NanoESI Mass Spectrometry Analyte Detection

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Solution Overview

Problem

Current mass spectrometry techniques face challenges in achieving sensitive detection of analytes from complex biological matrices, particularly due to matrix effects and low abundance of analytes, which limits detection sensitivity and requires high sample concentration, complicating high-throughput analysis.

Innovation Solution

A method involving pretreatment, derivatization, and dilution of samples followed by nanoESI mass spectrometry, using specific compounds to form covalent bonds with analytes and solvents for improved ionization and reduced matrix interference, allowing for sensitive detection without the need for extensive sample concentration or chromatographic separation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If normal flow ESI is used with HPLC separation, then chromatographic separation is achieved, but ion yield is reduced due to matrix effects

Engineering Contradiction:
Improvechromatographic separationVSAvoidion yield
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent introduces an intermediary step (sample pretreatment and derivatization) between the complex biological matrix and the mass spectrometry analysis. This intermediary processing transforms the analytes into forms that are less susceptible to matrix effects while maintaining separability, thus resolving the contradiction between achieving separation and maintaining ion yield.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical and chemical parameters of the sample through pretreatment and derivatization processes. By modifying the analyte structure and sample composition before analysis, the method alters the interaction between analytes and matrix components, thereby improving ion yield while preserving chromatographic separation capabilities.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If sample concentration is increased to improve detection sensitivity, then detection limits are improved, but analysis complexity and time increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidanalysis throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent performs preliminary actions (pretreatment and derivatization) on the sample before analysis to enhance analyte detectability. By preparing the sample in advance with these modification steps, the method achieves high detection sensitivity without requiring extensive sample concentration or repeated analyses, thus maintaining high throughput.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If derivatization reactions are used to improve detection limits, then sensitivity increases, but ionization is interfered with by auxiliary reagents

Engineering Contradiction:
Improvedetection limitsVSAvoidionization efficiency
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent carefully controls the parameters of the derivatization process, including reagent selection, concentration, and reaction conditions. By optimizing these parameters, the method achieves sufficient derivatization for enhanced sensitivity while minimizing the excess reagent concentration that would interfere with ionization, thus resolving the contradiction between detection limits and ionization efficiency.

Inventive Principle:
Principle #35Parameter changes

4Reliability

If nano-ESI sources are used to improve ion yields, then sensitivity increases, but sample volume is limited

Engineering Contradiction:
Improveion yieldVSAvoidsample volume
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent performs preliminary enrichment and concentration of the analyte in the sample matrix before nano-ESI analysis. By pre-concentrating the analyte of interest while removing or reducing matrix components, the method ensures sufficient analyte quantity for nano-ESI's low sample volume requirements while maintaining high ion yield and sensitivity.

Inventive Principle:
Principle #10Preliminary action

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 detection sensitivity and reduces matrix interference, enabling accurate and efficient analysis of low-concentration analytes like steroids in biological samples, improving signal-to-noise ratio and detection limits without the complexity of HPLC separation, thus facilitating high-throughput analysis.

Implementation Method 1

Derivatizing the analyte of interest, preferably in the pretreated sample

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

Determining the level of the analyte of interest in the pretreated sample using nanoESI mass spectrometry

Methodology Applied
Scientific EffectElectrospray ionization: Ionisation

Data Source

PatentUS20230333113A1Detection of an analyte of interest by nanoesi mass spectrometry
Publication Date: 2023.10.19 ROCHE DIAGNOSTICS OPERATIONS INC
  • US20230333113A1 patent drawing
  • US20230333113A1 patent drawing
  • US20230333113A1 patent drawing

AI summary

The present invention relates to a method, a diagnostic system, a kit and the use thereof for efficiently detection of an analyte of interest by nanoESI mass spectrometry.