Label-Free Optical Sensor for Rapid Nucleic Acid Sequencing
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Solution Overview
Problem
Existing nucleic acid sequencing techniques rely on molecular labeling, which can alter molecular binding kinetics, complicate the process, and require extensive processing steps, leading to increased time and cost.
Innovation Solution
A label-free enzymatic process monitoring system using an array of optical sensors with a fluid flow control module and resonant cavities to detect nucleotide base additions without labels, allowing for real-time monitoring and rapid sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If molecular labeling techniques are used to monitor nucleic acid sequencing, then the sequence can be identified, but the processing time increases and the process becomes more complex
Solution Approach 1:
The patent removes the labeling step entirely from the sequencing process. By using label-free detection with optical sensors that monitor refractive index changes directly at the sensor surface, the method eliminates label attachment, washing, and scanning steps, reducing processing time while maintaining sequence identification capability
Solution Approach 2:
The patent replaces the mechanical/chemical labeling system with an optical detection system. Instead of using physical labels (fluorescent, radioactive, or chemiluminescent molecules) attached to nucleotides, the system uses label-free optical sensing that detects refractive index changes caused by nucleotide incorporation, eliminating the need for labeling machinery and associated processing steps
2Measurement precision
If molecular labeling is used to attach to nucleic acid molecules, then sequencing can be performed, but the device complexity and processing steps increase
Solution Approach 1:
The patent extracts and removes the labeling component from the sequencing system. By implementing label-free detection where optical sensors directly monitor refractive index changes at the sensor surface, the method eliminates label attachment, washing, and scanning steps, significantly reducing device complexity and processing steps while maintaining sequence detection capability
Solution Approach 2:
The optical sensor system performs self-detection without requiring external labels. The sensor surface itself serves as both the binding platform and the detection element, where refractive index changes caused by nucleotide incorporation are detected directly, eliminating the need for separate labeling and detection systems
3Measurement precision
If labels are attached to molecules for monitoring, then the sequence can be identified, but the binding kinetics are altered and accuracy is reduced
Solution Approach 1:
The patent removes labels from the nucleic acid molecules entirely. By using label-free optical detection that monitors refractive index changes at the sensor surface, the method eliminates the disturbing presence of labels that alter binding kinetics, thereby maintaining reliable molecular interactions and accurate sequence identification
Solution Approach 2:
The patent replaces the label-based detection mechanism with a label-free optical sensing mechanism. Instead of using physical labels attached to molecules, the system uses optical fields to detect refractive index changes caused by molecular mass changes during nucleotide incorporation, preserving natural molecular binding kinetics while maintaining detection accuracy
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 reduces processing time significantly, enabling sequencing in seconds or milliseconds per base call, eliminates label-related complications, and provides accurate calibration and high sensitivity for nucleic acid detection.
Implementation Method 1
an optical evanescent field sensor to hold the respective target genetic structure within an evanescent field
Implementation Method 2
The array of label-free optical sensors can measure a shift in a resonant frequency of the resonant cavity
Data Source
Figure 1
Figure 2
Figure 3a
AI summary
A method comprising causing a known sequence of nucleotides to continuously flow by a label-free optical sensor (102) having a surface (103A) functionalized with an unknown species of nucleic acid (104); measuring changes in an output signal of the optical sensor (102) to detect synthesis reactions between the unknown species of nucleic acid and the known sequence of nucleotides; and identifying a sequence of nucleotides in the unknown species of nucleic acid based on the measured changes in the output signal and the known sequence of nucleotides. A device for carrying out the above method.