Electrode-Particle Bridge Sequencing for Single-Molecule Long Reads
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Solution Overview
Problem
Existing sequencing technologies, such as those using fluorescence-based detection, are complex, costly, and limited to short reads of DNA segments, necessitating the development of methods for long-read sequencing of single DNA molecules.
Innovation Solution
Devices and methods utilizing particle-based bridges between electrodes, where particles are coupled to electrodes via bonds, forming conductive or non-conductive bridges, and using labels to alter current changes for sequencing polynucleotides based on distinct electrical signals of each base.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If fluorescence-based detection is used for sequencing, then sequencing can be performed, but the system becomes complex, time-consuming, and costly with multiple optical components
Solution Approach 1:
The patent replaces the optical detection system (fluorescence-based) with an electrical detection system. Instead of using excitation light sources, imaging devices, and optical components to detect nucleotide incorporation, the invention uses electrical signals and conductive particles to detect the same process electronically, thereby eliminating complex optical machinery while maintaining sequencing capability
Solution Approach 2:
The patent introduces conductive particles as intermediary elements that bridge the gap between the biochemical sequencing process and electrical detection. These particles couple to electrodes and polymerases, translating the molecular events of nucleotide incorporation into measurable electrical signals, thus enabling electronic detection without direct optical interaction
2Reliability
If fluorescence-based detection is used, then sequencing can be performed, but it is time-consuming to operate
Solution Approach 1:
The patent substitutes the time-consuming optical imaging process with rapid electrical signal detection. Electrical measurements can be performed much faster than optical imaging sequences, allowing for quicker detection of nucleotide incorporation events and reducing overall sequencing operation time
3Reliability
If fluorescence-based detection is used, then sequencing can be performed, but it is costly due to expensive optical components
Solution Approach 1:
The patent replaces expensive optical components (excitation light sources, imaging devices) with more economical electrical detection components. Electrical signals and conductive particles can be implemented with simpler, less costly hardware than the optical systems required for fluorescence detection, thereby reducing overall system cost
Solution Approach 2:
The patent employs disposable or easily replaceable conductive particles that can be quickly synthesized and exchanged, eliminating the need for expensive, complex, and difficult-to-replace optical components. This approach reduces both capital expenditure and operational costs
4Reliability
If traditional sequencing strategies are used, then sequencing can be performed, but they are limited to short reads of ensemble clusters of DNA segments
Solution Approach 1:
The patent segments the DNA sequencing process into individual molecule analysis rather than ensemble clustering. By using single-molecule detection with conductive particles coupled to individual DNA molecules, the system can read entire sequences without the length limitations imposed by ensemble methods, enabling long reads of single DNA molecules
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
Enables robust, reproducible, and high-throughput sequencing of polynucleotides with single-molecule sensitivity by detecting transient changes in electrical conductivity during nucleotide incorporation, overcoming the limitations of existing fluorescence-based methods.
Implementation Method 1
the particle forms at least part of an electrically conductive bridge between the first and second electrodes
Implementation Method 2
The polymerase may be coupled to the particle
Implementation Method 3
The particle may be coupled to the first electrode via a plurality of bonds, and coupled to the second electrode via a plurality of bonds
Data Source
AI summary
In some examples, a device includes first and second electrodes separated from one another by a space; a particle coupled to the first electrode via a first plurality of bonds, and coupled to the second electrode via a second plurality of bonds; and a polymerase coupled to the particle. In some examples, a composition includes first and second electrodes separated from one another by a space; a fluid including a first electrically conductive label having a length at least as long as a length of the space; and detection circuitry to generate a first signal responsive to transient formation, using the first electrically conductive label, of a first electrically conductive bridge between the first and second electrodes.