Electrospray Solvent Blending for Higher Analyte Ionization Sensitivity

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Solution Overview

Problem

Current electrospray ionization methods face limitations in sensitivity, particularly in the detection of analytes, and existing solutions focus mainly on solvent composition, drying techniques, and miniaturization.

Innovation Solution

A method involving the addition of a second stream of liquid with a co-solvent of low boiling point and an enhancement solvent of high boiling point to the primary liquid stream before nebulization, enhancing ionization sensitivity by optimizing the electrospray ion source operation in both positive and negative ion modes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional electrospray ionization methods are used with standard solvent compositions, then the ionization process is simple and reliable, but the sensitivity of analyte detection is insufficient

Engineering Contradiction:
Improvesensitivity of analyte detectionVSAvoidcomplexity of solvent mixture composition
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by modifying the solvent composition parameters - specifically adding a co-solvent (acetonitrile or methanol) and an enhancement solvent (DMSO, propylene glycol, or 2-methoxyethanol) to the aqueous mobile phase. This chemical parameter modification directly increases ionization efficiency and analyte detection sensitivity without requiring changes to the electrospray hardware or operational parameters

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials by creating a multi-component solvent system that combines water, organic co-solvent, and enhancement solvent. This composite solvent mixture leverages the complementary properties of each component: water provides polarity, the co-solvent aids in analyte solubility and nebulization, and the enhancement solvent specifically boosts ionization efficiency, achieving superior detection sensitivity compared to single or dual-solvent systems

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If miniaturization techniques such as nanospray are employed to improve ionization efficiency, then sensitivity increases, but the device complexity and operational difficulty increase

Engineering Contradiction:
Improveionization efficiencyVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

Instead of miniaturizing the spray geometry (which would reduce ease of operation), the patent changes the chemical parameters of the mobile phase by incorporating enhancement solvents. This approach achieves improved ionization efficiency while maintaining standard electrospray hardware and operational simplicity, as the modification is purely chemical rather than mechanical or geometric

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If drying techniques are optimized to improve ionization, then sensitivity increases, but the energy consumption and process complexity increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidenergy consumption for drying
Core Design Contradiction:
Measurement precisionVSUse of energy by moving object

Solution Approach 1:

The patent modifies the chemical composition parameters of the mobile phase to inherently improve ionization efficiency, reducing the need for aggressive drying. The enhancement solvents facilitate more efficient ion formation during the electrospray process itself, achieving high detection sensitivity with standard drying conditions and without additional energy input for enhanced drying procedures

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If the electrospray source is operated in positive ion mode with DMSO as enhancement solvent, then ionization efficiency improves, but ion suppression occurs

Engineering Contradiction:
Improveionization efficiencyVSAvoidion suppression
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by selecting different enhancement solvents for different ionization modes: DMSO is specifically used for negative ion mode where it enhances ionization without suppression, while other enhancement solvents (propylene glycol, 2-methoxyethanol) are used for positive ion mode. This targeted selection optimizes ionization efficiency while avoiding the harmful ion suppression effect that occurs when DMSO is used in positive mode

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the operational parameter of ionization mode (positive vs. negative) in conjunction with selecting appropriate enhancement solvents. By matching the solvent choice to the ionization mode, the system achieves high ionization efficiency without ion suppression, effectively managing the interaction between solvent chemistry and ionization physics

Inventive Principle:
Principle #35Parameter changes

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 results in a significant increase in the sensitivity of analyte detection, with enhancements observed in both positive and negative ion modes, demonstrating improved ionization efficiency and detection sensitivity, potentially leading to at least a 2-fold increase in signal intensity.

Implementation Method 1

providing the first stream of liquid to the nebulizer of the ion source; nebulizing and ionizing the resulting liquid

Methodology Applied
Scientific EffectElectrospray ionization: Electrohydrodynamics

Implementation Method 2

adding a second stream of liquid to the first stream of liquid, where the second stream of liquid comprises a co-solvent that has a relatively low boiling point

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP3246936B1Methods for enhancing electrospray
Publication Date: 2024.04.24 AGILENT TECHNOLOGIES INC
  • EP3246936B1 patent drawingFigure 1
  • EP3246936B1 patent drawingFigure 1
  • EP3246936B1 patent drawingFigure 2

AI summary

Provided herein, among other things, is a method of ionizing a first stream of liquid by an electrospray ion source having a nebulizer, wherein the first stream of liquid may comprise an analyte. In some embodiments, the method may comprise: a) providing the first stream of liquid to the nebulizer; b) adding a second stream of liquid to the first stream of liquid, wherein the second stream of liquid comprises a co-solvent that has a relatively high boiling point and an enhancement solvent that a relatively high boiling; and c) nebulizing and ionizing the resulting liquid.