Biomarker Validation Using Internal Control Combinations
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for validating biomarker values in medical devices are limited by the need for multiple controls, which increase costs and complexity, and are not well-suited for multiplex qPCR due to limitations in multiplexing capability and the requirement for spike-ins and positive controls.
Innovation Solution
A method that determines a plurality of biomarker values and calculates control values using combinations of these values, comparing them to control references to validate the biomarker values and generate an indicator for medical conditions, reducing the need for external controls and improving statistical power.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple external controls are used to validate biomarker values, then measurement reliability is improved, but device complexity and cost increase
Solution Approach 1:
The patent extracts the control function from separate external controls and integrates it into the biomarker panel itself by designating specific biomarkers as internal controls. This eliminates the need for separate control reactions while maintaining validation capability.
Solution Approach 2:
The patent makes the biomarker panel serve dual functions: both diagnostic measurement and self-validation. The same sample and reaction conditions are used for both measuring disease-associated biomarkers and internal control biomarkers, making the system self-sufficient.
2Reliability
If multiple external controls are used to validate biomarker values, then measurement reliability is improved, but cost increases
Solution Approach 1:
The patent merges the control function with the diagnostic function by using the same reagents, sample, and reaction conditions for both internal control biomarkers and disease-associated biomarkers. This eliminates duplicate costs for separate control materials and processing.
Solution Approach 2:
The biomarker panel performs self-validation through internal control biomarkers that are measured simultaneously with disease biomarkers using the same resources. The system validates itself without requiring external control materials or additional processing steps.
3Measurement precision
If spike-in controls are used for multiplex qPCR, then measurement precision is improved, but multiplexing capability is limited
Solution Approach 1:
The patent uses internal control biomarkers that are naturally present in the sample as intermediaries to monitor and correct for technical variations. These endogenous controls better reflect the actual sample conditions compared to exogenous spike-in controls, enabling more accurate normalization in multiplex assays.
Solution Approach 2:
The patent changes from using exogenous spike-in controls to using endogenous internal control biomarkers. This parameter change enables better compatibility with multiplex qPCR by using naturally occurring samples that reflect true biological variation and technical performance simultaneously.
Data Source
Figure 1A
Figure 1B
Figure 1C
AI summary
A method for validating quantification of biomarkers, the biomarkers being quantified using a quantification technique of a selected type, and the method including determining a plurality of biomarker values, each biomarker value being indicative of a value measured or derived from a measured value, for at least one corresponding biomarker of the biological subject and being at least partially indicative of a concentration of the biomarker in a sample taken from the subject, determining at least one control value by determining a combination of biomarker values, comparing each control value to a respective control reference and determining if the biomarker values are valid using results of the comparison.