Nucleic Acid Bead Analysis Using Well Impedance Sensing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing optical methods for analyzing nucleic acid molecules require complex setups and limited field of view, making it difficult to analyze a large number of molecules simultaneously with single-base resolution.
Innovation Solution
A device using electrically conductive wells with varying cross-sections and impedance measurement to track the position of beads, allowing simultaneous analysis of multiple molecules with high precision.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical methods with microscope objectives are used to track bead position, then single-base resolution (1 nanometre) can be achieved, but the field of view is limited and only about 1000 beads can be analyzed simultaneously
Solution Approach 1:
The device divides the analysis system into multiple independent measurement zones, each with its own sensor and electrode configuration. This allows parallel measurement of bead positions across many beads simultaneously while maintaining the required nanometer-scale resolution for single-base detection.
Solution Approach 2:
The patent replaces the optical detection system (microscope objective, light source, camera) with an electrical measurement system using electrodes and impedance sensing. This substitution enables a much larger field of view and simultaneous analysis of up to 10^9 molecules while maintaining the required measurement precision through electrical rather than optical means.
2Measurement precision
If optical diffraction patterns are used to determine bead z-position, then position information can be obtained, but the system requires complex calibration procedures for each bead
Solution Approach 1:
The patent replaces the optical diffraction-based z-position determination with an electrical impedance measurement system. The impedance changes directly reflect bead position relative to the electrode plane, eliminating the need for complex optical calibration procedures while maintaining measurement precision.
Solution Approach 2:
The measurement system automatically adapts to each bead's position through real-time impedance sensing without requiring manual or computational calibration. The electrical field naturally interacts with each bead based on its position, providing self-calibrating measurements across all beads simultaneously.
3Measurement precision
If a 30× microscope objective is used to achieve the required resolution, then single-base resolution is possible, but the field of view is restricted to about 300 by 300 microns
Solution Approach 1:
The patent replaces the limited-field-of-view optical microscope system with an electrical impedance sensing system that can cover a much larger area. The electrode array configuration allows simultaneous monitoring of bead positions across a large surface area while maintaining nanometer-scale measurement precision through the electrical properties of the system.
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 the simultaneous analysis of a large number of nucleic acid molecules with single-base resolution without reducing resolution, improving throughput and reducing computational complexity.
Implementation Method 1
a sensor, adapted to measure an impedance of the well, said impedance depending on a distance between the bead and the surface
Implementation Method 2
an actuator, adapted to cause the bead to move relative to said surface in one direction of motion
Data Source
AI summary
The invention proposes a device for analyzing nucleic acid molecules (M), comprising: —a bead (20), on which one molecule can be anchored at one end, —a surface (520), on which the molecule can be anchored at the other end, —an actuator (30), adapted to cause the bead to move relative to said surface in one direction, —a sensor (50), adapted to measure a distance between the bead and the surface, the device further comprising a well (11), having an axis (X-X) extending along the direction of motion of the bead and a bottom (110) formed by said surface, said well being filled with electrically conductive solution (40), and receiving the bead, the sensor being adapted to measure an impedance of the well, depending on a distance between the bead and the surface, to determine, the distance between the bead and the surface.