GB2566713A

GB2566713A - Spectrometry system

Info

Publication number: GB2566713A
Application number: GB1715371.9A
Authority: GB
Inventors: Allsworth Max
Original assignee: Owlstone Medical Ltd; Owlstone Inc
Current assignee: Owlstone Medical Ltd; Owlstone Inc
Priority date: 2017-09-22
Filing date: 2017-09-22
Publication date: 2019-03-27
Also published as: GB201715371D0; WO2019058115A1

Abstract

A spectrometry system, preferably a field asymmetric ion mobility spectrometer (FAIMS), is provided comprising: an ionizer 210 for generating ions within a gas sample; an excitation source 240 for generating an excitation signal to modulate the ion mobility associated with ions from a target chemical within the gas sample; and an ion filter 220 for separating the ions having modulated ion mobility from the gas sample. The excitation source may emit an excitation signal at a predetermined frequency so as to provide a desired excitation of a rotation and/or vibration state of the ions of the target chemical, and may be an acoustic energy source, an optical light source, e.g. LEDs, lasers, or a source of electronic excitation. The spectrometry system may also be provided with lock-in amplifier 260 configured to receive an output from the ion detector 230 and extract an output signal at the predetermined frequency.

Description

TECHNICAL FIELD [0001] 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.

BACKGROUND [0002] The ability to ionize gases using ion mobility systems is useful for a wide range of applications including many chemical detection applications. Ionization techniques, in which a gas sample is ionized and then separated into constituent parts that can be detected individually, are widely used for gas composition sensing. Two well-known examples are Ion Mobility Spectrometry (IMS) and Field Asymmetric Ion Mobility Spectrometry (FAIMS), also known as Differential Mobility Spectrometry (DMS). Ion mobility detection techniques tend to be very well suited to measuring trace constituents of gas mixtures that often consist of a carrier gas with additional gases mixed in at low concentrations (for example part-per-million or part-per-billion levels).

[0003] 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.

[0004] 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) 119125. 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.

[0005] 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. [0006] Using the known techniques, 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.

SUMMARY [0007] According to the present invention there is provided a system and method as set forth in the appended claims. Other features of the invention will be apparent from the dependent claims, and the description which follows.

[0008] We describe 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.

[0009] 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). By modulating the ion mobility, we mean that the ion mobility is adjusted or changed. It is known that the ion mobility is affected by the effective temperature of the ions and thus the predetermined frequency may be selected based on a frequency range where the target chemical is known to have excitation levels.

[0010] For example, 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. In this arrangement, the excitation signal may be produced in a separate stage and then merged with the electric field.

[0011] Alternatively, the predetermined frequency may be determined based on the following equation:

/£ \²

T_eff = T + 8.09 X 1θ-³ζ(τχ_ο ² [0012] where T is the neutral gas temperature (i.e. the temperature in the absence of an electric field), ζ(Τ) is a dimensionless and analyte specific fitting parameter which accounts for ion energy loss as a function of gas temperature, K_o is the mobility coefficient under low field conditions in cm²V¹s¹, E_D/N is the dispersion field in Townsend.

[0013] 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.

[0014] 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.

[0015] We also describe a method of detecting ions of a target chemical in a gas sample, the method comprising: generating ions within the gas sample, wherein each generated ion for the target chemical has an associated ion mobility; modulating the ion mobility associated with ions from the target chemical within the gas sample by exciting the generated ions with an excitation signal; separating the ions having modulated ion mobility from the gas sample; and detecting the separated ions.

[0016] 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. As explained above, 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.

[0017] The method may be performed by a field asymmetric ion mobility spectrometry. Thus, 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.

BRIEF DESCRIPTION OF DRAWINGS [0018] For a better understanding of the invention, and to show how embodiments of the same may be carried into effect, reference will now be made, by way of example only, to the accompanying diagrammatic drawings in which:

[0019] Figure 1a is a schematic illustration of a spectrometry system;

[0020] Figure 1b is a schematic illustration of a channel within an ion filter in the system of Figure 1a;

[0021] Figure 1c is an alternative schematic illustration of the spectrometry system of Figure 1a;

[0022] Figure 1d is an example of the output from the system of Figure 1c;

[0023] Figure 2 is a schematic illustration of another spectrometry system;

DETAILED DESCRIPTION OF DRAWINGS [0024] Figures 1a to 1d 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. As shown in Figure 1a, 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. In the illustrated example, the ion filter has a plurality of ion channels each having a small gap width (g of around 30 to 50 pm) and relatively short length (e.g. L around 300 pm). 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.

[0025] As shown in Figure 1b, 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 t(s) and peak voltage V_D is applied to create the variable field of Vo/g (kVcm¹). The mobility of each ion within the ion separator oscillates between a low-field mobility K_o 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 (dt,-dt) through the ion filter which is determined by their high and low field drift velocity (v_D(h) and v_Dft)) and the high field and low field pulse durations. Only ions in a “balanced” condition such as the middle ion in Figure 1b 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.

[0026] As shown schematically in Figure 1c, 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 110. The output from the detector 110 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. For example, the processor may be configured to generate an output as shown in Figure 1d 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 (kVcrri¹) and the applied electric field resulting from the DC voltage which is known as the compensation field E_c (kVcrri¹). The spectral output may alternatively be presented as an mxn matrix of ion current measurements at m compensation field and n dispersion field settings.

[0027] Figure 1d shows the E_C:E_D peak trajectories for monomer and dimers of acetone, 2butanone 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 1d, the graphs for some chemicals are similar and thus identification is more difficult when the differences are less pronounced.

[0028] As explained in the background section, temperature is a factor which affects the output from the filter. At higher electric fields (such as those used in FAIMS), ions acquire substantial energy from the field and the frequency and strength of the ion-neutral interaction changes. As a result the mobility coefficient K_E at fixed bulk gas temperature becomes dependent on the electric field as shown:

K_E = K_O{1 + a(£_D)}

Where K_o is the mobility coefficient under low field conditions, 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. In addition, 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:

· 31,-,, where T is the neutral gas temperature (i.e. the temperature in the absence of an electric field), ζ is the ion-neutral collision efficiency factor, M is the molecular weight of the drift gas, K_o is the mobility coefficient under low field conditions, N_o is the standard gas density, E_D/N is the dispersion field in Townsend, N is the gas density and k_b is Boltzmann’s gas constant.

[0029] 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 1a and 1c. 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.

[0030] For example, 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.

[0031] 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) 119-125:

T_eff = T + 8.09 X 1θ-³ζ(τχ_ο ² where T is the neutral gas temperature (i.e. the temperature in the absence of an electric field), ζ(Τ) is a dimensionless and analyte specific fitting parameter which accounts for ion energy loss as a function of gas temperature, K_o is the mobility coefficient under low field conditions in cm²V¹s¹, E_d/N is the dispersion field in Townsend.

[0032] 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 modulating signal may be selected to target particular bonds such as C=O and/or P-C which may allow a particular functional group within the gas sample to be probed.

[0033] 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. Such lock-in amplifiers 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.

[0034] 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 (kVcm¹) and the compensation field E_c (kVcm¹).

[0035] At least some of the example embodiments described herein may be constructed, partially or wholly, using dedicated special-purpose hardware. Terms such as ‘p^rocessor’ °^r‘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. In some embodiments, 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. Although the example embodiments have been described with reference to the components discussed herein, such functional elements may be combined into fewer elements or separated into additional elements. Various combinations of optional features have been described herein, and it will be appreciated that described features may be combined in any suitable combination. In particular, the features of any one example embodiment may be combined with features of any other embodiment, as appropriate, except where such combinations are mutually exclusive. Throughout this specification, the term “comprising” or “comprises” means including the component(s) specified but not to the exclusion of the presence of others.

[0036] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0037] All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive.

[0038] Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0039] Although a few preferred embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes and modifications might be made without departing from the scope of the invention, as defined in the appended claims.

Claims

1. 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.

2. The spectrometry system of claim 1, wherein the excitation source is an acoustic energy source.

3. The spectrometry system of claim 1, wherein the excitation source is an optical light source.

4. The spectrometry system of claim 1, wherein the excitation source is an electronic excitation source.

5. The spectrometry system of any one of claims 1 to 5, further comprising a controller which is configured to control the excitation source.

6. The spectrometry system of claim 5, wherein the controller is configured to control the excitation source to emit an excitation signal at a predetermined frequency.

7. The spectrometry system of claim 4, further comprising a lock-in amplifier which is configured to receive the output from the detector and to extract an output signal at the predetermined frequency.

8. The spectrometry system of claim 7, wherein the controller is 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.

9. The spectrometry system of any one of claims 1 to 8, wherein the system is a field asymmetric ion mobility spectrometry comprising a drive signal system which applies a compensation field and a dispersion field to the ion filter to separate the ions.

10. The spectrometry system of claim 9, further comprising a processor which is configured to 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.

11. A method of detecting ions of a target chemical in a gas sample, the method comprising: generating ions within the gas sample, wherein each generated ion for the target chemical has an associated ion mobility;

modulating the ion mobility associated with ions from the target chemical within the gas sample by exciting the generated ions with an excitation signal;

separating the ions having modulated ion mobility from the gas sample; and detecting the separated ions.

12. The method of claim 11, comprising modulating the ion mobility using an excitation source in the form of an acoustic energy source.

13. The method of claim 11, comprising modulating the ion mobility using an excitation source in the form of an optical light source.

14. The method of claim 11, comprising modulating the ion mobility using an excitation source in the form of an electronic excitation source.

15. The method of any one of claims 11 to 14, further comprising setting the excitation signal at a predetermined frequency.

16. The method of claim 15, further comprising extracting an output signal at the predetermined frequency.

17. The method of claim 16, further comprising, in response to a change in the predetermined frequency of the excitation signal, automatically adjusting the predetermined frequency at which the separated ions are detected.

18. The method of any one of claims 11 to 17, wherein separating the ions comprises applying a compensation field and a dispersion field.

19. The method of claim 18, further comprising using 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.