Multicolor Imaging System for High-Density Sequencing Arrays
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Solution Overview
Problem
Next-generation sequencing methods face challenges in efficiently detecting and analyzing genomic fragments on high-density arrays, particularly due to the complexity of imaging systems required for high-resolution and high-throughput data acquisition.
Innovation Solution
The development of an imaging system that utilizes multiple independent sensor arrays and spatially separate excitation beams to simultaneously detect fluorescent emissions from multiple fluorophores, synchronized with the movement of a sample stage, allowing for rapid and efficient image acquisition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high-density arrays with increased feature density are used, then the quantity of features analyzed increases, but the distance between neighboring features decreases making detection more difficult
Solution Approach 1:
The imaging system divides the detection task into multiple independent sensor arrays, each capturing fluorescent emissions from different spectral regions. This segmentation allows simultaneous detection of multiple fluorophores with distinct emission spectra, effectively resolving the difficulty of detecting closely spaced features by distributing the detection burden across multiple specialized sensors.
Solution Approach 2:
The patent introduces spectral dimensionality by using multiple sensor arrays that detect fluorescent emissions at different wavelengths. This adds a spectral dimension to the spatial detection problem, allowing features to be distinguished not only by their spatial location but also by their emission spectrum, thereby overcoming the limitations imposed by reduced feature spacing.
2Productivity
If multiple fluorophores are detected simultaneously, then the throughput of sequencing increases, but the complexity of the imaging system increases
Solution Approach 1:
The imaging system is segmented into multiple independent sensor arrays, each optimized for detecting specific fluorophores. This modular architecture allows simultaneous detection of multiple fluorophores while maintaining manageable complexity through functional specialization of each sensor array.
Solution Approach 2:
Each sensor array is designed with multi-functionality to detect multiple fluorophores across different spectral ranges. This universal detection capability within each array reduces the total number of arrays needed while maintaining high throughput, thereby balancing productivity gains with system complexity constraints.
3Measurement precision
If high resolution optics with high numerical aperture are used, then the measurement precision improves, but the device complexity and cost increase
Solution Approach 1:
The optical system is segmented into multiple independent imaging paths, each with its own sensor array. This segmentation allows each optical path to be optimized for specific resolution requirements while distributing the overall system complexity across multiple simpler, specialized subsystems rather than requiring one extremely complex high-resolution 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
This approach enables high-speed image acquisition and improved analysis of features on substrates, enhancing the throughput and resolution of sequencing and imaging applications.
Implementation Method 1
the interaction of the first excitation beam with the first fluorophore generates a first fluorescent emission, and the interaction of the second excitation beam with the second fluorophore generates a second fluorescent emission
Implementation Method 2
the first fluorescent emission impinges upon and generates a first charge that travels across the first sensor array, wherein the second fluorescent emission impinges upon and generates a second charge that travels across the second sensor array
Data Source
AI summary
Disclosed herein, inter alia, are methods and systems of image analysis useful for rapidly identifying and/or quantifying features.