Abstract: An ion source may include an ionization chamber to be maintained at atmospheric-pressure. The ion source may further include a reduced-pressure chamber to be maintained at sub-atmospheric pressure, and an ion transfer device comprising an inlet in the ionization chamber and an outlet in the reduced-pressure chamber. The ion transfer device may define an ion path from the inlet to the outlet. The ion transfer device may be positioned to emit ions and neutral gas molecules from the outlet as an expanding beam comprising a low-gas density zone enveloped by a high-gas density region that includes a gas density that is higher than the low-gas density zone. The ion source may be utilized, for example, for ion mobility spectrometry (IMS), mass spectrometry (MS), and hybrid IM-MS.

Abstract: In an ion mobility-mass spectrometry (IM-MS) system, an ion mass-isolated data set is acquired by operating a mass filter to apply a mass isolation window having an m/z width such that the mass isolation window moves through a sequence of window positions, each window position being defined by an IM drift time value and an m/z ratio value. The m/z width of the mass isolation window and the sequence of window positions are determined such that the mass isolation window captures ions in a region of interest of a larger all-ions data set. The isolation window may be a wideband isolation window. In comparison to the all-ions data set, the mass-isolated data set may yield reduced ion signal interference and increased selectivity for analytes of interest.

Abstract: Multiplexed ion mobility spectrometry (IMS), mass spectrometry (MS) such as time-of-flight mass spectrometry (TOFMS), or hybrid IM-MS is carried out on a sample, and the resulting measurement data are deconvoluted. A pulse sequence controlling ion pulsing is utilized in conjunction with the multiplexing. The pulse sequence may be modified based on the raw measurement data acquired. A demultiplexing matrix based on the modified pulse sequence is utilized to improve deconvolution.

Abstract: An electrode assembly is provided in a high sub-atmospheric pressure region of an ion source, between an ionization chamber and a vacuum region of a spectrometer, such as a mass spectrometer, an ion mobility spectrometer, or an ion mobility-mass spectrometer. The electrode assembly is spaced at a distance from an outlet of an ion transfer device. A voltage source imparts a potential difference between the ion transfer device and the electrode assembly to accelerate ions emitted from the outlet to a collision energy. The collision energy is effective to cause collisional heating of ions in the high sub-atmospheric pressure region without voltage breakdown. The collision energy may be set to cause unfolding of folded biomolecular ions and/or dissociation of ions.

Abstract: An electrode assembly is provided in a high sub-atmospheric pressure region of an ion source, between an ionization chamber and a vacuum region of a spectrometer, such as a mass spectrometer, an ion mobility spectrometer, or an ion mobility-mass spectrometer. The electrode assembly is spaced at a distance from an outlet of an ion transfer device. A voltage source imparts a potential difference between the ion transfer device and the electrode assembly to accelerate ions emitted from the outlet to a collision energy. The collision energy is effective to cause collisional heating of ions in the high sub-atmospheric pressure region without voltage breakdown. The collision energy may be set to cause unfolding of folded biomolecular ions and/or dissociation of ions.

Abstract: In an ion mobility-mass spectrometry (IM-MS) system, an ion mass-isolated data set is acquired by operating a mass filter to apply a mass isolation window having an m/z width such that the mass isolation window moves through a sequence of window positions, each window position being defined by an IM drift time value and an m/z ratio value. The m/z width of the mass isolation window and the sequence of window positions are determined such that the mass isolation window captures ions in a region of interest of a larger all-ions data set. The isolation window may be a wideband isolation window. In comparison to the all-ions data set, the mass-isolated data set may yield reduced ion signal interference and increased selectivity for analytes of interest.

Abstract: The collision cross section (CCS) of a sample ion may be calculated by measuring a total drift time taken by the sample ion to travel through an ion mobility spectrometry drift cell to an ion detector. The CCS may be calculated based on the total drift time measured, and on a proportionality coefficient that defines the time taken by the sample ion to travel through a mobility dominated region between the drift cell and the detector. The proportionality coefficient may be determined from measuring the total drift times of reference ions. Calculation of the CCS of the sample ion may also be based on a proportionality coefficient that defines the time taken by the sample ion to travel through a mobility-independent region where the velocity of the ion depends on the electrostatic field strength, mass and the charge state of the ion.

Abstract: An interface for an ion mobility spectrometry-mass spectrometry (IMS-MS) system includes a first ion guide for receiving ions from an IMS drift cell, and a second ion guide for receiving ions from the first ion guide, and positioned in a chamber separate from the first ion guide. Electrodes of the second ion guide subject the ions to an axial DC electric field while the second ion guide is held at a lower pressure than the first ion guide. In some embodiments, the first ion guide may be an ion funnel and the second ion guide may be a linear multipole device.

Abstract: Multiplexed ion mobility spectrometry (IMS), mass spectrometry (MS) such as time-of-flight mass spectrometry (TOFMS), or hybrid IM-MS is carried out on a sample, and the resulting measurement data are deconvoluted. A pulse sequence controlling ion pulsing is utilized in conjunction with the multiplexing. The pulse sequence may be modified based on the raw measurement data acquired. A demultiplexing matrix based on the modified pulse sequence is utilized to improve deconvolution.

Abstract: An ion processing device includes electrically conductive vacuum manifold segments serially positioned and enclosing a volume along an axis. The segments are electrically isolated from each other and independently addressable by a voltage source. An ion optics device is positioned in the volume. A voltage differential between each manifold segment and the ion optics device is maintained below a maximum value by applying different voltages to respective manifold segments. The voltage differential may be controlled to avoid voltage breakdown in a low-pressure, high-voltage gas environment. The ion optics device may in some cases be an ion mobility drift cell.

Abstract: The collision cross section (CCS) of a sample ion may be calculated by measuring a total drift time taken by the sample ion to travel through an ion mobility spectrometry drift cell to an ion detector. The CCS may be calculated based on the total drift time measured, and on a proportionality coefficient that defines the time taken by the sample ion to travel through a mobility dominated region between the drift cell and the detector. The proportionality coefficient may be determined from measuring the total drift times of reference ions. Calculation of the CCS of the sample ion may also be based on a proportionality coefficient that defines the time taken by the sample ion to travel through a mobility-independent region where the velocity of the ion depends on the electrostatic field strength, mass and the charge state of the ion.

Abstract: An ion processing device includes electrically conductive vacuum manifold segments serially positioned and enclosing a volume along an axis. The segments are electrically isolated from each other and independently addressable by a voltage source. An ion optics device is positioned in the volume. A voltage differential between each manifold segment and the ion optics device is maintained below a maximum value by applying different voltages to respective manifold segments. The voltage differential may be controlled to avoid voltage breakdown in a low-pressure, high-voltage gas environment. The ion optics device may in some cases be an ion mobility drift cell.

Abstract: An interface for an ion mobility spectrometry-mass spectrometry (IMS-MS) system includes a first ion guide for receiving ions from an IMS drift cell, and a second ion guide for receiving ions from the first ion guide, and positioned in a chamber separate from the first ion guide. Electrodes of the second ion guide subject the ions to an axial DC electric field while the second ion guide is held at a lower pressure than the first ion guide. In some embodiments, the first ion guide may be an ion funnel and the second ion guide may be a linear multipole device.

Abstract: An orthogonal ion injection apparatus and process are described in which ions are directly injected into an ion guide orthogonal to the ion guide axis through an inlet opening located on a side of the ion guide. The end of the heated capillary is placed inside the ion guide such that the ions are directly injected into DC and RF fields inside the ion guide, which efficiently confines ions inside the ion guide. Liquid droplets created by the ionization source that are carried through the capillary into the ion guide are removed from the ion guide by a strong directional gas flow through an inlet opening on the opposite side of the ion guide. Strong DC and RF fields divert ions into the ion guide. In-guide orthogonal injection yields a noise level that is a factor of 1.5 to 2 lower than conventional inline injection known in the art. Signal intensities for low m/z ions are greater compared to convention inline injection under the same processing conditions.

Abstract: An ion mobility spectrometer instrument has a drift tube that is partitioned into a plurality of cascaded drift tube segments. A number of electric field activation sources may each be coupled to one or more of the plurality of drift tube segments. A control circuit is configured to control operation of the number of electric field activation sources in a manner that sequentially applies electric fields to the drift tube segments to allow only ions having a predefined ion mobility or range of ion mobilities to travel through the drift tube. The drift tube segments may define a linear drift tube or a closed drift tube with a continuous ion travel path. Techniques are disclosed for operating the ion mobility spectrometer to produce highly resolved ion mobility spectra.

Abstract: An orthogonal ion injection apparatus and process are described in which ions are directly injected into an ion guide orthogonal to the ion guide axis through an inlet opening located on a side of the ion guide. The end of the heated capillary is placed inside the ion guide such that the ions are directly injected into DC and RF fields inside the ion guide, which efficiently confines ions inside the ion guide. Liquid droplets created by the ionization source that are carried through the capillary into the ion guide are removed from the ion guide by a strong directional gas flow through an inlet opening on the opposite side of the ion guide. Strong DC and RF fields divert ions into the ion guide. In-guide orthogonal injection yields a noise level that is a factor of 1.5 to 2 lower than conventional inline injection known in the art. Signal intensities for low m/z ions are greater compared to convention inline injection under the same processing conditions.

Abstract: An ion mobility spectrometer instrument has a drift tube that is partitioned into a plurality of cascaded drift tube segments. A number of electric field activation sources may each be coupled to one or more of the plurality of drift tube segments. A control circuit is configured to control operation of the number of electric field activation sources in a manner that sequentially applies electric fields to the drift tube segments to allow only ions having a predefined ion mobility or range of ion mobilities to travel through the drift tube. The drift tube segments may define a linear drift tube or a closed drift tube with a continuous ion travel path. Techniques are disclosed for operating the ion mobility spectrometer to produce highly resolved ion mobility spectra.

Abstract: An ion mobility spectrometer instrument has a drift tube that is partitioned into a plurality of cascaded drift tube segments. A number of electric field activation sources may each be coupled to one or more of the plurality of drift tube segments. A control circuit is configured to control operation of the number of electric field activation sources in a manner that applies switched electric fields at a specified switching rate to the drift tube segments to thereby produce at the ion outlet only ions having a predefined ion mobility or range of ion mobilities.

Abstract: An ion mobility spectrometer instrument has a drift tube that is partitioned into a plurality of cascaded drift tube segments. A number of electric field activation sources may each be coupled to one or more of the plurality of drift tube segments. A control circuit is configured to control operation of the number of electric field activation sources in a manner that applies switched electric fields at a specified switching rate to the drift tube segments to thereby produce at the ion outlet only ions having a predefined ion mobility or range of ion mobilities.