Quantum Algorithm for DNA Melting Curve Background Removal

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Solution Overview

Problem

Existing methods for high-resolution DNA melting analysis face challenges in accurately removing background fluorescence, especially with unlabeled probes and small amplicons, leading to inaccurate genotyping and mutation detection due to low temperature distortions and artifacts.

Innovation Solution

A quantum method for background removal is introduced, involving rescaling the melting curve data using a quantum algorithm, specifically transforming the x-axis to (1/T−1/TREF) and y-axis to ln(I/IREF), allowing for accurate separation of background and sample signals, and proportionally calculating the melting curve to correct for temperature effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If fluorescence methods are used for DNA melting analysis, then the analysis speed increases and smaller quantities of nucleic acid can be used, but background fluorescence interference occurs that affects measurement accuracy

Engineering Contradiction:
Improvemelting curve generation speedVSAvoidmelting curve accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the fluorescence signal into two distinct components: background fluorescence and sample-specific melting signal. By applying mathematical decomposition to separate these overlapping signals, the method enables accurate extraction of the melting curve from the total fluorescence measurement, resolving the contradiction between using fluorescence for rapid analysis and maintaining measurement accuracy despite background interference

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces an intermediary mathematical model that acts as a mediator between the raw fluorescence signal and the final melting curve. This model includes parameters for background fluorescence intensity and sample melting characteristics, allowing the system to translate the composite fluorescence signal into accurate melting temperature data while accounting for background interference

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If conventional background removal methods are used, then processing is simpler, but low temperature distortions and artifacts occur that reduce genotyping accuracy

Engineering Contradiction:
Improvebackground removal simplicityVSAvoidgenotyping accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent changes the parameters used in background removal from simple linear subtraction to a multi-parameter mathematical model that accounts for temperature-dependent background fluorescence characteristics. By incorporating parameters that describe how background fluorescence varies with temperature, the method eliminates low-temperature distortions and artifacts while maintaining processing feasibility, thus resolving the contradiction between simplicity and accuracy

Inventive Principle:
Principle #35Parameter changes

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

The quantum method effectively removes background fluorescence, improving the accuracy of melting curve analysis for both small and large amplicons, and unlabeled probes, reducing low temperature distortions and artifacts, thereby enhancing the precision of genotyping and mutation detection.

Implementation Method 1

measuring the fluorescence of the nucleic acid sample as a function of temperature to produce a raw melting curve

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11066696B2Quantum method for fluorescence background removal in DNA melting analysis
Publication Date: 2021.07.20 UNIV OF UTAH RES FOUND
  • US11066696B2 patent drawing
  • US11066696B2 patent drawing
  • US11066696B2 patent drawing

AI summary

A method of background removal from melting curves generated using a fluorescent dye is provided for analyzing a melting profile of a nucleic acid sample. The method comprises measuring the fluorescence of the nucleic acid sample as a function of temperature to produce a raw melting curve having a melting transition, the nucleic acid sample comprising a nucleic acid and a molecule that binds the nucleic acid to form a fluorescently detectable complex, the raw melting curve comprising a background fluorescence signal and a nucleic acid sample signal; and separating the background signal from the nucleic acid sample signal by use of a quantum algorithm to generate a corrected melting curve, the corrected melting curve comprising the nucleic acid sample signal.