Equalizer-Based Image Correction for Spatial Crosstalk in Base Calling

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Solution Overview

Problem

Existing DNA sequencing systems face challenges in accurately distinguishing true light signals from adjacent wells due to spatial crosstalk, leading to sequencing errors and reduced base calling accuracy.

Innovation Solution

Implementing equalizer-based image processing techniques to generate lookup tables that attenuate spatial crosstalk from sensor pixels, using least squares estimation to maximize signal-to-noise ratio and correct cluster intensity data.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If spatial crosstalk attenuation is implemented using equalizer-based image processing, then base calling accuracy is improved, but device complexity increases

Engineering Contradiction:
Improvebase calling accuracyVSAvoidimage processing complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The equalizer coefficients are pre-calculated and stored in lookup tables before actual base calling operations. During sequencing, the system simply retrieves and applies these pre-computed coefficients to attenuate spatial crosstalk, rather than performing complex real-time calculations. This preliminary preparation resolves the contradiction by enabling high measurement precision through sophisticated processing while keeping the actual device operation relatively simple.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses lookup tables that contain pre-computed equalizer coefficients for different spatial positions and crosstalk conditions. Instead of performing complex iterative optimization during base calling, the system copies and applies appropriate coefficients from these lookup tables based on the specific imaging conditions. This copying approach maintains high base calling accuracy while significantly reducing the computational complexity required during actual sequencing operations.

Inventive Principle:
Principle #26Copying

2Productivity

If equalizer coefficients are pre-calculated and stored in lookup tables, then computational efficiency is maintained, but memory requirements increase

Engineering Contradiction:
Improvecomputational efficiencyVSAvoidmemory storage requirements
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The lookup tables store equalizer coefficients that are pre-calculated for specific parameter ranges including spatial position, crosstalk intensity, and signal-to-noise ratio conditions. During operation, the system changes parameters dynamically by selecting appropriate pre-calculated coefficients based on current imaging conditions, rather than performing full recalculations. This parameter-based selection maintains computational efficiency while the memory requirement is managed by only storing coefficients for representative parameter combinations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements a hybrid approach where equalizer coefficients are pre-calculated for common or representative conditions and stored in lookup tables, while allowing for partial recalculation or adjustment when novel conditions are encountered. This partial pre-computation strategy balances memory requirements against computational efficiency, storing only the most frequently needed coefficients while maintaining the ability to adapt to new conditions through selective recalculation.

Inventive Principle:
Principle #16Partial or excessive action

3Reliability

If spatial crosstalk is attenuated using lookup tables, then sequencing error rate is reduced, but processing time increases

Engineering Contradiction:
Improvesequencing accuracyVSAvoidprocessing time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The equalizer coefficients are pre-calculated and stored in lookup tables before sequencing operations begin. During actual base calling, the system rapidly retrieves and applies these pre-computed coefficients to attenuate spatial crosstalk, avoiding time-consuming real-time calculations. This preliminary preparation resolves the contradiction by enabling high sequencing accuracy through sophisticated crosstalk attenuation while maintaining fast processing speeds during actual sequencing runs.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces complex real-time iterative optimization algorithms with pre-computed lookup table retrieval and simple coefficient application. This substitution of complex mechanical/computational processes with simpler table-lookup operations maintains high sequencing accuracy while dramatically reducing the processing time required for crosstalk attenuation during base calling operations.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS12361525B2Equalizer-based intensity correction for base calling
Publication Date: 2025.07.15 ILLUMINA INC
  • US12361525B2 patent drawing
  • US12361525B2 patent drawing
  • US12361525B2 patent drawing

AI summary

The technology disclosed relates to equalizer-based intensity correction for base calling. In particular, the technology disclosed relates to accessing an image whose pixels depict intensity emissions from a target cluster and intensity emissions from additional adjacent clusters, selecting a lookup table that contains pixel coefficients that are configured to increase a signal-to-noise ratio, applying the pixel coefficients to intensity values of the pixels in the image to produce an output, and base calling the target cluster based on the output.