Dynamic Capillary Voltage Adjustment for LC-MS Sensitivity

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Solution Overview

Problem

Conventional Electrospray ionization methods in liquid chromatography suffer from compromised sensitivity when compounds of interest elute across the liquid chromatography gradient, as the constant capillary voltage fails to maintain optimal ionization conditions amidst varying solvent ratios.

Innovation Solution

Varying the voltage applied to the Electrospray ionization source electrode based on monitored liquid chromatography back pressure to maintain optimal ionization conditions, leveraging the relationship between back pressure and solvent viscosity to adjust the capillary voltage in real-time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If constant capillary voltage is applied during liquid chromatography separation, then the ion source structure is simple and operation is easy, but sensitivity is compromised when compounds elute across the gradient

Engineering Contradiction:
Improveionization stabilityVSAvoiddetection sensitivity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies dynamics by transitioning from a static constant voltage system to a dynamic voltage adjustment system. The capillary voltage is continuously adjusted based on real-time back pressure measurements, allowing the ionization conditions to adapt to changing solvent compositions throughout the chromatography gradient, thereby maintaining optimal sensitivity across all elution conditions

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent implements feedback control by using back pressure monitoring to inform voltage adjustment decisions. The system continuously measures back pressure, compares it to reference values corresponding to different solvent compositions, and automatically adjusts the capillary voltage accordingly. This closed-loop feedback mechanism ensures optimal ionization conditions are maintained without manual intervention

Inventive Principle:
Principle #23Feedback

2Measurement precision

If capillary voltage is varied to maintain optimal ionization conditions, then sensitivity is improved throughout the gradient, but the device complexity increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcontrol system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses back pressure as an intermediary parameter to control voltage adjustment. Instead of directly monitoring complex solvent composition changes and adjusting voltage based on multiple variables, the system uses back pressure—a single, easily measurable parameter that correlates with solvent composition—as an intermediary to simplify the control mechanism while maintaining effective voltage optimization

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system performs self-adjustment by automatically varying the capillary voltage based on back pressure measurements without requiring external intervention or complex user programming. The control system autonomously determines the appropriate voltage settings by comparing real-time back pressure readings to pre-established reference values, enabling the system to self-optimize ionization conditions throughout the chromatography run

Inventive Principle:
Principle #25Self-service

3Measurement precision

If additional sensors are added to monitor solvent composition for voltage adjustment, then ionization conditions can be optimized, but the device complexity and cost increase

Engineering Contradiction:
Improvesolvent composition monitoringVSAvoidsensor system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies universality by using the existing back pressure sensor—which serves multiple functions including system diagnostics and solvent composition indication—for the additional purpose of controlling voltage adjustment. This multi-functional use of the back pressure sensor eliminates the need for dedicated solvent composition sensors, maintaining optimization capability while avoiding additional hardware complexity and cost

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 significantly improves sensitivity by ensuring optimal ionization throughout the liquid chromatography separation, utilizing existing back pressure monitoring systems without additional sensors, and adapting to changing solvent compositions.

Implementation Method 1

The Electrospray ionisation ion source comprises a capillary tube which is maintained at a constant high voltage during the course of a liquid chromatography separation in order to cause eluent emerging from the liquid chromatography source to be ionised by the high voltage applied to the capillary tube

Methodology Applied
Scientific EffectElectrospray ionisation: Ionisation

Data Source

PatentEP3047506B1Automated adjustment of capillary voltage based on the elution conditions to retain optimal ionization conditions
Publication Date: 2017.06.28 MICROMASS UK LTD
  • EP3047506B1 patent drawingFigure 1~2
  • EP3047506B1 patent drawing

AI summary

A method of Electrospray ionisation is disclosed comprising passing a sample liquid through a liquid chromatography column 3, monitoring a liquid chromatography back pressure and varying a voltage applied to an Electrospray ionisation source electrode 4 in dependence upon said monitored liquid chromatography back pressure.