Nucleic Acid Load Normalization via Endogenous Control
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Solution Overview
Problem
Current methods for comparing target nucleic acid levels between samples, especially non-blood samples like saliva or swab samples, are hindered by variations in organic matter, making it difficult to determine changes in nucleic acid loads over time due to inconsistencies in sample collection and physiology.
Innovation Solution
A method involving the use of control samples with known concentrations to generate a standard curve, amplification of target and endogenous nucleic acids, and determination of correction factors based on relative endogenous nucleic acid levels to normalize target nucleic acid quantities across multiple samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If saliva or swab samples are used instead of blood samples, then ease of sample collection is improved, but measurement precision of target nucleic acid load deteriorates due to variations in organic matter
Solution Approach 1:
The patent introduces an endogenous control nucleic acid measurement to create a correction factor that normalizes the target nucleic acid quantity. This parameter change transforms the raw measurement into a corrected value that accounts for sample-to-sample variations in organic matter, thereby restoring measurement precision while maintaining the ease of using saliva or swab samples.
Solution Approach 2:
The endogenous control nucleic acid serves as an intermediary element that mediates between the variable sample matrix (organic matter) and the target nucleic acid measurement. By measuring the endogenous control and using it to generate a correction factor, the patent indirectly compensates for the variations in organic matter that would otherwise directly affect measurement precision.
2Device complexity
If absolute quantity of target nucleic acid is measured without normalization, then measurement process is simplified, but reliability of comparison between samples deteriorates due to sample composition variations
Solution Approach 1:
The patent adds a normalization parameter (correction factor based on endogenous control) to the measurement process. This transforms the simple absolute quantity measurement into a corrected quantity that enables reliable comparisons. The additional step, while increasing process complexity, is minimal and automated, providing significant gains in reliability.
3Measurement precision
If correction factors based on endogenous nucleic acid are applied, then measurement precision is improved, but device complexity increases due to additional amplification and calculation steps
Solution Approach 1:
The patent combines the target nucleic acid amplification and detection with the endogenous control nucleic acid amplification and detection into a single integrated process. The correction factor calculation is then applied to the target nucleic acid quantity based on the endogenous control measurement, merging two measurements into a coordinated workflow that improves precision while managing complexity through integration.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables accurate and meaningful comparisons of target nucleic acid loads between samples, allowing for effective monitoring of disease progression and treatment efficacy by accounting for variations in sample composition.
Implementation Method 1
amplifying at least a portion of the target nucleic acid in each of the test samples by subjecting each of the test samples to amplification conditions in the presence of target-specific primers
Data Source
AI summary
Disclosed are compositions, kits, and methods for quantifying a target nucleic acid from a sample. Compositions, kits, and methods enable the comparison of target nucleic acid loads between two or more test samples by normalizing measured levels (using a standard curve) of the target nucleic acid in each sample according to relative levels of endogenous nucleic acid in each test sample.