Polymer Bridge Electronic Sequencing via Conductivity Modulation
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Solution Overview
Problem
Current sequencing technologies, such as those using fluorescence-based detection, are complex, time-consuming, and costly due to the need for optical components, which can limit their efficiency and scalability.
Innovation Solution
The use of partially double-stranded polymer bridges with universal monomers and stabilization regions to detect nucleotide additions through changes in electrical signals, allowing for electronic sequencing without the need for optical components.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescence-based detection is used for sequencing, then detection capability is achieved, but device complexity and cost increase due to optical components
Solution Approach 1:
The patent replaces the optical detection system (fluorescence-based) with an electrical detection system. Specifically, it uses electron tunneling current measurements through DNA polymerases to detect nucleotide incorporation, substituting optical components with electrical measurement apparatus. This maintains detection capability while eliminating complex optical systems including excitation light sources, imaging devices, and associated infrastructure.
2Measurement precision
If fluorescence-based detection is used for sequencing, then detection capability is achieved, but time consumption increases
Solution Approach 1:
The electrical detection method using electron tunneling current provides real-time detection of nucleotide incorporation without the time delays inherent in fluorescence-based methods. The continuous electrical measurement allows for immediate detection of incorporation events, eliminating the need for repeated imaging cycles and reducing overall sequencing time.
3Measurement precision
If fluorescence-based detection is used for sequencing, then detection capability is achieved, but cost increases
Solution Approach 1:
The patent substitutes expensive optical components and infrastructure with relatively simple electrical measurement systems. The use of standard electrical measurement apparatus, microelectrode arrays, and computer-controlled potentiostats eliminates the need for costly optical microscopes, lasers, and imaging systems, significantly reducing both equipment and operational costs.
4Productivity
If polymer bridges with gap regions are used, then electronic sequencing is enabled, but manufacturing complexity increases
Solution Approach 1:
The polymer bridges with gap regions are pre-synthesized and prepared before the sequencing reaction. The gap regions are designed in advance with specific sequences that complement the template DNA, and the bridges are pre-assembled with polymerases attached. This preliminary preparation simplifies the actual sequencing process, allowing for high-throughput parallel processing without increasing operational complexity.
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 robust, reproducible, and high-throughput sequencing by modulating electrical conductivity or impedance in response to nucleotide hybridizations, providing a more efficient and cost-effective method compared to traditional fluorescence-based detection.
Implementation Method 1
The labels corresponding to those nucleotides respectively may hybridize to a portion of the bridge that is not double-stranded
Implementation Method 2
Detection circuitry may detect a sequence in which the polymerase adds the nucleotides to the first polynucleotide using at least changes in an electrical signal, for example current or voltage, through the bridge, the changes being responsive to the respective hybridizations
Data Source
AI summary
Provided herein are compositions and methods for electronically sequencing polynucleotides using partially double-stranded polymer bridges. The bridges may span the space between first and second electrodes. A plurality of nucleotides may be coupled to corresponding labels. A polymerase may add nucleotides to a first polynucleotide using at least a sequence of a second polynucleotide. The labels corresponding to those nucleotides respectively may hybridize to a portion of the bridge that is not double-stranded. Detection circuitry may detect a sequence in which the polymerase adds the nucleotides to the first polynucleotide using at least changes in an electrical signal through the bridge, the changes being responsive to the respective hybridizations between the non-double stranded portion of the bridge and the labels corresponding to those nucleotides.