Non-rectilinear Fiducial Layouts for Nucleic Acid Array Registration
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Solution Overview
Problem
As the density and size of features on nucleic acid arrays increase, accurate detection and alignment of sites become problematic, leading to challenges in identifying molecular sequences and increasing economic and time costs in detection and image processing.
Innovation Solution
The use of a non-rectilinear layout with fiducial features that are responsive to different wavelengths of light, allowing for precise registration and encoding of image data across successive cycles of fluorescent imaging, enabling accurate localization and sequencing of biological samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the density of features in the arrays increases and the size of features decreases, then the information capacity and analysis capability improve, but accurate detection and alignment of sites become problematic
Solution Approach 1:
The patent introduces fiducial features as intermediary reference markers that are not part of the actual sample features but serve as mediators for alignment and registration. These fiducial features provide stable reference points that enable accurate detection and alignment of the high-density sample features, resolving the contradiction between increased feature density and maintained measurement precision
Solution Approach 2:
The patent changes the spatial arrangement parameter of fiducial features from conventional rectilinear layouts to non-rectilinear layouts. This parameter change optimizes the distribution and visibility of reference markers across the array, improving alignment accuracy and reducing registration errors when dealing with high-density feature arrays
2Area of stationary object
If the overall size of the arrays expand to accommodate larger samples, then the sequencing capacity increases, but accurate detection and alignment become more problematic
Solution Approach 1:
The patent segments the large array into multiple regions with fiducial features distributed throughout. This segmentation approach allows each region to be independently registered and aligned using local fiducial references, maintaining detection accuracy across the entire expanded array area by breaking it into manageable segments
Solution Approach 2:
The patent transitions from one-dimensional or simple two-dimensional rectilinear fiducial arrangements to complex non-rectilinear two-dimensional layouts. This dimensional optimization ensures fiducial features are strategically positioned to provide comprehensive coverage and reference points across the expanded array area, maintaining alignment precision throughout the entire surface
3Quantity of substance
If the number and density of sites on the arrays increase, then the sequencing capability improves, but challenges include the ability to accurately locate and align sites in successive cycles
Solution Approach 1:
The fiducial features serve as stable intermediary reference markers that remain constant across successive imaging cycles. These intermediaries enable consistent localization and alignment of the high-density sites by providing invariant reference points that can be used to register images from different cycles, ensuring reliable alignment despite the increased number of sites
Solution Approach 2:
The fiducial features are pre-positioned on the array before sample loading and imaging. This preliminary placement of reference markers allows for consistent alignment and registration across all successive cycles, establishing a stable coordinate system that facilitates accurate location of sites throughout multiple imaging operations
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 enhances the accuracy and efficiency of nucleic acid sequencing by improving the registration of images and reducing errors in sequence analysis, thereby reducing costs and processing time.
Implementation Method 1
the fluorescent material of the fiducial features is responsive to both of the at least two different wavelengths
Data Source
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AI summary
Fiducial markers are provided on patterned arrays of the type that may be used for molecular analysis, such as sequencing. The fiducials may have configurations and layouts that that enhance their detection in image or detection data, that facilitate or improve processing, that provide encoding of useful information, and so forth. Examples of the fiducials may include non-rectilinear layouts that may provide for more robust location of both the fiducials and sites of the array.