Accelerator Mass Spectrometry Isotope Normalization

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Solution Overview

Problem

Current accelerator mass spectrometry methods require radiolabelled compounds for sensitive isotope analysis, which are costly and limited in application, especially for biological samples and compounds containing fluorine or transition metals, and lack flexibility in measured isotopes.

Innovation Solution

An accelerator mass spectrometry method that measures at least one isotope of a first element and one isotope of a second element, using the measurement of the second element for normalization to determine the quantity or concentration of the first element with high sensitivity, avoiding the need for radiolabelled compounds and allowing for flexible isotope analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If radiolabelled compounds are used for sensitive isotope analysis, then measurement sensitivity is improved, but cost increases and application flexibility decreases

Engineering Contradiction:
Improvemeasurement sensitivityVSAvoidapplication flexibility
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent introduces an internal standard compound containing a different isotope as an intermediary reference. This internal standard serves as a mediator to normalize measurements of the analyte isotope, enabling sensitive quantification without requiring radiolabelled versions of the actual analyte compounds. The internal standard acts as a reference point that allows flexible application across different compounds while maintaining measurement sensitivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the measurement parameter from requiring radiolabelled analyte compounds to measuring isotope ratios relative to an internal standard. By normalizing the analyte isotope measurement to the internal standard isotope measurement, the method transforms the measurement approach to achieve sensitivity comparable to radiolabelled methods while allowing analysis of any compound containing the target element, thus improving application flexibility.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If radiolabelled compounds are used for isotope analysis, then sensitivity is improved, but cost increases

Engineering Contradiction:
ImprovesensitivityVSAvoidcost
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent replaces expensive radiolabelled compounds with a cheap, stable internal standard compound that contains a different isotope. The internal standard can be a simple compound with a stable isotope that is inexpensive to produce and handle. This disposable-like approach uses a single internal standard for multiple measurements, eliminating the need to purchase expensive radiolabelled versions of each analyte compound while maintaining high sensitivity through isotope ratio normalization.

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

3Measurement precision

If conventional AMS methods are used requiring radiolabelling, then measurement sensitivity is improved, but device complexity and preparation requirements increase

Engineering Contradiction:
Improvemeasurement sensitivityVSAvoidpreparation requirements
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent enables the measurement system to self-normalize by incorporating an internal standard that undergoes the same preparation and measurement process as the analyte. The internal standard automatically compensates for variations in sample preparation, instrument conditions, and measurement parameters. This self-service mechanism eliminates the need for complex external calibration procedures and reduces preparation requirements while maintaining measurement sensitivity through automatic normalization.

Inventive Principle:
Principle #25Self-service

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

Enables determination of element concentrations at extremely low levels (e.g., <1 pg/mL) without radiolabelling, facilitating mass balance and pharmacokinetic studies for compounds like fluorine or platinum-containing drugs, and providing flexibility in measured isotopes.

Implementation Method 1

The method comprises ionizing the sample such that ions of both the first and the second isotope are simultaneously released from the sample

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

measuring with an accelerator mass spectrometry system at least one isotope of a first element and at least one isotope of a second element

Methodology Applied
Scientific EffectMagnetic field separation: Magnetic Field

Implementation Method 3

accelerator mass spectrometry method for analysing a sample

Methodology Applied
Scientific EffectElectric field acceleration: Electric Field

Data Source

PatentUS10573502B2Accelerator mass spectrometry method
Publication Date: 2020.02.25 NEDERLANDSE ORG VOOR TOEGEPAST NATUURWETENSCHAPPELIJK ONDERZOEK TNO
  • US10573502B2 patent drawing

AI summary

Accelerator mass spectrometry methods for analyzing a sample are provided. In an embodiment, the method includes measuring with an accelerator mass spectrometry system, an isotope of a first element and an isotope of a second element, wherein the measurement of the second element is used for normalizing the measurement of the first element.