Gene Sequencing Structure Eliminates Fluorescence Labeling

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current gene sequencing technologies, particularly second-generation high-throughput sequencing, require complex optical systems and expensive fluorescence labeling, leading to high costs and prolonged sequencing times, while also being complex in process and costly to manufacture.

Innovation Solution

A gene sequencing structure comprising a first and second electrode, a semiconductor layer, an insulating layer, and a sensitive film layer that generates charges in response to ions from base pairing, eliminating the need for fluorescence labeling and optical systems, and can be fabricated using existing thin film transistor processes, reducing costs and simplifying the sequencing process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple primers are mixed in a reaction system for parallel sequencing, then sequencing efficiency and productivity are improved, but primer-dimer formation increases causing false positives and reducing measurement precision

Engineering Contradiction:
Improvesequencing efficiencyVSAvoiddetection accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by designing primers with differentiated properties: detection primers contain detection sequences while amplification primers contain binding sequences. This local differentiation allows the system to maintain high productivity through parallel sequencing while preventing primer-dimer formation by ensuring that only intended target sequences are amplified and detected, thus resolving the contradiction between sequencing efficiency and detection accuracy

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent introduces detection sequences as an intermediary element that mediates between the amplification process and the detection process. These detection sequences are incorporated into the amplified products but do not participate in the amplification reaction itself, allowing multiple primers to work in parallel without interfering with each other, thereby maintaining both high productivity and measurement precision

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If conventional PCR amplification is used with multiple primers, then amplification efficiency is improved, but primer-dimer formation occurs leading to false positives

Engineering Contradiction:
Improveamplification efficiencyVSAvoidresult accuracy
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies segmentation by dividing the primer structure into distinct functional segments: amplification primers are segmented from detection primers, with each having specific binding sites and functions. This segmentation prevents primer-dimer formation by ensuring that amplification primers only bind to their intended targets and not to detection primers or other amplification primers, thereby maintaining both amplification efficiency and result accuracy

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent inverts the conventional approach by having detection sequences incorporated into the amplified product rather than being separate probes. The detection primers bind to the amplified products and carry the detection sequences, reversing the traditional role assignment and preventing false positives while maintaining amplification efficiency

Inventive Principle:
Principle #13The other way round (Inversion)

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 solution reduces the time and cost of gene sequencing, improves efficiency, and simplifies the sequencing device by eliminating the need for fluorescence labeling and optical systems, while maintaining accurate base pairing detection.

Implementation Method 1

the sensitive film layer generates charges in response to receiving ions generated by base pairing during gene sequencing

Methodology Applied
Scientific EffectIon generation from base pairing: Chemical Bonding

Data Source

PatentEP3656843B1Gene sequencing structure, chip, system and gene sequencing method
Publication Date: 2022.07.06 BOE TECHNOLOGY GROUP CO LTD
  • EP3656843B1 patent drawingFigure 1~2
  • EP3656843B1 patent drawingFigure 3~4
  • EP3656843B1 patent drawingFigure 5A~5B

AI summary

The present disclosure relates to a gene sequencing structure, chip, system, and method. The gene sequencing structure comprises: a first electrode and a second electrode spaced apart from each other, a semiconductor layer, a sensing electrode, an insulating layer, and a sensitive film layer. The first electrode is connected to the second electrode via the semiconductor layer, the sensing electrode is in contact with the sensitive film layer, and the insulating layer isolates each of the sensitive film layer and the sensing electrode from each of the first electrode, the second electrode, and the semiconductor layer, wherein the sensitive film layer generates charges in response to receiving ions generated by base pairing during gene sequencing.