Biomarker Panel for Acute Ischemic Stroke Diagnosis

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Solution Overview

Problem

Current diagnostic methods for acute ischemic stroke are inadequate due to the rapid onset and progression of the condition, leading to delayed diagnosis and inappropriate treatment, with existing biomarkers being non-specific and difficult to detect, especially in non-stroke specialists.

Innovation Solution

A set of biomarkers including chemokine receptor 7 (CCR7), chondroitin sulfate proteoglycan 2 (CSPG2), IQ motif-containing GTPase activation protein 1 (IQGAP1), orosomucoid 1 (ORM1), arginase 1 (ARG1), lymphocyte antigen 96 (LY96), matrix metalloproteinase 9 (MMP9), carbonic anhydrase 4 (CA4), and s100 calcium binding protein A12 (s100A12) are identified for use in rapid and specific diagnostic assays to differentiate acute ischemic stroke from other stroke types and transient ischemic attacks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If current diagnostic methods are used for acute ischemic stroke, then diagnosis can be made, but the diagnosis is delayed and treatment is inappropriate due to rapid onset and progression

Engineering Contradiction:
Improvediagnosis timeVSAvoiddiagnosis accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by developing and validating a panel of biomarkers (including S100B, GFAP, UCH-L1, and NEFL) that can detect acute ischemic stroke immediately upon onset. These biomarkers are measured in blood samples taken at the time of presentation, allowing diagnosis before clinical symptoms fully develop or progress, thereby eliminating the time loss associated with waiting for symptom evolution while maintaining high diagnostic accuracy through multi-marker panels.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces mechanical/neurological examination systems with a biochemical detection system. Instead of relying on physical examinations, imaging, or waiting for clinical symptom progression, the invention uses blood-based biomarker detection to diagnose acute ischemic stroke. This substitution enables immediate objective measurement of brain injury markers in the bloodstream, providing rapid and accurate diagnosis without the time delays inherent in traditional mechanical diagnostic approaches.

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

2Measurement precision

If existing biomarkers are used, then stroke detection is possible, but the biomarkers are non-specific and difficult to detect

Engineering Contradiction:
Improvebiomarker specificityVSAvoidbiomarker detection difficulty
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent merges multiple individual biomarkers into a comprehensive diagnostic panel. By combining S100B (astrocyte marker), GFAP (astrocyte marker), UCH-L1 (neuronal marker), and NEFL (neuronal marker), the invention creates a synergistic diagnostic system where each marker contributes specific information about different aspects of brain injury. This combination approach increases overall specificity by requiring concordant elevation of multiple markers while maintaining ease of detection through standardized assays for each individual marker that are already clinically available.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent applies universality by selecting biomarkers that serve multiple diagnostic functions simultaneously. The biomarker panel not only detects acute ischemic stroke with high specificity but also differentiates between ischemic and hemorrhagic stroke types, monitors disease progression, and predicts outcomes. Each biomarker in the panel is detectable using universal, standardized laboratory methods that are widely available in clinical settings, thereby maintaining ease of detection while achieving high measurement precision across multiple diagnostic objectives.

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

3Productivity

If rapid diagnosis is achieved, then appropriate treatment can be facilitated, but the diagnostic methods must be complex and specialized

Engineering Contradiction:
Improvetreatment speedVSAvoiddiagnostic assay complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent segments the diagnostic process into discrete, independently measurable components. Instead of using a single complex test, the invention divides diagnosis into measurements of four separate biomarkers (S100B, GFAP, UCH-L1, NEFL), each of which can be measured using standardized, commercially available assays. This segmentation allows laboratories to implement the diagnostic panel using existing infrastructure and procedures, reducing overall system complexity while enabling rapid diagnosis through parallel processing of multiple simple tests rather than one complex test.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses blood as an intermediary medium to detect brain injury. Instead of requiring direct examination of brain tissue or complex neuroimaging, the invention measures biomarkers that have migrated from damaged brain cells into the bloodstream. This intermediary approach simplifies the diagnostic system by using readily accessible blood samples and standard laboratory equipment, thereby increasing treatment speed through rapid, simple blood tests while maintaining high diagnostic accuracy through the specificity of the biomarker panel.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS9200322B2Biomarkers for acute ischemic stroke
Publication Date: 2015.12.01 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES
  • US9200322B2 patent drawing
  • US9200322B2 patent drawing
  • US9200322B2 patent drawing

AI summary

The present invention provides methods and compositions for the diagnosis of acute ischemic stroke. The invention further provides methods and compositions for distinguishing acute ischemic stroke from other forms of stroke and TIAs and “stroke mimic” events. Moreover, methods and compositions are provided to facilitate the treatment of acute ischemic stroke patients.