Fiducial Markers for Nucleic Acid Array Alignment
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Solution Overview
Problem
As the density and size of features on nucleic acid arrays increase, accurate detection and alignment become challenging, leading to issues in comparing successive images and determining molecular sequences, which complicates genetic sequencing and increases economic and time costs.
Innovation Solution
Incorporating a fiducial feature with fluorescent material on the array that responds differently at various wavelengths, allowing for distinct signal production in successive cycles of fluorescent imaging, aiding in image registration and data processing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the density of features on the array increases and feature size decreases, then the array can sequence more complex genomes and increase productivity, but accurate detection and alignment become problematic, worsening measurement precision
Solution Approach 1:
The patent introduces fiducial features as intermediary reference elements on the array. These fiducial features with distinct fluorescent properties serve as mediators between the imaging system and the dense biological features, enabling accurate localization and alignment even when biological features become too small and dense to detect reliably on their own.
Solution Approach 2:
The patent utilizes changes in fluorescent emission parameters (wavelength, intensity) of fiducial features in response to different excitation frequencies. By measuring how fiducial features respond to multiple excitation wavelengths, the system can accurately determine their positions and use these positions to align successive images, maintaining measurement precision despite increased feature density.
2Quantity of substance
If the overall size of the array expands to accommodate larger samples, then more complex genomes can be sequenced, but accurate alignment and comparison of successive images becomes more difficult, worsening manufacturing precision
Solution Approach 1:
The patent divides the large array into multiple regions, each containing fiducial features that serve as local reference points. This segmentation allows the imaging and alignment process to be performed independently in each region, maintaining high precision across the entire large array by combining results from multiple smaller, more manageable segments.
Solution Approach 2:
Fiducial features act as intermediary reference markers distributed across the expanded array. These intermediaries provide stable, detectable points that bridge the gap between the imaging system and the biological samples, enabling accurate alignment even as the overall array size increases to accommodate larger genomic samples.
3Productivity
If imaging speed is increased to reduce processing time, then productivity improves, but image quality and detection accuracy may deteriorate, worsening measurement precision
Solution Approach 1:
The patent employs periodic excitation of fiducial features at multiple frequencies to generate characteristic emission responses. By using this periodic action with multiple excitation wavelengths, the system can rapidly identify and locate fiducial features and biological features through their unique fluorescent signatures, maintaining high imaging speed while ensuring accurate detection through the distinctive temporal and spectral patterns.
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 of feature alignment and sequence determination, reducing errors and costs associated with image processing and sequencing by providing a reliable method for registering and processing image data from nucleic acid arrays.
Implementation Method 1
a fiducial feature on the support having a fluorescent material that responds by producing a detectable signal in the successive cycles of fluorescent imaging
Data Source
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 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 an “always on” type that respond to multiple frequencies of radiation used during processing and detection so as to return signals during successive cycles of imaging.