Surrogate Polymer Sequencing via Dimensional Expansion
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Solution Overview
Problem
Current DNA sequencing technologies face challenges in achieving high throughput, cost-effectiveness, and quality, particularly in whole genome sequencing for personalized medicine, due to limitations in read length, signal noise, and spatial resolution.
Innovation Solution
The development of surrogate polymers, such as Xpandomers and S-Xpandomers, which encode base sequence information through template-directed synthesis, allowing for extended length and improved detection by increasing the linear separation of sequence data, thereby enhancing spatial resolution and signal strength.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional DNA sequencing methods (Sanger, 454, Illumina) are used, then sequencing can be performed with current technology, but read length is limited and signal-to-noise ratio deteriorates
Solution Approach 1:
The patent transforms the compact DNA sequence into an expanded surrogate polymer structure by adding spatial dimensions through tether extensions. Each nucleotide is represented by a tether of adjustable length, creating a three-dimensional expanded structure that increases the physical distance between adjacent nucleotides from angstroms to nanometers, thereby improving spatial resolution for detection
Solution Approach 2:
The patent introduces surrogate polymers as intermediary structures between the DNA template and the detection system. These surrogates act as mediators that convert the compact genetic information into an expanded format with improved spatial separation, allowing detection systems to resolve individual nucleotides more effectively without directly interacting with the original DNA structure
2Area of stationary object
If DNA sequencing is performed with compact structure, then space is efficiently used, but signal detection quality deteriorates due to insufficient spatial separation
Solution Approach 1:
The patent adds spatial dimensions to the detection process by expanding the DNA sequence into a three-dimensional surrogate polymer structure. The tethers extend in space, creating a detection area that is orders of magnitude larger than the original compact DNA, while maintaining the sequence information. This dimensional expansion directly improves signal-to-noise ratio by increasing the physical separation between signal-generating elements
Solution Approach 2:
The patent creates composite surrogate polymer structures that combine the genetic information-carrying component with detection-optimized components. The surrogate polymer comprises nucleotide-like units with extended tethers that may include fluorescent labels or other detection moieties, creating a composite material that simultaneously preserves genetic information and enhances detectability through improved spatial separation
3Measurement precision
If surrogate polymers with extended tethers are used, then spatial resolution and signal strength improve, but molecular weight and structure complexity increase
Solution Approach 1:
The patent segments the surrogate polymer into repeating modular units, each representing a nucleotide with its associated tether. This segmentation allows the complex structure to be built from standardized, interchangeable components, making the complexity manageable and systematic. Each module follows the same structural pattern, reducing the cognitive load of understanding the overall complex structure
Solution Approach 2:
The patent employs parameter changes by allowing the tether length to be varied within a defined range (e.g., 5-50 nanometers) to optimize spatial resolution for different detection applications. This parameter adjustment capability enables tuning of the surrogate polymer's physical properties without changing its fundamental modular structure, managing complexity through controllable variation rather than structural diversity
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 high-fidelity sequencing with read lengths greater than 100 bases, reducing post-processing costs and improving signal-to-noise ratios, facilitating low-cost, high-throughput DNA sequencing.
Implementation Method 1
providing an electric potential to the first and second electrodes, wherein the electric potential is sufficient to translocate the at least one analyte and the at least one indicator moiety through the at least one nanopore channel
Implementation Method 2
detecting a change in an optical signal emitted from the at least one indicator moiety at or near the at least one nanopore channel as the at least one analyte translocates through the at least one nanopore channel
Data Source
Figure 1A~1B
Figure 2A~2D
Figure 3A
AI summary
Nucleic acid sequencing methods and related products and methods for detection and presentation of the same are disclosed. Methods for sequencing a target nucleic acid comprise providing a daughter strand produced by a template-directed synthesis, the daughter strand comprising a plurality of subunits coupled in a sequence corresponding to contiguous nucleotide sequence of all or a portion of the target nucleic acid.