Ordered 3D Probe Structures for Accurate Nanopore DNA Detection
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Solution Overview
Problem
Existing nanopore-based methods for identifying multiple types of DNA sequences suffer from reduced accuracy due to overlapping ionic current changes when probes with different sizes pass through, limiting the number of distinguishable DNA sequences that can be identified with high precision.
Innovation Solution
A probe design featuring a sequence recognition portion with a plurality of 3-dimensional structures arranged downstream, where the order of these structures corresponds one-to-one with the DNA sequence, allowing for accurate identification by analyzing the unique electric current patterns generated as the probe-DNA conjugate passes through a nanopore.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If probes with different sizes are used to identify multiple DNA sequences, then the number of distinguishable DNA sequences increases, but the measurement precision decreases due to overlapping ionic current changes
Solution Approach 1:
The probe is segmented into multiple distinct structural domains (e.g., PNA region, DNA region, PEG region, antibody region) that each contribute to a specific ionic current signature. This segmentation allows multiple DNA sequences to be distinguished simultaneously while maintaining high measurement precision through the unique combined signature of each probe type.
Solution Approach 2:
The invention transitions from using single-parameter detection (overall ionic current blockage) to multi-parameter detection by analyzing the temporal sequence and magnitude of current changes as different probe regions pass through the nanopore. This dimensional expansion in the detection space enables simultaneous identification of multiple DNA sequences without sacrificing precision.
2Adaptability or versatility
If multiple probes with different sizes are introduced, then more DNA sequence types can be detected, but the device complexity increases
Solution Approach 1:
The probe design incorporates universal functional regions (such as the nanopore-translocating backbone and standardized structural domains) that can be combined with different sequence-specific recognition regions. This modular universal design enables detection of multiple DNA sequence types while managing device complexity through standardized components.
Solution Approach 2:
The probe structure employs a nested organization where smaller functional regions (PNA, DNA, PEG sequences) are contained within larger structural frameworks. This nesting allows multiple functional elements to be integrated in a compact, organized manner, enabling complex multi-sequence detection capabilities without proportionally increasing overall device 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
Enables high-accuracy identification and counting of multiple DNA sequences by ensuring distinct electric current signatures for each probe, overcoming the limitations of conventional methods and allowing for the detection of a greater number of sequence types without accuracy loss.
Implementation Method 1
When a detection target substance passes through a nanopore, the detection target substance blocks a part of the nanopore. Thus, electrical resistance increases, and therefore ionic current decreases.
Implementation Method 2
introducing a detection target substance as a target for the measurement in one of the chambers so that the electrodes provided in both the chambers are given a potential difference between the electrodes provided in both the chambers so that the detection target substance is electrophoresed to pass through the nanopores
Data Source
AI summary
The present disclosure proposes a probe including a sequence recognition portion that is capable of specifically binding to a desired DNA sequence, and a first probe portion that includes a plurality of 3-dimensional structures arranged downstream from an end of the sequence recognition portion, in which the plurality of 3-dimensional structures are arranged in an order so that the order corresponds one-to-one with the DNA sequence.