Dynamic Ion Detector Gain Control for Mass Spectrometry Saturation

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Solution Overview

Problem

Mass spectrometers face challenges in extending their dynamic range, particularly in handling complex mixtures with varying ion current intensities, leading to saturation issues due to interference from background ions, which affects the accuracy of ion detection and data quality.

Innovation Solution

A method that adjusts the ionization efficiency, attenuation factor, and gain of the ion detector system based on multi-dimensional data analysis, specifically using ion mobility separation to target analytes across multiple physico-chemical properties, ensuring that the most intense ion peaks do not saturate the detector and allowing for equal intensity adjustment of all detected ions irrespective of their mass-to-charge ratio.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ion mobility separation is added to concentrate ion signal, then detection sensitivity is improved, but dynamic range is reduced due to detector saturation

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddynamic range
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The system dynamically adjusts the gain of the ion detector and ADC recording system based on real-time ion signal intensity. The gain is increased during periods of low ion signal to improve sensitivity, and decreased during periods of high ion signal to prevent saturation, thereby maintaining optimal performance across varying signal conditions and extending the effective dynamic range.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the operating parameters of the ion detector and ADC system by adjusting gain settings in response to ion signal intensity. This parameter adjustment allows the system to adapt to different signal levels, improving detection sensitivity when signals are weak while preventing saturation when signals are strong, thus resolving the contradiction between sensitivity and dynamic range.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If gain is adjusted based on largest peak intensity, then detector saturation is avoided, but accuracy is reduced due to background ion interference

Engineering Contradiction:
Improvedetector saturation controlVSAvoidaccuracy
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent segments the ion signal analysis by distinguishing between analyte ions and background matrix ions using multiple dimensions of separation (ion mobility, mass-to-charge ratio, retention time). By segmenting the data into different components, the system can selectively adjust gain based on analyte ion intensity while excluding background ions, thereby maintaining accuracy while preventing saturation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system uses multiple dimensions of separation (ion mobility, mass-to-charge ratio, retention time) to differentiate between analyte ions and background ions. This dimensional approach allows the system to identify and target specific analyte ion peaks for gain adjustment while ignoring background interference, thus improving accuracy while maintaining saturation control.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Measurement precision

If transmission or sensitivity is adjusted to keep target analyte within dynamic range, then quantitative data quality is improved, but signals from other mass to charge ratio values may exceed dynamic range

Engineering Contradiction:
Improvequantitative data qualityVSAvoidsignal handling capability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The system applies local quality control by adjusting transmission or sensitivity settings specifically for the target analyte's mass-to-charge ratio range while allowing other mass-to-charge ratio values to be handled separately. This localized adjustment ensures quantitative data quality for the target analyte without necessarily limiting the system's ability to detect and record signals from other mass-to-charge ratio values that may exceed the dynamic range.

Inventive Principle:
Principle #3Local quality

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enhances the dynamic range of mass spectrometers, reduces the likelihood of over-attenuating analyte ions, and allows for more accurate intensity control and targeting of chemically similar analytes, excluding background matrix ions and improving data-dependent attenuation.

Implementation Method 1

separating or filtering ions according to a first physico-chemical property and separating or filtering ions according to a second physico-chemical property

Methodology Applied
Scientific EffectIon mobility separation: Electrophoresis

Implementation Method 2

separating or filtering ions according to a first physico-chemical property and separating or filtering ions according to a second physico-chemical property and obtaining a multi-dimensional array of data

Methodology Applied
Scientific EffectMass to charge ratio separation: Time of Flight

Data Source

PatentEP2973644B1Data dependent control of the intensity of ions separated in multiple dimensions
Publication Date: 2020.05.06 MICROMASS UK LTD
  • EP2973644B1 patent drawingFigure 1
  • EP2973644B1 patent drawingFigure 2
  • EP2973644B1 patent drawingFigure 3

AI summary

A method of mass spectrometry is disclosed comprising setting an attenuation factor of an attenuation device to a first value and then separating or filtering ions according to a first physico-chemical property and separating or filtering ions according to a second physico-chemical property and obtaining a multi-dimensional array of data. The most intense ion peak within one or more subsets of the multi-dimensional array of data is determined. If it is determined that the most intense ion peak would cause saturation of an ion detector or ion detection system then the method further comprises adjusting the attenuation factor of the attenuation device to a second value and obtaining mass spectral data wherein the adjustment of the attenuation factor substantially alters the intensity of all ions which are detected by the ion detector or ion detection system equally and irrespective of the mass to charge ratio of the ions. The intensity of the mass spectral data is then scaled based upon the degree to which the attenuation factor of the attenuation device was increased or reduced.