EP-4742299-A1 - ION GUIDE WITH SWITCHABLE OPERATION MODES

EP4742299A1EP 4742299 A1EP4742299 A1EP 4742299A1EP-4742299-A1

Abstract

An ion guide includes a series of electrodes disposed between first and second ends of the ion guide. A controller is configured to determine that the ion guide is to operate in a mass-to-charge ratio ( m / z ) separation mode to separate ions primarily based on m / z of the ions or an ion mobility separation mode to separate ions primarily based on a mobility of the ions. The controller is further configured to set an attribute of radio-frequency (RF) voltage waveforms that are to be applied to the series of electrodes and to cause the RF voltage waveforms to be applied while the ion guide operates in the select mode. The RF voltage waveforms cause spatial separation of the ions within the ion guide and generate a plurality of moving pseudopotential wells that exert forces that urge the ions to migrate towards the second end of the ion guide.

Inventors

SENKO, MICHAEL W.
GOODWIN, MICHAEL P.

Assignees

THERMO FINNIGAN LLC

Dates

Publication Date: 20260513
Application Date: 20251106

Claims (15)

A system comprising: a memory storing instructions; and one or more processors communicatively coupled to the memory and configured to execute the instructions to perform a process comprising: determining that an ion guide is to operate in a select mode of two modes, the ion guide comprising a first end, a second end, and a series of electrodes disposed between the first end and the second end, the series of electrodes defining an ion occupation volume between the first end and the second end, wherein the two modes include a mass-to-charge ratio ( m / z ) separation mode configured to separate ions within the ion occupation volume primarily based on m / z of the ions and an ion mobility separation mode configured to separate the ions within the ion occupation volume primarily based on a mobility of the ions; setting, based on the determining, an attribute of radio-frequency (RF) voltage waveforms that are to be applied to the series of electrodes to operate the ion guide in the select mode, wherein the setting comprises: setting the attribute of the RF voltage waveforms to be within a first range when the ion guide is to operate in the m / z separation mode, and setting the attribute of the RF voltage waveforms to be within a second range when the ion guide is to operate in the ion mobility separation mode; and causing the RF voltage waveforms having the set attribute to be applied to the series of electrodes while the ion guide operates in the select mode, the RF voltage waveforms configured to cause spatial separation of the ions within the ion guide and to generate a plurality of moving pseudopotential wells that exert forces that urge the ions to migrate towards the second end of the ion guide.
The system of claim 1, wherein the setting the attribute of the RF voltage waveforms includes setting one or more of a frequency of the RF voltage waveforms, a magnitude of the RF voltage waveforms, or a speed of the RF voltage waveforms.
The system of any one of claims 1-2, wherein the first range of the attribute of the RF voltage waveforms includes a first range of RF voltage waveform frequencies, wherein the second range of the attribute of the RF voltage waveforms includes a second range of RF voltage waveform frequencies that are lower than the first range of RF voltage waveform frequencies.
The system of any one of claims 1-3, wherein the ion guide includes a gas within the ion occupation volume at a gas pressure greater than or equal to 0.01 Torr.
The system of claim 4, wherein the process further includes setting, based on the determining, the gas pressure of the gas within the ion occupation volume to operate the ion guide in the select mode, wherein the setting the gas pressure comprises: setting the gas pressure to be within a first pressure range when the ion guide is to operate in the m / z separation mode, and setting the gas pressure to be within a second pressure range when the ion guide is to operate in the ion mobility separation mode, optionally wherein the first pressure range includes gas pressures that are lower than gas pressures included in the second pressure range.
The system of any one of claims 1-5, wherein the process further comprises adjusting the attribute of the RF voltage waveforms to switch between the m / z separation mode and the ion mobility separation mode.
The system of any one of claims 1-6, wherein the determining that the ion guide is to operate in the select mode is based on a user input designating the select mode.
The system of any one of claims 1-7, wherein the determining that the ion guide is to operate in the select mode is based on determining an attribute of a sample containing ions to be received by the ion guide, optionally wherein the attribute of the sample includes multiple ions having a same m / z range.
The system of any one of claims 1-8, wherein the process further includes causing, simultaneously with the application of the RF voltage waveforms, direct-current (DC) electrical potentials to be applied either to the series of electrodes or to a set of auxiliary electrodes that generate forces on the ions within the ion guide that are independent of m / z and that urge the ions to migrate from the second end to the first end, and optionally wherein the applying of the DC electrical potentials comprises applying a set of two or more electrical potentials, one of the electrical potentials generating a static, uniform DC field within a portion of the ion guide, whereby ions having a particular m / z are caused to accumulate within the ion guide and ions having other mass-to-charge ratios are caused to migrate out of the ion guide, and further optionally wherein the process further includes ramping a magnitude of an applied DC electrical potential or an amplitude of an applied RF voltage waveform, whereby the accumulated ions having a particular m / z are caused to migrate out of the ion guide through either the first or second end.
The system of any one of claims 1-9, wherein the applying of the RF voltage waveforms to the series of electrodes comprises: applying the RF voltage waveforms to a first series of electrodes disposed on a surface of a first substrate plate or wafer and to a second series of electrodes disposed on a surface of a second substrate plate or wafer, wherein the first substrate plate or wafer is substantially parallel to the second substrate plate or wafer and separated therefrom by a gap.
A method of operating an ion guide comprising a first end, a second end, and a series of electrodes disposed between the first end and the second end, the series of electrodes defining an ion occupation volume between the first end and the second end, the method comprising: determining that the ion guide is to operate in a select mode of two modes, the two modes including a mass-to-charge ratio ( m / z ) separation mode configured to separate ions within the ion occupation volume primarily based on m / z of the ions and an ion mobility separation mode configured to separate the ions primarily based on a mobility of the ions; setting, based on the determining, an attribute of radio-frequency (RF) voltage waveforms that are to be applied to the series of electrodes to operate the ion guide in the select mode, wherein the setting comprises: setting the attribute of the RF voltage waveforms to be within a first range when the ion guide is to operate in the m / z separation mode, and setting the attribute of the RF voltage waveforms to be within a second range when the ion guide is to operate in the ion mobility separation mode; and causing the RF voltage waveforms having the set attribute to be applied to the series of electrodes while the ion guide operates in the select mode, the RF voltage waveforms configured to cause spatial separation of the ions within the ion guide and to generate a plurality of moving pseudopotential wells that exert forces that urge the ions to migrate towards the second end of the ion guide.
The method of claim 11, wherein the setting the attribute of the RF voltage waveforms includes setting one or more of a frequency of the RF voltage waveforms, a magnitude of the RF voltage waveforms, or a speed of the RF voltage waveforms.
The method of any one of claims 11-12, wherein the first range of the attribute of the RF voltage waveforms includes a first range of RF voltage waveform frequencies, wherein the second range of the attribute of the RF voltage waveforms includes a second range of RF voltage waveform frequencies that are lower than the first range of RF voltage waveform frequencies.
The method of any one of claims 1-13, further comprising setting, based on the determining, a gas pressure of a gas within the ion occupation volume to operate the ion guide in the select mode, wherein the setting the gas pressure comprises: setting the gas pressure to be within a first pressure range when the ion guide is to operate in the m / z separation mode, and setting the gas pressure to be within a second pressure range when the ion guide is to operate in the ion mobility separation mode.
The method of any one of claims 1-14, further comprising adjusting the attribute of the RF voltage waveforms to switch between the m / z separation mode and the ion mobility separation mode.

Description

BACKGROUND INFORMATION Mass spectrometry has often been referred to as a "Gold Standard" tool for the identification and analysis of various classes of compounds. In no small measure, the power of mass spectrometry resides in the ability of modern mass spectrometers to separately isolate, store, and subsequently manipulate - via ion fragmentation or ion-ion chemical reaction - specific ion species of interest that are chosen from among the multitude of ion species that are generally produced by ionization of any sample mixture. In many types of mass spectrometers, quadrupole mass filters are often employed to perform the ion isolation function. For example, in a mass spectrometer of the triple-quadrupole type or of the quadrupole-time-of-flight (Q-TOF) type, a mass filter is disposed upstream from a mass analyzer. The mass filter may receive a stream of ions composed of a variety of ion species comprising a variety of mass-to-charge (m/z) ratios. To isolate a particular ion species comprising a specific m/z, a specific pair of direct-current (DC) and oscillatory radio-frequency (RF) voltages may be applied to rod electrodes of the mass filter. The application of DC and RF voltages of the appropriate magnitude permits transmission, through the mass filter, of only a narrow range of m/z values that encompasses the specific m/z of interest. Under such operation, ions having all other m/z values are ejected from the apparatus and neutralized. The ion species that comprises the specific m/z that is of interest is thus transmitted, without significant contamination from other ion species, through the mass filter to other, downstream mass spectrometer components that may manipulate and analyze ions of the isolated ion species in various ways. Although mass filters perform an important function, they are nonetheless inefficient in that, at any one time, they cause the elimination of all ions except for those specific ions that are permitted to pass through the apparatus by the choice of filter passband. As a result, typically more than ninety percent of potentially available compositionally relevant information may be wasted by the mass filter at any particular time. To improve overall analytical efficiency, various types of pre-separation apparatuses have been employed, generally upstream from a mass filter, as a means of providing non-destructive initial coarse separation of ion species. Once separated by the pre-separation apparatus, the various coarsely separated groups of ions may then be separately transferred to a mass filter for narrow-band isolation of ion species of interest. Because of the earlier pre-separation, a lesser proportion of ions will be discarded by the mass filter during each such isolation. As one example of such a pre-separation method, ion mobility spectrometry (IMS) is often used to separate ionized molecules in the gas phase based on their mobility in a carrier buffer gas. The reader is referred to Kanu et al. (Kanu, Abu B., Prabha Dwivedi, Maggie Tam, Laura Matz, and Herbert H. Hill Jr. "Ion mobility-mass spectrometry." Journal of mass spectrometry 43, no. 1 (2008): 1-22.) for a general review of coupling of ion mobility spectrometers to mass spectrometers. According to another separation method, which is known as trapped ion mobility spectrometry (TIMS), ions are trapped along a non-uniform electric DC field (field gradient) by a counteracting gas flow or along a uniform electric DC field by a counteracting gas flow which has a non-uniform axial velocity profile (gas velocity gradient). The trapped ions are separated in space according to ion mobility and subsequently eluted (released) over time according to their mobility by adjusting one of the gas velocity and the DC electric field. The details of the TIMS technique are described, for example, in U.S. Pat. No. 6,630,662 in the name of inventor Loboda; U.S. Pat. No. 7,838,826 B1 in the name of inventor Park; and U.S. Patent No. 11,226,308 in the names of Rather and Michelmann. Additional descriptions are provided in Michelmann et al. (Michelmann, Karsten, Joshua A. Silveira, Mark E. Ridgeway, and Melvin A. Park. "Fundamentals of trapped ion mobility spectrometry." Journal of the American Society for Mass Spectrometry 26, no. 1 (2014): 14-24.) as well as in Silveira et al. (Silveira, Joshua A., Karsten Michelmann, Mark E. Ridgeway, and Melvin A. Park. "Fundamentals of trapped ion mobility spectrometry part II: fluid dynamics." Journal of the American Society for Mass Spectrometry 27, no. 4 (2016): 585-595.) Both the ion mobility spectrometry technique and the trapped ion mobility spectrometry technique make use of ion guides that are configured to provide an axial DC field along their length. Such axial fields may be provided by proportioning a voltage that is applied between entrance and exit ends of the ion guide among a plurality of electrodes that are disposed between the entrance and exit ends of the ion guide. As one example, t