Microparticle Alignment via Digital Template Matching for Sequencing

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current image processing techniques for polynucleotide sequencing face challenges in accurately identifying and aligning microparticles across images, especially after chemical reactions, due to changes in position, orientation, and scale, which hinders precise nucleotide sequencing.

Innovation Solution

A method involving the capture of initial and subsequent images of microparticles, where unique subportions are identified and used for pattern matching to align and match microparticles, allowing for determination of nucleotide sequences by analyzing fluorescence patterns across images.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If microparticles are distributed randomly on a substrate for parallel sequencing, then productivity is improved, but measurement precision deteriorates due to difficulty in identifying and aligning individual particles

Engineering Contradiction:

Improveparallel sequencing throughputVSAvoidmicroparticle identification accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent creates a digital template copy of the microparticle arrangement from an initial image. This template is then used to match and identify the same microparticles in subsequent images after chemical reactions, enabling accurate tracking of particle positions despite random distribution

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The system performs preliminary imaging and template creation before chemical reactions occur. By establishing the initial microparticle positions and creating a reference template in advance, the system enables subsequent identification and alignment operations to be performed accurately on the same particles

Inventive Principle:

Principle #10Preliminary action

2Loss of information

If chemical reactions are performed on microparticles to determine nucleotide sequences, then information about nucleotide types is obtained, but microparticle position and orientation change making re-identification difficult

Engineering Contradiction:

Improvenucleotide sequence informationVSAvoidmicroparticle position alignment

Core Design Contradiction:

Loss of informationVSMeasurement precision

Solution Approach 1:

The system uses the template image as a reference feedback mechanism. After chemical reactions alter microparticle positions and orientations, the system compares subsequent images against the original template to re-identify and realign particles, compensating for positional changes caused by the chemical reactions

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

By capturing and storing the initial microparticle arrangement as a template before chemical reactions occur, the system establishes a reference state that enables subsequent alignment and identification operations to correctly associate reaction outcomes with the appropriate particles

Inventive Principle:

Principle #10Preliminary action

3Adaptability or versatility

If image analysis is performed to identify microparticles in random distribution, then sequencing capability is enabled, but image processing complexity increases

Engineering Contradiction:

Improvesequencing capabilityVSAvoidimage processing complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent segments the complex task of microparticle identification into distinct phases: initial template creation, subsequent image capture, template matching, and nucleotide determination. This segmentation simplifies the overall processing complexity by breaking down the adaptive sequencing capability into manageable computational steps

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 enables accurate alignment and identification of microparticles, facilitating precise determination of nucleotide sequences by overcoming positional, orientational, and scaling issues, thus improving the efficiency of polynucleotide sequencing.

Implementation Method 1

the chemical reactions may cause oligonucleotides which have a terminal nucleotide of a certain type to fluoresce or emit light at a specific wavelength or wavelength band

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS9135497B2Identifying randomly distributed microparticles in images to sequence a polynucleotide

Publication Date: 2015.09.15 NATIONAL INSTRUMENTS CORP

AI summary

Performing sequencing of a polynucleotide. A first image of microparticles that are distributed in a random fashion on a substrate may be received. Each of the microparticles may include a plurality of similar oligonucleotides of the polynucleotide. A second image of the microparticles may be received. A plurality of first subportions of the first image may be determined. Each subportion may include a respective plurality of microparticles distributed in a random fashion. The second image may be analyzed to identify a plurality of second subportions in the second image. Each of the plurality of second subportions may correspond to a respective one of the plurality of first subportions. A plurality of the microparticles may be matched from the first and second images based on said analyzing. At least a portion of the sequence of nucleotides of the polynucleotide may be determined based on said matching.