Composite Dilution Modeling for Consistent Urine Aptamer Measurements

Solution Overview

Problem

Inter-sample variability of analyte measurements in biological samples poses challenges for biomarker discovery, metabolic analyses, gene expression analysis, and diagnostic tools, particularly when quantitative biological signals differ by a small magnitude, leading to inconsistent and less meaningful datasets.

Innovation Solution

A method for generating a composite dilution model by determining analyte levels in multiple dilutions of biological samples, performing horizontal translations, and fitting a function to create a lined composite translation series, thereby normalizing biological signals in complex matrices.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional analyte measurement methods are used in biological samples, then the measurement process is simple, but inter-sample variability is high leading to inconsistent datasets

Engineering Contradiction:

Improveconsistency of analyte measurementsVSAvoidcomplexity of measurement method

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary actions by creating composite dilution models from reference samples before measuring test samples. Multiple dilutions are prepared and analyzed in advance to establish normalization curves, which then serve as the basis for correcting variability in subsequent measurements. This preliminary modeling approach enables consistent analyte quantification across different biological samples.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent systematically varies dilution parameters across multiple concentration levels to create comprehensive dilution series. By measuring analyte levels at different dilutions (e.g., 1:2, 1:4, 1:8, 1:16, 1:32, 1:64), the method captures the relationship between dilution factor and signal intensity, enabling robust normalization that accounts for matrix effects and variability in complex biological samples.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If multiple dilutions are analyzed to reduce variability, then measurement consistency improves, but the time and resources required increase

Engineering Contradiction:

Improveprecision of analyte level determinationVSAvoidtime for performing measurements

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary actions by creating composite dilution models from reference samples before measuring test samples. Multiple dilutions are prepared and analyzed in advance to establish normalization curves, which then serve as the basis for correcting variability in subsequent measurements. This preliminary modeling approach enables consistent analyte quantification across different biological samples.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent creates standardized dilution series that can be replicated across different samples and experiments. By establishing a composite dilution model from reference materials, the method produces a reusable template that can be applied to multiple test samples, reducing the need to perform complete multi-dilution analyses for each individual sample and thereby saving time while maintaining precision.

Inventive Principle:

Principle #26Copying

Data Source

PatentUS12480956B2Controlling intersample analyte variability in complex biological matrices

Publication Date: 2025.11.25 SOMALOGIC OPERATING CO INC

AI summary

Described herein are compositions and methods for normalizing the variability of inter-sample analyte measurements from a biological matrix. In some embodiments, the present disclosure relates to methods for normalizing the levels of one or more proteins from urine as measured by an aptamer based assay.