Negative-Ion Mass Spectrometry Using LDTD Superoxide Adducts

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Solution Overview

Problem

Current mass spectrometry techniques face challenges in efficiently detecting and quantifying trace compounds in complex or heterogeneous matrices, particularly due to limitations in the 'limit of quantification' (LOQ), accuracy, linearity, and interferences.

Innovation Solution

The method involves using negative ion mode mass spectrometry with laser diode thermal desorption (LDTD) to desorb and ionize samples, generating a superoxide radical anion (O2.−) adduct that can be detected, thereby facilitating the detection of target analytes such as metabolites of vitamin D, estrogenic steroids, and phenolic compounds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional mass spectrometry methods are used for trace compound detection, then sensitivity and selectivity are improved, but analysis time and costs increase due to required sample preparation steps

Engineering Contradiction:
Improvedetection sensitivityVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention extracts and eliminates the chromatographic separation step from the conventional MS analysis workflow. By using direct ambient ionization techniques (DESI, DART, APCI), the method takes out the time-consuming liquid chromatography component while retaining the essential function of analyte delivery to the mass spectrometer, thereby reducing analysis time without sacrificing detection sensitivity

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The method performs preliminary concentration and preparation of the sample in the ambient environment before introduction to the mass spectrometer. Techniques like DESI and DART perform on-site ionization and preliminary separation in the ambient space, preparing the sample for MS detection without requiring extensive laboratory-based sample preparation steps

Inventive Principle:
Principle #10Preliminary action

2Productivity

If ambient ionization techniques are used for direct sample analysis, then analysis time is reduced, but limit of quantification and accuracy worsen

Engineering Contradiction:
Improveanalysis speedVSAvoidlimit of quantification
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The invention merges multiple ambient ionization techniques (DESI, DART, APCI) with negative ion mode mass spectrometry to create a hybrid approach that combines the speed advantages of ambient ionization with the enhanced sensitivity of negative ion mode detection, thereby maintaining fast analysis speeds while improving limit of quantification

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The method changes the ionization mode parameter from conventional positive ion mode to negative ion mode, which significantly improves the limit of quantification for certain analyte classes. By operating in negative ion mode with ambient ionization, the system achieves both rapid analysis and enhanced detection sensitivity through optimized ionization parameters

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If sample preparation steps are performed to reduce matrix effects, then detection accuracy is improved, but device complexity and costs increase

Engineering Contradiction:
Improvedetection accuracyVSAvoidsample preparation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The ambient ionization techniques perform self-service sample preparation and matrix effect mitigation at the point of analysis. The DESI, DART, or APCI processes automatically handle ionization and preliminary separation in the ambient environment, eliminating the need for complex laboratory-based sample preparation devices and procedures while maintaining detection accuracy

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention introduces an intermediary ambient ionization interface between the sample and the mass spectrometer. This intermediary layer (DESI, DART, or APCI source) performs the function of reducing matrix effects and preparing the sample for analysis without requiring complex sample preparation equipment, thereby simplifying the overall system while improving accuracy

Inventive Principle:
Principle #24Intermediary (Mediator)

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 accuracy of trace compound detection, reduces sample preparation time and costs, and minimizes interference, thereby improving the overall efficiency of mass spectrometry analysis.

Implementation Method 1

desorbing at least a portion of the sample prepared for mass spectrometry analysis by laser diode thermal desorption (LDTD) to obtain a desorbed sample

Methodology Applied
Scientific EffectLaser diode thermal desorption: Laser

Implementation Method 2

desorbing at least a portion of the sample prepared for mass spectrometry analysis by laser diode thermal desorption (LDTD)

Methodology Applied
Scientific EffectThermal desorption: Desorption

Implementation Method 3

ionizing the desorbed sample under conditions to generate an ionized analyte flow comprising a superoxide radical anion (O2.−) adduct detectable by negative ion mode mass spectrometry

Methodology Applied
Scientific EffectAtmospheric pressure chemical ionization: Ionisation

Implementation Method 4

ionizing the desorbed sample under conditions to generate an ionized analyte flow

Methodology Applied
Scientific EffectChemical ionization: Chemical Bonding

Data Source

PatentUS12203885B2Methods and systems for detecting and quantifying a target analyte in a sample by negative ion mode mass spectrometry
Publication Date: 2025.01.21 PHYTRONIX TECH
  • US12203885B2 patent drawing
  • US12203885B2 patent drawing
  • US12203885B2 patent drawing

AI summary

Laser diode thermal desorption coupled with tandem mass spectrometry systems and methods are described to detect at least one target analyte in a sample by negative ion mode mass spectrometry. For instance, the system and method involve desorbing a sample prepared for mass spectrometry analysis by laser diode thermal desorption to obtain a desorbed sample, and then ionizing the desorbed sample under conditions to generate an ionized analyte flow comprising a superoxide radical anion (O2.−) adduct detectable by negative ion mode mass spectrometry; and then detecting the O2.− adduct by negative ion mode mass spectrometry, to thereby detect the target analyte.