Solid Phase Isotope Dilution Mass Spectrometry Automation

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Solution Overview

Problem

Current methods for isotope dilution mass spectrometry (IDMS) and speciated isotope dilution mass spectrometry (SIDMS) face challenges in achieving efficient and rapid equilibration of enriched isotope species with natural isotopes, which limits their automation and application in field-deployable, high-throughput analysis systems, especially in handling reactive and toxic materials.

Innovation Solution

The use of solid phase isotope ratio equilibration and measurement methods, involving immobilized enriched isotope reagents and algorithms for mathematical concentration determination, allows for simultaneous equilibration and extraction, reducing analysis time and improving stability and safety of handling toxic materials.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If conventional liquid/thermal equilibration and separation protocols are used, then equilibration can be achieved, but the time required to equilibrate and separate the analyte is significantly long

Engineering Contradiction:
Improveequilibration timeVSAvoidanalysis throughput
Core Design Contradiction:
Loss of timeVSProductivity

Solution Approach 1:

The patent applies phase transition by transferring the equilibration process from liquid phase to solid phase. Immobilized isotopically enriched reagents on solid phase carriers enable rapid equilibration with analytes, reducing equilibration time from hours/days to minutes while maintaining measurement accuracy.

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The patent replaces conventional thermal/mechanical equilibration methods with a solid phase-based system where immobilized reagents provide catalytic surfaces for rapid isotope exchange, eliminating the need for prolonged thermal incubation and manual separation steps.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Object-affected harmful factors

If enriched isotope reagents are handled in bulk liquid form, then isotope dilution analysis can be performed, but safety issues arise from handling reactive and toxic materials

Engineering Contradiction:
Improvesafety of handling toxic materialsVSAvoidsimplicity of sample preparation
Core Design Contradiction:
Object-affected harmful factorsVSEase of operation

Solution Approach 1:

The patent uses solid phase carriers that act as containment structures, immobilizing toxic and reactive enriched isotope reagents on solid surfaces. This eliminates the need to handle bulk liquid reagents, reducing safety hazards while maintaining analytical performance through surface-based equilibration.

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

The patent extracts the hazardous liquid reagent phase and replaces it with solid phase immobilized reagents. The enriched isotopes are bound to solid carriers, removing the toxic liquid component while preserving the isotopic exchange functionality needed for analysis.

Inventive Principle:
Principle #2Taking out (Extraction)

3Stability of the object's composition

If conventional liquid phase equilibration methods are used, then isotope exchange can occur, but reagents and samples degrade during storage and shipment

Engineering Contradiction:
Improvestability of reagents and samplesVSAvoidstorage duration
Core Design Contradiction:
Stability of the object's compositionVSDuration of action of stationary object

Solution Approach 1:

The patent transitions reagents from liquid phase to solid phase immobilization. Solid phase carriers provide a stable matrix that prevents degradation of both reagents and samples during storage and shipment, maintaining compositional integrity for extended periods while enabling field deployment.

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The patent employs solid phase cartridges that can be pre-prepared, stored stably, and used on-demand. These disposable or reusable solid phase carriers eliminate the need for complex storage conditions required by liquid reagents, enabling stable long-term storage and field use.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Extent of automation

If manual sample preparation and manipulation steps are used, then isotope dilution analysis can be performed, but automation and high-throughput capability are limited

Engineering Contradiction:
Improveautomation of IDMS analysisVSAvoidcomplexity of sample preparation system
Core Design Contradiction:
Extent of automationVSDevice complexity

Solution Approach 1:

The patent segments the sample preparation process into discrete solid phase cartridge steps (spiking, equilibration, separation). Each cartridge performs a specific function, enabling modular assembly and automated handling through standard fluidic interfaces, thereby facilitating high-throughput automation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The solid phase cartridges serve multiple functions: they contain immobilized reagents, provide equilibration surfaces, enable separation, and facilitate automated handling. This multi-functionality reduces the number of separate components needed, simplifying the overall system for automation while maintaining capability.

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

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 significantly accelerates the equilibration and separation process, enabling cost-effective, high-throughput, and portable analytical systems suitable for environmental forensics, homeland security, and clinical research, with improved accuracy and reduced false positives.

Implementation Method 1

immobilizing by absorption or chemical attachment said isotopically tagged analyte

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Implementation Method 2

immobilizing by absorption or chemical attachment said isotopically tagged analyte

Methodology Applied
Scientific EffectChemical attachment: Chemical Bonding

Implementation Method 3

conducting an equilibration step with said solid phase carrier by incubating the solid phase carrier and said sample

Methodology Applied
Scientific EffectEquilibration: Diffusion

Implementation Method 4

subjecting said equilibrated sample containing said isotopically tagged analyte analogue to direct ionization and transport into a mass spectrometer

Methodology Applied
Scientific EffectIonization: Ionisation

Data Source

PatentEP2108111B1Solid phase and catalyzed enabled automated isotope dilution and speciated isotope dilution mass spectrometry
Publication Date: 2019.04.24 DEFINITEK INC
  • EP2108111B1 patent drawingFigure 1
  • EP2108111B1 patent drawingFigure 2~3
  • EP2108111B1 patent drawingFigure 4

AI summary

A method for the equilibration of enriched isotope species and natural isotope species prior to mass spectrometric analysis using solid phase and/or microwave isotope ratio equilibration and measurement.