Polymerase Charge Sensor Sequencing
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Solution Overview
Problem
Current nucleic acid sequencing technologies are costly and complex, hindering their use in clinical and research settings, and there is a need for more cost-effective, rapid, and convenient methods.
Innovation Solution
A method involving a polymerase attached to a solid support charge sensor that differentiates nucleotide triphosphates by unique signal patterns, allowing for the determination of nucleic acid sequences through the incorporation of nucleotides into a nascent strand against a template, using mixtures with distinguishable nucleotide triphosphates to produce distinct signals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If sequencing-by-synthesis is used with template DNA and nucleotide monomers, then DNA sequencing can be performed, but the hardware cost and system complexity increase significantly
Solution Approach 1:
The patent extracts and eliminates the need for complex sequencing-by-synthesis hardware (lasers, detection optics, fluid delivery systems) by using a simplified polymerase-based detection method where the polymerase itself serves as the detection mechanism through its interaction with nucleotide triphosphates having different impedances
Solution Approach 2:
The patent replaces expensive, complex hardware with a more economical approach using polymerase enzymes and simplified detection reagents that can be easily replaced or discarded, reducing the overall system cost and complexity while maintaining sequencing capability
2Reliability
If expensive reagents and hardware are used for DNA amplification and sequencing, then sequencing can be performed, but the cost effectiveness decreases
Solution Approach 1:
The patent employs disposable or easily replaceable components including polymerase enzymes, nucleotide triphosphates with impedance labels, and simplified detection reagents, eliminating the need for expensive, complex amplification hardware and reagents while maintaining reliable sequencing results
Solution Approach 2:
The patent changes the detection parameter from optical signals requiring lasers and optics to electrical impedance signals that can be detected by simpler electronics, reducing hardware costs while maintaining detection reliability through the use of nucleotide triphosphates with different impedance characteristics
3Measurement precision
If complex fluid delivery systems and detection optics are used, then nucleotide incorporation can be monitored, but the system becomes less convenient and faster
Solution Approach 1:
The patent replaces complex mechanical fluid delivery systems and optical detection mechanisms with a simpler enzymatic reaction-based system where polymerase incorporation of nucleotide triphosphates is detected through electrical impedance changes, enabling faster and more convenient sequencing operations
Solution Approach 2:
The patent employs periodic cycles of nucleotide triphosphate addition and polymerase incorporation reactions, allowing for rapid sequential sequencing without requiring complex continuous fluid delivery systems, thereby increasing productivity while maintaining detection precision
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 long nucleic acid sequencing reads, high-throughput capability, and a scalable platform for sequencing, providing accurate and efficient DNA sequencing while reducing costs and complexity.
Implementation Method 1
detecting the incorporation of the nucleotides via the charge sensor, wherein the first type of the nucleotide triphosphates produces a signal that is unique compared to signals produced by other nucleotide triphosphates in the mixture
Data Source
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AI summary
The present disclosure provides a method for sequencing nucleic acids. The method can include polymerase catalyzed incorporation of nucleotides into a nascent nucleic acid strand against a nucleic acid template, wherein the polymerase is attached to a charge sensor that detects nucleotide incorporation events. One or more non-natural nucleotide types that each produce a unique signatures at the charge sensor can be used to uniquely identify different nucleotides in the template nucleic acid.