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DE-112015002758-B4 - Marking ADC coalescence

DE112015002758B4DE 112015002758 B4DE112015002758 B4DE 112015002758B4DE-112015002758-B4

Abstract

Mass spectrometry methods, which include: Digitizing at least one individual signal; Determine, with respect to each digitized signal, an indication of overlap of ion arrival amplitudes in the digitized signal by processing the respective digitized signal to identify a peak profile that is distorted due to overlap of ion arrival amplitudes; Determining intensity and arrival time data for each peak profile that is distorted due to overlapping ion arrival amplitudes, so that each peak profile is reduced to a time-intensity pair; and Marking, based on the indication, of the digitized signal as suffering from an overlap of ion arrival amplitudes, wherein the step of marking the digitized signal includes marking the time and intensity pair as suffering from an overlap of ion arrival amplitudes.

Inventors

  • Martin Raymond Green
  • Keith Richardson
  • Jason Lee Wildgoose

Assignees

  • MICROMASS UK LIMITED

Dates

Publication Date
20260513
Application Date
20150611
Priority Date
20140611

Claims (15)

  1. A mass spectrometry method comprising: Digitizing at least one individual signal; Determining, with respect to each digitized signal, an indication of overlapping ion arrival amplitudes in the digitized signal by processing the respective digitized signal to identify a peak profile that is distorted due to overlapping ion arrival amplitudes; Determining intensity and arrival time data for each peak profile that is distorted due to overlapping ion arrival amplitudes, such that each peak profile is reduced to a time-intensity pair; and Labeling, based on the indication, the digitized signal as suffering from overlapping ion arrival amplitudes, wherein the step of labeling the digitized signal includes labeling the time-intensity pair as suffering from overlapping ion arrival amplitudes.
  2. Procedure according to Claim 1 , where the indication of overlapping ion arrival amplitudes includes one or more geometric features of the ion arrival amplitude in the digitized signal.
  3. Procedure according to Claim 2 , wherein the one or more geometric features include at least one of profile, shape, symmetry, peak purity, peak area, intensity quantile, standard deviation, center of mass, peak width, skewness and curvature.
  4. Procedure according to Claim 3 , wherein determining an indication of the proportion and/or severity of cases in which the digitized signals suffer an overlap of ion arrival amplitudes includes comparing at least one of the geometric features with an expected, known or calibrated value.
  5. A method according to one of the preceding claims, further comprising summing several of the digitized signals or data relating to the digitized signals to generate a set of aggregated mass spectral data.
  6. Procedure according to Claim 5 , which further includes determining, with reference to the set of mass spectral data, an indication of the proportion and/or severity of cases in which the digitized signals have suffered an overlap of ion arrival amplitudes.
  7. Procedure according to Claim 5 or 6 , wherein determining an indication of the proportion and/or severity of cases in which the digitized signals have suffered overlap of ion arrival amplitudes includes counting the number of digitized signals that have been marked as suffering an overlap of ion arrival amplitudes.
  8. Procedure according to Claim 5 , 6 or 7 , wherein determining an indication of the proportion and/or severity of cases in which the digitized signals have suffered an overlap of ion arrival amplitudes comprises determining a ratio A:B indicating the proportion and/or severity of cases in which the digitized signals have suffered an overlap of ion arrival amplitudes, where A represents the number of digitized signals that are marked as suffering an overlap of ion arrivals within a given arrival time, and B represents a total number of digitized signals that have been summed within the given arrival time.
  9. Procedure according to one of the Claims 5 - 8 , which further includes changing one or more operating parameters of a mass spectrometer in response to determining one or more regions of the set of aggregated mass spectral data that suffer an overlap of ion arrival amplitudes.
  10. Procedure according to Claim 9 , where the step of changing one or more operating parameters of a mass spectrometer involves changing an ion transfer efficiency an ion transfer control device to reduce the effects of overlapping ion arrival amplitudes in one or more regions.
  11. Method according to one of the preceding claims, which, in addition to determining intensity and arrival time data, comprises determining mass and/or mass-to-charge ratio data for at least one peak profile that is distorted due to overlap of ion arrival amplitudes.
  12. A method according to one of the preceding claims, further comprising processing the characterized digitized signals or data corresponding to the characterized digitized signals in order to reduce the effect of overlap of ion arrival amplitudes in one or the set of aggregated mass spectral data.
  13. Procedure according to Claim 12 , where processing includes the devaluation of data corresponding to the digitized signals in one or the set of aggregated mass spectral data.
  14. A mass spectrometer comprising: a digitizer configured and adapted to digitize at least one individual signal; and a control system configured and adapted to: (i) determine, with respect to each digitized signal, an indication of overlapping ion arrival amplitudes in the digitized signal by processing the respective digitized signal to identify a peak profile that is distorted due to overlapping ion arrival amplitudes; (ii) determine intensity and arrival time data for each peak profile that is distorted due to overlapping ion arrival amplitudes, such that each peak profile is reduced to a time-intensity pair; and to mark the digitized signal based on the indication as suffering from an overlap of ion arrival amplitudes, wherein the step of marking the digitized signal includes marking the time and intensity pair as suffering from an overlap of ion arrival amplitudes.
  15. Mass spectrometer according to Claim 14 , which is designed to determine mass and/or mass-to-charge ratio data for at least one peak profile, in addition to data on intensity and arrival time.

Description

AREA OF THE PRESENT INVENTION The present invention relates generally to mass spectrometry and, in particular, to methods of mass spectrometry and mass spectrometers. The embodiments may involve digitizing several individual signals or transients using an analog-to-digital converter (“ADC”) and summing the time and intensity values of the digitized signals or transients to generate a composite mass spectrum. BACKGROUND It is known to record or digitize individual signals or transients arising from ion arrivals at an ion detector or electron multiplier using an analog-to-digital recorder or an analog-to-digital converter (ADC). Time-of-flight mass spectrometers with orthogonal acceleration can digitize ion arrival signals or transients with respect to several thousand individual time-of-flight separations. The digitized signals or transients are summed to produce a final summed or aggregated time-of-flight mass spectrum. Each individual time-of-flight spectrum signal or transient can be processed in real time before summation. In the simplest case, this processing can involve applying an amplitude threshold to isolate signals arising from ion arrivals from background or baseline noise. The signal at an individual digitized sample (i.e., a single analog-to-digital converter time step) or within a time-of-flight spectrum that exceeds the threshold is recorded, and all other sample or intensity values in analog-to-digital converter time steps are set to zero or a baseline value. Such a procedure is used, for example, in US 2011/0049353 A1 (Micromass) reveals. Several time-of-flight spectra processed in this way can then be summed or averaged to produce a final summed spectrum with reduced noise. It is also known to process individual signals or transients that have been digitized in order to reduce the ion arrival signals or transients to time-intensity pairs. Such a method is used, for example, in US 8063358 B2 (Micromass) reveals. Individual signals or transients reduced to time-intensity pairs can then be summed with other time-intensity pairs based on other time-of-flight spectra, signals, or transients to produce a final summed, aggregated, or averaged spectrum. This method essentially removes the profile or linewidth of the digitized signal from the final summed spectra, thereby increasing the effective time-of-flight resolution. It also simplifies the implementation of dual analog-to-digital converter approaches for extending the dynamic range, e.g. US 8354634 B2 (Micromass) and enables easy upsampling of output spectral data rates. Other methods for reducing the contribution of the single-ion pulse width are described in US 6870156 B2 (Rather) described. In methods that involve reducing individual transients to time-intensity pairs, each ion arrival has a linked analog peak width. If two or more ions arrive simultaneously, these analog peak widths can partially overlap, making it impossible to isolate the arrival time and intensity of the individual ions using a simple finite impulse response filter, peak maximum, or similar peak detection method. In such a case, a response based on the averaged ion arrival time and the summed area can be obtained rather than two separate ion arrival times and intensities. This coalescing of two or more ion arrivals within a transient into a single time-intensity pair can lead to artifacts in the final summed data. Furthermore, the analog peak widths of ions with different mass-to-charge ratio species can overlap considerably within a single transient. This results in an inaccurate representation of the signal intensity and an inaccurate measurement of the ion arrival time for all mass-to-charge ratio species. A method for unfolding such overlapping signals is described in US 8735808 B2 (Micromass) described. However, this method can be computationally intensive. GB 2457112 A (Micromass) discloses a method and a device for detecting ions. GB 2506714 A (Micromass) reveals the calibration of dual ADC acquisition systems. GB 2439795 A (Micromass) reveals the obtaining of mass spectra from a time-of-flight mass spectrometer. WO 98/21742 A1 (Rockwood) reveals a multi-anode time-to-digital converter. EP 2447980 B1 (Makarov) discloses a method for generating a mass spectrum with improved mass resolution. US 2005/0114042 A1 (Pappin) discloses a method and a device for unfolding a folded spectrum. US 2004/0083063 A1 (McClure) discloses a method and a device for the automated detection of peaks in spectroscopic data. The provision of an improved mass spectrometry method and an improved mass spectrometer is desired. DE 10 2011 013 600 A1 discloses a method and devices for processing digitized ion current signals in time-of-flight mass spectrometers, in which a multitude of individual spectra are recorded and processed into a sum spectrum. SUMMARY According to one aspect, a mass spectrometry procedure is provided which includes: Digitizing at least one individual signal; Determine,