Memory-Efficient Phasing Correction for Nucleic Acid Sequencers
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Solution Overview
Problem
Existing nucleic acid sequencing technologies suffer from phasing artifacts due to synchronization loss among fluorescence signals from multiple nucleic acid molecules within a cluster, leading to noise and reduced signal purity, which conventional methods like empirical phasing correction require significant computational resources.
Innovation Solution
Implement real-time phasing correction methods using processors and memory to adjust fluorescence signals by applying coefficients based on previous and subsequent cycle intensities, reducing memory requirements and improving signal synchronization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If empirical phasing correction methods are used to correct synchronization loss among fluorescence signals, then signal purity is improved, but computational resources and processing time are significantly increased
Solution Approach 1:
The patent applies preliminary phasing correction by using intensity values from immediately preceding and succeeding cycles to correct phasing errors in the current cycle. This preliminary correction approach avoids the need for extensive iterative computational methods while still achieving effective signal purity improvement through proactive use of available cycle data.
Solution Approach 2:
The patent changes the correction parameters by using only intensity values from immediately adjacent cycles (preceding and succeeding) rather than analyzing multiple historical cycles. This parameter simplification reduces computational complexity while maintaining correction effectiveness, directly addressing the trade-off between signal purity and processing time.
2Reliability
If conventional phasing correction methods are applied to ensure accurate base calling, then sequencing accuracy is improved, but memory requirements and device complexity increase
Solution Approach 1:
The patent applies local quality correction by focusing phasing correction only on the immediately preceding and succeeding cycles rather than processing all historical cycle data. This localized approach maintains sequencing accuracy by correcting the most relevant phasing errors while minimizing memory usage and device complexity.
Solution Approach 2:
The patent extracts only the essential correction data needed for phasing correction - specifically intensity values from immediately adjacent cycles - and discards the need to store and process extensive historical sequencing data. This extraction principle reduces memory requirements while preserving sequencing accuracy.
3Stability of the object's composition
If real-time phasing correction is implemented using intensity values from multiple cycles, then signal synchronization is improved, but computational resources are significantly consumed
Solution Approach 1:
The patent applies partial action by using only the minimum necessary cycle data - intensity values from immediately preceding and succeeding cycles - to achieve phasing correction. This partial approach provides sufficient signal synchronization without the excessive computational resource consumption that would result from analyzing all available cycle data.
Data Source
AI summary
Memory efficient methods determine corrected color values from image data acquired by a nucleic acid sequencer during a base calling cycle. Such methods may: (a) obtain an image of a substrate (e.g., a portion of a flow cell) including a plurality of sites where nucleic acid bases are read; (b) measure color values of the plurality of sites from the image of the substrate; (c) store the color values in a processor buffer of the sequencer's one or more processors; (d) retrieve partially phase-corrected color values of the plurality of sites, where the partially phase-corrected color values were stored in the sequencer's memory during an immediately preceding base calling cycle; (e) determine a prephasing correction; and (f) determine the corrected color values. In various implementations, these operations are all performed during a single base calling cycle. In certain embodiments, the methods additionally include using the corrected color values to make base calls for the plurality of sites. Sequencers may be designed or configured to implement such methods.