Abstract: A mass spectrometer that includes a mass filter and a TOF mass analyzer receives the ion beam from an ion source device that ionizes a compound of a sample. The mass filter selects a precursor ion mass range and the mass analyzer mass analyzes the mass range. A continuous flow of selected precursor ions is maintained between the mass filter and the mass analyzer. A first set of parameters is applied to the mass spectrometer to produce a resolution above a first resolution threshold. A space charge effect is detected by determining if the measured TIC exceeds a TIC threshold or the measured resolution is less than the first resolution threshold. If a space charge effect is detected, at least one precursor ion transmission window with a width smaller than the mass range is applied to the ion beam by the mass filter and mass analyzed to reduce the space charge.

Abstract: During an accumulation time period of each time cycle of an ion guide and before a ramped AC voltage is applied to at least one set of axial rods to eject ions according to m/z value, a number of steps are performed. Ions are received from outside of the ion guide through an entrance aperture and into a first cell. A low DC voltage is applied to a barrier electrode to receive ions from the first cell into a second cell. And, a high DC voltage is applied to an exit electrode to prevent ions from exiting the ion guide. During a cooling time period before the AC time period, a high DC voltage is applied to the barrier electrode to trap and cool ions in the second cell and to continue to receive ions into the first cell without being affected by the ramped AC voltage.

Abstract: A method for assigning charge state in mass spectrometry includes receiving a detector response signal corresponding to a plurality of ion arrival events. The detector response signal includes information related to individual ion responses generated by a detector for each ion arrival event. Detector response profiles are generated for mass-to-charge (m/z) bins of a mass spectrum generated from the ion arrival events based on the detector response signal. The m/z bins are grouped into a plurality of groups based on a similarity of the detector response profiles of the m/z bins. A charge state is assigned to one or more features based on the groups of m/z bins.

Abstract: Devices and methods are described for assigning charge state to detected ions from a mass analysis instrument. In one of the methods, the charge state may be assigned, for instance, by evaluation a detector response signal including information related to individual ion responses generated by an ion detector for each ion arrival event captured by the detector. The detector response signal may then be evaluated in combination with one or more additional features corresponding to the ion arrival event to assign a charge state for that ion arrival event.

Abstract: Methods and systems for identifying or classifying charge states of detected ions. An example method for classifying a charge state of detected ions may include generating a pulse for each ion in a plurality of ions detected by a detector, wherein each pulse has a pulse characteristic; generating a pulse-characteristic distribution of the generated pulses; and based on the pulse-characteristic distribution, generating an identification of the charge state of one or more ions in the plurality of ions.

Abstract: In one aspect, a method of performing mass spectrometry is disclosed, which includes acquiring mass detection signals generated by an ion detector during an ion extraction event in a time-of-flight (ToF) mass analyzer in response to incidence of ions thereon, and applying an adjustable gain to the mass detection signals, wherein the step of applying the adjustable gain to the mass detection signals is performed dynamically based on m/z regions associated with said mass detection signals.

Abstract: In one aspect, a method of performing mass spectrometry is disclosed, which includes selecting a precursor ion having an m/z ratio in a range of interest from among a plurality of ions, identifying a charge state of the selected precursor ion, e.g., based on distribution of mass peaks associated with different isotopes in a mass spectrum. The charge state of the selected precursor ion can be reduced to generate a respective charge-reduced ion at a known m/z ratio. The charge-reduced ion can be subjected to fragmentation to generate a plurality of product ions (which are herein also referred to as fragment ions). A mass analysis of the product ions can then be performed.

Abstract: In one aspect, a mass spectrometer is disclosed, which includes an ion source configured to receive a sample and ionize at least one analyte in the sample to generate a plurality of ions of that analyte, at least a first ion routing device having a first inlet for receiving at least a portion of the plurality of the analyte ions and at least a first and a second outlet through which a first and a second portion of the received analyte ions can exit the ion-routing device, respectively, and at least two charge reduction devices one of which is coupled via a first inlet thereof to the first outlet and the other is coupled via an inlet thereof to the second outlet of the ion routing device to receive the first and second portions of the ions exiting the ion routing device.

Abstract: In one aspect, a method for mass spectrometric analysis of analyte ions is disclosed, which includes filtering a plurality of ions to sequentially transmit a plurality of precursor ion subsets to a charge reduction device (e.g., a proton reaction device). For each precursor ion subset, a charge reduction reaction is performed within the proton reaction device to generate a set of charge-reduced precursor ions associated with one of the precursor ion subsets. One or more portions of the set of charged-reduced product ions associated with each respective precursor ion subset are selectively transmitted to a fragmentation device. The charge-reduced precursor ions are fragmented in the fragmentation device to generate a set of fragment ions associated with each respective precursor ion subset and mass spectra of each set of fragment ions associated with a respective precursor ion subset are generated.

Abstract: In one aspect, a mass spectrometer is disclosed, which comprises an ion source configured to receive a sample and ionize at least one analyte in the sample to generate a plurality of analyte ions, and at least a first ion routing device having a first inlet for receiving at least a portion of the plurality of the analyte ions and at least a first and a second outlet through which a first and a second portion of the received analyte ions can exit the ion-routing device, respectively. The mass spectrometer can further include at least two charge reduction devices one of which is coupled via a first inlet thereof to the first outlet and the other is coupled via an inlet thereof to the second outlet of the ion routing device to receive said first and second portions of the ions exiting the ion routing device.

Abstract: Methods and systems for identifying or classifying charge states of detected ions. An example method for classifying a charge state of detected ions may include generating a pulse for each ion in a plurality of ions detected by a detector, wherein each pulse has a pulse characteristic; generating a pulse-characteristic distribution of the generated pulses; and based on the pulse-characteristic distribution, generating an identification of the charge state of one or more ions in the plurality of ions.

Abstract: A system for applying RF voltages to a multipole ion processing device, configured for use in a mass spectrometer, includes a first RF generator configured to generate a first RF voltage and apply to a first pole electrode set, a second RF generator configured to generate a second RF voltage and apply to a second pole electrode set, a first amplitude adjustor configured to adjust an amplitude of the first RF voltage, a second amplitude adjustor configure to adjust an amplitude of the second RF voltage, and a phase adjustor in communication with the first RF generator and the second RF generator to adjust phase output of at least one of the first RF generator and the second RF generator so as to adjust a phase differential between the first RF voltage and the second RF voltage to be within a desired range.

Abstract: Methods and systems for controlling a filament of an electron emitter associated with an ion reaction cell in accordance with various aspects of the present teachings may account for inter-filament and inter-instrument variability and can provide improved reproducibility in EAD experiments and ease of use. In some aspects, a method of operating an ion reaction device of a mass spectrometer system is provided. The method comprises applying a calibration drive voltage to a filament of an electron emitter associated with an ion reaction cell and determining a value representative of the calibration electron emission current generated by the filament while having the calibration drive voltage applied thereto. A calibration saturation voltage can be determined by iteratively increasing the calibration drive voltage applied to the filament and determining the value of the calibration electron emission current at each corresponding calibration drive voltage until the filament reaches a saturation condition.

Abstract: The present disclosure provides methods and systems for performing mass spectrometry in which at least two batches of precursor ions generated via ionization of at least two different portions of a sample are exposed to electron beams at different energies to cause fragmentation of at least a portion of the precursor ions. In some embodiments, the electron energies can be selected such at one of the electron energies, EIEIO fragmentation can occur while at the other electron energy, EIEO fragmentation channel is not available. The mass spectra corresponding to the two energies can then be utilized to generate a resultant mass spectrum in which mass peaks corresponding to ion fragments generated by EIEIO dissociation are more readily identifiable.

Abstract: Method and devices for performing top down analysis of an antibody are described which involve utilizing an ion source to generate a plurality of ions from a sample containing at least one intact antibody. Further, transmitting said plurality of ions through a quadrupole rod set while applying an RF signal thereto and in the absence of a resolving DC voltage so as to preferentially transmit precursor ions having an m/z value greater than a low mass cutoff of about 1500 m/z from the quadrupole rod set to an ECD cell. The method and device can also performing an ECD reaction in the ECD cell on said precursor ions and also detect reaction products from the ECD reaction.

Abstract: A mass spectrometer that includes a mass filter and a TOF mass analyzer receives the ion beam from an ion source device that ionizes a compound of a sample. The mass filter selects a precursor ion mass range and the mass analyzer mass analyzes the mass range. A continuous flow of selected precursor ions is maintained between the mass filter and the mass analyzer. A first set of parameters is applied to the mass spectrometer to produce a resolution above a first resolution threshold. A space charge effect is detected by determining if the measured TIC exceeds a TIC threshold or the measured resolution is less than the first resolution threshold. If a space charge effect is detected, at least one precursor ion transmission window with a width smaller than the mass range is applied to the ion beam by the mass filter and mass analyzed to reduce the space charge.

Abstract: During an accumulation time period of each time cycle of an ion guide and before a ramped AC voltage is applied to at least one set of axial rods to eject ions according to m/z value, a number of steps are performed. Ions are received from outside of the ion guide through an entrance aperture and into a first cell. A low DC voltage is applied to a barrier electrode to receive ions from the first cell into a second cell. And, a high DC voltage is applied to an exit electrode to prevent ions from exiting the ion guide. During a cooling time period before the AC time period, a high DC voltage is applied to the barrier electrode to trap and cool ions in the second cell and to continue to receive ions into the first cell without being affected by the ramped AC voltage.

Abstract: An ion source ionizes a compound, producing precursor ions with different m/z values. A reagent source supplies charge reducing reagent. An ion guide is positioned between a mass filter and both the ion source and the reagent source. The ion guide applies an AC voltage and DC voltage to its electrodes that creates a pseudopotential to trap the precursor ions in the ion guide below a threshold m/z. This AC voltage, in turn, causes the trapped precursor ions to be charge reduced by the reagent so that m/z values of the trapped precursor ions increase to a single m/z value above the threshold m/z. The ion guide applies the DC voltage to its electrodes relative to a DC voltage applied to electrodes of the mass filter that causes the precursor ions with m/z values increased to the single m/z value to be continuously transmitted to the mass filter.

Abstract: Intensity measurements made by electron multiplier and image-charge detectors are proportional to charge state. These intensities are used to separate detected ions into different data sets and create mass spectra from the different data sets. Ion measurements are separated by charge state using (i) a single electron multiplier detector, (ii) a single image-charge detector, or (iii) multiple electron multiplier ADC detectors. Using (i), the intensity of a peak calculated from each measured pulse is compared to predetermined intensity ranges and each peak is stored in a corresponding data set. Using (ii), each measured transient time-domain signal is converted to frequency-domain peaks, the intensity of each frequency-domain peak is compared to predetermined intensity ranges, and each peak is stored in a corresponding data set. Using (iii), each detector is adapted to measure a predetermined intensity range and store calculated peaks from the measured pulses in corresponding data sets.

Abstract: Methods and systems for identifying or classifying charge states of detected ions. An example method for classifying a charge state of detected ions may include generating a pulse for each ion in a plurality of ions detected by a detector, wherein each pulse has a pulse characteristic; generating a pulse-characteristic distribution of the generated pulses; and based on the pulse-characteristic distribution, generating an identification of the charge state of one or more ions in the plurality of ions.