Aqueous Humor Biomarker Profiling for Early Vitreoretinal Monitoring

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Solution Overview

Problem

The molecular physiology of aqueous humor in the eye is poorly understood due to its small sample volume, low protein concentration, and sparse cellular components, limiting effective methods for monitoring molecular pathophysiology and human health.

Innovation Solution

Identifying and measuring specific biomarkers such as stromelysin-2 (MMP10), neuropilin-1 (NRP1), semaphorin 3C (SEMA3C), hes family bHLH transcription factor 5 (HES5), and fibroblast growth factor receptor like 1 (FGFRL1) in aqueous humor samples, using assays like aptamer-based proteomic analysis, to predict biological age and age-related pathologies, and monitoring diseases like AMD, diabetic retinopathy, and other vitreoretinal conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If aqueous humor is used for molecular analysis, then early detection of age-related diseases is enabled, but the small sample volume and low protein concentration limit effective monitoring

Engineering Contradiction:
Improvebiomarker detection accuracyVSAvoidsample volume and protein concentration
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by switching from traditional bulk analysis methods to targeted proteomic approaches that measure specific biomarkers at ultra-low concentrations. This involves changing the detection parameters to achieve femtomolar to attomolar sensitivity, enabling accurate measurement despite limited sample volume and low protein concentration in aqueous humor.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent extracts and measures specific biomarkers of interest from the complex aqueous humor matrix. By focusing on particular proteins and peptides that indicate age-related pathology, the method overcomes the limitation of low overall protein concentration by concentrating analytical effort on detecting specific molecular signatures at trace levels.

Inventive Principle:
Principle #2Taking out (Extraction)

2Loss of information

If comprehensive proteomic profiling is performed on aqueous humor, then molecular pathophysiology can be monitored, but the sparse cellular components and low protein concentration make exploration difficult

Engineering Contradiction:
Improvemolecular composition dataVSAvoidprotein concentration
Core Design Contradiction:
Loss of informationVSQuantity of substance

Solution Approach 1:

The patent transforms the analytical approach by changing from quantitative bulk proteomics to qualitative and semi-quantitative targeted proteomics. This parameter change enables comprehensive molecular profiling by detecting specific proteins at very low concentrations, recovering information that would be lost in traditional methods requiring higher protein abundance.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces traditional mechanical separation and concentration methods with highly sensitive mass spectrometry-based detection systems. This substitution allows direct detection of low-abundance proteins in aqueous humor without requiring physical concentration steps, preserving the native molecular composition information.

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

3Loss of time

If biomarker levels are measured to predict biological age, then early intervention is enabled, but accurate measurement requires sophisticated analytical methods

Engineering Contradiction:
Improvetime for disease interventionVSAvoidanalytical assay complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The patent segments the complex analytical task into targeted measurement of specific biomarker panels. By dividing the proteomic analysis into focused assays for age-related biomarkers, the method achieves rapid results suitable for clinical timing while managing analytical complexity through modular, targeted approaches rather than comprehensive untargeted analysis.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS20250347701A1Methods for monitoring molecular biomarkers for aging and disease
Publication Date: 2025.11.13 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US20250347701A1 patent drawing
  • US20250347701A1 patent drawing
  • US20250347701A1 patent drawing

AI summary

Compositions, methods, and kits are provided for diagnosing vitreoretinal diseases and age-related pathologies. In particular, aqueous humor biomarkers have been identified that correlate with biological aging and age-related pathologies and morbidity. The use of such biomarkers may allow earlier intervention in treatment of aging-related diseases. In addition, methods of using aqueous humor biomarkers for prognosis, diagnosis, and monitoring treatment of vitreoretinal diseases are also provided.