WO2022136882A1 - Spectrométrie de masse et/ou de mobilité ionique - Google Patents

Spectrométrie de masse et/ou de mobilité ionique Download PDF

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Publication number
WO2022136882A1
WO2022136882A1 PCT/GB2021/053427 GB2021053427W WO2022136882A1 WO 2022136882 A1 WO2022136882 A1 WO 2022136882A1 GB 2021053427 W GB2021053427 W GB 2021053427W WO 2022136882 A1 WO2022136882 A1 WO 2022136882A1
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WIPO (PCT)
Prior art keywords
ion
charge
detector
ions
separation device
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Application number
PCT/GB2021/053427
Other languages
English (en)
Inventor
Jason WILDGOOSE
Martin Green
David Langridge
Kevin Giles
Jakub Ujma
Original Assignee
Micromass Uk Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB2020575.3A external-priority patent/GB202020575D0/en
Application filed by Micromass Uk Limited filed Critical Micromass Uk Limited
Priority to EP21835817.4A priority Critical patent/EP4268263A1/fr
Priority to US18/259,015 priority patent/US20240047191A1/en
Priority to CN202180084246.XA priority patent/CN116615648A/zh
Publication of WO2022136882A1 publication Critical patent/WO2022136882A1/fr

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Classifications

    • 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
    • H01J49/34—Dynamic spectrometers
    • H01J49/40—Time-of-flight spectrometers
    • 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
    • G01N27/623—Ion mobility spectrometry combined with mass spectrometry

Definitions

  • the present invention relates generally to methods of analysing particles and/or ions, and in particular to methods of analysing particles and/or ions using mass and/or ion mobility spectrometry.
  • CDMS Charge detection mass spectrometry
  • a method of analysing ions comprising: separating ions according to a first physico-chemical property by passing the ions through an ion separation device; measuring the transit time of an ion through the ion separation device, so as to determine a transit time of the ion; detecting the ion using a charge-resolving ion detector so as to determine a charge of the ion; and using the transit time and the charge of the ion to determine a second physico-chemical property of the ion.
  • Various embodiments are directed to a method of analysing ions in which ions are separated according to a first physico-chemical property by passing the ions through an ion separation device. For each (individual) ion of one or more of the ions, the transit time of that ion through the separation device is measured, so as to determine a transit time (i.e. “drift time”) for the ion. In addition, the ion is detected using a charge-resolving ion detector, so as to determine the charge (i.e. “charge state” or “charge number”) of the ion. The transit time and the charge of the ion are then used (e.g. combined) to determine a second physico-chemical property of the ion.
  • a transit time i.e. “drift time”
  • charge-resolving ion detector so as to determine the charge (i.e. “charge state” or “charge number”) of the ion.
  • the transit time of each ion will be related to its mass to charge ratio.
  • the mass of the ion or a property related to mass
  • this process is repeated for each ion of multiple ions, e.g. so to determine the second physico-chemical property (e.g. mass) of each individual ion, and the results are combined so as to produce a spectrum (e.g. a mass spectrum) for the ions under analysis.
  • a spectrum e.g. a mass spectrum
  • Embodiments are particularly suitable for the analysis of particles that can produce ions with different charge states but which are relatively close in mass to charge ratio (m/z). This can often be the case for high-mass particles (which are usually highly charged), e.g. having a mass > 1 MDa.
  • CDMS charge detection mass spectrometry
  • embodiments exploit the inherent speed of separation-based approaches (such as, e.g. time of flight (ToF) mass spectrometry). Moreover, embodiments utilise the charge state resolution provided by the charge-resolving ion detector (in addition to the e.g. mass to charge ratio (m/z) resolution of the separation device) to resolve ions e.g. with similar or the same mass to charge ratio (m/z) but different charges (z).
  • ToF time of flight
  • CDMS charge detection mass spectrometry
  • the method may comprise ionising particles to as to produce the ions.
  • the particles, the ions and/or the ion may (each) have a mass > 1 MDa.
  • the first physico-chemical property may comprise mass to charge ratio (m/z) or ion mobility.
  • the ion separation device may comprise a time of flight (ToF) separation device configured to separate ions according to their mass to charge ratio.
  • the ion separation device may comprise a time of flight (ToF) mass analyser.
  • the ion separation device may comprise an ion separation device in which one or more time-varying electric fields is used to urge ions through a gas such that ions are separated according to mass to charge ratio.
  • the ion separation device may be a travelling wave separation device.
  • the method may comprise successively applying one or more voltages to different electrodes of the ion separation device so as to form one or more travelling potential barriers that move along the ion separation device so as to urge ions through the gas.
  • the ion separation device may comprise an ion mobility separation device configured to separate ions according to their ion mobility.
  • the step of measuring the transit time of the ion through the ion separation device may comprise using the charge-resolving ion detector to measure the transit time of the ion.
  • the charge-resolving ion detector may comprise (i) a faraday cup or cylinder electrode detector; (ii) an electron multiplier detector; (iii) a photomultiplier or scintillation counter detector; and/or (iv) a superconducting tunnel junction (STJ) detector.
  • the method may comprise determining the charge of the ion from the intensity, amplitude and/or area of a signal generated by the chargeresolving ion detector when the ion is detected.
  • the step of measuring the transit time of the ion through the ion separation device may comprise using a second (different) ion detector to measure the transit time of the ion.
  • the (each) ion may be detected by a first chargeresolving ion detector so as to determine the charge of the ion, and a second different ion detector so as to determine the transit time of the ion.
  • the charge-resolving ion detector may comprise any suitable (non-destructive) charge-resolving ion detector that is configured to measure the charge of an ion.
  • the charge-resolving ion detector may comprise an induction charge detector such as and induction plate or an induction tube.
  • the second ion detector may comprise (i) a faraday cup or cylinder electrode detector; (ii) an electron multiplier detector; (iii) a photomultiplier or scintillation counter detector; and/or (iv) a superconducting tunnel junction (STJ) detector.
  • the charge-resolving ion detector may be arranged upstream of the second ion detector.
  • Using the transit time and the charge of the ion to determine a second physico-chemical property of the ion may comprise combining the transit time and the charge of the ion to determine the second physico-chemical property of the ion.
  • the method may comprise controlling the flux of the ions at the detector or detectors such that (some, most or all) individual ions are distinguishable from each other when detected by the detector or detectors.
  • the method may comprise, for each ion of multiple (individual) ions: measuring the transit time of the ion through the ion separation device, so as to determine a transit time of the ion; detecting the ion using the charge-resolving ion detector so as to determine a charge of the ion; and using the transit time and the charge of the ion to determine the second physico-chemical property of the ion.
  • the method may further comprise: combining the determined second physico-chemical property of each ion of the multiple ions so as to produce a spectrum for the ions.
  • the second physico-chemical property may comprise mass, or collision or reaction cross section.
  • the spectrum may comprise a mass spectrum or a collision or reaction cross section spectrum.
  • the method may comprise reducing the charge of the ions before separating the ions.
  • an analytical instrument comprising: an ion separation device, wherein the ion separation device is configured to separate ions according to a first physico-chemical property when the ions are passed through the ion separation device; and an ion detector arranged downstream of the ion separation device, wherein the analytical instrument is configured such that ions eluting from the ion separation device can be detected by the ion detector; wherein the analytical instrument is configured to measure the transit time of an ion passing through the ion separation device, so as to determine a transit time of the ion; wherein the ion detector comprises a charge-resolving ion detector configured to determine the charge of the ion; and wherein the analytical instrument is configured to use the transit time and the charge of the ion to determine a second physico-chemical property of the ion.
  • the analytical instrument may comprise an ion source configured to ionise particles so as to produce the ions.
  • the particles, the ions and/or the ion may (each) have amass > 1 MDa.
  • the first physico-chemical property may comprise mass to charge ratio (m/z) or ion mobility.
  • the ion separation device may comprise a time of flight (ToF) separation device configured to separate ions according to their mass to charge.
  • the ion separation device may comprise a time of flight (ToF) mass analyser.
  • the ion separation device may comprise an ion separation device in which one or more time-varying electric fields is used to urge ions through a gas such that ions are separated according to mass to charge ratio.
  • the ion separation device may be a travelling wave separation device.
  • the analytical instrument may be configured to successively apply one or more voltages to different electrodes of the ion separation device so as to form one or more travelling potential barriers that move along the device so as to urge ions through the gas.
  • the ion separation device may comprise an ion mobility separation device configured to separate ions according to their ion mobility.
  • the analytical instrument may be configured to use the charge-resolving ion detector to measure the transit time of the ion passing through the ion separation device.
  • the charge-resolving ion detector may comprise (i) a faraday cup or cylinder electrode detector; (ii) an electron multiplier detector; (iii) a photomultiplier or scintillation counter detector; and/or (iv) a superconducting tunnel junction (STJ) detector.
  • the analytical instrument may be configured to determine the charge of the ion from the intensity, amplitude and/or area of a signal generated by the charge-resolving ion detector when the ion is detected.
  • the analytical instrument may comprise a second ion detector, and the analytical instrument may be configured to measure the transit time of the ion passing through the ion separation device using the second ion detector.
  • the analytical instrument may be configured to use a first charge-resolving ion detector to determine the charge of the (each) ion, and a second different ion detector to determine the transit time of the (each) ion.
  • the charge-resolving ion detector may comprise any suitable (non-destructive) charge-resolving ion detector that is configured to measure the charge of an ion.
  • the charge-resolving ion detector may comprise an induction charge detector such as and induction plate or an induction tube.
  • the second ion detector may comprise (i) a faraday cup or cylinder electrode detector; (ii) an electron multiplier detector; (iii) a photomultiplier or scintillation counter detector; and/or (iv) a superconducting tunnel junction (STJ) detector.
  • STJ superconducting tunnel junction
  • the charge-resolving ion detector may be arranged upstream of the second ion detector.
  • the analytical instrument may be configured to combine the transit time and the charge of the ion to determine the second physico-chemical property of the ion.
  • the analytical instrument may be configured to control the flux of the ions at the detector or detectors such that (some, most or all) individual ions are distinguishable from each other when detected by the detector or detectors.
  • the analytical instrument may be configured to: for each ion of multiple (individual) ions: measure the transit time of the ion through the ion separation device, so as to determine a transit time of the ion; detect the ion using the charge-resolving ion detector so as to determine a charge of the ion; and use the transit time and the charge of the ion to determine the second physico-chemical property of the ion.
  • the analytical instrument may be further configured to: combine the determined second physico-chemical property of each ion of the multiple ions so as to produce a spectrum for the ions.
  • the second physico-chemical property may comprise mass or collision or reaction cross section.
  • the spectrum may comprise a mass spectrum or a collision or reaction cross section spectrum.
  • the analytical instrument may comprise one or more devices configured to reduce the charge of the ions, which may be arranged upstream of the ion separation device.
  • a method of analysing ions comprising: detecting an ion using an induction charge detector; determining a charge of the ion from a signal generated by the induction charge detector when the ion is detected; determining a transit time of the ion from the signal generated by the induction charge detector when the ion is detected; and using the transit time and the charge of the ion to determine a (second) physico-chemical property of the ion.
  • an analytical instrument comprising: an induction charge detector configured to detect ions; wherein the analytical instrument is configured to: determine a charge of an ion from a signal generated by the induction charge detector when the ion is detected; determine a transit time of the ion from the signal generated by the induction charge detector when the ion is detected; and use the transit time and the charge of the ion to determine a (second) physico-chemical property of the ion.
  • the method may comprise: for each ion of multiple ions: detecting the ion using the induction charge detector; determining a charge of the ion from a signal generated by the induction charge detector when the ion is detected; determining a transit time of the ion from the signal generated by the induction charge detector when the ion is detected; and using the transit time and the charge of the ion to determine a
  • the second physico-chemical property may comprise (i) mass or (ii) collision or reaction cross section.
  • a method of analysing ions comprising: isolating an ion that has a first value of a first physico-chemical property by passing ions through an ion filtering device; detecting the ion using a charge-resolving ion detector so as to determine a charge of the ion; and using the first value of the first physico-chemical property and the charge of the ion to determine a second physico-chemical property of the ion.
  • an analytical instrument comprising: an ion filtering device, wherein the a ion filtering device is configured to filter ions according to a first physico-chemical property when ions are passed through the ion separation device; and an ion detector arranged downstream of the ion filtering device, wherein the analytical instrument is configured such that ions eluting from the ion filtering device can be detected by the ion detector; wherein the analytical instrument is configured to isolate an ion that has a first value of the first physico-chemical property by passing ions through the ion filtering device; wherein the ion detector comprises a charge-resolving ion detector configured to determine the charge of the ion; and wherein the analytical instrument is configured to use the first value of the first physico-chemical property and the charge of the ion to determine a second physico-chemical property of the ion.
  • the method may comprise: isolating ions having different values of the first physico-chemical property by passing ions through the ion filtering device, optionally while varying (e.g. scanning) a (first physico-chemical property) transmission window of the ion filtering device; and for each ion of multiple ions: detecting the ion using a charge-resolving ion detector so as to determine a charge of the ion; and using the value of the first physico-chemical property of the ion and the charge of the ion to determine a second physico-chemical property of the ion; and combining the determined second physico-chemical property of each ion of the multiple ions so as to produce a spectrum for the ions.
  • the first physico-chemical property may comprise mass to charge ratio (m/z).
  • the second physico-chemical property may comprise mass.
  • the ion filtering device may comprising a quadrupole mass filter.
  • a method of mass spectrometry comprising: separating a population of ions in time where the time is related to two or more physico-chemical properties, and where one of the physico-chemical properties is number of charges; detecting ions using a detector that has a response that is a function of the charge state of ions detected; controlling the ion flux at the detector so that responses of individual ions are distinguishable from each other and measurable; and processing the detector signal each separation cycle so as to produce a spectrum based on one or more physicochemical properties other than charge state.
  • FIG. 1 shows schematically an analytical instrument configured in accordance with embodiments
  • Figure 2 shows the percentage reduction in average particle velocity as a function of a and y for a one-dimensional smoothly moving travelling wave devices
  • Fig. 3 shows schematically an analytical instrument configured in accordance with embodiments
  • Fig. 4 shows schematically an analytical instrument configured in accordance with embodiments
  • Fig. 5 shows schematically an analytical instrument configured in accordance with embodiments.
  • Fig. 6 shows simulated data from a simple listening tube.
  • CDMS is becoming a popular method of mass spectrometry for highly charged species, as the technique employs approaches that allow ions with similar or the same mass to charge ratio (m/z) but different charges (z) to be separated, ultimately improving the resolution and mass measurement of mass spectra.
  • These approaches typically use ion trapping techniques to simultaneously measure m/z and z.
  • these approaches are relatively slow when compared with other m/z separations such as time of flight mass spectrometry (ToF-MS).
  • the speed is further compromised by the restriction of being limited to analysing single particles and/or molecules to avoid space charge effects as well as overlapping signals due to trapped ions following non-unique flight paths and/or trajectories.
  • Various embodiments are directed to a method of analysing ions in which ions are separated according to a first physico-chemical property by passing the ions through an ion separation device. For each (individual) ion of one or more of the ions, the transit time of that ion through the separation device is measured, so as to determine a transit time (i.e. “drift time”) for the ion. In addition, the ion is detected using a charge-resolving ion detector, so as to determine the charge (i.e. “charge state” or “charge number”) of the ion. The transit time and the charge of the ion are then used (e.g. combined) to determine a second physico-chemical property of the ion.
  • a transit time i.e. “drift time”
  • charge-resolving ion detector so as to determine the charge (i.e. “charge state” or “charge number”) of the ion.
  • the transit time of each ion will be related to its mass to charge ratio.
  • the mass (or a property related to mass) of the ion can be determined.
  • the transit time of each ion will be related to its ion mobility.
  • the collision or reaction cross section or a property related to collision or reaction cross section of the ion can be determined.
  • this process is repeated for each ion of multiple ions, e.g. so to determine the second physico-chemical property (e.g. mass) of each individual ion, and the results are combined so as to produce a spectrum (e.g. a mass spectrum) for the ions under analysis.
  • the flux of the ions at the detector or detectors may be controlled such that (some, most or all) individual ions are distinguishable from each other when detected by the detector or detectors.
  • Embodiments are particularly suitable for the analysis of particles that can produce ions with different charge states but which are relatively close in mass to charge ratio (m/z). This can often be the case for high-mass particles (which are usually highly charged), e.g. having a mass > 1 MDa.
  • CDMS charge detection mass spectrometry
  • embodiments exploit the inherent speed of separation-based approaches (such as, e.g. time of flight (ToF) mass spectrometry). Moreover, embodiments utilise the charge state resolution provided by the charge-resolving ion detector (in addition to the e.g. mass to charge ratio (m/z) resolution of the separation device) to resolve ions e.g. with similar or the same mass to charge ratio (m/z) but different charges (z).
  • ToF time of flight
  • CDMS charge detection mass spectrometry
  • Figure 1 shows schematically an analytical instrument in the form of a mass and/or ion mobility spectrometer in accordance with embodiments.
  • the analytical instrument comprises an ion source 10, an ion separation device 20 arranged downstream from the ion source 10, and a detector 30 that is arranged downstream from the ion source 10 and downstream from the ion separation device 20.
  • the analytical instrument may be configured such that ions can be provided by (sent from) the ion source 10 to the analyser 30 via the ion separation device 20.
  • the analytical instrument may comprise a control system 40 that is configured to control the operation of the analytical instrument, for example in the manner of the various embodiments described herein.
  • the control system may comprise suitable control circuitry that is configured to cause the instrument to operate in the manner of the various embodiments described herein.
  • the control system may comprise suitable processing circuitry configured to perform any one or more or all of the necessary processing and/or post-processing operations in respect of the various embodiments described herein.
  • the control system may comprise one or more of a suitable computing device, a microprocessor system, a programmable FPGA (field programmable gate array), and the like.
  • the ion source 10 is configured to ionise particles so as to produce ions.
  • the particles may be high-mass particles, e.g. where each particle has a mass > 1 MDa. Equally, the ions may each have a mass > 1 MDa. Such high- mass particles (which are usually highly charged) can often produce ions with different charge states but which are relatively close in mass to charge ratio (m/z).
  • High mass particles can include any high mass particles, such as for example viruses, capsids, nanoparticles such as nanoparticles comprising surface active molecules (e.g. vesicles, nano-discs), lipoprotein particles (e.g. cholesterol), polyoxo-metallates and other supramolecular constructs, metal clusters, polymer chains, and the like.
  • high mass particles such as for example viruses, capsids, nanoparticles such as nanoparticles comprising surface active molecules (e.g. vesicles, nano-discs), lipoprotein particles (e.g. cholesterol), polyoxo-metallates and other supramolecular constructs, metal clusters, polymer chains, and the like.
  • the ion source 10 may comprise any suitable ion source, such as an ambient ionisation ion source, that is, an ion source configured to ionise the particles at ambient or atmospheric pressure.
  • an ambient ionisation ion source that is, an ion source configured to ionise the particles at ambient or atmospheric pressure.
  • the ion source 10 may be an ion source selected from the group consisting of: (i) an Electrospray ionisation (“ESI”) ion source; (ii) an Atmospheric Pressure Photo Ionisation (“APPI”) ion source; (iii) an Atmospheric Pressure Chemical Ionisation (“APCI”) ion source; (iv) a Matrix Assisted Laser Desorption Ionisation (“MALDI”) ion source; (v) a Laser Desorption Ionisation (“LDI”) ion source; (vi) an Atmospheric Pressure Ionisation (“API”) ion source; (vii) a Desorption Ionisation on Silicon (“DIOS”) ion source; (viii) an Electron Impact ("El”) ion source; (ix) a Chemical Ionisation (“Cl”) ion source; (x) a Field Ionisation (“Fl”) ion source; (xi) a Field Desorption (“FD”) ion source; (xi
  • the ion source 10 is an electrospray ionisation (ESI) ion source.
  • ESI electrospray ionisation
  • the analytical instrument may optionally comprise a chromatography or other separation device (not shown in Figure 1) upstream of (and coupled to) the ion source 10.
  • the chromatography separation device may comprise a liquid chromatography or gas chromatography device.
  • the separation device may comprise: (i) a Capillary Electrophoresis (“CE”) separation device; (ii) a Capillary Electrochromatography (“CEC”) separation device; (iii) a substantially rigid ceramic-based multilayer microfluidic substrate (“ceramic tile”) separation device; or (iv) a supercritical fluid chromatography separation device.
  • the ion separation device 20 is configured to receive ions from the ion source 10 (optionally via one or more ion guides or other ion optical elements), separate the ions according to a first physico-chemical property, and then pass the separated ions to the detector 30 for detection (optionally via one or more ion guides or other ion optical elements). Ions may be separated within the ion separation device 20 as they travel through the ion separation device 20.
  • Ions may be separated according to the first physico-chemical property such that ions having different values of the first physico-chemical property arrive at an exit region of the ion separation device 20 at different times, for example such that ions with relatively high values of the first physico-chemical property arrive at the exit region ahead of ions with relatively low values of the first physico-chemical property (or such that ions with relatively low values of the first physico-chemical property arrive at the exit region ahead of ions with relatively high values of the first physico-chemical property).
  • the ion separation device 20 may comprise any suitable device configured to (temporally) separate ions according to the first physico-chemical property.
  • the first physico-chemical property may comprise any suitable physicochemical property.
  • the first physico-chemical property is (i) mass to charge ratio (m/z), or (ii) ion mobility collision or reaction cross section.
  • the ion separation device 20 may comprise a time of flight (ToF) separation device, such as a time of flight (ToF) mass analyser, configured to separate ions according to their mass to charge ratio (m/z).
  • TOF time of flight
  • the mass analyser may comprise an acceleration (pusher) electrode, an acceleration region, and a field free or drift region (e.g. in the form of a “drift tube”).
  • the mass analyser may also comprise a (pusher) drive unit and circuitry configured to supply electrical pulses generated by the drive unit to the acceleration (pusher) electrode of the mass analyser.
  • Ions from the ion source 10 may be arranged to enter the acceleration region where they may be driven into the field free or drift region by application of an electrical pulse (generated by the (pusher) drive unit) to the acceleration (pusher) electrode.
  • the time of flight (ToF) mass analyser may be configured to cause ions to be accelerated into the field free or drift region as a result of an electrical pulse being supplied to the acceleration electrode.
  • the ions may be accelerated to a velocity determined by the energy imparted by the pulse and the mass to charge ratio (m/z) of the ions. Ions having a relatively low mass to charge ratio will achieve a relatively high velocity and reach the exit of the field free or drift region prior to ions having a relatively high mass to charge ratio. Thus, ions may arrive at the exit of the field free or drift region after a transit time determined by their velocity and the distance travelled, which enables the mass to charge ratio of the ions to be determined.
  • ions may be separated according to their mass to charge ratio (m/z), and a transit time of a (each) ion through the ion separation device may be measured so as to determine the transit time of the ion (which transmit time may be related to the mass to charge ratio of the ion).
  • the (drift tube of the) ion separation device 20 may be maintained at a relatively low pressure, such as a pressure of around (i) ⁇ 0.00001 mbar; (ii) 0.00001-0.0001 mbar; (iii) 0.0001-0.001 mbar; (iv) 0.001-0.01 mbar; or (iv) 0.01-0.1.
  • the ion separation device 20 may comprises a high pressure m/z separation device.
  • the ion separation device 20 may be configured to separate ions according to mass to charge ratio by using one or more time-varying electric fields to urge ions through a gas.
  • a separation region of the ion separation device 20 may be filled with a gas, such as an inert (buffer) gas, such as nitrogen. Ions may be separated within the ion separation device 20 according to their mass to charge ratio (m/z) as they pass through the gas.
  • a gas such as an inert (buffer) gas, such as nitrogen. Ions may be separated within the ion separation device 20 according to their mass to charge ratio (m/z) as they pass through the gas.
  • the (separation region of the) ion separation device 20 may be operated (maintained) at any suitable pressure, such as (i) ⁇ O.lmbar; (ii) 0.1-0.5 mbar; (iii) 0.5-1 mbar; (iv) 1-2 mbar; (v) 2-5 mbar; (vi) 5-10 mbar; (vii) 10-15 mbar; (viii) 15-20 mbar; (ix) 20-25 mbar; (x) 25-30 mbar; or (xi) > 30 mbar.
  • the (separation region of the) ion separation device 20 is maintained at a pressure between about 0.1 and 20 mbar.
  • Embodiments therefore provide a particularly simple and low- cost method of analysing particles, and a particularly simple and low-cost analytical instrument.
  • the ion separation device 20 may be configured such that one or more time-varying electric fields is used to urge ions through the gas such that ions are separated according to mass to charge ratio (m/z).
  • the ion separation device 20 comprises a travelling wave (TW) ion separation device.
  • the ion separation device 20 may comprise a plurality of electrodes, e.g. in the form of an ion guide. Electrodes of the ion guide may define an ion path along which ions are transmitted in use.
  • the ion separation device 20 may comprise any suitable ion guide, such as an ion guide comprising a plurality of electrodes each having an aperture through which ions are transmitted in use (such as a stacked ring (or stacked plate) ion guide), or a segmented quadrupole ion guide.
  • a segmented quadrupole ion guide can provide a more uniform radial distribution of charge states.
  • the ion guide may be a linear (straight) ion guide, or a closed loop or cyclic ion guide.
  • the ion separation device 20 may comprise one or more voltage sources configured to apply voltages to the electrodes of the ion guide. Voltages may be successively applied to the electrodes of the device 20 so as to form a wave of potential barriers that move in a first direction along the device so as to urge ions in the first direction through the gas.
  • the first direction may be an axial direction along the length of the ion guide.
  • a travelling wave may be formed along the device 20, moving in a direction from an entrance end to an exit end of the separation device 20.
  • the moving DC potential barrier may urge the ions through the gas towards the exit end of the separation device 20.
  • the first direction may be a circumferential (azimuth) direction around the circumference of the ion guide.
  • the moving DC potential barrier may urge the ions around the ion guide one or more times.
  • Ions may be separated according to their mass to charge ratio such that ions having different mass to charge ratios arrive at an exit region of the ion guide at different times, for example such that ions with relatively high mass to charge ratios arrive at the exit region ahead of ions with relatively low mass to charge ratios (or such that ions with relatively low values of mass to charge ratio arrive at the exit region ahead of ions with relatively high values of mass to charge ratio).
  • Multiple DC potential barriers may be sequentially applied to (and travelled along or around) the separation device 20.
  • the parameters of the DC potential may be selected such that each ion is passed by the DC travelling potentials multiple times as it travels through the separation device 20, i.e. the ion will roll over multiple DC potential barriers. This may be achieved, for example, by selecting an appropriate speed and voltage amplitude for the DC potential barrier.
  • the amplitude of each DC voltage may be around (i) ⁇ 1 V; (ii) 1-10 V; (iii) 10-20 V; (iv) 20-30 V; (v) 30-40 V; (vi) 40-50 V; (vii) 50-60 V; (viii) 60- 70 V; (ix) 70-80 V; (x) 80-90 V; (xi) 90-100 V; and (xii) > 100 V.
  • Each voltage may be applied to an electrode for between around 10' 4 ms and 5 ms.
  • the wave(s) may have any suitable velocity such as around (i) ⁇ 50 m/s; (ii) 50-100 m/s; (iii) 100-200 m/s; (iv) 200-300 m/s; (v) 300-400 m/s; (vi) 400-500 m/s; (vii) 500-1000 m/s; (viii) 1000-1500 m/s; (ix) 1500-2000 m/s; or (x) > 2000 m/s.
  • Travelling wave (TW) induced ion transport depends on both ion mobility and mass to charge ratio (m/z).
  • m/z dependence has been previously characterized in terms of velocity relaxation, which (for a chosen set of operating parameters) increases with the mass to charge ratio (m/z) of the ions.
  • operating parameters can be tailored to yield separation dominated by either m/z or mobility, or a combination of the two.
  • Figure 2 shows the percentage reduction in average particle velocity as a function of a and y for a one-dimensional smoothly moving travelling wave device. Qualitative behaviour in more realistic devices in which ions can move off-axis and in which waves move forward in steps rather than moving smoothly is similar, and can be characterized numerically or in simulation.
  • the parameters of the DC potential may be selected such that ions are separated (predominantly) according to mass to charge ratio.
  • the applied travelling wave(s) may be smoothly moving or stepped.
  • the step size may be adjusted to optimize the relative amounts of mass to charge ratio (m/z) and ion mobility separation.
  • the ion separation device 20 may be operated with or without radially confining RF voltages. Where the ion separation device 20 is operated without radially confining RF voltages, the travelling wave conditions may be chosen to produce sufficient m/z separation and confinement simultaneously.
  • the ion separation device 20 may comprise one or more further voltage supplies configured to supply an AC or RF voltage to the electrodes. Opposite phases of an AC or RF voltage may be applied to successive electrodes.
  • the AC or RF voltage may have an amplitude selected from the group consisting of: (i) ⁇ 50 V peak to peak; (ii) 50-100 V peak to peak; (iii) 100-150 V peak to peak; (iv) 150- 200 V peak to peak; (v) 200-250 V peak to peak; (vi) 250-300 V peak to peak; (vii) 300-350 V peak to peak; (viii) 350-400 V peak to peak; (ix) 400-450 V peak to peak; (x) 450-500 V peak to peak; and (xi) > 500 V peak to peak.
  • the AC or RF voltage may have a frequency selected from the group consisting of: (i) ⁇ 100 kHz; (ii) 100- 200 kHz; (iii) 200-300 kHz; (iv) 300-400 kHz; (v) 400-500 kHz; (vi) 0.5-1.0 MHz; (vii) 1.0-1.5 MHz; (viii) 1.5-2.0 MHz; (ix) 2.0-2.5 MHz; (x) 2.5-3.0 MHz; (xi) 3.0-3.5 MHz; (xii) 3.5-4.0 MHz; (xiii) 4.0-4.5 MHz; (xiv) 4.5-5.0 MHz; (xv) 5.0-5.5 MHz; (xvi) 5.5- 6.0 MHz; (xvii) 6.0-6.5 MHz; (xviii) 6.5-7.0 MHz; (xix) 7.0-7.5 MHz; (xx) 7.5-8.0 MHz; (xxi) 8.0-8.5 MHz; (xxii) 8.5
  • the ion separation device 20 may be configured to (receive and) separate packets (groups) of ions. Where the ion source 10 comprises a pulsed ion source, packets of ions may be generated by the ion source 10.
  • the analytical instrument furthers comprises an ion trap (not shown in Figure 1), which may be arranged between the ion source 10 and the ion separation device 20. Ions generated by the ion source 10 may be accumulated in the ion trap, and the ion trap may be configured to pass packets of ions to the ion separation device 20, such as by periodically passing a packet of ions to the ion separation device 20. Each packet of ions may comprise ions of the mixture of particles to be analysed.
  • the ion trap may comprise any suitable ion trap, such as for example (i) a 2D or linear quadrupole ion trap; (ii) a Paul or 3D quadrupole ion trap; (iii) a Penning ion trap; (iv) a stacked ring ion trap; or (v) another type of ion trap.
  • a 2D or linear quadrupole ion trap such as for example (i) a 2D or linear quadrupole ion trap; (ii) a Paul or 3D quadrupole ion trap; (iii) a Penning ion trap; (iv) a stacked ring ion trap; or (v) another type of ion trap.
  • a gas-filled ion separation device 20 for mass to charge ratio separation, where a travelling voltage wave (TW) propels ions along the device 20.
  • the device 20 may be implemented between an ion source 10 (for example an electrospray ionisation (ESI) ion source) and a detector 30. Ions may be delivered to the TW device 20 in packets for subsequent separation.
  • the TW device 20 may be operated under conditions such that substantially temporal m/z separation is achieved during ion propulsion through the gas. The ions may be subsequently detected.
  • Embodiments therefore provide a particularly simple and low-cost method of analysing particles, and a particularly simple and low-cost analytical instrument.
  • Figure 3 shows schematically an analytical instrument in the form of a mass and/or ion mobility spectrometer in accordance with these embodiments.
  • the instrument may comprise an ambient ion source 10 in the form of a nano-ESI ion source. Ions generated by the ion source 10 may be sampled into an initial vacuum chamber 11 of the instrument via an atmospheric pressure interface 12.
  • the initial vacuum chamber 11 may be operated (maintained) at any suitable pressure, such as (i) ⁇ 1 mbar; (ii) 1-2 mbar; (iii) 2-5 mbar; (iv) 5-10 mbar; (v) 10-15 mbar; (vi) 15-20 mbar; (vii) 20-25 mbar; (viii) 25-30 mbar; or (ix) > 30 mbar.
  • the initial vacuum chamber 11 is maintained at a pressure between about 1 and 20 mbar. To do this, as shown in Figure 3, the initial vacuum chamber 11 may be pumped by a backing pump (roughing pump) 13.
  • one or more ion guides or other ion optical elements 14, e.g. in the form of a dual conjoined ion guide, are provided in the initial vacuum chamber 11, where the one or more ion guides or other ion optical elements 14 are configured to transfer ions received from the atmospheric pressure interface 12 to (and through) an aperture 15 arranged between the initial vacuum chamber 11 and a second vacuum chamber 21 of the analytical instrument.
  • the ion separation device 20 is a travelling wave (TW) ion separation device, which (as described above) comprises a plurality of electrodes in the form of an ion guide 22.
  • the ion guide 22 may be arranged within the second vacuum chamber 22, and the second vacuum chamber 21 may be maintained at a pressure between about 0.1 and 20 mbar.
  • ions are passed to the detector 30 via a second aperture 23 arranged between the second vacuum chamber 21 and a third vacuum chamber 31 of the analytical instrument.
  • the third vacuum chamber houses (at least) a detection surface 32 of the detector 30, and may be maintained at a pressure of around 0.0001 mbar. To do this, as shown in Figure 3, the initial third chamber 31 may be pumped by a turbomolecular pump 33.
  • the first physicochemical property is ion mobility.
  • the ion separation device 20 may comprise an ion mobility separator configured to separate ions according to their ion mobility.
  • the ion mobility separator may comprise a drift tube that may be pressurised with gas.
  • An electric field for example comprising a DC voltage gradient and/or a travelling DC voltage wave, may be arranged to urge ions along the length of the ion mobility separator, that is through the gas, so that ions separate according to their ion mobility.
  • the ions may optionally be urged against a counter flow of gas.
  • a gas flow may be arranged to urge ions along the length of the ion mobility separator, while an electric field, for example comprising a DC voltage gradient and/or a travelling DC voltage wave, may be arranged to oppose the gas flow so that ions separate according to their ion mobility.
  • an electric field for example comprising a DC voltage gradient and/or a travelling DC voltage wave
  • the ion mobility separator may operate in-line with the ion optical path of the analytical instrument.
  • the ion mobility separator may be configured substantially in accordance with the mass to charge ratio separator described above and shown in Figure 3, except that the separator 20 (e.g. TW device 20) may be operated under conditions such that substantially temporal ion mobility separation is achieved during ion propulsion through the gas.
  • the ion mobility separator may comprise a cyclic (closed-loop) ion separator.
  • the ion mobility separation device may include any or all of the features of the ion separation devices disclosed in US 9984861, entitled “Ion Entry/Exit Device", in the name of Micromass UK Limited, the entire contents of which is incorporated herein by reference. Using a cyclic ion mobility separator can allow a higher degree of separation, and so higher ion mobility resolution.
  • the detector 30 is configured to detect ions received from the ion separation device 20.
  • the analytical instrument may be configured such that ions eluting from the ion separation device 20 are detected by the detector 30.
  • Ions may arrive at the ion detector 30 after a time determined by their velocity and the distance travelled. As such, the transit time may be related to the first physico-chemical property (and may enable the first physico-chemical property of the ion to be determined).
  • the detector 30 may be configured to output a signal from which the transit time (i.e. “drift time”) for each ion may be measured.
  • the detector 30 may be configured to detect the intensity of each ion received at the detector 30 as a function of time.
  • Each ion arriving at the detector 30 may be sampled by the detector 30, and the signal from the detector 30 may be digitised, for example, using an ADC (analogue to digital converter).
  • a processor may then determine a value indicative of the transit time (e.g. time of flight) of that ion. This may use a known or measured start time together with the time at which the ion is detected. For example, where an ion gives rise to a peak having some width, a centroid or weighted average of that peak may be determined (from the digitised signal), and used as the detection time for that ion. The start time may be subtracted from the detection time so as to determine the transit time.
  • a value indicative of the transit time e.g. time of flight
  • This may use a known or measured start time together with the time at which the ion is detected. For example, where an ion gives rise to a peak having some width, a centroid or weighted average of that peak may be determined (from the digitised signal), and used as the detection time for that ion. The start time may be subtracted from the detection time so as to determine the transit time.
  • the instrument is configured to use the detector 30 to measure the transit time (i.e. “drift time”) of each ion.
  • the detector 30 is a charge-resolving ion detector configured to determine the charge (i.e. “charge state” or charge number”) of each (individual) ion.
  • the charge-resolving ion detector may be configured to output a signal from which the charge (i.e. “charge state” or charge number”) of each ion may be determined.
  • the charge of each ion may be determined from the same signal or from a different signal from which the transit time of that ion is measured.
  • the charge of an ion may be determined from the intensity, amplitude and/or area of the (digitised) signal. Area can be a more precise measurement than amplitude or intensity in practice, e.g. due to the limitations of the acquisition electronics such as sampling rate and number of ADC bits.
  • the charge state can be determined from the area and/or intensity of a signal because the response of some detectors can vary with the charge state. For example, a Faraday cup will directly convert the amount of charge to a signal.
  • standard ToF detectors such as e.g. electron multipliers, have an impact energy dependent response, and the impact energy can depend on charge.
  • the charge-resolving ion detector 30 may comprise (i) a faraday cup or cylinder electrode detector; (ii) an electron multiplier detector; (iii) a photomultiplier or scintillation counter detector; and/or (iv) a superconducting tunnel junction (STJ) detector.
  • the analytical instrument may comprise two ion detectors.
  • a first ion detector may be configured to determine the charge of each ion and a second detector may be configured to determine the transit time of each ion.
  • the first ion detector may be arranged upstream of (and in proximity with) the second ion detector.
  • the second ion detector may be configured substantially as described above, and e.g. may comprise any suitable ion detector such as, for example, (i) a faraday cup or cylinder electrode detector; (ii) an electron multiplier detector; (iii) a photomultiplier or scintillation counter detector; and/or (iv) a superconducting tunnel junction (STJ) detector.
  • any suitable ion detector such as, for example, (i) a faraday cup or cylinder electrode detector; (ii) an electron multiplier detector; (iii) a photomultiplier or scintillation counter detector; and/or (iv) a superconducting tunnel junction (STJ) detector.
  • STJ superconducting tunnel junction
  • the first, charge-resolving ion detector may comprise any suitable chargeresolving ion detector that is configured to output a signal from which the charge of each ion can be determined.
  • the first, charge-resolving ion detector may comprise a non-destructive charge-resolving ion detector, i.e. such that ions detected by the first ion detector will continue on to be detected by (and produce a signal on) the second detector.
  • the charge-resolving ion detector may comprise an induction charge detector, e.g. configured such that a passing ion will induce a charge within the detector.
  • the charge-resolving ion detector comprises an induction plate or an induction tube.
  • the shape of the signal derived from an induction charge detector can give mass to charge ratio (m/z) information, e.g. where the difference in time between two (positive and negative) peaks is in effect a time of flight measurement, from which mass to charge ratio (m/z) can be determined.
  • the transit time of each (individual) ion passing through the ion separation device 20 is determined, together with the charge state of that ion.
  • the transit time (i.e. “drift time”) and the charge (i.e. “charge state” or “charge number”) for each ion are then used (e.g. combined), e.g. on an ion-by-ion basis, to determine a second physicochemical property for each ion.
  • the flux of the ions at the detector or detectors may be controlled such that (some, most or all) individual ions are distinguishable from each other when detected by the detector or detectors.
  • the ions are separated according to their mass to charge ratio (m/z) (i.e. where the first physico-chemical property comprises mass to charge ratio)
  • the transit time of each ion will be related to its mass to charge ratio.
  • the mass (or a property related to mass) of the ion can be determined.
  • the transit time of each (individual) ion will be related to its ion mobility.
  • the collision or reaction cross section or a property related to collision or reaction cross section of the ion can be determined.
  • the transit time and the charge may be combined in any suitable manner to derive the second physico-chemical property.
  • the mass to charge ratio (m/z) value may be multiplied by the charge state to get the mass (m). If however, the initial time measurement is scaled, then the time measurement would be scaled e.g. by the square root of charge, to account for the non-linear relationship between the time measurement and mass to charge ratio (m/z).
  • this process is repeated for each (individual) ion of multiple ions, e.g. so to determine the second physicochemical property (e.g. mass, or collision or reaction cross section) of each individual ion, and the results are combined (e.g. summed, binned and/or histogrammed) so as to produce a spectrum (such as a mass spectrum or a collision or reaction cross section spectrum) for the ions under analysis.
  • a spectrum such as a mass spectrum or a collision or reaction cross section spectrum
  • the transit time (i.e. “drift time”) and the charge (i.e. “charge state” or “charge number”) of each (individual) ion of multiple ions is used (e.g. combined) to determine the second physicochemical property of each (individual) ion of the multiple ions.
  • the so-determined second physico-chemical property of each (individual) ion of the multiple ions are then used (combined) to produce a spectrum (e.g. a mass spectrum or a collision or reaction cross section spectrum).
  • Embodiments exploit the inherent speed of separation-based approaches, and also utilise the charge state resolution provided by the charge-resolving ion detector (in addition to the first physico chemical property resolution of the separation device 20) to resolve ions.
  • This can allow ions with similar or the same value of the first physico chemical property (e.g. mass to charge ratio (m/z)) but different charges (z) to be resolved in the second physico chemical property (e.g. mass), even where the ion separator 20 lacks sufficient resolution to resolve the different charge states in the first physico chemical property.
  • this can allow ions with similar or the same mass to charge ratio (m/z) but different charges (z) to be resolved, even where the ion separator 20 lacks sufficient m/z resolution to resolve the different charge states.
  • CDMS charge detection mass spectrometry
  • ions may enter a time of flight (ToF) mass analyser at a time determined by the electronics of the mass analyser. This start time is either measured or known.
  • the ions separate according to m/z so that ions having different mass to charge ratios arrive at a detector at different times, where the different arrival times are measured.
  • the data from multiple separations would be summed and/or binned into a histogram to provide a time of flight (ToF) spectrum, that may then be converted into a m/z spectrum.
  • TOF time of flight
  • the time of flight measurement for each (individual) ion is combined with the charge state of each (individual) ion, before data for multiple ions is summed and/or binned into a histogram so as to produce a final spectrum (e.g. a mass spectrum).
  • the charge state information for each (individual) ion may be determined based on the intensity of the signal from the same detection event that was used to measure the time of flight. Alternatively, a separate detector may be used to measure the charge state independently.
  • ToF-MS time of flight mass spectrometry
  • ions follow a unique flight path and/or trajectory meaning that multiple ions can be analysed in the same time of flight mass spectrometry (ToF-MS) experiment, provided that the signals from different ions can be differentiated at the detector.
  • Figure 4 shows schematically an analytical instrument configured in accordance with embodiments.
  • the analytical instrument comprises a temporal ion separation device 20 such as a ToF mass analyser, and an ion detector 30 located downstream of the ion separation device 20.
  • the ion separation device 20 is configured to separate ions according to a first physicochemical property such as m/z when the ions are passed through the ion separation device.
  • the ion detector 30 comprises a charge-resolving ion detector configured to detect an ion, so as to determine the charge of the ion. Additionally, the detector 30 is configured to measure the drift time of the ion, so as to determine the transit time for the ion.
  • the single detector 30 may have a charge dependent characteristic, and may be configured to output a signal from which the charge of the ion may be determined and from which the transit time of the ion may be measured.
  • the charge of the ion may be determined from the area of the signal output from the detector 30 and the drift time for the ion may be determined by the weighted average of the signal.
  • the transit time and the charge of the ion are combined to determine a second physico-chemical property, such as mass, of the ion. This occurs before the data from the ion is summed with data from other ions across multiple separations and/or binned into a histogram or spectrum. For example, if the charge state of a detected ion is linear with the area of the signal from the detector 30, then the product of the transit time and the area of the signal may be determined, and binned into a histogram.
  • Example detectors for which the charge state is linear with the signal include faraday cups and inductive “listening” electrodes. Also superconducting tunnel junction (STJ) detectors exhibit this property.
  • FIG. 5 shows schematically an analytical instrument configured in accordance with an alternative embodiment.
  • the analytical instrument comprises a temporal ion separation device 20 (which may be configured as described above), a first detector 30 and second detector 40 located downstream of the ion separation device 20.
  • the first detector 30 comprises a charge-resolving ion detector configured to measure or determine the charge state of an ion.
  • the second detector 40 is configured to measure or determine the time or flight or arrival time for the ion.
  • the time or flight or arrival time and the charge state of the ion are combined to determine a second physico-chemical property of the ion, such as mass. This is done before the data for the ion is summed with data from other ions across multiple separations and/or binned into a histogram (spectrum).
  • Figure 6 shows simulated data from a simple listening tube. Particles with a mass of 4 MDa and 200 charges were accelerated with 5kV, and passed through the tube. The tube had a 5mm inner diameter and a length of 10mm. The resulting induced charge and associated current are illustrated in Figure 6.
  • the simulations indicate that individual charge state resolution is possible with an approach as described herein. For example, assuming that the response is linear with charge, the spread in total induced charge considering ions with no divergence entering the tube on axis or offset by 1mm equates to about 2/3 of a charge state.
  • the charge of the ions may be reduced prior to entering the ion separation device 20. This may be done (i) in order to charge reduce ions to the point where charge state peaks can be distinguished, (ii) in order to increase the m/z and thus amplify the velocity relaxation effect, and/or (iii) such that the percentage charge differences between unresolved charge states are increased to the point where they can be distinguished by a low-charge-resolution detector.
  • Charge reduction may be induced by any suitable technique(s), such as for example solution additives (charge reducing agents and/or charge reducing surfactants), and/or reactant vapours (comprising either neutral and/or ionised molecules). Evaporation of solution additives may also result in the formation of suitable reactant vapours.
  • solution additives charge reducing agents and/or charge reducing surfactants
  • reactant vapours comprising either neutral and/or ionised molecules
  • the ion separation device 20 may comprise an ion trap and/or sector device optionally driven by a substantially pulsed electric field, such as for example a 3D quadrupole ion trap, a linear ion trap, a toroidal ion trap, a pulsed electric sector filter, a parallel electrode filter, a co-axial electrode filter, and the like.
  • a substantially pulsed electric field such as for example a 3D quadrupole ion trap, a linear ion trap, a toroidal ion trap, a pulsed electric sector filter, a parallel electrode filter, a co-axial electrode filter, and the like.
  • the separations can be any time based approach such as, for example, high pressure m/z separation, scanning quadrupoles, etc.
  • a scanning resolving quadrupole will only let ions within a restricted mass to charge ratio (m/z) range pass at any given time, as it operates as a mass to charge ratio (m/z) filter. Varying (scanning) the mass to charge ratio (m/z) range being transmitted with time results in ions having different mass to charge ratios (m/z) arriving at the detector at different times. Where the ion detector has a charge resolving characteristic, the determined charge of each ion can be combined with the mass to charge ratio (m/z) of the ion, so as to determine the mass of each ion, i.e. in a corresponding manner to that described above.
  • IMS ion mobility spectrometry
  • characteristics of the induced charge and/or current profile may be used to calculate the mass to charge ratio (m/z) of each (individual) ion of the one or more ions.
  • the shape of the signal derived from the induction tube 30 can give mass to charge ratio (m/z) information.
  • the difference in time between the two (positive and negative) peaks is in effect a time of flight measurement, from which mass to charge ratio (m/z) can be determined.

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Abstract

La présente invention concerne un procédé d'analyse ionique qui consiste à séparer les ions en fonction d'une première propriété physico-chimique en faisant passer les ions à travers un dispositif de séparation ionique, et à mesurer le temps de transit d'un ion à travers le dispositif de séparation ionique. Le procédé consiste en outre à détecter l'ion à l'aide d'un détecteur d'ions à résolution de charge de manière à déterminer la charge de l'ion, et à utiliser le temps de transit et la charge de l'ion pour déterminer une seconde propriété physico-chimique de l'ion.
PCT/GB2021/053427 2020-12-24 2021-12-23 Spectrométrie de masse et/ou de mobilité ionique WO2022136882A1 (fr)

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EP21835817.4A EP4268263A1 (fr) 2020-12-24 2021-12-23 Spectrométrie de masse et/ou de mobilité ionique
US18/259,015 US20240047191A1 (en) 2020-12-24 2021-12-23 Mass and/or ion mobility spectrometry
CN202180084246.XA CN116615648A (zh) 2020-12-24 2021-12-23 质谱和/或离子迁移谱

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GB2020575.3 2020-12-24
GBGB2020575.3A GB202020575D0 (en) 2020-12-24 2020-12-24 Characterising mixtures of high-mass particles using m/z seperation
GB2106850.7 2021-05-13
GBGB2106850.7A GB202106850D0 (en) 2020-12-24 2021-05-13 Characterisation of high mass particles
GB2107491.9 2021-05-26
GBGB2107491.9A GB202107491D0 (en) 2020-12-24 2021-05-26 Mass and/or ion mobility spectrometry

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023161646A1 (fr) * 2022-02-25 2023-08-31 Micromass Uk Limited Mesure d'ions avec réduction de charge

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9984861B2 (en) 2014-04-11 2018-05-29 Micromass Uk Limited Ion entry/exit device
US20190164735A1 (en) * 2015-03-12 2019-05-30 Thermo Finnigan Llc Methods for Data-Dependent Mass Spectrometry of Mixed Biomolecular Analytes
US20200161119A1 (en) 2017-07-21 2020-05-21 Micromass Uk Limited Mobility and mass measurement using time-varying electric fields

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9984861B2 (en) 2014-04-11 2018-05-29 Micromass Uk Limited Ion entry/exit device
US20190164735A1 (en) * 2015-03-12 2019-05-30 Thermo Finnigan Llc Methods for Data-Dependent Mass Spectrometry of Mixed Biomolecular Analytes
US20200161119A1 (en) 2017-07-21 2020-05-21 Micromass Uk Limited Mobility and mass measurement using time-varying electric fields

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023161646A1 (fr) * 2022-02-25 2023-08-31 Micromass Uk Limited Mesure d'ions avec réduction de charge
GB2618189A (en) * 2022-02-25 2023-11-01 Micromass Ltd Measuring ions with charge reduction

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