Capillary Immiscible Solvent Extraction for Mass Spectrometry

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Solution Overview

Problem

The analysis of complex biological samples using mass spectrometry is hindered by matrix effects due to non-target components competing with target analytes for charges during ionization, requiring time-consuming and costly chromatography-based sample preparation and separation protocols.

Innovation Solution

A method involving liquid-liquid extraction in a capillary of small diameter, where immiscible solvents are used to extract target analytes while leaving non-target components behind, allowing for controlled extraction and ionization within an ionization probe, thereby combining sample preparation and ionization processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If chromatography-based sample preparation and separation protocols are used, then matrix effects are minimized and analyte ionization is improved, but analysis time increases and equipment cost increases

Engineering Contradiction:

Improveanalyte ionization efficiencyVSAvoidsample preparation time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent combines sample preparation (extraction) and ionization into a single integrated process within the electrospray ionization source. The extraction solvent serves dual purposes: it extracts analytes from the sample matrix and simultaneously acts as the medium for electrospray ionization, eliminating the need for separate chromatography-based preparation steps

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent extracts only the essential function of sample preparation (analyte separation from matrix) using a simple liquid-liquid extraction approach with immiscible solvents, removing the complex chromatography equipment and protocols while retaining the core benefit of matrix effect minimization

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If chromatography-based sample preparation and separation protocols are used, then matrix effects are minimized and analyte ionization is improved, but equipment cost increases

Engineering Contradiction:

Improveanalyte ionization efficiencyVSAvoidequipment cost

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent replaces expensive, complex chromatography equipment with simple, inexpensive liquid-liquid extraction using common immiscible solvents. The extraction solvent is consumed in the process but is cheap and readily available, eliminating the need for costly chromatography systems while achieving the same matrix effect minimization goal

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Ease of operation

If a small diameter capillary is used for liquid-liquid extraction, then sample handling is improved and extraction control is enhanced, but the interface area between liquids is reduced

Engineering Contradiction:

Improveextraction controlVSAvoidliquid-liquid interface area

Core Design Contradiction:

Ease of operationVSArea of stationary object

Solution Approach 1:

The patent introduces dynamic movement (back-and-forth motion) of the extraction solvent plug within the capillary to continuously renew the liquid-liquid interface. This dynamic approach compensates for the limited static interface area by creating repeated extraction cycles, enhancing mass transfer efficiency despite the small capillary diameter

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent employs periodic back-and-forth movement of the extraction solvent, creating cyclic extraction cycles. This periodic action allows the solvent to repeatedly contact the sample matrix, accumulating extraction efficiency over multiple cycles and compensating for the small interface area in the narrow capillary

Inventive Principle:

Principle #19Periodic 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 effectively suppresses matrix effects, pre-concentrates target analytes, and eliminates the need for expensive chromatography equipment, enabling rapid and efficient analysis of biological samples without separate sample preparation protocols.

Implementation Method 1

liquid-liquid extraction in a capillary of small diameter, where immiscible solvents are used to extract target analytes while leaving non-target components behind

Methodology Applied

Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Implementation Method 2

An electrode is then operably coupled to the solvent within the body of the ionization probe and the target analyte is ionized and injected into the mass spectrometer

Methodology Applied

Scientific EffectElectrospray ionization: Ionisation

Data Source

PatentEP3108496B1Analyzing an extracted sample using an immiscible extraction solvent

Publication Date: 2021.04.28 PURDUE RES FOUND

Figure 1A
Figure 1B
Figure 2a~2c

AI summary

The invention generally relates to systems and methods for analyzing an extracted sample using an immiscible extraction solvent. In certain embodiments, the invention provides a system for analyzing an analyte in a sample. The system includes an ionization probe and a mass spectrometer. The ionization probe includes a hollow body that optionally includes a distal tip. The hollow body is configured such that there is no substrate within the body and no electrode disposed on a surface of the body. An electrode is at least partially disposed within the hollow body.