miRNA Biomarker Normalization for Non-Invasive Health Diagnosis

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Solution Overview

Problem

Current methods for diagnosing health status using miRNAs are invasive, costly, and lack reliable non-invasive biomarkers for broad disease detection, particularly in conditions like cancer and neurodegenerative diseases, with limited understanding of miRNA function in blood cells.

Innovation Solution

A method involving the isolation of total intracellular RNA from erythrocytes, leukocytes, and thrombocytes to determine expression profiles of specific miRNAs, using disease-regulated and disease-preserved miRNAs for relative normalization, providing non-invasive, robust biomarkers for health status assessment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If miRNA biomarkers are used for non-invasive diagnosis, then diagnostic accessibility and cost-effectiveness are improved, but measurement precision and reliability are insufficient due to lack of standardized biomarker panels

Engineering Contradiction:
Improvediagnostic accessibilityVSAvoidbiomarker detection accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent segments the miRNA detection into two functional groups: disease-regulated miRNAs (biomarkers) and disease-preserved miRNAs (normalizers). This segmentation allows independent optimization of each component, with biomarkers providing diagnostic specificity and normalizers ensuring measurement stability, thereby resolving the contradiction between accessibility and precision.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces disease-preserved miRNAs as intermediary normalizers that mediate between the raw miRNA measurements and the final diagnostic assessment. These normalizers act as reference standards that correct for technical variations, enabling precise measurements while maintaining non-invasive sampling.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If blood cell fractions are used for miRNA analysis, then non-invasive sampling is achieved, but contamination from extra-cellular matrix leakage occurs

Engineering Contradiction:
Improvesampling simplicityVSAvoidcontamination
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and analyzes miRNAs specifically from blood cell fractions (erythrocytes, leukocytes, thrombocytes) rather than from the extra-cellular matrix. By taking out the miRNAs from their potential contamination source and analyzing them in their cellular origin, the method eliminates leakage contamination while maintaining simple blood sampling.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies local quality by analyzing miRNAs from specific blood cell types (erythrocytes, leukocytes, thrombocytes) rather than treating blood as a homogeneous sample. This localized analysis within specific cell fractions prevents contamination from the extra-cellular matrix while preserving diagnostic information from the peripheral immune system.

Inventive Principle:
Principle #3Local quality

3Device complexity

If global normalization methods are used, then analysis complexity is reduced, but reliability decreases due to lack of disease-specific internal controls

Engineering Contradiction:
Improveanalysis complexityVSAvoiddiagnostic robustness
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent applies local quality by using disease-preserved miRNAs as internal normalizers specific to the blood cell fraction being analyzed. Instead of applying a single global normalization method, the patent identifies and uses miRNAs that are preserved across disease states, providing disease-specific internal controls that enhance diagnostic robustness without excessively complicating the analysis.

Inventive Principle:
Principle #3Local quality

Data Source

PatentEP3265580B1Signature of health
Publication Date: 2022.03.30 HUMMINGBIRD DIAGNOSTICS GMBH
  • EP3265580B1 patent drawingFigure 1~2
  • EP3265580B1 patent drawingFigure 3
  • EP3265580B1 patent drawingFigure 4

AI summary

The present invention relates to a method for diagnosis of a change of the status of health of a subject based on the determination of expression profiles of miRNAs.