated at low temperatures.
  • a mobility based analyzer such as a DMS, operating at atmospheric pressure, can separate the components of the distribution.
  • the sensitivity for the targeted analyte, as detected by, for example, a MS will be reduced in addition to the mobility resolution and peak capacity.
  • heterogeneous clusters of different sizes and compositions may be present in addition to small droplets. These clusters will show a much greater range of differential mobility values and a correspondingly greater peak width.
  • Electrospray sources operating at liquid flows in the nanolitre to low microlitre per minute range produce fewer clusters and, depending on the analyte and solvent chemistry, will often produce unclustered molecular ions prior to the vacuum inlet of an MS. This is apparent when Vc scans of an electrosprayed solution of a standard compound are done at high and low liquid flow rates. The apparent loss of resolution as the flow rate is raised can be attributed to the formation of increasingly heterogeneous analyte/cluster ion populations and possibly the persistence of small droplets within the mobility based analyzer.
  • a dissociation region is established before ion mobility based filtering.
  • a low pressure DMS is used to filter ions based on the rigid sphere collision (or scattering) model after dissociation of ion clusters.
  • an atmospheric pressure DMS provides ion mobility based filter based on the clusterization model.
  • an ion analyzer system includes both a low pressure DMS and atmospheric pressure DMS that combines the advantages of ion mobility based filtering using both models. Further details regarding the rigid sphere collision and clustering models are provided later herein with respect to FIG. 12 .
  • FIG. 2 shows a diagram of a mass analysis system 200 with a vacuum chamber 202 including a DMS 204 and dissociation region 206 according to an illustrative embodiment of the invention.
  • the system 200 also includes an ion source 208 , vacuum chamber inlet and/or orifice 210 , vacuum plate 212 , an outlet orifice 214 , a mass spectrometer 224 , a voltage source 226 , and controller 228 .
  • the DMS 204 includes filter electrodes 216 and 218 , a DMS inlet 220 , and DMS outlet 222 .
  • the mass spectrometer 224 includes an ion optics assembly 230 and mass analyzer 232 , and ion detector (not shown).
  • the dissociation region 206 includes at least one of a collision region, declustering region, desolvation region, and gas expansion region.
  • the vacuum chamber inlet 210 is in communication with the ion source 208 and may include an orifice, a pipe, a heated capillary, a resistive capillary, or any suitable sample inlet configuration known to one of ordinary skill in the art.
  • the vacuum chamber inlet 210 may be part of a sample inlet system that includes components such as a source extension ring or the like to facilitate ion introduction into the vacuum chamber 202 via the sample inlet 210 .
  • the ion source 208 may be integrated with the vacuum chamber inlet 210 or an inlet system or, alternatively, may be separate from the inlet system.
  • the ion source 208 may be any suitable ion source known to one of skill in the art.
  • the ion source 208 may include an electrospray ionization source with the ability to generate ions from a sample analyte dissolved in solution.
  • Other example arrangements of the ion source 208 may include an atmospheric pressure chemical ionization (APCI), atmospheric pressure photo-ionization (APPI), direct analysis in real time (DART), desorption electrospray (DESI), atmospheric pressure matrix-assisted laser desorption ionization (AP MALDI), liquid chromatography (LC) column, gas chromatography (GC) column, multimode ionization sources, surface analysis sources, or configurations with multiple inlet systems and/or sources.
  • APCI atmospheric pressure chemical ionization
  • APPI atmospheric pressure photo-ionization
  • DART direct analysis in real time
  • DESI desorption electrospray
  • AP MALDI atmospheric pressure matrix-assisted laser desorption ionization
  • LC liquid chromatography
  • GC gas chromatography
  • multimode ionization sources surface analysis sources,
  • the vacuum chamber 202 is configured to include a low pressure dissociation region 206 and/or declustering region located upstream of the DMS 204 .
  • the low pressure dissociation region 206 may be configured to accelerate sample ions from the vacuum chamber inlet 210 within a free jet expansion.
  • the vacuum chamber 202 may be defined or bounded by a vacuum plate 212 and/or housing. Sample ions travel through the inlet 210 , where a vacuum expansion occurs, as a result of the pressure differential on either side of the inlet 210 .
  • the low pressure dissociation region 206 may include a pressure gradient along the sample ion flow path 234 whereby the pressure is reduced from about atmospheric pressure in proximity to the vacuum chamber inlet 210 to a set pressure below atmospheric pressure in proximity to the DMS inlet 220 .
  • the pressure in proximity to the DMS inlet may be from about 1 Torr to less than atmospheric pressure (e.g., 760 Torr).
  • the DMS can operate at about 50 to about 760 Torr.
  • the DMS can operate from about 200 to about 500 Torr.
  • the DMS can operate at about 200 Torr.
  • the pressure may be from about 1 Torr to less than or equal to about 100 Torr.
  • the sample ions are accelerated in the low pressure dissociation region 206 with voltage and collided into a background gas to effect declustering and/or fragmentation prior to delivery of the sample ions to the DMS 204 .
  • DMS residence time and gap height can be affected by the operating pressure, with lower pressures requiring wider gaps and longer residence time.
  • Table 1 below shows typical gap widths and residence times for the DMS at different operating pressures. Long residence times can limit sample throughput, therefore it may be advantageous to operate the DMS in the about 100 to about 760 Torr pressure regime.
  • the DMS 204 may include filter electrodes 216 and 218 that are formed and/or configured as parallel plates, curved plates, concentric rings/surface, and the like.
  • the DMS 204 may include a plurality of filter electrode pairs.
  • the filter electrodes 216 and 218 may be formed on or connected to insulating surfaces or components.
  • the DMS 204 may have form factor including a generally planar, circular, concentric, and/or curved structure.
  • the voltage source 226 applies RF and DC voltages to at least one of the filter electrodes 216 and 218 to generate an electric field to enable sample ion filtering based on the mobility characteristics of the sample ion species while traveling through the DMS 204 .
  • the DC voltage is referred to as the compensation voltage, Vc, because the Vc may be adjusted to select a desired ion species to pass through the DMS 204 .
  • the controller 228 may control the voltage 226 so that the voltage source 226 sweeps Vc over a range of DC voltages to produce a ionogram or spectrum of sample ion species that are allowed to pass through the DMS 204 .
  • IMS Ion Mobility Spectrometry
  • DMA Differential Mobility Analyzer
  • hybrid ion mobility based analyzer a high-field/low-field filter, and the like.
  • the DMS assembly 204 may be mounted so as to provide vacuum seal to exit aperture 214 so that gas drag through aperture 214 establishes a laminar gas flow through the DMS 204 .
  • DC potentials may be provided to electrodes 216 and/or 218 to adjust the DC offset potential between DMS 204 and aperture 214 to optimize transmission.
  • the ion optics assembly 230 may use RF fields to focus the sample ions from the orifice 214 on to an ion optical path and direct the ions toward the mass analyzer 232 .
  • the ion optics assembly 230 used in system 200 may be made up of any ion optics known to one of skill in the art, such as, without limitation, a multipole array, a ring guide, a resistive ion guide, an ion funnel, a traveling wave ion guide, or the like.
  • the ion optics assembly is operated at a pressure in the range of about 1-10 millitorr.
  • the ion optics assembly 230 is connected with the mass analyzer 232 to enable sample ions to travel via ion optical path to mass analyzer 232 where the ions are separated based on their mass-to-charge ratios (m/z) and detected.
  • the detected ion data may be stored in memory and analyzed by a processor or computer software.
  • the controller 228 includes a processor and memory or data storage. The controller 228 may also control the operation of the mass analyzer 232 .
  • the mass analyzer 232 may function as at least one of a linear ion trap and a quadrupole analyzer, time-of-flight MS, or include multiple mass analyzers.
  • the ion optics assembly may include the Q0 RF ion guide or any like ion guide.
  • An ion guide may be used to capture and focus sample ions from the orifice 214 using a combination of gas dynamics and radio frequency fields.
  • An ion guide, such as Q0, may then transfer sample ions from the orifice 214 to subsequent ion optics or the mass analyzer 232 .
  • the API 5000TM system manufactured by AB Sciex is one type of exemplary mass spectrometer 224 that may be utilized by the mass analysis system 200 .
  • a mass spectrometer typically includes instrumental optics, a mass analyzer, curtain plate and orifice.
  • Instrumental optics comprise a QJET® RF ion guide and Q0 RF ion guide separated by an IQ0 lens.
  • the QJET® RF ion guide is used to capture and focus ions using a combination of gas dynamics and radio frequency fields.
  • the QJET® transfers ions from the orifice to subsequent ion optics such as the Q0 RF ion guide.
  • the Q0 RF ion guide transports ions through an intermediate pressure region (e.g., at about ⁇ 6 mTorr) and delivers ions through an IQ1 lens to a high vacuum chamber containing a mass analyzer.
  • the mass analyzer region comprises a Q1 quadrupole analyzer, Q2 quadrupole collision cell, Q3 quadrupole analyzer and CEM detector.
  • the instrumental optics comprising an ion guide and/or Q0 RF ion guide are an example of optics that can be used in ion optics assembly 230 of FIG. 2 .
  • the elements can be used individually, in combination with other types of ion optics, or not used in mass spectrometer system 224 at all.
  • a Q0 ion guide may be capacitively coupled to either the Q1 or Q3 quadrupole.
  • the ion optics and mass analyzer can include one or more pressure regions, separated by apertures, operating at various range of pressures.
  • the first region may be set at 2.5 Torr
  • Q0 set at 6 mTorr and mass analyzer, comprising Q1, Q2 and Q3, may be set at 10 ⁇ 5 Torr.
  • Q2 can comprises a collision cell for fragmenting ions, and the gas pressure within the Q2 cell may be substantially higher than the pressure in Q1 and Q3 of the API 5000TM device.
  • the first region can be set to 50 to 760 Torr
  • the second QJET® region can be set to 2.5 Torr
  • Q0 can be set to 6 mTorr
  • the mass analyzer comprising Q1, Q2, and Q3 can be set to 10 ⁇ 5 Torr.
  • the controller 220 includes a processor that enables the control of the various components of the mass analysis system 200 including the DMS 204 , the voltage source 226 , the ion source 208 , the mass spectrometer 224 , and, more particularly, the ion optics 230 , and mass analyzer 232 .
  • the controller may include a user interface, network interface, and data storage.
  • the processor may include an interface with a memory having software and/or hardware code configured to enable the control of the system 200 .
  • the controller 228 may include program code embedded on program media to enable the processor to perform instructions to effect control of the system 200 and/or analysis or processing of data acquired from the operation of the system 200 .
  • the mass spectrometer 224 may include at least one electrode, e.g., a linear accelerator (LINAC) in close proximity to the ion optics assembly 230 .
  • the electrode or electrodes may be used for accelerating ions through an RF multipole or expelling residual ions from the RF multipole.
  • the voltage source 226 e.g., power supply
  • the electrodes may also accelerate ions to reduce the residence time within the ion optics assembly 230 and, thereby, reduce or substantially eliminate ion beam spreading.
  • the voltage source 226 may include an RF/DC auxiliary alternating current (AC) power supply that supplies RF and/or DC signals, and/or an auxiliary AC signal to a quadrupole rod set of the mass analyzer 232 .
  • the system 200 may include a shortened quadrupole rod set, which can act as Brubaker lenses, adjacent to the mass analyzer 232 or other component of the system 200 .
  • the mass spectrometer 224 may include a collision cell having an inert gas (for example, helium, nitrogen, argon, or the like) that can be pumped into the collision cell to initiate collision induced dissociation (CID) of ions. Ions in a collision cell, such as parent ions, can collide with gas molecules and break into fragments, referred to as daughter ions.
  • an RF power supply can be used to create an electric field within a quadrupole rod set of the ion trap. By changing the amplitude and waveform of the applied field, ions of a selected m/z can be trapped within the quadrupole rod set.
  • the mass analysis system 200 performs Multiple reaction monitoring (MRM).
  • MRM Multiple reaction monitoring
  • FIG. 3 is a flow diagram of a process 300 for analyzing ions using the system 200 of FIG. 2 according to an illustrative embodiment of the invention.
  • the ion source 208 includes an electrospray ionization source that delivers sample ions from a solution to the vacuum inlet 210 .
  • electrospray ionization particularly at high flow rates, can produce heterogeneous ions which are undesirable.
  • One approach to mitigating the adverse effects of heterogeneous clusters is to dissociate the ion clusters before ion mobility based filtering.
  • the pressure at the ion source 208 may be at about atmospheric pressure, while the pressure inside the vacuum chamber may be at a pressure less that atmospheric pressure.
  • the pressure differential across the vacuum inlet 210 can create a free jet within the vacuum chamber 202 to pass and accelerate sample ions through the low pressure collision region 206 along the flow path 234 toward the DMS inlet (Step 302 ).
  • the arrangement and use of the low pressure collision region 206 advantageously enables declustering of the heterogeneous sample/solvent cluster ions because the sample ion clusters in the wet spray from the ion source 208 are accelerated within the free jet expansion of the low pressure collision region 206 .
  • the sensitivity of the system 200 is advantageously improved because the DMS 204 is allowed to filter the desired sample ions, as opposed to filtering clusters.
  • clusters are homogeneous and, therefore, form well-defined structures and resulting well-defined detection peaks.
  • homogeneous cluster ion populations are formed in the gas phase during the interaction of an ion with the background transport gas (e.g., neutral molecules).
  • a modifier and/or dopant may be introduced into the gas flow that drives the equilibrium toward a desired homogeneous cluster ion population.
  • Homogeneous clusters have well-defined DMS characteristics.
  • the voltage source applies RF (Vrf) and DC (Vc) voltages to at least one of a pair of filter electrodes 216 and 218 (Step 304 ). With the applied RF and DC voltages, the filter electrodes 216 and 218 generate an electric field in the flow path between the pair of filter electrodes 216 and 218 (Step 306 ).
  • the controller 228 controls the RF and DC voltages applied from the voltage source 226 to the filter electrodes 216 and 218 so as to pass through the electric field a selected portion of the sample ions based on the mobility characteristics of the sample ions (Step 308 ).
  • Some or all of the selected portion of sample ions that exit the DMS outlet 222 may then be received at a mass spectrometer 224 (Step 310 ) via the orifice 214 .
  • the transfer of ions from the DMS to mass spectrometer 224 may be effected by sealing the outlet of the DMS with the aperture 214 to establish a vacuum drag of gas from the DMS 204 into the mass spectrometer 224 .
  • the mass spectrometer 224 may employ any number of known techniques and operations using the ion optics assembly 230 and mass analyzer 232 to analyze and detect the sample ions from the DMS 204 .
  • FIG. 4 shows a diagram of a mass analysis system 400 like system 200 in FIG. 2 with the addition of an ion guide 402 according to an illustrative embodiment of the invention.
  • the ion guide 402 is included in the low pressure collision region 206 to focus and direct sample ions from the vacuum inlet 210 .
  • a potential may be applied to accelerate the sample ions and facilitate declustering and/or desolvation of the sample ions before entry into the DMS 204 .
  • the ion guide may include a QJET®.
  • a potential difference between the vacuum inlet and the QJET® may enable acceleration and declustering of sample ions from the ion source 208 .
  • the system may also include a free jet expansion due to the pressure differential across the vacuum inlet/orifice 210 that also propels ions through the ion guide 402 toward the DMS inlet 220 .
  • the ion guide 402 may include a quadrupole ion guide.
  • the ion guide 402 may include dual ion guides or a plurality of ion guides to effect acceleration of sample ions and declustering. The inclusion of an ion guide 402 enables the introduction of substantially dry sample ions into the DMS inlet 220 .
  • the ion guide 402 operating as an ion focusing element, may focus and guide sample ions entering the vacuum chamber 202 via the vacuum inlet 210 toward the DMS inlet 220 . Collisions between the sample ions and a collision gas may occur before, within, or after the ion guide 402 .
  • the ion guide 402 may include RF rods, DC lenses, and/or RF lenses.
  • the vacuum chamber 202 includes an intermediate region 406 , located downstream of the ion guide 402 and upstream of the DMS 204 .
  • the intermediate region may include some type of ion control element such as, without limitation, a second ion guide and/or an RF multipole, or the like to further effect control of the sample ions in the vacuum chamber 202 .
  • a lens element may be included in region 406 to limit electrical interference for the RF potentials applied to the ion guide 402 and DMS 204 .
  • the DMS 204 is moved from a location within the atmospheric pressure source region 404 to a new location within the vacuum region and/or chamber 202 of the system 400 .
  • This may be accomplished on systems that include a QJET® or dual QJET® ion optics configuration.
  • the DMS 204 could be located in the first vacuum region downstream of a slightly shortened QJET quadrupole ion guide.
  • the DMS/MS system such as the system 400 , would retain the identical desolvation/declustering configuration of a standard 5500 QTRAP® platform, however, ion filtering can be accomplished for dry ions downstream of the QJET®.
  • Other benefits and advantages of employing a low pressure collision region 206 and/or ion guide 402 upstream of the low pressure DMS 204 may include:
  • an additional vacuum stage can be included prior to region 202 .
  • the pressure can be set to about 50 to 760 Torr, and the region can include the DMS and a declustering region as well as an optional ion guide. With this configuration, the region 202 would not include a DMS.
  • FIG. 5A shows a diagram of a mass analysis system 500 , like the system 400 shown in FIG. 4 , with an additional atmospheric pressure DMS 502 pre-filter according to an illustrative embodiment of the invention.
  • the DMS 502 is located in the atmospheric pressure source region 404 and receives sample ions from the ionization source 208 at the DMS inlet 504 .
  • the DMS 502 passes through selected sample ions by applying an asymmetric RF field and DC compensation field between the DMS filter electrodes 506 and 508 .
  • the voltage source under the control of controller 228 , applies both a Vrf and Vc voltage to at least one of the DMS filter electrodes 506 and 508 to generate the RF and DC electric field.
  • FIG. 5A also shows that the ion flow 234 in the low pressure collision region 206 is at least partially due to a vacuum drag created by the difference in pressure from the DMS 502 , operating at or near atmospheric pressure, and the vacuum chamber 202 , operating at about 1 Torr to about atmospheric pressure.
  • the mass analysis system 500 advantageously combines an atmospheric pressure DMS 502 with a low pressure DMS 204 to combine the benefits of performing ion mobility based separation at both conditions. This can provide a dramatic improvement in separation power and peak capacity when the separation conditions are different in the 2 mobility analyzers.
  • Ion separation in DMS occurs as a result of differences in ion mobility at high and low electric fields.
  • the field dependence of the ion mobility can be symbolically represented as the ⁇ function, as shown in the following equation,
  • FIG. 12 illustrates the 3 general types of mobility behavior observed in a DMS, including monotonically increasing ⁇ (Type A), monotonically decreasing ⁇ (Type C), and first increasing then decreasing ⁇ (Type B).
  • the addition of polar modifiers to the transport gas within a DMS cell can improve selectivity as a result of cluster formation.
  • Different chemical species cluster to different extents with chemical modifiers, and this imparts additional selectivity.
  • the asymmetric waveform used in DMS varies between high field and low field regimes at a rate in the MHz range. This variation can be modeled as a field-dependent effective temperature synchronous with the Vrf field because of the high collision frequency at atmospheric pressure.
  • the time-varying effective temperature can cause a time-varying change in ion size and, therefore, a synchronous change in ion-mobility cross-section.
  • Ions are clustered during the low field portion of the waveform and undergoing declustering due to heating during the high field portion of the waveform.
  • the extent of clustering and the relative change in mobility due to clustering dictates the magnitude of Vc shift observed for the compounds, and the structural and chemical differences of compounds leads to a spread in peak position in the presence of clustering modifiers or dopants.
  • This reversible cluster formation provides a method for the amplification of differential mobility effects in DMS. Because the change in cluster number occurs between the low and high field regimes during the SV waveform in DMS, the differential mobility is greatly enhanced.
  • the hard sphere collision model can be used to predict the motion of colliding particles at high separation fields. Such predictions are widely used in molecular dynamics (MD) to understand and predict properties of physical systems at the particle level.
  • the hard sphere collision model is based on the kinetic theory of gases in which, unlike the viscous damping models, the individual collisions between ion and gas particles are modeled.
  • the expected frequency of collisions, measured as a distance (the mean-free-path) is predicted by the kinetic theory of gases as a function of the known pressure, temperature, and collisional cross sections of colliding particles.
  • Collisions between ion and gas particles result in positive and negative energy transfers as well as scattering (deflection of ion velocity vectors), or even absorptions (e.g. in electron-gas collisions).
  • the energy transfers provide for the kinetic cooling of a fast moving ion as well as the kinetic heating of a slow moving ion.
  • colliding particles are treated as hard spheres.
  • the background gas is non-stationary and has a Maxwell-Boltzmann distribution of velocities, which can be a function of temperature.
  • Such a configuration of an atmospheric pressure DMS 502 with a low pressure DMS 204 , in combination with the mass spectrometer 224 , provides for enhanced system 500 analysis selectivity.
  • Such solution as in system 500 can simplify the incorporation of DMS into existing analyzer instruments such as, for example, the QTRAP® 5500 system, and provide substantial improvements in detection limits. This will increase the number of assays where DMS and ion mobility based filtering is useful.
  • the region 202 may not include an RF ion guide.
  • a DMS can include a plurality of filter electrode pairs.
  • the DMS can comprise four electrodes, and the separation voltage can be applied across two of the electrodes. A focusing potential can be applied to the other two electrodes.
  • FIG. 6 shows a diagram of a mass analysis system 600 , like the system 500 shown in FIG. 5A , with a clustering and/or reaction region 612 prior to the atmospheric pressure DMS 502 according to an illustrative embodiment of the invention.
  • the mass analysis system 600 also includes a curtain plate 602 , a curtain chamber 604 , curtain gas inlet 606 , curtain gas control valve 608 , curtain gas source 610 , and aperture 614 .
  • the curtain plate 602 may be configured to direct the curtain gas flow 616 and 618 out of the aperture 614 and towards the ion source 208 .
  • a high-purity curtain gas e.g., N 2
  • the counter current gas flow e.g., curtain gas
  • a curtain gas is delivered to the curtain chamber 604 from a source 610 via a control valve 608 and inlet 606 .
  • the source 610 may provide a clustering reagent (e.g., a dopant or modifier) with the curtain gas.
  • the reagent may be in the form of a gas, vapor, and/or liquid.
  • the DMS 502 performs ion mobility based filtering and/or separation consistent with the clusterization model.
  • the alpha function becomes increasingly positive, indicating that the mobility under high field conditions is getting larger as an ion becomes smaller with increasing amounts of declustering.
  • the mobility during the low field portion of the waveform becomes smaller relative to the high field condition because the ion is larger and highly clustered.
  • the declustering mechanism dominates the separation process and the selectivity achieved is highly influenced by the chemical characteristics of the ion in relation to its immediate surroundings. Higher fields typically improve the declustering which accentuates the difference in the state of the ion, and thus mobility, under the two field conditions.
  • Clusterization model separations are considered to be chemically dominated separations (Type A).
  • the mass analysis system 600 enables tandem DMS operations, using atmospheric pressure DMS 502 and low pressure DMS 204 where the DMS 502 advantageously filters doped sample ions (e.g., reagent clustered sample ions) that were formed in the reaction/clustering region 612 due to mixing with the clustering reagent. But, after filtering by the DMS 502 , the sample ions are then declustered in the low pressure collision region 206 to remove the clustering reagent and/or other clustering. Once declustering/desolvation is performed, the dry and/or declustered sample ions then are subjected to further ion mobility based filtering by the low pressure DMS 204 .
  • doped sample ions e.g., reagent clustered sample ions
  • the DMS 204 performs ion mobility based filtering and/or separation consistent with the hard sphere collision model.
  • the behavior of the sample ions shift towards a Type C classification.
  • the mobility is decreasing relative to the low field condition which remains constant.
  • the hard sphere collision (or rigid sphere scattering) mechanism becomes dominant
  • the short-range repulsive potential becomes important, resulting in a decreasing mobility.
  • the separation process and the selectivity achieved is less under these conditions, since it has more to do with collision dynamics.
  • the negative shift in ⁇ shifts the compensation voltage in the opposite direction of what is observed when clustering phenomena dominate.
  • the sample ions that pass through the second DMS 204 are then analyzed and detected by the mass spectrometer 224 .
  • a DMS analyzer e.g., DMS 204
  • DMS 502 may be located within the first reduced vacuum pressure stage, e.g., vacuum chamber 202
  • modifiers may be added in the typical manner to the curtain gas stream to provide a DMS separation based upon clustering modifiers.
  • the clusters are lost upon expansion into the first vacuum chamber 202 , and this can be further facilitated by increasing the potential difference between the orifice 210 and QJET® ion guide 402 .
  • a second ion mobility based separation can be achieved within the first vacuum chamber 202 , in the absence of modifiers.
  • the tandem mobility analyzer e.g., system 600
  • the transmitted ion population is modified between the stages of DMS mobility based separation.
  • ions may be fragmented by application of a high potential difference between the orifice 210 and QJET ion guide 402 to provide additional selectivity.
  • This workflow would involve mobility selection of a particular ion in DMS 502 , followed by fragmentation in the interface, e.g., low pressure collision region 206 , followed by mobility selection in DMS 204 of a particular daughter ion.
  • the RF ion guide 402 can be removed, and the DMS can comprise for electrodes as shown in FIG. 5B .
  • FIG. 7A includes plots 702 , 704 , and 706 of normalized ion intensity peaks in a DMS without reagent modifiers at various Vrf settings. As shown in the plots 702 , 704 , 706 , is can be difficult to differentiate or separate the ion intensity peaks associated with this particular series of isobaric compounds under conditions where no dopant or modifier is added to sample ions passing through a DMS such as DMS 502 . As shown in FIG. 7A , there is a shift toward positive Vc values in all the compounds tested under these “dry ion” conditions.
  • FIG. 7B includes plots 708 , 710 , 712 , 714 , and 716 of normalized ion intensity peaks in a DMS with reagent modifiers introduced at various Vrf settings.
  • the various plots 708 , 710 , 712 , 714 , 716 illustrate the advantageous effect of adding a modifier, e.g., n-Propanol, 2-Propanol, and/or water, to the curtain gas which illustrate substantially improved peak capacity and substantially improved peak separation for many compounds in a DMS such as DMS 502 .
  • a modifier e.g., n-Propanol, 2-Propanol, and/or water
  • FIG. 7B there is a shift toward negative Vc values in all the compounds tested with a modifier and/or dopant added to the transport gas which is described based upon the clusterization model.
  • FIG. 8 shows a diagram of dopant introduction system 800 via a mixing chamber 802 according to an illustrative embodiment of the invention.
  • the system 800 may be included in the source 610 of FIG. 6 or may be included in the system 600 in addition to the source 610 .
  • the system 800 also includes a curtain/transport gas inlet 804 , a clustering reagent reservoir 806 , and a curtain chamber inlet 808 .
  • clustering reagent is stored in a liquid reservoir 806 and mixed in mixing chamber 802 with the curtain/transport gas.
  • the mixture of curtain gas and modifier are then delivered via the inlet 808 to the curtain gas chamber 604 and, more particularly, to the reaction/clustering region 612 .
  • the clustering reagent may be added to carrier/transport gas prior to introduction into the mixing chamber 802 .
  • FIG. 9 shows a diagram of an alternative dopant introduction system 900 according to an illustrative embodiment of the invention.
  • the system 900 includes a mixing region 902 within the curtain chamber 604 , a curtain/transport gas inlet 904 , and a clustering reagent reservoir 906 .
  • the clustering reagent and curtain gas are mixed in a mixing region 902 of the curtain gas chamber 604 .
  • the clustering reagent may be added to carrier/transport gas prior to introduction into the mixing chamber 902 .
  • FIG. 10 shows a diagram of a mass analysis system 1000 , like the system 600 in FIG. 6 , with a turbulent heated region 1002 according to an illustrative embodiment of the invention.
  • the system 1000 also includes a clustering reagent inlet 1004 , curtain gas inlet 1006 , and reagent/curtain gas mixing region 1008 .
  • the system 1000 employs a dopant introduction system like system 900 of FIG. 9 .
  • the system 1000 employs a dopant introduction system like system 800 of FIG. 8 .
  • the clustering reagent may be added directly to carrier/transport gas prior to introduction into the system.
  • the system 1000 also advantageous employs a turbulent heated region 1002 to enable turbulent heating of the sample ions from the ion source 208 .
  • One or more heating elements 1010 may be included in the heated region 1002 to generate a selected temperature for heating the sample ions.
  • a heating element 1010 may include a resistive element.
  • the controller 228 may control the application of current and/or voltage to a heating element 1010 via the voltage source 226 to regulate the temperature in the heated region 1002 .
  • One or more temperature sensors may be in communication with the controller 228 to enable the controller to regulate the temperature of the heated region.
  • the number and location of heating elements may vary in the system 1000 .
  • one or more heating elements may be located in the atmospheric pressure ion source region 404 , in the curtain chamber 604 , in the vacuum chamber 202 , in the intermediate region 406 , in the low pressure collision region 206 , or in any combination of the regions/locations within the system 1000 .
  • the sensitivity of the system 1000 is enhanced by improving declustering/desolvation at desired locations within the system 1000 .
  • the RF multipole 402 can be removed, and the DMS can comprise four electrodes as shown in FIG. 5B .
  • FIG. 11 is a graph 1100 including plots 1102 and 1104 of normalized ion intensity vs. compensation voltage when the inlet to the atmospheric pressure DMS is not heated and heated respectively ( 1102 includes the data without heat).
  • Plot 1102 shows the Vc (CV) at about ⁇ 2.5 volts with substantial peak tailing which is likely due to undesired clustering from moisture, for example, due to wet spray from an electrospray ionization source.
  • Plot 1104 shows a shift in Vc to about 0 volts with an increased ion intensity and improved peak shape after the DMS inlet is heated, which illustrates how heating can improve declustering and/or desolvation and enhance analysis system sensitivity such as for system 1000 .
  • heterogeneous clusters can be eliminated or reduced by employing heating techniques.
  • RF ion heating and bulk gas heating effects in DMS are closely related.
  • bulk heating can reduce the heterogeneous cluster ion population in an ion analyzer system.
  • the goal is to desolvate/decluster electrospray generated clusters, and then recluster with a desired gas-phase reaction forming a homogeneous population in the DMS cell and/or filter.
  • Heat transfer is highly efficient at atmospheric pressure due to the high frequency of molecular collisions and radiative heat transfer.
  • Various means for heating the cluster ions in the gas prior to the entrance of a DMS filter can be envisioned in addition to RF heating just described.
  • One approach uses a wall-less mixing region with counter-current gas flows to accomplish this. Hot desolvation gas containing a mixture of the inert nitrogen curtain/transport gas with the modifier/dopant flows counter to the incoming ion clusters and source gas in a wall-less area.
  • Flow can be non-laminar in this region which maximizes the residence time of the cluster ion species in the heated region to drive desolvation to the extent possible.
  • the background gas may have a high concentration of modifier/dopant that drives the equilibrium toward the desired homogeneous cluster ion population.
  • the outflow of drying gas in front of the DMS analyzer region also helps to prevent neutral solvents and very large droplets from entering and contaminating the mobility analyzer region. Heterogeneous ion clusters can be reduced using this approach.
  • the controller 228 controls various parameters of the analysis process such as, without limitation, dopant concentration, temperature, flow rate, Vc, Vrf, and pressure within the various portions of the analyzer system, such as system 1000 .
  • FIG. 12 is a graph of the alpha behavior for type A, B, and C ion mobility behavior.
  • the Type A curve is associated with the clusterization model and exhibits a monotonic increase in alpha (a) with the increase in field strength.
  • the Type C curve is associated with the hard sphere collision model and exhibits a monotonic decrease in alpha with the increase in field strength.
  • the Type B curve is associated with a bi-model mode (combination of Type A first, then Type C) where an initial increase then decrease in alpha occurs with an increase in field strength.
  • the classification describes the dominant separation mechanism at play which in turn is controlled by the degree to which an ion is clustered or adducted to neutral molecules.
  • Types A and C represent limits (extremes) where one mechanism dominates, and type B is observed under conditions such that a mixture of mechanisms is apparent.
  • the alpha function becomes increasingly positive indicating that the mobility under high field conditions is getting larger as the ion becomes smaller with increasing amounts of declustering.
  • the mobility during the low field portion of the waveform becomes smaller relative to the high field condition because the ion is larger and highly clustered.
  • the declustering mechanism dominates the separation process and the selectivity achieved is highly influenced by the chemical characteristics of the ion in relation to its immediate surroundings.
  • the alpha function rapidly climbs with increasing Rf field.
  • the separation mechanism Under inert transport gas conditions, the separation mechanism exhibits declustering behavior at low Rf amplitudes. Compounds that exhibit this behavior are present as adducts or clusters even under dry transport gas conditions. As the field strength increases, the Vc reverses direction and shifts toward positive values exhibiting a negative trend in alpha. This bimodal behavior is illustrated in the Type B alpha plot of FIG. 12 .
  • the alpha function for a given ion within a DMS is constant, regardless of instrumental variations such as potential and pressure.
  • This principal forms the basis for DMS sensors employing ionization sources such as nickel 63 beta emitters in combination with ion current detectors.
  • ionization sources such as nickel 63 beta emitters in combination with ion current detectors.
  • the correlation of peaks at various Vc positions at different locations in the world necessitates this.
  • DMS peak capacity can not be significantly improved by simply providing two DMS filters and conducting two separations on the same ion population rather than one. Dramatic improvements in peak capacity can require significant alterations of the alpha function for a given ion population between the two separations.
  • an ion population passes through a reaction/cluster region and is carried through a first DMS with a transport gas containing clustering modifiers.
  • the ⁇ function for the clustered ions may have the form of the Type A behavior illustrated in FIG. 12 .
  • the selected subset of the ion population then passes through the dissociation region where the equilibrium is driven towards the declustered ion species.
  • a second DMS separation is carried out on the subset of ions, where the ⁇ function may display either Type B or Type C behavior.
  • FIG. 13 shows an example of the transformation of the ⁇ function for norfentanyl ions.
  • the trace labeled i) shows the alpha function for this ion under modified DMS separations where 1.5% 2-propanol was added to the nitrogen transport gas.
  • the trace labeled ii) shows a radically different alpha function that is obtained when operating with nitrogen transport gas.
  • the compound dependencies observed in the alpha functions under the two different conditions present the opportunity to dramatically improve peak capacity.
  • FIGS. 14A-C show the alpha functions for a series of ion separations in a DMS.
  • FIG. 14A shows chemically modified separations using 2-propanol modifier
  • FIGS. 14B and 14C show separations with inert nitrogen transport gas, respectively.
  • 36 compounds showed predominantly Type A behavior with positive values for the alpha function.
  • none of the 36 ions displayed Type A behavior, with all of them displaying a shift towards negative alpha values at high field.
  • the observed compensation voltages Vc for the chemical species were predominantly negative for the modified separation and positive for the inert gas separation.
  • the alpha function may also be altered in other ways including but not limited to a) maintaining a constant concentration of clustering modifier and varying the temperature within the two DMS analyzers to effect the degree of clustering, altering the transport gas composition without adding liquid modifiers, and fragmenting the ion of interest in the dissociation region such that the ion monitored in the second DMS has a different m/z than the ion monitored in the first DMS cell.
  • a computer program product that includes a computer usable and/or readable medium.
  • a computer usable medium may consist of a read only memory device, such as a CD ROM disk or conventional ROM devices, or a random access memory, such as a hard drive device or a computer diskette, or flash memory device having a computer readable program code stored thereon.
  • the dissociation region may comprise other means of heating ions including a source of radiation such as a laser, or other devices.

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Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120267548A1 (en) * 2009-01-14 2012-10-25 Sociedad Europea De Analisis Diferencial De Movili Ionizer for vapor analysis decoupling the ionization region from the analyzer
US20120273673A1 (en) * 2011-04-26 2012-11-01 Bruker Daltonik Gmbh Selective Ion Mobility Spectrometer
WO2012167254A1 (en) * 2011-06-03 2012-12-06 Dh Technologies Development Pte. Ltd. Method and system for reducing interferences in the spectrometric analysis of steroids
WO2013061141A1 (en) * 2011-10-26 2013-05-02 Dh Technologies Development Pte. Ltd. Apparatus and method for fractionation
WO2013152344A1 (en) * 2012-04-06 2013-10-10 Implant Sciences Corporation Selective ionization using high frequency filtering of reactive ions
US20150129762A1 (en) * 2012-05-18 2015-05-14 Dh Technologies Development Pte. Ltd. Reducing interferences in isobaric tag-based quantification
US20150179421A1 (en) * 2013-12-24 2015-06-25 Waters Technologies Corporation Ion optical element
WO2015101821A1 (en) * 2013-12-31 2015-07-09 Dh Technologies Development Pte. Ltd. Vacuum dms with high efficiency ion guides
CN104833761A (zh) * 2015-06-01 2015-08-12 华质泰科生物技术（北京）有限公司 一种快速分析样品中的糖类化合物的方法
US20150340218A1 (en) * 2012-06-24 2015-11-26 Fasmatech Science & Technology SA Improvements in and relating to the control of ions
US20160118234A1 (en) * 2013-06-21 2016-04-28 Dh Technologies Development Pte. Ltd. Contamination Filter for Mass Spectrometer
US20160189949A1 (en) * 2013-08-08 2016-06-30 Shimadzu Corporation Triple quadrupole mass spectrometer
US9390898B1 (en) * 2013-08-30 2016-07-12 Leidos, Inc. System and method for fusing chemical detectors
CN106461609A (zh) * 2014-06-06 2017-02-22 英国质谱公司 迁移率选择性衰减
US9607817B1 (en) 2015-09-11 2017-03-28 Thermo Finnigan Llc Systems and methods for ion separation
US20170219526A1 (en) * 2014-08-05 2017-08-03 Dh Technologies Development Pte. Ltd. Methods for Distinguishing Dioleinates of Aged and Non-Aged Olive Oil
US20180003675A1 (en) * 2014-12-31 2018-01-04 DH Technologies Development Pte Ltd. Differential Mobility Spectrometry Method
US20180350582A1 (en) * 2015-11-27 2018-12-06 Shimadzu Corporation Ion transfer apparatus
CN109065435A (zh) * 2018-08-28 2018-12-21 山东省分析测试中心 一种微电离喷雾离子源差分离子迁移谱及其应用方法
GB2563752A (en) * 2014-06-11 2018-12-26 Micromass Ltd Monitoring ion mobility spectrometry environment for improved collision cross section accuracy and precision
US10192725B2 (en) 2013-12-24 2019-01-29 Waters Technologies Corporation Atmospheric interface for electrically grounded electrospray
US20190228124A1 (en) * 2018-01-19 2019-07-25 Nikolai Kislov Analytical Tools and Methods for Modeling Transport Processes in Fluids
US10388505B2 (en) 2014-06-11 2019-08-20 Micromass Uk Limited Monitoring ion mobility spectrometry environment for improved collision cross section accuracy and precision
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US10663428B2 (en) 2018-06-29 2020-05-26 Thermo Finnigan Llc Systems and methods for ion separation using IMS-MS with multiple ion exits
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EP4018469A1 (en) * 2019-08-21 2022-06-29 DH Technologies Development Pte. Ltd. Apparatus and methods for thermal dissociation in a mass spectrometry system
US11424114B2 (en) * 2017-11-28 2022-08-23 Dh Technologies Development Pte. Ltd. Predicting molecular collision cross-section using differential mobility spectrometry
US20220397552A1 (en) * 2021-06-10 2022-12-15 GP Ionics LLC Molecular identification using field induced fragmentation spectra by reactive stage tandem differential mobility spectrometry
US20230003686A1 (en) * 2018-02-13 2023-01-05 Jp Scientific Limited Ion mobility spectrometer and method of analyzing ions
US20240170273A1 (en) * 2014-06-16 2024-05-23 Purdue Research Foundation Sample analysis systems and methods of use thereof
US20240282564A1 (en) * 2021-06-22 2024-08-22 Dh Technologies Development Pte. Ltd. Automated systems and methods for separating compounds
DE112013001062B4 (de) 2012-02-21 2024-09-05 Thermo Fisher Scientific (Bremen) Gmbh Vorrichtung und Verfahren für die lonenmobilitätsspektrometrie
US12100583B2 (en) * 2020-05-29 2024-09-24 Bruker Scientific Llc Electrospray ion source for spectrometry using inductively heated gas
US12235239B2 (en) 2022-04-05 2025-02-25 Thermo Finnigan Llc Ion mobility enhanced qualitative and quantitative methods
US12578307B2 (en) 2020-04-03 2026-03-17 Micromass Uk Limited De-clustering ion guide

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2850644B1 (en) * 2012-05-18 2018-10-31 DH Technologies Development Pte. Ltd. Modulation of instrument resolution dependant upon the complexity of a previous scan
GB2517670B (en) * 2013-03-15 2020-04-29 Smiths Detection Watford Ltd Ion modification
US9057699B2 (en) 2013-11-21 2015-06-16 Hamilton Sundstrand Corporation High temperature differential ion mobility spectroscopy
JP6549130B2 (ja) * 2013-12-31 2019-07-24 ディーエイチ テクノロジーズ デベロップメント プライベート リミテッド 微分移動度分光計のための噴射注入器入口
WO2015189545A1 (en) * 2014-06-11 2015-12-17 Micromass Uk Limited Ion mobility spectrometry data directed acquisition
GB2531285B (en) 2014-10-14 2017-07-26 Smiths Detection-Watford Ltd Ion mobility spectrometer with ion modification
WO2016063236A1 (en) * 2014-10-22 2016-04-28 Dh Technologies Development Pte.Ltd. Methods and systems for cross-talk elimination in continuous beam mobility-based spectrometers
US20180033598A1 (en) * 2015-02-06 2018-02-01 Dh Technologies Development Pte. Ltd. Lipid Screening Platform Allowing a Complete Solution for Lipidomics Research
CN104637777B (zh) * 2015-02-16 2017-05-17 江苏天瑞仪器股份有限公司 一种质谱仪反吹气结构
US10541122B2 (en) 2017-06-13 2020-01-21 Mks Instruments, Inc. Robust ion source
CN111758146A (zh) 2018-01-17 2020-10-09 Dh科技发展私人贸易有限公司 用于提高msms置信度的dm-swath获取
US11293898B2 (en) 2020-02-06 2022-04-05 Thermo Finnigan Llc Duty cycle improvement for a mass spectrometer using ion mobility separation
US11273465B1 (en) * 2020-09-17 2022-03-15 Desaraju Subrahmanyam Tunable electrostatic ion and fluid flow generator and electroacoustic transducer
WO2024194832A1 (en) * 2023-03-23 2024-09-26 Dh Technologies Development Pte. Ltd. Method and system for introducing modifier into a curtain gas stream for a differential mobility spectrometer

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5432343A (en) * 1993-06-03 1995-07-11 Gulcicek; Erol E. Ion focusing lensing system for a mass spectrometer interfaced to an atmospheric pressure ion source
US20030020012A1 (en) * 2000-03-14 2003-01-30 Roger Guevremont Tandem high field asymmetric waveform ion mobility spectrometry (faims)tandem mass spectrometry
US7164122B2 (en) * 2000-02-29 2007-01-16 Ionwerks, Inc. Ion mobility spectrometer
US20080067367A1 (en) * 2006-09-20 2008-03-20 Bruker Daltonics, Inc. Means and method for field asymmetric ion mobility spectrometry combined with mass spectrometry

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4802104B2 (ja) * 2003-11-25 2011-10-26 サイオネックス コーポレイション サンプルの分析を改善するための分散特性、サンプル解離及び／又は圧力制御を用いた移動度ベースの装置及び方法
GB0503010D0 (en) 2005-02-14 2005-03-16 Micromass Ltd Mass spectrometer
EP1982349B1 (en) * 2006-02-07 2018-07-25 DH Technologies Development Pte. Ltd. Chemical noise reduction for mass spectrometry
US7812305B2 (en) * 2006-06-29 2010-10-12 Sionex Corporation Tandem differential mobility spectrometers and mass spectrometer for enhanced analysis
US7863562B2 (en) * 2007-06-22 2011-01-04 Shimadzu Corporation Method and apparatus for digital differential ion mobility separation
EP2281297B1 (en) * 2008-05-30 2019-01-16 DH Technologies Development Pte. Ltd. Method and system for vacuum driven differential mobility spectrometer/mass spectrometer interface with adjustable resolution and selectivity

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5432343A (en) * 1993-06-03 1995-07-11 Gulcicek; Erol E. Ion focusing lensing system for a mass spectrometer interfaced to an atmospheric pressure ion source
US7164122B2 (en) * 2000-02-29 2007-01-16 Ionwerks, Inc. Ion mobility spectrometer
US20030020012A1 (en) * 2000-03-14 2003-01-30 Roger Guevremont Tandem high field asymmetric waveform ion mobility spectrometry (faims)tandem mass spectrometry
US20080067367A1 (en) * 2006-09-20 2008-03-20 Bruker Daltonics, Inc. Means and method for field asymmetric ion mobility spectrometry combined with mass spectrometry

Cited By (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8461523B2 (en) * 2009-01-14 2013-06-11 Sociedad Europea de Analisis Diferencial de Movilidad Ionizer for vapor analysis decoupling the ionization region from the analyzer
US20120267548A1 (en) * 2009-01-14 2012-10-25 Sociedad Europea De Analisis Diferencial De Movili Ionizer for vapor analysis decoupling the ionization region from the analyzer
US20120273673A1 (en) * 2011-04-26 2012-11-01 Bruker Daltonik Gmbh Selective Ion Mobility Spectrometer
US8941054B2 (en) * 2011-04-26 2015-01-27 Bruker Daltonik Gmbh Selective ion mobility spectrometer formed from two consecutive mass selective filters
WO2012167254A1 (en) * 2011-06-03 2012-12-06 Dh Technologies Development Pte. Ltd. Method and system for reducing interferences in the spectrometric analysis of steroids
WO2013061141A1 (en) * 2011-10-26 2013-05-02 Dh Technologies Development Pte. Ltd. Apparatus and method for fractionation
DE112013001062B4 (de) 2012-02-21 2024-09-05 Thermo Fisher Scientific (Bremen) Gmbh Vorrichtung und Verfahren für die lonenmobilitätsspektrometrie
US9070542B2 (en) 2012-04-06 2015-06-30 Implant Sciences Corporation Selective ionization using high frequency filtering of reactive ions
WO2013152344A1 (en) * 2012-04-06 2013-10-10 Implant Sciences Corporation Selective ionization using high frequency filtering of reactive ions
US9164060B2 (en) * 2012-05-18 2015-10-20 Dh Technologies Development Pte. Ltd. Reducing interferences in isobaric tag-based quantification
US20150129762A1 (en) * 2012-05-18 2015-05-14 Dh Technologies Development Pte. Ltd. Reducing interferences in isobaric tag-based quantification
US20150340218A1 (en) * 2012-06-24 2015-11-26 Fasmatech Science & Technology SA Improvements in and relating to the control of ions
US9589777B2 (en) * 2012-06-24 2017-03-07 Fasmatech Science & Technology SA Control of ions
US9564302B2 (en) * 2013-06-21 2017-02-07 Dh Technologies Development Pte. Ltd. Contamination filter for mass spectrometer
US20160118234A1 (en) * 2013-06-21 2016-04-28 Dh Technologies Development Pte. Ltd. Contamination Filter for Mass Spectrometer
US9733215B2 (en) * 2013-06-21 2017-08-15 Dh Technologies Development Pte. Ltd. Contamination filter for mass spectrometer
US20170122908A1 (en) * 2013-06-21 2017-05-04 Dh Technologies Development Pte. Ltd. Contamination Filter for Mass Spectrometer
US20160189949A1 (en) * 2013-08-08 2016-06-30 Shimadzu Corporation Triple quadrupole mass spectrometer
US9466474B2 (en) * 2013-08-08 2016-10-11 Shimadzu Corporation Triple quadrupole mass spectrometer
US9390898B1 (en) * 2013-08-30 2016-07-12 Leidos, Inc. System and method for fusing chemical detectors
US10249481B2 (en) 2013-08-30 2019-04-02 Leidos, Inc. System and method for fusing chemical detectors
US9362098B2 (en) * 2013-12-24 2016-06-07 Waters Technologies Corporation Ion optical element
US20150179421A1 (en) * 2013-12-24 2015-06-25 Waters Technologies Corporation Ion optical element
US10192725B2 (en) 2013-12-24 2019-01-29 Waters Technologies Corporation Atmospheric interface for electrically grounded electrospray
WO2015101821A1 (en) * 2013-12-31 2015-07-09 Dh Technologies Development Pte. Ltd. Vacuum dms with high efficiency ion guides
US9921183B2 (en) * 2013-12-31 2018-03-20 Dh Technologies Development Pte. Ltd. Vacuum DMS with high efficiency ion guides
US20170212081A1 (en) * 2014-06-06 2017-07-27 Micromass Uk Limited Mobility Selective Attenuation
US10371665B2 (en) * 2014-06-06 2019-08-06 Micromass Uk Limited Mobility selective attenuation
DE112015002693B4 (de) 2014-06-06 2022-03-10 Micromass Uk Limited Mobilitätsselektive Dämpfung
CN106461609A (zh) * 2014-06-06 2017-02-22 英国质谱公司 迁移率选择性衰减
EP3961202A1 (en) 2014-06-11 2022-03-02 Micromass UK Limited Monitoring ion mobility spectrometry environment for improved collision cross section accuracy and precision
US10388505B2 (en) 2014-06-11 2019-08-20 Micromass Uk Limited Monitoring ion mobility spectrometry environment for improved collision cross section accuracy and precision
GB2563752A (en) * 2014-06-11 2018-12-26 Micromass Ltd Monitoring ion mobility spectrometry environment for improved collision cross section accuracy and precision
GB2563752B (en) * 2014-06-11 2019-04-10 Micromass Ltd Monitoring ion mobility spectrometry environment for improved collision cross section accuracy and precision
US20240170273A1 (en) * 2014-06-16 2024-05-23 Purdue Research Foundation Sample analysis systems and methods of use thereof
US9970900B2 (en) * 2014-08-05 2018-05-15 Dh Technologies Development Pte. Ltd. Methods for distinguishing dioleinates of aged and non-aged olive oil
US20170219526A1 (en) * 2014-08-05 2017-08-03 Dh Technologies Development Pte. Ltd. Methods for Distinguishing Dioleinates of Aged and Non-Aged Olive Oil
US10345261B2 (en) * 2014-12-31 2019-07-09 Dh Technologies Development Pte. Ltd. Differential mobility spectrometry method
US20180003675A1 (en) * 2014-12-31 2018-01-04 DH Technologies Development Pte Ltd. Differential Mobility Spectrometry Method
CN104833761A (zh) * 2015-06-01 2015-08-12 华质泰科生物技术（北京）有限公司 一种快速分析样品中的糖类化合物的方法
US9607817B1 (en) 2015-09-11 2017-03-28 Thermo Finnigan Llc Systems and methods for ion separation
US20180350582A1 (en) * 2015-11-27 2018-12-06 Shimadzu Corporation Ion transfer apparatus
US10770279B2 (en) * 2015-11-27 2020-09-08 Shimadzu Corporation Ion transfer apparatus
US20180350581A1 (en) * 2015-11-27 2018-12-06 Shimadzu Corporation Ion transfer apparatus
US11424114B2 (en) * 2017-11-28 2022-08-23 Dh Technologies Development Pte. Ltd. Predicting molecular collision cross-section using differential mobility spectrometry
US10467362B2 (en) * 2018-01-19 2019-11-05 Nikolai Kislov Analytical tools and methods for modeling transport processes in fluids
US20190228124A1 (en) * 2018-01-19 2019-07-25 Nikolai Kislov Analytical Tools and Methods for Modeling Transport Processes in Fluids
US11874251B2 (en) * 2018-02-13 2024-01-16 Jp Scientific Limited Ion mobility spectrometer and method of analyzing ions
US20230003686A1 (en) * 2018-02-13 2023-01-05 Jp Scientific Limited Ion mobility spectrometer and method of analyzing ions
CN112703578A (zh) * 2018-06-04 2021-04-23 印地安纳大学理事会 用于将离子从大气压力环境输送到低压力环境的接口
US11119070B2 (en) 2018-06-29 2021-09-14 Thermo Finnigan Llc Systems and methods for ion mobility separation using a lens array
US10663428B2 (en) 2018-06-29 2020-05-26 Thermo Finnigan Llc Systems and methods for ion separation using IMS-MS with multiple ion exits
US10663430B2 (en) 2018-08-08 2020-05-26 Thermo Finnigan Llc Quantitation throughput enhancement by differential mobility based pre-separation
CN110828286A (zh) * 2018-08-08 2020-02-21 萨默费尼根有限公司 通过基于差分迁移率的预分离的定量通量增强
CN109065435A (zh) * 2018-08-28 2018-12-21 山东省分析测试中心 一种微电离喷雾离子源差分离子迁移谱及其应用方法
US20220293406A1 (en) * 2019-08-21 2022-09-15 Dh Technologies Development Pte. Ltd. Apparatus and methods for thermal dissociation in a mass spectrometry system
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US12578307B2 (en) 2020-04-03 2026-03-17 Micromass Uk Limited De-clustering ion guide
US12100583B2 (en) * 2020-05-29 2024-09-24 Bruker Scientific Llc Electrospray ion source for spectrometry using inductively heated gas
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US12235239B2 (en) 2022-04-05 2025-02-25 Thermo Finnigan Llc Ion mobility enhanced qualitative and quantitative methods

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