Single-Molecule Image Correction via Fourier Offset Alignment

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Solution Overview

Problem

In single-molecule sequencing, the positional drift of molecules in a liquid on a chip causes variations in image positions over time, making it difficult to accurately determine DNA sequences from images taken at different moments.

Innovation Solution

A method involving the acquisition of intensity matrices for each pixel in images, conversion to simplified matrices, performing two-dimensional Fast Fourier Transform (DFT) on these matrices to obtain Fourier matrices, and calculating offsets to correct image positions, allowing for accurate alignment and correction of images taken at different times.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If single-molecule images are taken at different moments to capture DNA sequences, then more sequence information can be acquired, but positional drift of molecules in liquid causes image position variations that reduce measurement precision

Engineering Contradiction:
ImproveDNA sequence informationVSAvoidimage position accuracy
Core Design Contradiction:
Loss of informationVSMeasurement precision

Solution Approach 1:

The patent introduces an intermediary reference molecule (such as a fluorescent bead or known-position molecule) that remains stationary or has predictable movement. By tracking the position of this reference molecule across multiple images, the system can calculate and compensate for positional drift, thereby maintaining measurement precision while capturing DNA sequence information over time.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system implements feedback by continuously monitoring the positions of molecules across sequential images and using this information to adjust and correct positioning errors. The calculated offset from reference molecule positions is fed back into the system to realign subsequent images, ensuring accurate DNA sequence determination despite molecular movement in liquid.

Inventive Principle:
Principle #23Feedback

2Productivity

If images are captured over time to obtain DNA sequence information, then sequencing capability is improved, but the complexity of image processing and correction increases

Engineering Contradiction:
Improvesequencing capabilityVSAvoidimage processing complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-processing images to identify and track reference molecules before performing the main DNA sequence analysis. By establishing reference frames and calculating drift patterns in advance, the system simplifies subsequent image alignment and reduces the computational complexity of the overall processing pipeline.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The image processing is segmented into distinct stages: reference molecule identification, position tracking, offset calculation, and image correction. This segmentation allows each step to be optimized independently and processed efficiently, reducing overall system complexity while maintaining high sequencing productivity.

Inventive Principle:
Principle #1Segmentation

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 effectively corrects for positional drift, enabling precise determination of DNA sequences by aligning images taken at different moments, thereby improving the accuracy of single-molecule sequencing.

Implementation Method 1

performing two-dimensional Fast Fourier Transform (DFT) on these matrices to obtain Fourier matrices

Methodology Applied
Scientific EffectFast Fourier Transform:

Data Source

PatentEP3336797B1Single-molecule image correction method, device and system, and computer-readable storage medium
Publication Date: 2020.07.01 GENEMIND BIOSCIENCES CO LTD
  • EP3336797B1 patent drawingFigure 1~2
  • EP3336797B1 patent drawingFigure 3
  • EP3336797B1 patent drawingFigure 4~5

AI summary

An embodiment of the present disclosure discloses a method and a device of correcting a single-molecule image, the method includes: acquiring the first target simplified matrix corresponding to the first image according to the intensity matrix corresponding to each of pixels in the first image, and acquiring the second target simplified matrix corresponding to the second image according to the intensity matrix corresponding to each of the pixels in the second image; the two-dimensional DFT is performed to the first target simplified matrix and the second target simplified matrix respectively to acquire the first Fourier matrix corresponding to the first target simplified matrix and the second Fourier matrix corresponding to the second target simplified matrix; the method of correcting a single-molecule image acquire the offset of the second image with respect to the first image according to the first Fourier matrix and the second Fourier matrix; and correcting the second image according to the offset. Such method can correct the images of single molecules taken at different moments.