Charge Sensor Nucleotide Detection in High-Salt Sequencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing nucleic acid sequencing technologies face challenges in efficiently detecting and identifying nucleotides at biologically relevant concentrations due to high salt interference, which affects the sensitivity and accuracy of detection methods.
Innovation Solution
A sensing system utilizing a charged moiety attached to an electrically conductive channel in a charge sensor that undergoes conformational changes upon binding with target labels, generating distinct detectable signals even in the presence of high salt concentrations, allowing for single molecule detection and nucleotide identification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional optical or electronic detection systems are used for nucleotide detection, then detection can be performed, but sensitivity and accuracy deteriorate due to high salt interference at biologically relevant concentrations
Solution Approach 1:
The patent replaces optical and electronic detection systems with a mechanical/conformational sensing mechanism. The charged molecule undergoes conformational changes upon nucleotide binding, which mechanically opens or closes an ion channel, generating detectable electrical signals that are insensitive to salt interference. This substitution of detection modality resolves the contradiction by using a mechanism unaffected by the harmful salt environment.
Solution Approach 2:
The patent introduces a charged molecule as an intermediary between the nucleotide target and the detection system. This intermediary undergoes conformational changes that translate molecular binding events into detectable electrical signals through ion channel modulation. The intermediary mechanism provides salt-resistant signal transduction, resolving the detection accuracy problem in high salt conditions.
2Reliability
If high salt concentrations are present in the detection environment, then biologically relevant conditions are maintained, but detection sensitivity deteriorates due to shielding effects
Solution Approach 1:
The patent replaces salt-sensitive optical/electronic detection with a mechanical ion channel gating mechanism. The conformational changes in the charged molecule directly gate the ion channel, producing electrical signals that bypass the Debye screening effects of high salt. This allows maintenance of biologically relevant salt concentrations while preserving detection sensitivity.
Solution Approach 2:
The patent changes the detection parameter from optical/electronic signals that are screened by salt to electrical currents through ion channels that are insensitive to salt shielding. By measuring ion flux rather than optical properties, the system maintains sensitivity in high salt environments while preserving biological relevance.
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 system enables accurate nucleotide identification by leveraging conformational changes and binding kinetics, providing unique fingerprint signals for precise nucleotide detection even in high salt environments, enhancing the sensitivity and specificity of nucleic acid sequencing.
Implementation Method 1
the charged molecule is capable of undergoing reversible binding with a target label... As a result of the target label binding to the charge moiety, the bound charged molecule undergoes a conformation change that alters the spatial distribution of the charges
Implementation Method 2
the conformation change that alters the spatial distribution of the charges... the charge sensor responds to the newly presented charges and produces a detectable signal
Implementation Method 3
A charged moiety attached to an electrically conductive channel in a charge sensor... generating distinct detectable signals
Data Source
Figure 1A~3A
Figure 3B~3D3E
Figure 4
AI summary
A sensing system includes a charge sensor including two electrodes and an electrically conductive channel connecting the two electrodes. The sensing system also includes a charged molecule attached to the electrically conductive channel. The charged molecule includes a recognition site to reversibly bind a label of a labeled nucleotide; has an unbound favored conformation associated with an unbound charge configuration; and has a favored conformation associated with a charge configuration when the recognition site is bound to the label. The charge configuration is different from the unbound charge configuration. The sensing system further includes a polymerase attached to the electrically conductive channel or to the charged molecule.