Nanogap Electrical Sensor for Early Nucleic Acid Detection
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Solution Overview
Problem
Current molecular diagnostic tools relying on nucleic acid amplification technologies are cumbersome and expensive, primarily due to their dependence on optical measurements, necessitating a more cost-effective and efficient detection mechanism.
Innovation Solution
A nanogap-based electrical sensor system utilizing a metal-insulator-metal electrode configuration with redox-tagged nucleotides to detect polynucleotide strands by measuring current changes through tunneling and electrochemical redox processes, allowing for early-stage detection during amplification cycles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical measurement systems are used for nucleic acid detection, then detection accuracy can be achieved, but device complexity and cost increase significantly
Solution Approach 1:
The patent replaces optical measurement systems with an electrical measurement system based on nanogap electrodes. The nanogap electrodes detect nucleic acid amplification through electrical current changes caused by redox reactions of tagged nucleotides, eliminating the need for complex optical components while maintaining detection capability
Solution Approach 2:
The patent changes the detection parameter from optical signals to electrical current signals. By using redox-tagged nucleotides that generate electrical current during incorporation by polymerase, the system transforms the detection mechanism from optical to electrical, simplifying the overall device architecture
2Measurement precision
If optical measurement systems are used for nucleic acid detection, then detection accuracy can be achieved, but cost increases significantly
Solution Approach 1:
The patent replaces expensive optical measurement systems with a simpler electrical measurement system using nanogap electrodes and redox chemistry. This substitution dramatically reduces manufacturing costs while preserving the ability to detect nucleic acid amplification with high precision
Solution Approach 2:
The patent employs a disposable nanogap electrode device that can be manufactured at low cost. The device is designed for single-use or limited-use applications, eliminating the need for expensive, maintenance-intensive optical systems while providing sufficient detection accuracy for diagnostic purposes
3Reliability
If traditional detection methods are used, then reliable detection can be achieved, but detection time increases
Solution Approach 1:
The patent enables continuous monitoring of nucleic acid amplification in real-time through electrical current measurement. The nanogap electrodes continuously detect the incorporation of redox-tagged nucleotides during PCR amplification, allowing for rapid detection without waiting for endpoint analysis, thus reducing detection time while maintaining reliability
Solution Approach 2:
The replacement of optical detection with electrical detection using nanogap electrodes enables faster signal generation and processing. Electrical current changes can be detected and processed more rapidly than optical signals, contributing to reduced detection time while maintaining reliable identification of amplification events
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
Facilitates rapid, sensitive, and cost-effective detection of nucleic acids in patient samples, reducing detection time and enabling point-of-care applications with high throughput and accuracy.
Implementation Method 1
Nanogap-based electrical measurement of current via tunneling
Implementation Method 2
the electrochemical redox process
Data Source
AI summary
Systems and methods to detect a polynucleotide strand in a sample during the early stage of amplification cycles. A metal-insulator-metal (MIM) electrode unit with two metal electrodes separated by a dielectric layer may be utilized as a nanogap sensor. Primers for amplifying a target polynucleotide strand may be immobilized on the surface of the dielectric layer. Polymerases, nucleotides, templates and primers may be added to the sample. At least one type of nucleotide may be labeled with a redox label that may enhance electron transport through the nanogap via tunneling and/or diffusion-based redox cycles. Signals (e.g., voltage pulses) may be directed through each of the electrodes. Current values from each electrode may be measured to establish a baseline signal. Alterations in the baseline signal may indicate the presence of target polynucleotide strands. The time to detect an alteration in the baseline signal may facilitate quantification of target polynucleotide strands.