Electronic Nucleic Acid Sequencing via FET Sensor
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Solution Overview
Problem
Current nucleic acid sequencing technologies face challenges with accuracy and cost, as optical detection methods suffer from photodegradation and high costs, while electronic detection methods are less accurate and expensive, hindering clinical adoption.
Innovation Solution
An electronic sensor system that includes a first electrode, a second electrode, and a conduction channel, with a primed template nucleic acid immobilized and a polymerase bound to a next correct nucleotide in a stabilized ternary complex, preventing covalent incorporation, allowing for accurate detection of nucleotides through signal monitoring.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical detection is used to detect fluorescently labeled nucleotides, then detection accuracy is improved, but photodegradation of reaction components occurs and costs increase
Solution Approach 1:
The patent replaces optical detection methods with electronic detection using field-effect transistors (FETs) to detect electrical signals from charged reaction components. This substitution eliminates the need for high energy light, preventing photodegradation of DNA and fluorescent labels while maintaining detection accuracy through electrical signal measurement.
2Measurement precision
If optical detection platforms are used to achieve high accuracy, then detection precision is improved, but expensive optical components are required
Solution Approach 1:
The patent substitutes complex optical detection systems with simpler electronic FET-based detection. The FETs detect electrical signals from charged nucleotides and reaction components, eliminating the need for expensive lasers, fluorophores, and optical lenses while achieving comparable or superior detection accuracy.
Solution Approach 2:
The patent uses inexpensive electronic components (FETs, electrodes) instead of costly optical components. The detection system relies on naturally occurring electrical charges in DNA and nucleotides, requiring no expensive labels or specialized optics, thereby dramatically reducing system cost.
3Object-generated harmful factors
If electronic detection is used to avoid photodegradation, then harmful factors are reduced, but accuracy decreases and costs increase
Solution Approach 1:
The patent implements electronic detection using FETs that measure electrical signals from charged reaction components. This electronic approach replaces optical detection, avoiding photodegradation while maintaining accuracy through direct electrical signal measurement from the DNA polymerase reaction components.
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 and cost-effective nucleic acid sequencing by avoiding photodegradation and reducing noise, providing single molecule detection and reducing the need for expensive optical components, thus facilitating clinical uptake.
Implementation Method 1
a conduction channel operably connecting the first electrode to the second electrode
Implementation Method 2
a polymerase that is immobilized at the sensor, wherein the polymerase is bound to a primed template nucleic acid and next correct nucleotide in a stabilized ternary complex
Data Source
AI summary
A sensor having a first electrode and a second electrode operably connected by a conduction channel, wherein a polymerase, primed template nucleic acid and nucleotide form a stabilized ternary complex that is immobilized in or on the conduction channel, whereby association and dissociation of the ternary complex is detected due to changes in electrical properties of the sensor. Identification of the nucleotide type that participates in the complex indicates the identity of the next template base in the template. Repeated cycles of extending the primer and detecting stabilized ternary complexes can allow determination of the sequence of nucleotides for the template.