Urinary Exosomal Thyroglobulin Detection for Thyroid Cancer Prognosis

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Solution Overview

Problem

Current biomarkers for thyroid cancer prognosis, such as serum thyroglobulin, are insufficient for detecting recurrence, especially when undetectable, and require costly recombinant human thyrotropin stimulation, limiting their reliability and sensitivity.

Innovation Solution

The method involves analyzing exosomes from bodily fluids, particularly urine, for the presence of thyroglobulin using peptide sequencing with mass spectrometry, allowing for early detection of thyroid cancer recurrence without the need for thyroid hormone withdrawal or rhTSH stimulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If serum thyroglobulin is used as a biomarker for detecting thyroid cancer recurrence, then the method is simple and widely available, but the sensitivity is insufficient when thyroglobulin levels are undetectable

Engineering Contradiction:
Improvedetection sensitivityVSAvoidprognosis reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts thyroglobulin from exosomes isolated from bodily fluids (urine, serum, plasma) and analyzes it separately using mass spectrometry. This extraction approach allows detection of thyroglobulin that would be undetectable in total serum, thereby improving detection sensitivity while maintaining diagnostic reliability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses exosomes as an intermediary carrier to deliver and concentrate thyroglobulin for detection. By isolating exosomes first and then analyzing thyroglobulin within them, the method achieves higher sensitivity compared to direct serum thyroglobulin measurement

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If recombinant human thyrotropin (rhTSH) stimulation is used to enhance serum thyroglobulin detection, then the sensitivity for detecting local recurrence or distant metastasis is improved, but the cost increases significantly

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcost
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent extracts and concentrates thyroglobulin from exosomes, allowing direct detection without requiring rhTSH stimulation. This extraction and concentration approach achieves high sensitivity detection while eliminating the need for expensive stimulation protocols

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs mass spectrometry technology which, while advanced, does not require the repeated administration of expensive rhTSH. The method uses disposable exosome isolation and analysis that can be performed without ongoing costly stimulation requirements

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

3Measurement precision

If thyroid hormone withdrawal or rhTSH stimulation is performed to prepare for serum thyroglobulin measurement, then the accuracy of recurrence detection is improved, but the complexity and time required for the procedure increases

Engineering Contradiction:
Improvedetection accuracyVSAvoidprocedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts thyroglobulin from exosomes directly from bodily fluids without requiring thyroid hormone withdrawal or rhTSH stimulation. This direct extraction approach simplifies the procedure while maintaining or improving detection accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The exosomes naturally concentrate and protect thyroglobulin, allowing the biological system itself to prepare the analyte for detection without external stimulation protocols. The method uses the body's own exosomal transport mechanism to facilitate accurate detection

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

This approach provides a non-invasive, sensitive, and reliable method for monitoring thyroid cancer recurrence, reducing costs and improving prognosis accuracy by detecting urinary exosomal thyroglobulin levels, even when serum thyroglobulin is undetectable.

Implementation Method 1

detecting whether thyroglobulin is present in the exosome by peptide sequencing with mass spectrometry

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS12007394B2Biomarker for prognosis of thyroid cancer
Publication Date: 2024.06.11 NAT TAIWAN UNIV
  • US12007394B2 patent drawing
  • US12007394B2 patent drawing
  • US12007394B2 patent drawing

AI summary

The present disclosure provides a method of prognosis of thyroid cancer including obtaining an exosome from a subject who had received a therapy of thyroid cancer such as thyroidectomy, and detecting whether thyroglobulin is present in the exosome. Moreover, the present disclosure provides the use of urinary exosomal thyroglobulin in being a non-invasive, reproducible, convenient, serial, and accurate follow-up marker for patient with thyroid cancer.