Biological Nanopore Detection Using Guide Polymers for Trace Targets
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Solution Overview
Problem
Existing polymer sequencing technologies are slow and expensive due to reliance on amplification techniques and require high quantities of fluorescent chemicals for signal detection.
Innovation Solution
Utilizing biological pores in combination with guide polymers and polymer-guided effector proteins, such as RNA-guided effector proteins, to detect target polymers through electrical measurements, eliminating the need for separate separation steps and enabling rapid detection of trace amounts directly from crude samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If amplification techniques and fluorescent chemicals are used for polymer detection, then detection sensitivity is improved, but detection time and cost increase
Solution Approach 1:
The patent replaces chemical detection methods (amplification and fluorescent chemicals) with a physical detection method using biological nanopores that detect polymers through ionic current changes. This substitution eliminates the need for time-consuming amplification steps and expensive fluorescent reagents while maintaining detection sensitivity, directly resolving the contradiction between detection sensitivity and detection time
Solution Approach 2:
The patent introduces a biological pore as an intermediary detector that transduces polymer presence into electrical signals. The pore acts as a mediator between the target polymer and the detection system, enabling direct detection without amplification or fluorescent labeling, thus reducing both time and cost while preserving sensitivity
2Quantity of substance
If amplification techniques are used to produce large volumes of polynucleotide, then signal strength is improved, but process complexity and cost increase
Solution Approach 1:
The patent replaces the complex chemical amplification process with a direct physical detection approach using biological nanopores. The system detects polymers in their native state without requiring volume amplification, thereby eliminating the associated process complexity and cost while maintaining sufficient signal strength through the pore's sensitive ionic current measurement
3Measurement precision
If separate separation steps are performed to extract target polymer, then measurement precision is improved, but productivity decreases
Solution Approach 1:
The patent merges the detection function into a single integrated step using biological nanopores that can directly analyze polymers in crude samples without prior separation or purification. The nanopore system inherently discriminates target polymers from background material through selective current blockage patterns, achieving both high measurement precision and high productivity by eliminating separate separation steps
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
The method allows for rapid and sensitive detection of target polymers without complex enrichment steps, reducing time and cost, and enabling sequencing of specific regions of interest, such as V(D)J regions in T-cells, with improved sensitivity and efficiency.
Implementation Method 1
When a potential is applied across a nanopore, there is a change in the current flow when an analyte, such as a nucleotide, resides transiently in the barrel for a certain period of time. Nanopore detection of the nucleotide gives a current change of known signature and duration.
Implementation Method 2
When a potential is applied across a nanopore, there is a change in the current flow when an analyte, such as a nucleotide, resides transiently in the barrel
Data Source
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AI summary
The invention relates generally to a method of detecting and/or analysing target polymers, especially target polynucleotides, using a biological pore. The invention also relates to a novel system for carrying out the method. The method has many uses. In particular, the method may be used for diagnosis, detection of polymorphisms and V(D)J repertoire analysis.