FAIMS Ion Inlet Orifice Optimization for LC-MS Throughput

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Solution Overview

Problem

Conventional FAIMS apparatuses coupled with mass spectrometers face limitations in ion transit time and throughput, restricting their use in LC/MS/MS workflows and data-dependent acquisition techniques, leading to reduced analytical efficiency and detection limits.

Innovation Solution

The development of second-generation FAIMS apparatuses that can operate in a non-dispersive mode, allowing for intelligent ion filtering and reduced ion transit time, enabling higher isolation rates and improved ion throughput by optimizing ion inlet orifice design and gas flow dynamics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If conventional FAIMS apparatuses are coupled with mass spectrometers, then ion filtering capability is improved, but ion transit time increases and throughput decreases

Engineering Contradiction:
Improveion filtering capabilityVSAvoidion throughput
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent applies parameter changes by optimizing the ion inlet orifice dimensions (diameter and length) and gas flow parameters to reduce ion transit time through the FAIMS apparatus while maintaining effective ion filtering capability, thereby increasing ion throughput to the mass spectrometer

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements dynamics by making the FAIMS apparatus operable in both dispersive mode (for ion filtering) and non-dispersive mode (for high throughput), allowing dynamic switching between operational states to optimize performance for different analytical requirements

Inventive Principle:
Principle #15Dynamics

2Measurement precision

If FAIMS apparatus is used in dispersive mode for ion filtering, then specificity is improved, but ion transit time increases

Engineering Contradiction:
Improveanalytical specificityVSAvoidion transit time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent changes physical parameters by optimizing the ion inlet orifice geometry and gas flow rate to reduce ion transit time through the FAIMS apparatus while maintaining dispersive mode ion filtering capability, thus improving throughput without sacrificing specificity

Inventive Principle:
Principle #35Parameter changes

3Productivity

If ion inlet orifice is optimized for reduced transit time, then productivity is improved, but ion transmission efficiency may worsen

Engineering Contradiction:
Improveion throughputVSAvoidion transmission efficiency
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent optimizes multiple parameters simultaneously including ion inlet orifice diameter, orifice length, and gas flow rate to achieve the optimal balance between reduced ion transit time (improved productivity) and maintained ion transmission efficiency (improved reliability)

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies pneumatic principles by optimizing gas flow dynamics through the ion inlet orifice to ensure efficient ion transport while minimizing transit time, using gas flow rate and pressure parameters to control ion transmission efficiency

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 sensitivity and throughput of mass spectral analysis, allowing for more efficient LC-FAIMS-MS systems that maintain high detection and quantitation limits, enabling faster and more accurate data-dependent acquisition techniques.

Implementation Method 1

an ion mobility spectrometer, such as a high-field asymmetric ion mobility spectrometer (FAIMS) apparatus

Methodology Applied
Scientific EffectIon mobility: Electrophoresis

Implementation Method 2

a mass spectrometer apparatus that is coupled to and receives ions from an ion-mobility spectrometer

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentEP3270153B1Methods for operating a system comprising a mass spectrometer, ion mobility spectrometer and chromatograph
Publication Date: 2019.07.24 THERMO FINNIGAN LLC
  • EP3270153B1 patent drawingFigure 1
  • EP3270153B1 patent drawingFigure 2
  • EP3270153B1 patent drawingFigure 3~4

AI summary

A method of operating a system comprising a mass spectrometer, ion mobility spectrometer and chromatograph is characterized by: (a) providing a list comprising respective entries for each of two or more precursor ion species of interest comprising respective precursor-ion m/z ratios; (b) performing a first analysis of a sample by chromatographically separating the sample into sample fractions and detecting an ion abundance at each of a plurality m/z ratios within each fraction; (c) identifying a respective elution time period for each m/z ratio that corresponds to a precursor-ion m/z ratio; and (d) performing a second analysis of the sample comprising chromatographically separating the sample into sample fractions, generating a plurality of ions from each fraction, operating the ion mobility spectrometer, during each elution time period, such that ions of each respective precursor-ion species are preferentially transmitted through the ion mobility spectrometer to the mass spectrometer for fragmentation and mass analysis.