Capillary Extraction-Ionization for Matrix-Effect-Limited Analyte Analysis

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Solution Overview

Problem

Current methods for analyzing complex biological samples using mass spectrometry face challenges due to matrix effects caused by non-target components, which require separate and time-consuming sample preparation and chromatography processes, limiting their application to laboratory settings and increasing costs.

Innovation Solution

A system and method for combined sample preparation and ionization using a capillary with a small diameter, allowing for liquid-liquid extraction and ionization within the same capillary, enabling control over the extraction process and eliminating the need for separate chromatography, by moving immiscible fluids to induce circulation and extract analytes directly for mass spectrometry analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If separate sample preparation and chromatography processes are used to minimize matrix effects, then measurement precision is improved, but device complexity and loss of time increase

Engineering Contradiction:
Improveanalyte quantification accuracyVSAvoidchromatography equipment requirement
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines sample preparation (liquid-liquid extraction) and ionization processes within a single capillary interface, eliminating the need for separate chromatography equipment. The capillary serves as both the extraction chamber and the ionization probe, integrating multiple functions into one device component.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The capillary is designed to perform multiple functions: it serves as the extraction vessel for liquid-liquid extraction, the separation interface for immiscible fluids, and the ionization probe for mass spectrometry. This multi-functional design replaces the need for dedicated chromatography equipment.

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

2Quantity of substance

If traditional liquid-liquid extraction is used with large sample volumes, then analyte pre-concentration is achieved, but loss of time and device complexity increase due to separate preparation protocols

Engineering Contradiction:
Improveanalyte pre-concentrationVSAvoidsample preparation time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent merges the pre-concentration extraction step with the ionization step by conducting liquid-liquid extraction directly within the capillary that serves as the ionization probe. This eliminates the need for separate preparation protocols and reduces overall processing time.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The extraction process is performed preliminarily within the capillary before ionization, allowing analyte pre-concentration to occur in the same device that will subsequently perform ionization. This preliminary action within the extraction capillary eliminates the need for separate preparation steps.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If matrix effects are reduced through chromatography separation, then measurement precision is improved, but loss of time and productivity decrease due to time-consuming protocols

Engineering Contradiction:
Improveanalyte detection accuracyVSAvoidanalysis throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent combines matrix effect reduction (through liquid-liquid extraction) with the ionization process in a single integrated system. The extraction capillary directly interfaces with the mass spectrometer, eliminating the time-consuming chromatography separation step while maintaining analyte detection accuracy.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent extracts the analyte from the complex biological matrix using liquid-liquid extraction within the capillary, removing interfering substances before ionization. This extraction process eliminates matrix effects without requiring subsequent chromatography separation, thereby improving productivity.

Inventive Principle:
Principle #2Taking out (Extraction)

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 allows for efficient extraction and ionization of analytes from large volume samples without separate sample preparation, reducing matrix effects and enabling point-of-care analysis by integrating sample preparation and ionization, thus reducing costs and time while improving analytical efficiency.

Implementation Method 1

The sample and the solvent are moved within the capillary to induce circulation within the sample and the solvent, thereby causing the analyte to be extracted from the sample and into the solvent

Methodology Applied
Scientific EffectCirculation induction through liquid movement: Convection

Implementation Method 2

causing the analyte to be extracted from the sample and into the solvent

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Data Source

PatentUS11875983B2Systems and methods for quantifying an analyte extracted from a sample
Publication Date: 2024.01.16 PURDUE RES FOUND
  • US11875983B2 patent drawing
  • US11875983B2 patent drawing
  • US11875983B2 patent drawing

AI summary

The invention generally relates to systems and methods for quantifying an analyte extracted from a sample. In certain embodiments, the invention provides methods that involve introducing a solvent into a capillary, introducing the capillary into a vessel including a sample such that a portion of the sample is introduced into the capillary, moving the sample and the solvent within the capillary to induce circulation within the sample and the solvent, thereby causing the analyte to be extracted from the sample and into the solvent, analyzing the analyte that has been extracted from the sample, and quantifying the analyte. In certain embodiments, the quantifying step is performed without knowledge of a volume of the sample and/or solvent.