Genetic Analyzer Dynamic Amplification Termination

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Solution Overview

Problem

Existing nucleic acid analysis systems lack the ability to selectively choose optimal conditions for amplification termination and subsequent processing based on the sample, leading to inefficiencies and unnecessary steps, such as uniform Melting analysis after amplification, which can result in reduced throughput and unnecessary resource usage.

Innovation Solution

A genetic analyzer with individually controlled temperature blocks and user-selectable conditions for terminating amplification reactions and choosing next processing steps, allowing for optimal analysis methods based on amplification results, enabling automatic performance of selected analysis operations and improving throughput.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If uniform Melting analysis or HRM analysis is performed after a predetermined measurement completion time for all reaction solutions, then the system maintains a simple uniform processing protocol, but unnecessary processing is performed on samples that do not require it, reducing overall throughput and wasting resources

Engineering Contradiction:
ImprovethroughputVSAvoidprocessing control complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system dynamically adjusts the processing protocol for each reaction solution based on real-time amplification detection results. Instead of a static uniform protocol, the apparatus can terminate amplification early for samples that have reached plateau and proceed directly to Melting analysis, while continuing amplification for samples that have not yet plateaued. This dynamic adaptation resolves the contradiction by making the processing complexity conditional and sample-specific, thereby improving overall throughput without requiring complex pre-planning for all samples.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system changes the processing parameters (amplification termination time, subsequent analysis timing) based on the detected amplification state of each sample. By monitoring amplification curves and detecting plateau conditions, the apparatus adjusts the timing and sequence of operations for individual samples, allowing early termination of unnecessary amplification cycles and reducing overall processing time for the batch, thus improving throughput while maintaining manageable control complexity through automated parameter adjustment.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If the amplification reaction is continued until a predetermined measurement completion time for all samples, then the system ensures complete analysis for all reaction solutions, but time is wasted on samples that have already reached amplification plateau, reducing processing speed

Engineering Contradiction:
Improveprocessing speedVSAvoidanalysis completeness
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The system continuously monitors amplification fluorescence signals and uses this feedback to determine when to terminate amplification for individual samples. When the amplification curve reaches a plateau (indicating complete amplification), the system receives feedback and automatically terminates further amplification cycles for that sample, allowing it to proceed to the next analysis step. This feedback mechanism ensures that amplification is terminated at the optimal point for each sample, improving processing speed while maintaining analysis completeness through real-time monitoring.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system performs preliminary detection of amplification plateau condition during the amplification process itself, before the predetermined measurement completion time arrives. By detecting the plateau condition in advance, the system can prepare for early termination and transition to the next analysis step, ensuring that no time is wasted on completed amplification reactions while maintaining readiness for samples that require the full amplification cycle, thus improving overall processing speed without compromising reliability.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If multiple judgment conditions for amplification detection are available (plateau detection, Ct value detection), then users have flexibility in selecting detection methods, but without a unified judgment definition, it becomes difficult to optimize termination conditions for different samples

Engineering Contradiction:
Improvedetection method flexibilityVSAvoidoperation simplicity
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The system implements a unified amplification judgment framework that can accommodate multiple detection methods (plateau detection, Ct value detection, other criteria) through a common interface and control logic. This universal framework allows users to select different detection methods for different samples or experiments while maintaining consistent operation procedures and data processing workflows. The unified judgment definition enables optimization of termination conditions across all samples using the selected method, resolving the contradiction by making the system versatile in detection approach while simple in operation through standardized control.

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

Enables the selection of optimal amplification termination conditions and subsequent processing, reducing unnecessary steps and improving processing speed by allowing users to customize analysis methods based on sample-specific needs, thereby enhancing overall system throughput.

Implementation Method 1

The PCR method is a method of repeating temperature change (temperature cycle) to reaction solutions containing target nucleic acids to selectively amplify specific base sequences.

Methodology Applied
Scientific EffectTemperature cycling:

Implementation Method 2

a real time PCR method. In the existent real time PCR apparatus, identical temperature cycle is started to perform amplification reaction for a plurality of reaction solutions simultaneously.

Methodology Applied
Scientific EffectFluorescence detection: Fluorescence

Implementation Method 3

A genetic analyzer with individually controlled temperature blocks and user-selectable conditions for terminating amplification reactions

Methodology Applied
Scientific EffectTemperature control:

Data Source

PatentEP2671942B1Nucleic acid test device
Publication Date: 2016.09.21 HITACHI HIGH TECH CORP
  • EP2671942B1 patent drawingFigure 1
  • EP2671942B1 patent drawingFigure 2
  • EP2671942B1 patent drawingFigure 3

AI summary

A nucleic acid analysis apparatus capable of selecting an optimal analysis method for every user and improving throughput is provided. In a genetic analyzer for measuring and analyzing amplification reaction of a nucleic acid in real time, an amplification curve is analyzed and a user can select conditions for terminating the amplification reaction upon detection of amplification. Further, a user can select conditions for selecting next processing after termination of the amplification reaction. A user can select, in situ, conditions for terminating the amplification reaction and conditions for selecting next processing upon detection of amplification and after the termination of amplification reaction. Alternatively, conditions for terminating the amplification reaction and conditions for selecting the next processing are registered previously and processing is performed automatically upon detection of amplification and after termination of the amplification reaction.