Redox-Active Charge Tag for Single-Molecule Sequencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current nucleic acid sequencing methods face challenges in achieving single-molecule detection sensitivity and efficient differentiation of nucleotides due to limitations in detecting charge state alterations in real-time during sequencing reactions.
Innovation Solution
Development of labeled nucleotides with a redox-active charge tag attached to a phosphate group, which undergoes oxidation or reduction when in proximity to an electrically conductive channel, allowing for charge state alteration detection and subsequent identification of nucleotides through a redox reaction, enabling precise sequencing cycles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional nucleic acid sequencing methods are used, then sequencing can be performed, but single-molecule detection sensitivity and efficient nucleotide differentiation are not achieved
Solution Approach 1:
The invention changes the charge state parameter of the nucleotide label through redox reactions. The redox-active charge tag undergoes oxidation or reduction when in proximity to the electrically conductive channel, altering its charge state from neutral to charged (or vice versa). This parameter change enables detection of single nucleotide incorporation events with high sensitivity, as each incorporation event produces a detectable charge state change signal.
Solution Approach 2:
The invention introduces a redox-active charge tag as an intermediary between the nucleotide and the detection system. This charge tag serves as a mediator that translates the biochemical nucleotide incorporation event into an electrical signal that can be detected by the electrically conductive channel, thereby enabling single-molecule detection without requiring direct detection of the nucleotide itself.
2Productivity
If charge state alterations are detected in real-time, then nucleotide identification efficiency is improved, but detection sensitivity and precision are compromised
Solution Approach 1:
The invention applies preliminary action by pre-attaching redox-active charge tags to nucleotides before the sequencing reaction. These charge tags are positioned on the nucleotides in advance, ready to undergo redox reactions upon incorporation. This preliminary preparation enables immediate detection of charge state changes upon nucleotide incorporation, improving both the speed and precision of nucleotide identification without requiring complex post-reaction analysis.
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 single-molecule sensitivity and efficient nucleotide identification, facilitating accurate nucleic acid sequencing by leveraging the charge state changes induced by the redox reaction, thereby improving sequencing precision and efficiency.
Implementation Method 1
a redox-active charge tag attached to the linking molecule, the redox-active charge tag to be oxidized or reduced by an electrically conductive channel when maintained in proximity of a sensing zone of the electrically conductive channel
Data Source
AI summary
A labeled nucleotide includes a nucleotide, a linking molecule attached to a phosphate group of the nucleotide, and a redox-active charge tag attached to the linking molecule. The redox-active charge tag is to be oxidized or reduced by an electrically conductive channel when maintained in proximity of a sensing zone of the electrically conductive channel.