US-12626899-B2 - Mass spectrometer and method

Abstract

A charge detection mass spectrometer, CDMS, is described. The CDMS 4 , comprises: an electrostatic sector field ion trap 40 and an inductive charge detector 400 ; wherein the electrostatic sector field ion trap 40 is configured to define, at least in part, an ion path via the inductive charge detector 400 . A method is also described.

Inventors

• John Brian Hoyes

Assignees

• TRUEMASS LTD

Dates

Publication Date

20260512

Application Date

20210903

Priority Date

20200903

Claims (14)

1. 1 . A charge detection mass spectrometer (CDMS), comprising: an electrostatic sector field ion trap; an inductive charge detector; and a set of electrostatic focus lenses including a first focus lens; wherein the electrostatic sector field ion trap is configured to define, at least in part, an ion path via the inductive charge detector; wherein a mass m of an ion moving around the ion path is determined by determining a mass to charge m/z and a charge z of the ion using signals induced by the ion in the inductive charge detector; wherein the electrostatic sector field ion trap comprises a set of electrostatic sectors, including a first electrostatic sector and a second electrostatic sector, wherein the ion moves with a constant speed around the ion path; wherein the first electrostatic sector and the second electrostatic sector are spherical electrostatic sectors; wherein the first electrostatic sector and the second electrostatic sector are mutually opposed; wherein the ion path defined by the electrostatic sector field ion trap includes a crossover; wherein the set of electrostatic focus lenses, including the first focus lens, is arranged to constrain, at least in part, the ion path in a first dimension; wherein the first dimension is orthogonal to a direction of the ion path via the inductive charge detector; and wherein the first focus lens comprises and/or is a cylinder lens, an einzel lens and/or a plate lens disposed across the crossover in the ion path.
2. 2 . The CDMS according to claim 1 , wherein the set of electrostatic sectors includes only the first electrostatic sector and the second electrostatic.
3. 3 . The CDMS according to claim 1 , wherein the first electrostatic sector comprises a set of shunts, including a first shunt, arranged to delimit a field due to the first electrostatic sector.
4. 4 . The CDMS according to claim 1 , wherein the electrostatic sector field ion trap is isochronous.
5. 5 . The CDMS according to claim 1 , wherein the electrostatic sector field ion trap is configured to define, at least in part, the ion path in two or three mutually-orthogonal dimensions.
6. 6 . The CDMS according to claim 1 , wherein the electrostatic sector field ion trap comprises an ion inlet for introduction of ions therethrough into the ion path.
7. 7 . The CDMS according to claim 1 , wherein the inductive charge detector comprises a first set of charge detector tubes, including a first charge detector tube.
8. 8 . The CDMS according to claim 7 , wherein the first charge detector tube, having a length L and a width W, has a ratio of the length L to the width W in a range from 3:2 to 5:2.
9. 9 . The CDMS according to claim 1 , wherein a portion of the ion path via the inductive charge detector is in a range from 30% to 70% of the ion path defined by the electrostatic sector field ion trap.
10. 10 . The CDMS according to claim 1 , wherein a cross-section of the ion path via the inductive charge detector is arcuate, having a central angle in a range from −3° to +3°.
11. 11 . The CDMS according to claim 1 , wherein the inductive charge detector is configured to operate at ground potential.
12. 12 . The CDMS according to claim 1 , comprising a lift device configured to increase an ion energy of ions to be introduced into the ion path.
13. 13 . The CDMS according to claim 12 , wherein the lift device is configured to trap the ions to be introduced into the ion path, to introduce the ions into the ion path by pulsing the ions into the ion path, or both.
14. 14 . A method of determining a mass of an ion, the method comprising: moving an ion with a constant speed along an ion path having a crossover by an electrostatic sector field ion trap comprising a plurality of electrostatic sectors including a first spherical electrostatic sector and a second spherical electrostatic sector disposed in opposition to the first spherical electrostatic sector, wherein the ion path is constrained in a first dimension orthogonal to a direction of the ion path via an inductive charge detector and a plurality of electrostatic focus lenses including a first focus lens disposed across the crossover in the ion path, the first focus lens comprising a cylinder lens, an einzel lens, or a plate lens, and wherein the moving ion induces signals in the inductive charge detector; and determining the mass of the ion by determining a mass-to-charge ratio from the induced signals and a charge of the ion from the induced signals.

Description

FIELD The present invention relates to charge detection mass spectrometers (CDMS). BACKGROUND TO THE INVENTION Charge Detection Mass Spectrometry (CDMS) is a technique that allows deconvolution of complex spectra of macromolecules. As molecules increase in size, the number of different charge states they may acquire increases. In the limit, overlapping charge states of molecules having different masses cause a blurred continuum on the mass to charge m/z scale of conventional mass spectrometers (MS). Such mass spectra yield little or no analytically useful information because individual species no longer stand out as distinct peaks. This is particularly problematic in the case of the electrospray of macromolecules as this ionisation technique yields many different charge states as molecular mass increases. In contrast to MS, which determines mass to charge m/z of ions, CDMS determines masses (i.e. not merely mass to charge m/z) by determining both mass to charge m/z and charge z of the ions. In conventional CDMS, individual ions are injected into an ion trap and are made to oscillate backwards and forwards through an inductive charge detection tube. As a particular ion enters the inductive charge detection tube, the particular ion induces a small, measurable voltage, the amplitude of which is proportional to its charge. The measured periodic time of the oscillation yields the mass to charge ratio m/z of the particular ion and the product of these two measurements gives the true mass of the particular ion. Allowing many oscillations within the ion trap and analysing the resulting signal by Fourier Transform (FT) improves the accuracy of both the charge and the mass to charge ratio m/z measurements. The measurement of true mass is in contrast to conventional MS such as orthogonal-acceleration time-of-flight (oa-TOF) MS which determine only mass to charge ratios m/z. The accuracy of CDMS depends on two limiting factors: electronic noise in the detection electronics giving uncertainty in charge measurements; and energy spread of incoming ions giving variations in oscillation periods. In 2012, Contino and Jarrold [1] presented a Charge Detection Mass Spectrometer (CDMS, clear from context, also known as CDMS analyser) with a limit of detection of 30 elementary charges for a single ion. This paper gives a comprehensive review of CDMS at that time and is incorporated in its entirety by reference herein. This CDMS comprised an electrospray source coupled to a dual hemispherical deflection analyser (HDA) followed by a cone trap incorporating an image charge detector. Ions were energy selected by the dual HDA prior to entering the trap. The fundamental oscillation frequency of the trapped ions was extracted by a fast Fourier transform (FFT). The oscillation frequency and kinetic energy provided the mass to charge ratios m/z of the trapped ions. The magnitude of the FFT at the fundamental frequency was proportional to the charge. Particularly, this CDMS required use of the dual HDA as an energy filter to limit the spread of ion energies entering the electrostatic cone trap and thereby reduce the variation in oscillation frequency, so as to achieve the limit of detection of 30 elementary charges for a single ion. However, limiting the spread of ion energies entering the electrostatic cone trap reduced the throughput of the CDMS. Lower noise electronics meant that by 2015, Keifer, Shinholt and Jarrold [2] demonstrated improved charge accuracy to better than integer level-which is sufficient for true mass determination. In 2018, Hogan and Jarrold [3] employed a segmented Electrostatic Linear Ion Trap (ELIT), which had a lower dependence on oscillation period with ion energy than the cone trap of their previous CDMS. This CDMS also required use of the dual HDA energy filter while significant dependence on oscillation frequency due to ion energy spread and radial position remained. Particularly, for this CDMS, the kinetic energy dependence of the ion oscillation frequency was reduced by an order of magnitude, which should have led to an order of magnitude reduction in the uncertainty of the mass to charge ratio m/z ratio determination. However, only a factor of four improvement was achieved, attributed to the trajectory dependence of the ion oscillation frequency. Hence, there is a need to improve CDMS. SUMMARY OF THE INVENTION It is one aim of the present invention, amongst others, to provide a CDMS which at least partially obviates or mitigates at least some of the disadvantages of the prior art, whether identified herein or elsewhere. For instance, it is an aim of embodiments of the invention to provide a CDMS having an ion trap geometry which eliminates the requirement for an upstream energy filter or selector. For instance, it is an aim of embodiments of the invention to provide a CDMS that improves isochronicity of ion oscillation periods, for example by reducing dependency on ion initial conditions. For instance, it