DICE Ionization for Low-Polarity Molecules

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Solution Overview

Problem

Current ambient desorption ionization techniques, such as DESI and DART, face limitations in ionizing low-polarity molecules and have a limited dynamic range, leading to inefficient ion generation and complex mass spectrometry interpretations due to the production of protonated or sodiated molecular ions and fragments.

Innovation Solution

The Desorption Ionization by Charge Exchange (DICE) method uses a low-polarity solvent electrochemically oxidized through a conductive capillary at high voltage, combined with pneumatic nebulization, to generate a DICE-reagent spray that effectively ionizes analytes on surfaces with minimal sample preparation, and can be combined with DESI techniques to broaden analyte characterization capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If DESI technique is used to ionize analytes, then high dynamic range and ability to ionize high molecular weight samples are achieved, but ionization efficiency for low-polarity molecules is poor

Engineering Contradiction:
Improveability to ionize high molecular weight samplesVSAvoidionization efficiency for low-polarity molecules
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The invention changes the ionization mechanism parameter from electrospray-based (DESI) to charge exchange-based (DICE). By using a different physical principle (charge exchange between reagent ions and analyte molecules), the system achieves high ionization efficiency for low-polarity molecules while maintaining the ability to handle high molecular weight samples.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention employs a reactive reagent spray containing species capable of charge exchange reactions. The reagent ions (such as He+, N2H+, or other reactive species) act as strong ionizing agents that efficiently transfer charge to low-polarity analyte molecules, overcoming the limitation of DESI for non-polar compounds.

Inventive Principle:
Principle #38Strong oxidants (Accelerated oxidation)

2Adaptability or versatility

If DESI technique is used, then high dynamic range is achieved, but mass spectograph interpretation is complicated by production of protonated or sodiated molecular ions and fragments

Engineering Contradiction:
Improvedynamic rangeVSAvoidcomplexity of mass spectograph interpretation
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention applies local quality by using different reagent ions for different analyte types. By selecting specific reagent species (e.g., He+ for non-polar compounds, N2H+ for polar compounds), the system tailors the ionization process to the specific analyte, producing cleaner spectra with fewer unwanted adducts and fragments.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention converts the harmful effect of complex ionization products into a benefit by using charge exchange reactions that produce primarily molecular ions with minimal fragmentation. The reactive reagent spray that could cause unwanted reactions instead promotes clean charge transfer, simplifying spectral interpretation while maintaining high dynamic range.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Productivity

If DART technique is used, then analysis of low molecular weight samples is achieved, but dynamic range is very limited

Engineering Contradiction:
Improveability to analyze low molecular weight samplesVSAvoiddynamic range
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The invention creates a universal ionization system (DICE) that can handle both low and high molecular weight samples across a wide dynamic range. By using atmospheric pressure charge exchange with可调 reagent sprays, the system maintains effectiveness for small molecules like DART while extending capability to large biomolecules, achieving multi-functionality.

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

Solution Approach 2:

The invention uses composite reagent systems combining multiple components (carrier gas, reagent species, and optional modifiers) to achieve broad applicability. The reagent spray may contain combinations of He, N2, H2O, and other species that work synergistically to ionize diverse analytes from small molecules to large proteins, expanding the dynamic range beyond what single-technique methods achieve.

Inventive Principle:
Principle #40Composite materials

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

DICE techniques enhance ionization efficiency for low-polarity molecules, reduce metal adduct formation, and provide clearer mass spectra with better signal-to-noise ratios, enabling the detection of a broader range of compounds, including those poorly ionized by existing methods.

Implementation Method 1

a DICE-reagent spray is generated by passing any low-polarity solvent that can be electrochemically oxidized through an electrically-conductive capillary held at a high voltage

Methodology Applied
Scientific EffectElectrochemical oxidation: Oxidation

Implementation Method 2

The resulting spray comprises fluid droplets containing molecular ions of the solvent. Analytes are then desorbed and ionized as the DICE-reagent spray is brought into contact with the analytes

Methodology Applied
Scientific EffectCharge exchange: Ionisation

Implementation Method 3

The spray is nebulized by pneumatic assistance provided by a stream of chemically-inert gas directed coaxially with the flow of the solvent. The resulting spray comprises fluid droplets

Methodology Applied
Scientific EffectPneumatic nebulization: Aerosol

Implementation Method 4

Analytes are then desorbed and ionized as the DICE-reagent spray is brought into contact with the analytes on a surface

Methodology Applied
Scientific EffectMomentum transfer: Impact Force

Data Source

PatentEP2483910B1Analyte ionization by charge exchange for sample analysis under ambient conditions
Publication Date: 2014.09.10 STEVENS INSTITUTE OF TECHNOLOGY
  • EP2483910B1 patent drawingFigure 1~2
  • EP2483910B1 patent drawingFigure 3~5
  • EP2483910B1 patent drawingFigure 6~8

AI summary

Etectrospray ionization techniques are used to generate reagents that ionize analytes for mass spectrometry analysis by charge transfer. Such techniques may be performed under ambient conditions. Suitable precursors for such reagents include ioπizabte nonpolar solvents, such as toluene or xylenes : polar solvents, such as water or alchohois. inert gases, such as helium or nitrogen, or combinations thereof. Environmental conditions in the ionization chamber of the mass spectrograph can be manipulated to generate a selected ion of an analyte in preference to other ions.