WO2019058115A1 - Système de spectrométrie - Google Patents

Système de spectrométrie Download PDF

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Publication number
WO2019058115A1
WO2019058115A1 PCT/GB2018/052675 GB2018052675W WO2019058115A1 WO 2019058115 A1 WO2019058115 A1 WO 2019058115A1 GB 2018052675 W GB2018052675 W GB 2018052675W WO 2019058115 A1 WO2019058115 A1 WO 2019058115A1
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Prior art keywords
ions
ion
ion mobility
excitation source
spectrometry system
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PCT/GB2018/052675
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English (en)
Inventor
Max ALLSWORTH
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Owlstone Medical Ltd
Owlstone Inc
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Owlstone Medical Ltd
Owlstone Inc
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Classifications

    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H01J49/0045—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction
    • 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]

Definitions

  • the present invention relates to devices and methods for ion mobility systems. More specifically, the invention relates to a method and apparatus for detecting chemicals using a Field Asymmetric Ion Mobility Spectrometry (FAIMS) system.
  • FIMS Field Asymmetric Ion Mobility Spectrometry
  • IMS Ion Mobility Spectrometry
  • FAMMS Field Asymmetric Ion Mobility Spectrometry
  • DMS Differential Mobility Spectrometry
  • Ion mobility techniques can also be used effectively over a range of gas pressures, including pressures close to one atmosphere. This makes them useful for, amongst other things, measuring low-level impurities in air.
  • the sample gas is passed through an ionizer to produce a population of ionized molecules that are then manipulated in some way involving separation or selection of ionized molecules according to their behaviour in an electric field, before being detected.
  • Ionizers commonly in use include radioactive sources, light-based devices such as ultra-violet lamps, and electrostatic devices such as corona discharge ionizers.
  • Stability and repeatability of DMS spectra are important issues in the use of DMS in analytical applications, as explained for example in "Temperature effects in differential mobility spectrometry" by Krylov et al in International Journal of Mass Spectrometry 279 (2009) 1 19- 125.
  • Drift gas pressure and temperature are known to influence the field dependence of ion mobility, changing peak positions in the DMS spectra and the paper by Krylov provides a model which can be used for temperature correction of DMS Spectra.
  • US2016/0266007A1 describes a system using a micro-fabricated ion filter for detecting, identifying, classifying and/or quantifying chemical species in a gas flow.
  • the system is adapted to extract numerical parameters from the measured output of the ion filter.
  • the selectively of the FAIMS system may be limited once the compounds of the target chemical get larger or if the system has to run at higher temperature, e.g. when targeting chemicals having higher boiling points.
  • the applicant has recognised the need for a system having improved selectivity.
  • a spectrometry system comprising an ionizer for generating ions within a gas sample, wherein each ion has an associated ion mobility; an excitation source for generating an excitation signal to modulate the ion mobility associated with ions from a target chemical within the gas sample; an ion filter for separating the ions having modulated ion mobility from the gas sample; and a detector for detecting an output from the ion filter.
  • the excitation source may be an acoustic energy source, an optical light source (e.g. LEDs, lasers or quantum cascade lasers) or a source of electronic excitation.
  • the excitation source may emit an excitation signal at a predetermined frequency.
  • the predetermined frequency may be selected so as to provide a desired excitation of a rotation and/or vibration state of the generated ions from the target chemical (e.g. as examples: 2-Undecanone, Diethyl phthalate, Dimethyl methylphosphonate).
  • the target chemical e.g. as examples: 2-Undecanone, Diethyl phthalate, Dimethyl methylphosphonate.
  • an optical light source may emit an excitation signal at a predetermined frequency within an absorption band for the target chemical, e.g. near infrared defined as 214 to 400THz or mid infrared defined as 80 to 100THz.
  • the absorption band for the target chemical may be determined by reference to an appropriate spectral database.
  • the source of electronic excitation may add an excitation signal to an electric field being applied to the ion filter to separate ions.
  • the excitation may have a predetermined frequency which is high when compared to a radio frequency of the electric field.
  • the high frequency may be in the range of 800MHz to 2GHz and a typical frequency of the electric field may be around 25MHz.
  • the excitation signal may be produced in a separate stage and then merged with the electric field.
  • the predetermined frequency may be determined based on the following equation:
  • the system may comprise a controller which is configured to control the excitation source, for example, to emit an excitation signal at the predetermined frequency.
  • the system may further comprise a lock-in amplifier which is configured to receive the output from the detector and to extract an output signal at the predetermined frequency.
  • the controller may be configured to automatically adjust the predetermined frequency at the lock-in amplifier, in response to a change in the predetermined frequency being emitted by the excitation source. In this way, the lock-in amplifier is always selecting the ion of the target chemical.
  • the system may be a field asymmetric ion mobility spectrometry system.
  • the system may further comprise a drive signal system which applies a compensation field and a dispersion field to the ion filter to separate the ions.
  • the system may further comprise a processor which is configured use measurements of ion current as a function of compensation field and dispersion field to facilitate one or more of detection, identification and quantification of the target chemical.
  • the method may comprise modulating the ion mobility using an excitation source in the form of an acoustic energy source or an optical light source.
  • the excitation signal may be set at a predetermined frequency and an output signal may be selected at the predetermined frequency. Accordingly, in response to a change in the predetermined frequency of the excitation signal, the method may comprise automatically adjusting the predetermined frequency of the output signal.
  • the method may be performed by a field asymmetric ion mobility spectrometry.
  • the ions may be generated using an ionizer, the ions may be separated by an ion filter and may be detected by a detector. Separating the ions may comprise applying a compensation field and a dispersion field, e.g. using a drive signal system. Measurements of ion current may be output by the detector. The measurements may be used, e.g. by a processor, as a function of compensation field and dispersion field to facilitate one or more of detection, identification and quantification of the target chemical.
  • Figure 1 a is a schematic illustration of a spectrometry system
  • Figure 1 b is a schematic illustration of a channel within an ion filter in the system of Figure 1 a;
  • Figure 1 c is an alternative schematic illustration of the spectrometry system of Figure 1 a;
  • Figure 1 d is an example of the output from the system of Figure 1 c;
  • FIG. 2 is a schematic illustration of another spectrometry system
  • Figures 1 a to 1 d shows a schematic illustration of a spectrometry system which may be a miniature device as described in "Characterisation of a miniature, ultra-high field, ion mobility spectrometer" by Wilks et al published in Int. J. Ion Mobil Spec. (2012) 15:199-222.
  • gas flows into an ionizer 10 and the generated ions then pass through an ion filter 12.
  • the ion filter separates the ions and may thus be termed an ion separator.
  • the ion filter has a plurality of ion channels each having a small gap width (g of around 30 to 50 ⁇ ) and relatively short length (e.g.
  • the gap surfaces are made of high-conductivity silicon (or similar material) and are electrically connected via wire bonding to metal pads on the face of the silicon. Ions exiting from the ion separator are detected by an ion detector 14. It is known that temperature and pressure can affect the results and thus a temperature sensor 16 and/or a pressure sensor 18 may also be included in the system. These are shown schematically on the output gas flow but could be incorporated into another appropriate location within the device.
  • an oscillating electric field is applied to the ion separator.
  • a variable high-voltage asymmetric waveform of low voltage pulse duration t(s) and high voltage pulse duration (s) and peak voltage V D is applied to create the variable field of Vo/g (kVcm ).
  • the mobility of each ion within the ion separator oscillates between a low-field mobility K 0 and a high-field mobility K E and the difference between the high-field mobility and low field mobility is termed AK.
  • Ions of different chemicals will have different values of AK and the ions adopt a net longitudinal drift path length (d h -d t ) through the ion filter which is determined by their high and low field drift velocity (v D(h) and v D(lj ) and the high field and low field pulse durations. Only ions in a "balanced" condition such as the middle ion in Figure 1 b will exit from the ion separator and be detected by the ion detector. Ions which contact either of the sides of the ion channel will not be detected.
  • a bias DC "tuning voltage" (V c ) is applied on top of the applied waveform to enable subtle adjustment of the peak voltage V D to counter the drift experienced by an ion of a specific AK.
  • a drive signal system 130 applies the asymmetric waveform and the tuning voltage to the ion filter 100 as described above.
  • the output ions from the ion filter 100 are detected by the detector 1 10.
  • the output from the detector 1 10 is sent to a processor 120 which may be local (i.e. within the ion filter) or remote (i.e. in a separate computer/server).
  • the processor is adapted to extract numerical parameters which facilitate chemical detection, identification, classification and/or quantification of the ions.
  • the processor may be configured to generate an output as shown in Figure 1 d in which the measurement of ion current at the detector is plotted as a function of the applied electric field resulting from the asymmetric waveform which is known as the dispersion field E D (kVcm ) and the applied electric field resulting from the DC voltage which is known as the compensation field E c (kVcm -1 ).
  • the spectral output may alternatively be presented as an mxn matrix of ion current measurements at m compensation field and n dispersion field settings.
  • Figure 1 d shows the E C :E D peak trajectories for monomer and dimers of acetone, 2- butanone and dimethyl methyl phosphonate (DMMP). These trajectories are used to identify whether ions of a particular chemical are present in a gas sample by comparing the resulting graph with previously collected graphs of known chemicals generated under the same conditions. However, as illustrated in Figure 1 d, the graphs for some chemicals are similar and thus identification is more difficult when the differences are less pronounced.
  • DMMP dimethyl methyl phosphonate
  • K E K 0 ⁇ 1 + a ⁇ E D ) ⁇
  • a(E) is a non-dimensional function characterising the field mobility dependence (called the alpha function) and E D is the dispersion field.
  • Temperature affects the ion mobility in two ways, namely by changing gas density, N.
  • gas temperature changes the ion and neutral kinetic energy distributions and hence changes the distribution of ion-neutral collision energies and the ion mobility.
  • the effective temperature of an ion T eff may be defined as:
  • T is the neutral gas temperature (i.e. the temperature in the absence of an electric field)
  • ⁇ is the ion-neutral collision efficiency factor
  • M is the molecular weight of the drift gas
  • K 0 is the mobility coefficient under low field conditions
  • N 0 is the standard gas density
  • E D /N is the dispersion field in Townsend
  • N is the gas density
  • k b is Boltzmann's gas constant.
  • Figure 2 shows an alternative spectrometry system which comprises an ionizer 210, an ion filter 220 and an ion detector 230. Each of these components may be the same as the corresponding components shown in Figures 1 a and 1 c.
  • the system of Figure 2 additionally comprises an excitation source 240 which may be an optical light source, an electronic excitation source or an acoustic energy source.
  • the excitation source 240 is controlled by a controller 250 to emit energy, preferably having a selected frequency which provides a desired excitation of the rotation state and/or vibration state of ions generated by the ionizer.
  • the predetermined frequency may be selected based on a frequency range where the target chemical is known to have excitation levels.
  • an optical light source may emit an excitation signal at a predetermined frequency within an absorption band for the target chemical, e.g. near infrared defined as 214 to 400THz or mid infrared defined as 80 to 100THz.
  • the absorption band for the target chemical may be determined by reference to an appropriate spectral database.
  • the source of electronic excitation may add an excitation signal to an electric field being applied to the ion filter to separate ions.
  • the excitation may have a predetermined frequency which is high frequency when compared to a radio frequency of the electric field. High frequency may be in the range of 800MHz to 2GHz and a typical frequency of the electric field may be around 25MHz. In this arrangement, the excitation signal may be produced in a separate stage and then merged with the electric field.
  • Suitable optical light sources include LEDs, lasers or quantum cascade lasers depending on the wavelength.
  • the use of an excitation source may be particularly useful when analysing large ions which have more rotational and vibrational degrees of freedom.
  • Such large ions distribute collision energy differently when compared with smaller ions and in particular, as the collision energy increases more energy goes into the internal states when compared to lower energy collisions. This different distribution of collision energy can be accounted for in the following modified expression of T eff from "Temperature effects in differential mobility spectrometry" by Krylov et al in International Journal of Mass Spectrometry 279 (2009) 1 19-125:
  • T is the neutral gas temperature (i.e. the temperature in the absence of an electric field)
  • ⁇ ( ⁇ ) is a dimensionless and analyte specific fitting parameter which accounts for ion energy loss as a function of gas temperature
  • K 0 is the mobility coefficient under low field conditions in cm ' W
  • E D /N is the dispersion field in Townsend.
  • the excitation source 240 generates a modulating signal which modulates (i.e. changes) the ion mobility.
  • the change to the ion mobility should be of the order of tens of milli- Townsends so that it is significant to be measured and hence output.
  • the system also comprises a lock-in amplifier 260 which as is well known in the art is a type of amplifier that can extract a signal at a particular target frequency from an extremely noisy environment.
  • a lock-in amplifier 260 typically take the input signal (which in this arrangement is the output from the ion detector 230) and multiply the input signal by the reference signal (which in this arrangement is the signal from the excitation source 240).
  • the result of the multiplication is integrated over a specific time window, which is typically in the order of milliseconds or few seconds and the output signal is a DC signal where the contribution from any signal within the input signal that is not at the same frequency as the reference signal is attenuated close to zero.
  • the lock-in amplifier 260 is connected to the controller 250 which controls the excitation source 240.
  • the controller 250 is configured to adjust the reference signal sent to the lock-in amplifier 260 in line with any adjustment to the signal from the excitation source 240.
  • a processor 270 receives the output from the lock-in amplifier 260 and extracts information to identify the chemical(s) in the gas sample. As described above, the processor may be configured to generate an output in which the measurement of ion current from the lock-in amplifier is plotted as a function of the dispersion field E D (kVcm ) and the compensation field E c (kVcm 1 ).
  • At least some of the example embodiments described herein may be constructed, partially or wholly, using dedicated special-purpose hardware.
  • Terms such as 'processor' or 'controller' used herein may include, but are not limited to, a hardware device, such as circuitry in the form of discrete or integrated components, a Field Programmable Gate Array (FPGA) or Application Specific Integrated Circuit (ASIC), which performs certain tasks or provides the associated functionality.
  • FPGA Field Programmable Gate Array
  • ASIC Application Specific Integrated Circuit
  • the described elements may be configured to reside on a tangible, persistent, addressable storage medium and may be configured to execute on one or more processors.
  • These functional elements may in some embodiments include, by way of example, components, such as software components, object-oriented software components, class components and task components, processes, functions, attributes, procedures, subroutines, segments of program code, drivers, firmware, microcode, circuitry, data, databases, data structures, tables, arrays, and variables.
  • components such as software components, object-oriented software components, class components and task components, processes, functions, attributes, procedures, subroutines, segments of program code, drivers, firmware, microcode, circuitry, data, databases, data structures, tables, arrays, and variables.
  • components such as software components, object-oriented software components, class components and task components, processes, functions, attributes, procedures, subroutines, segments of program code, drivers, firmware, microcode, circuitry, data, databases, data structures, tables, arrays, and variables.

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  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Electrochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
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Abstract

La présente invention concerne un système de spectrométrie. Le système de spectrométrie comprend un ioniseur (210) pour générer des ions à l'intérieur d'un échantillon avec une mobilité ionique associée. Le système de spectrométrie a une source d'excitation (240) pour générer un signal d'excitation pour moduler la mobilité ionique associée à des ions à partir d'un produit chimique cible à l'intérieur de l'échantillon de gaz. Le système de spectrométrie a un filtre à ions (220) pour séparer les ions ayant une mobilité ionique modulée de l'échantillon de gaz. Le système de spectrométrie a un détecteur (230) pour détecter une sortie du filtre à ions (220).
PCT/GB2018/052675 2017-09-22 2018-09-19 Système de spectrométrie Ceased WO2019058115A1 (fr)

Applications Claiming Priority (2)

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GB1715371.9 2017-09-22
GB1715371.9A GB2566713A (en) 2017-09-22 2017-09-22 Spectrometry system

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WO2019058115A1 true WO2019058115A1 (fr) 2019-03-28

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020240201A1 (fr) 2019-05-31 2020-12-03 Owlstone Medical Limited Système de capteur

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Publication number Priority date Publication date Assignee Title
WO2025124734A1 (fr) * 2023-12-15 2025-06-19 Shimadzu Corporation Améliorations de l'analyse d'ions et s'y rapportant

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US20100320375A1 (en) * 2009-06-22 2010-12-23 Uwe Renner Measurement of ion mobility spectra with analog modulation
EP2343546A2 (fr) * 2005-04-23 2011-07-13 Smiths Group PLC Spectromètre à mobilité ionique
US20120061563A1 (en) * 2009-05-18 2012-03-15 Fernandez-Pola Fernando Briones Ion mobility spectrometer
US20120235032A1 (en) * 2009-09-30 2012-09-20 Eads Deutschland Gmbh Ionization Method, Ion Producing Device and Uses of the Same in Ion Mobility Spectrometry

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US8242442B2 (en) * 2008-02-05 2012-08-14 Excellims Corporation Method and apparatus for chemical and biological sample separation
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EP2343546A2 (fr) * 2005-04-23 2011-07-13 Smiths Group PLC Spectromètre à mobilité ionique
US20120061563A1 (en) * 2009-05-18 2012-03-15 Fernandez-Pola Fernando Briones Ion mobility spectrometer
US20100320375A1 (en) * 2009-06-22 2010-12-23 Uwe Renner Measurement of ion mobility spectra with analog modulation
US20120235032A1 (en) * 2009-09-30 2012-09-20 Eads Deutschland Gmbh Ionization Method, Ion Producing Device and Uses of the Same in Ion Mobility Spectrometry

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Title
ADAMSON B D ET AL: "An ion mobility mass spectrometer for investigating photoisomerization and photodissociation of molecular ions", REVIEW OF SCIENTIFIC INSTRUMENTS, AIP, MELVILLE, NY, US, vol. 85, no. 12, 15 December 2014 (2014-12-15), XP012192826, ISSN: 0034-6748, [retrieved on 19010101], DOI: 10.1063/1.4903753 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020240201A1 (fr) 2019-05-31 2020-12-03 Owlstone Medical Limited Système de capteur
US12196708B2 (en) 2019-05-31 2025-01-14 Owlstone Medical Limited Sensor system

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GB201715371D0 (en) 2017-11-08

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