Electrical Sequencing Bridge Polymerase Nucleotide Detection
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Solution Overview
Problem
Current sequencing technologies, such as those using 'sequencing by synthesis' and fluorescence-based detection, are complex, time-consuming, and costly due to the requirement of optical components like excitation light sources and imaging devices.
Innovation Solution
The method involves altering electrical characteristics of bridges between electrodes using polymer chains and nucleotide labels, allowing for the detection of nucleotide additions through changes in electrical signals, eliminating the need for optical components by using a polymerase to add nucleotides to a polynucleotide, with labels altering the electrical conductivity or impedance of the bridge.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescence-based detection is used for sequencing, then sequencing accuracy can be achieved, but device complexity and cost increase due to optical components
Solution Approach 1:
The patent replaces the optical detection system with an electrical detection system. Instead of using fluorescence excitation and imaging, the invention uses labels that alter electrical characteristics (conductivity, impedance, capacitance) of polymer bridges, which are then detected by electrical circuits. This substitution eliminates complex optical components while maintaining detection capability for sequencing accuracy.
Solution Approach 2:
The invention changes the detection parameter from optical (fluorescence intensity) to electrical (conductivity, impedance, or capacitance changes). By using labels that modify electrical properties of the polymer bridge rather than emitting light, the system achieves sequencing detection through electrical signal changes, thereby reducing optical complexity while preserving measurement precision.
2Productivity
If fluorescence-based sequencing is used, then polynucleotide sequencing can be performed, but time consumption increases due to optical detection processes
Solution Approach 1:
The replacement of optical detection with electrical detection accelerates the sequencing process. Electrical signal detection occurs more rapidly than optical imaging processes, eliminating time-consuming steps associated with light source activation, fluorescence emission waiting, and image capture. This substitution directly improves sequencing throughput by reducing detection time.
3Measurement precision
If optical components are used for sequencing detection, then nucleotide addition can be detected, but cost increases due to expensive optical systems
Solution Approach 1:
The patent substitutes expensive optical detection systems with more affordable electrical detection circuits. The electrical components required to measure conductivity, impedance, or capacitance changes in polymer bridges are significantly less costly than optical systems requiring precision light sources, filters, and imaging devices. This substitution maintains nucleotide detection capability while reducing overall system cost.
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, real-time sequencing of polynucleotides with high throughput and sensitivity, capable of detecting single molecules without the need for optical detection systems, thus reducing complexity and cost.
Implementation Method 1
a polymerase to add nucleotides of the plurality of nucleotides to the first polynucleotide using at least a sequence of the second polynucleotide
Implementation Method 2
The labels corresponding to those nucleotides respectively may alter an electrical characteristic of at least one of the first and second polymer chains
Implementation Method 3
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
Data Source
AI summary
Provided herein are compositions and methods for sequencing using at least altering electrical characteristics of polymer bridges. In some examples, the bridges may span the space between first and second electrodes and may include first and second polymer chains that are hybridized to one another. A plurality of nucleotides may be coupled to corresponding labels. A polymerase may be coupled to the bridge and may add nucleotides to a first polynucleotide using at least a sequence of a second polynucleotide. The labels corresponding to those nucleotides respectively may alter hybridization between the first and second polymer chains. 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 alterations of hybridization using the labels corresponding to those nucleotides.