Automated Nucleic Acid Size Selection via Imaging Feedback

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current DNA size-selection technologies are labor-intensive and lack high throughput, necessitating a more efficient method for accurate size selection of nucleic acids.

Innovation Solution

The method involves loading DNA samples into agarose channels with controlled electrophoresis, imaging, and software algorithms to predict the arrival time of target DNA fractions at extraction wells, allowing for automated and synchronized extraction across multiple channels using a robotic system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If manual gel electrophoresis with manual cutting and extraction is used, then DNA size selection can be performed, but the process becomes labor intensive and low throughput

Engineering Contradiction:

ImprovethroughputVSAvoidmanual operation

Core Design Contradiction:

ProductivityVSExtent of automation

Solution Approach 1:

The system enables self-service automation where the electrophoresis apparatus automatically tracks DNA fragment positions via imaging, calculates arrival times at extraction wells, and triggers automated extraction without manual intervention. The software algorithm continuously monitors gel images, predicts when target-size DNA will arrive at extraction wells, and coordinates robotic extraction accordingly.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

Manual mechanical operations (cutting gel, extracting DNA) are replaced with an automated system combining imaging algorithms, computational prediction, and robotic automation. The mechanical extraction process is substituted with an automated pipeline that uses software to determine extraction timing and coordinates robotic systems to perform the extraction.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Extent of automation

If automated extraction is implemented, then labor is reduced, but system complexity increases

Engineering Contradiction:

Improveautomated extractionVSAvoidsystem complexity

Core Design Contradiction:

Extent of automationVSDevice complexity

Solution Approach 1:

The system employs multi-functional integration where a single imaging system serves multiple purposes: visualizing DNA fragments, tracking their migration through the gel, determining fragment sizes, predicting arrival times at extraction wells, and triggering automated extraction. This multi-functionality reduces the need for separate specialized devices for each function.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system implements continuous feedback loops where real-time images of the gel are analyzed by software algorithms that track DNA fragment positions, calculate migration rates, predict arrival times at extraction wells, and dynamically adjust extraction timing. This feedback mechanism enables the system to adapt to variations in electrophoresis conditions and maintain accurate size selection.

Inventive Principle:

Principle #23Feedback

3Measurement precision

If DNA fragments of different sizes are separated by electrophoresis, then size selection is achieved, but adjacent samples running at different speeds require different extraction times

Engineering Contradiction:

Improvesize selection accuracyVSAvoidextraction timing coordination

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The system dynamically adjusts extraction timing for each sample based on its specific migration rate and the predicted arrival time of target-size fragments at the extraction well. Rather than using fixed extraction schedules, the system continuously monitors gel images, calculates real-time migration rates, and dynamically schedules extraction to occur at the optimal moment for each individual sample, accommodating variations in speed and position.

Inventive Principle:

Principle #15Dynamics

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

This approach enables high-throughput, automated size selection of nucleic acids with reduced labor, ensuring accurate extraction of desired DNA fractions while accommodating variations in sample mobility and channel configurations.

Implementation Method 1

moving nucleic acids from a sample along a channel by electrophoresis

Methodology Applied

Scientific EffectElectrophoresis: Electrophoresis

Implementation Method 2

The channel is imaged at regular intervals during this process

Methodology Applied

Scientific EffectOptical imaging: Photography

Data Source

PatentUS9952176B2Automated size selection of nucleic acids

Publication Date: 2018.04.24 BRITISH COLUMBIA CANCER AGENCY BRANCH

AI summary

Apparatus and methods for size selecting nucleic acid molecules having wide range of applications including the production of DNA libraries for sequencing technologies. An automated high throughput system for size selection of multiple nucleic acid samples that uses imaging technique to detect the progress of a target fraction and feedback from the imaging to control electrophoresis. Predictive algorithms for timed nucleic acid extractions are generated to provide size selected nucleic acid molecules of required size ranges.