Metabolomic Blood Plasma Signature for Radiation Dose Detection

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Solution Overview

Problem

Current methods for accurately determining whole-body radiation dose after exposure are limited by saturation issues with metabolite markers and lack of specificity, making it difficult to provide timely and appropriate medical attention for radiation sickness.

Innovation Solution

A kit and method using a mass spectrometer to quantify metabolite levels in body fluids, combined with an algorithm to determine the radiation dose, which includes metabolites from both the subject and the intestinal microbiota, enabling accurate dose determination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If single metabolite markers (e.g., thymidine, deoxycytidine) are used to detect radiation exposure, then detection simplicity is improved, but measurement precision deteriorates due to saturation beyond 3 Gy

Engineering Contradiction:
Improvedetection simplicityVSAvoiddose determination accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent divides the radiation dose detection task into multiple independent metabolite measurements instead of relying on a single marker. By analyzing a panel of metabolites (including thymidine, deoxycytidine, and other pyrimidine derivatives) separately and integrating their signals, the system maintains detection simplicity while overcoming the saturation limitation of individual markers, thereby improving dose determination accuracy across a broader dose range.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a composite biomarker profile by combining multiple metabolite markers into an integrated radiation response signature. This composite approach synthesizes information from various metabolites measured in blood plasma, allowing the system to maintain operational simplicity through a unified detection protocol while achieving superior measurement precision through the cumulative information from multiple markers that do not all saturate at the same dose level.

Inventive Principle:
Principle #40Composite materials

2Reliability

If specific tissue-origin metabolites (e.g., citrulline, amylase, Flt3-ligand) are used, then detection specificity is improved, but measurement precision deteriorates due to lack of dynamic range data

Engineering Contradiction:
Improveradiation exposure confirmationVSAvoiddose quantification accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent employs metabolites from multiple biological sources (host tissues and intestinal microbiota) within a single universal detection system. This multi-functional approach allows the same analytical platform to detect radiation exposure confirmation through various metabolite changes while simultaneously providing dose quantification, thereby achieving both reliability and measurement precision without requiring separate specialized assays.

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

Solution Approach 2:

The patent monitors multiple parameters (concentrations of different metabolites) simultaneously to capture the dynamic response to radiation exposure. By measuring changes in multiple metabolite levels and analyzing their temporal patterns, the system overcomes the limitation of single-parameter markers that lack dynamic range data, enabling both reliable exposure confirmation and precise dose quantification through multi-parameter analysis.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If comprehensive metabolite panels from multiple sources are analyzed, then measurement precision is improved, but device complexity increases

Engineering Contradiction:
Improveradiation dose determination fidelityVSAvoidanalysis system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical or procedural analysis systems with a computational algorithm that processes metabolite data. Instead of requiring complex physical separation or identification methods for each metabolite, the system uses mass spectrometry to detect metabolite levels and applies an algorithm to integrate the data, thereby achieving high measurement precision while minimizing device complexity through computational rather than mechanical processing.

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

Solution Approach 2:

The patent creates a simplified computational model (algorithm) that replicates the complex biological response to radiation. The algorithm processes the metabolite panel data to generate a radiation dose estimate, effectively copying the information extraction function without requiring the physical complexity of analyzing each metabolite individually. This computational copy enables high-fidelity dose determination with relatively simple analytical instrumentation.

Inventive Principle:
Principle #26Copying

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

The solution achieves 68% fidelity in determining radiation dose, overcoming saturation issues and providing a robust biomarker system for radiation exposure assessment, allowing for timely and appropriate medical interventions.

Implementation Method 1

a mass spectrometer to measure a plurality of metabolite levels in the sample

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS11092591B2Host and intestinal microbiota derived metabolomic blood plasma signature for prior radiation injury
Publication Date: 2021.08.17 ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV
  • US11092591B2 patent drawing
  • US11092591B2 patent drawing
  • US11092591B2 patent drawing

AI summary

Provided are methods of determining prior radiation dose exposure levels for subjects, and kits therefor. Also provided are methods of treatment.