Electrochemical Mass Spectrometry Quantification Without Standards

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Solution Overview

Problem

Mass spectrometry (MS) faces challenges in accurate quantification due to signal fluctuations and the lack of commercially available or easily synthesizable chemical standards, particularly for complex samples like drug metabolites or proteins, necessitating a highly sensitive and selective method that does not rely on standard compounds.

Innovation Solution

Combining mass spectrometry with electrochemistry, using liquid chromatography (LC) and an electrochemical cell to separate and oxidize/reduce target compounds, allowing for online MS detection and quantification without the need for standard compounds, applicable to both small organic molecules and large biomolecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard compounds are used for calibration in mass spectrometry, then quantification accuracy is improved, but the method becomes inapplicable when standards are not commercially available or difficult to synthesize

Engineering Contradiction:

Improvequantification accuracyVSAvoidapplicability to compounds without available standards

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent introduces an electrochemical cell as an intermediary between the sample introduction and mass spectrometry detection. This electrochemical mediator enables quantification by measuring the current response during electrochemical oxidation/reduction of the analyte, providing a calibration-free quantification method that works for compounds without available standards

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the traditional mechanical/calibration-based quantification system with an electrochemical detection system. Instead of relying on standard compound calibration curves, the system uses electrochemical current measurements combined with mass spectrometry to achieve absolute quantification without standards

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Difficulty of detecting and measuring

If mass spectrometry signal intensity is used for quantification, then detection capability is provided, but signal fluctuations prevent accurate quantification

Engineering Contradiction:

Improvedetection capabilityVSAvoidquantification accuracy

Core Design Contradiction:

Difficulty of detecting and measuringVSMeasurement precision

Solution Approach 1:

The patent employs a feedback mechanism where the electrochemical current response is used to correct and normalize the mass spectrometry signal. The electrochemical detection provides real-time feedback on the analyte amount, enabling accurate quantification despite MS signal fluctuations

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The patent changes the detection parameter from relying solely on mass spectrometry signal intensity to using electrochemical current response. This parameter change from MS intensity to electrochemical current provides a stable quantification basis that is not subject to MS signal fluctuations

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If electrochemical oxidation/reduction is performed on target compounds, then information about analyte amount is obtained, but the process requires coupling with additional equipment

Engineering Contradiction:

Improvequantification informationVSAvoidsystem configuration

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges the electrochemical cell with the mass spectrometry system in a unified configuration. The electrochemical cell is positioned between the sample introduction and MS detection, combining both electrochemical and mass spectrometric functions in a single integrated system that provides synergistic quantification capability

Inventive Principle:

Principle #5Merging (Combining)

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 method enables precise quantification of target compounds in complex mixtures, achieving high sensitivity and accuracy, as demonstrated by successful analysis of dopamine, norepinephrine, rutin, and proteins, with low measurement errors and wide applicability across various samples.

Implementation Method 1

A target compound in mixture is subjected to LC separation, followed by electrochemical oxidation or reduction in the electrochemical cell and online MS detection

Methodology Applied

Scientific EffectElectrochemical oxidation or reduction: Electrolysis

Data Source

PatentUS11360058B2Method and device for chemical quantification using electrochemical mass spectrometry without the use of standard target compounds

Publication Date: 2022.06.14 OHIO UNIV

AI summary

A method of quantifying a target compound includes applying an oxidation/reduction potential to an electrochemical cell (14); measuring an electrochemical current during the application of the oxidation/reduction potential; and ionizing and directing the target compound before and after the application of the oxidation/reduction potential to a mass spectrometer (16) that measures a target compound ion intensity. The method further includes determining a target compound ion intensity change due to the application of the oxidation/reduction potential and determining a total amount of the target compound in the sample using the measured electrochemical current and the target compound ion intensity change. Determining the target compound ion intensity change may comprise either comparing the target compound ion intensity before and after the electrolysis relative to a reference peak or comparing the integrated peak area of a target compound ion in an extracted ion chromatogram before and after the electrolysis.