Curved-Substrate Fluorescence Imaging for Accurate Sequencing
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Solution Overview
Problem
Fluorescence-based genomic testing assays face errors due to dense packing of labeled molecules and low contrast-to-noise ratio, leading to incorrect attribution of fluorescence signals.
Innovation Solution
The use of a curved substrate with binding moieties and an optical system that includes a light source, focusing elements, and imaging sensors to probe the presence of analytes, such as nucleic acids, with specific wavelength ranges and configurations to enhance imaging accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If labeled molecules are densely packed on the substrate to increase throughput, then productivity is improved, but measurement precision deteriorates due to detection errors and signal attribution errors
Solution Approach 1:
The patent transitions from 2D planar substrates to 3D curved surfaces (spheres, cylinders, or other curved geometries). This dimensional change allows molecules to be distributed over a larger surface area while maintaining high density, enabling simultaneous imaging of multiple binding sites without excessive crowding in any single region, thus resolving the contradiction between throughput and measurement precision
2Measurement precision
If the optical system uses a flat substrate configuration, then device complexity is reduced, but measurement precision deteriorates due to limited field of view and inability to capture multiple binding sites simultaneously
Solution Approach 1:
The patent employs curved surfaces (spherical, cylindrical, or other curved geometries) instead of flat substrates. This curvature enables a single optical system to capture multiple binding sites simultaneously across a broader field of view, improving imaging resolution and the ability to monitor multiple reactions at once, while the curvature itself serves as the primary structural feature rather than requiring complex optical arrangements
3Measurement precision
If fluorescence imaging is performed with standard optical systems, then ease of operation is maintained, but measurement precision deteriorates due to low contrast-to-noise ratio and detection errors
Solution Approach 1:
The patent utilizes the curved surface geometry to optimize optical parameters including illumination angles, collection angles, and focal points. By configuring the light source and optical system to match the curved substrate geometry, the system enhances fluorescence signal collection efficiency and contrast-to-noise ratio while maintaining operational simplicity through standardized optical components adapted to the curved format
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
Improves imaging accuracy and reduces errors by providing enhanced spatial resolution and contrast, allowing for precise detection of nucleic acid reactions.
Implementation Method 1
In typical fluorescence-based genomic testing assays, e.g., genotyping or nucleic acid sequencing, dye molecules that are attached to nucleic acid molecules tethered on a substrate are excited using an excitation light source, a fluorescence photon signal is generated
Data Source
AI summary
Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the fields-of-view, improved imaging system duty cycle and a more compact system, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications at a lower cost.