Modified Primers for Reliable Nucleic Acid Detection

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current PCR kits for detecting nucleic acid patterns in capillary electrophoresis are prone to errors due to signal noise, artefacts, and lack of objectivity, making it difficult to automate the analysis and quantify results reliably.

Innovation Solution

A PCR kit using groups of modified primers (n-AMC) that generate redundant and distinguishable amplifications, allowing for robust pattern detection and reduced sensitivity to noise, enabling automated analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If classic PCR kits are used for detecting nucleic acid patterns, then the detection can be performed with standard reagents and procedures, but the results are prone to errors due to signal noise, artifacts, and lack of objectivity

Engineering Contradiction:
Improvereliability of detection resultsVSAvoidsignal noise and artifacts
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies primer parameters by adding specific sequences (5'-3' direction: a sequence complementary to a tail added by the polymerase during PCR, and a tag sequence) to traditional primers. This parameter change in primer structure enables the generation of distinctive patterns that can be objectively detected and differentiated from noise and artifacts, thereby improving reliability while maintaining compatibility with standard PCR procedures

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates redundant copies of detection information by generating multiple distinctive patterns from a single nucleic acid target through the modified primer system. Each target produces a characteristic pattern that can be objectively identified, allowing for automated analysis and reducing the impact of random noise or artifacts on detection reliability

Inventive Principle:
Principle #26Copying

2Extent of automation

If automated analysis is implemented, then productivity and objectivity improve, but the system requires highly reliable and noise-resistant detection methods that current PCR kits do not provide

Engineering Contradiction:
Improveautomation of analysisVSAvoidprecision of pattern detection
Core Design Contradiction:
Extent of automationVSMeasurement precision

Solution Approach 1:

By modifying primer parameters to include complementary sequences and tag sequences, the patent creates detection systems with distinctive, objectively measurable patterns. These modified primers generate amplified products with unique characteristics that can be automatically identified and quantified, enabling precise automated analysis without requiring expert interpretation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The modified primer system incorporates feedback mechanisms where the primer structure itself responds to PCR conditions (polymerase activity, temperature cycling) by generating consistent, reproducible patterns. This built-in feedback ensures that the detection signal is inherently resistant to variations in experimental conditions, providing the precision required for automated analysis

Inventive Principle:
Principle #23Feedback

3Reliability

If modified primers with additional sequences are used, then pattern detection reliability improves, but the complexity of the PCR kit and primer design increases

Engineering Contradiction:
Improveobjectivity of detectionVSAvoidcomplexity of PCR kit
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the primer structure into distinct functional components: the original target-specific sequence, a complementary sequence for polymerase tail recognition, and a tag sequence for pattern identification. This segmentation allows each component to perform its specific function independently, improving detection objectivity while organizing the complexity into manageable, well-defined modules

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The modified primers serve multiple functions simultaneously: they amplify the target sequence, incorporate polymerase-added tails, and generate distinctive detection patterns. This multi-functionality reduces the need for separate reagents or procedures, thereby improving objectivity without proportionally increasing overall kit complexity

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 PCR kit provides a highly objective and reliable method for detecting nucleic acid patterns, minimizing errors and noise, and allowing for automated analysis with high confidence in the accuracy of the results.

Implementation Method 1

PCR kit containing, for each motif of interest to be identified on a nucleic acid, at least two pairs of primers specific to said motif

Methodology Applied
Scientific EffectPolymerase chain reaction:

Implementation Method 2

Capillary gel electrophoresis is now widely used to obtain DNA profiles for detecting allelic variations

Methodology Applied
Scientific EffectCapillary electrophoresis: Capillary Electrophoresis

Data Source

PatentEP3109327B1PCR kit for capillary electrophoresis
Publication Date: 2019.06.12 IDEMIA IDENTITY & SECURITY FRANCE SAS
  • EP3109327B1 patent drawingFigure 1
  • EP3109327B1 patent drawingFigure 2
  • EP3109327B1 patent drawingFigure 3

AI summary

The present invention relates to a PCR kit for improving the detection of specific nucleic acid motifs and increasing the reliability of the results obtained. More specifically, the invention proposes using modified primers with specific characteristics that, during electrophoresis, allow the detection, on samples containing nucleic acids, of the equivalent of a characteristic coding of specific nucleic acid motifs, this coding being such that it allows for better detection of the presence of these motifs. The invention also provides a method for detecting nucleic acid motifs of interest (for example, STRs, mini-STRs, or VNTRs) using such primers. It finds advantageous—but not limited to—application in the field of capillary electrophoresis.