Cluster Location Tracking on Nucleotide Slides

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Solution Overview

Problem

Existing sequencing systems inaccurately estimate the locations of clusters of oligonucleotides on nucleotide-sample slides due to image jitter, thermal expansion, and variations in cluster locations, leading to incorrect base calls and reduced sequencing throughput.

Innovation Solution

A location-error-prediction system that estimates and modifies the predicted location of clusters based on intensity-value errors and signals from adjacent clusters to improve cluster location tracking, using a tracking loop to iteratively adjust the predicted locations for more accurate signal detection and base calling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing sequencing systems use conventional cluster location estimation methods with fiducials and interpolation, then the system can track cluster locations, but the location estimation accuracy deteriorates due to image jitter, thermal expansion, and cluster location variations

Engineering Contradiction:

Improvecluster location estimation accuracyVSAvoidbase call accuracy

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The system employs a feedback mechanism where the equalizer output is used to update the predicted cluster location for the next sequencing cycle. The equalizer minimizes mean-squared-error between the observed signal and the expected signal from the cluster, and this optimized location information feeds back into the location tracking model, continuously improving location estimation accuracy while compensating for jitter and thermal expansion effects

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The system dynamically adjusts the equalizer parameters (filter coefficients) based on the observed signal characteristics and minimizes mean-squared-error in real-time. This parameter adaptation allows the system to compensate for changing conditions such as thermal expansion and image jitter, maintaining accurate cluster location tracking without requiring additional fiducials

Inventive Principle:

Principle #35Parameter changes

2Productivity

If the equalizer is not centered on the cluster location, then the system can process signals, but the signal-to-noise ratio deteriorates and base call accuracy decreases

Engineering Contradiction:

Improvesequencing throughputVSAvoidsignal detection accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The equalizer location is updated using feedback from the mean-squared-error minimization process. The system continuously adjusts the equalizer's center position based on where the signal is actually detected, ensuring the equalizer remains centered on the cluster location even when jitter or thermal expansion occurs, thereby maintaining optimal signal-to-noise ratio

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The system transitions from a static equalizer position to a dynamic one that adapts in real-time. The equalizer location is no longer fixed but changes with each sequencing cycle based on the actual cluster position detected through signal processing, allowing the system to maintain optimal performance despite environmental variations

Inventive Principle:

Principle #15Dynamics

3Measurement precision

If additional fiducials are added to improve location tracking, then location estimation may improve, but device complexity and computational costs increase

Engineering Contradiction:

Improvelocation tracking accuracyVSAvoidsystem complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The system uses the signal from the clusters themselves to determine their locations, eliminating the need for external fiducials. The clusters serve their dual purpose: as the objects being sequenced and as the reference points for location tracking. This self-service approach reduces device complexity while maintaining location tracking accuracy through the equalizer-based location refinement

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The equalizer serves multiple functions: it optimizes the signal-to-noise ratio for base calling and simultaneously provides accurate cluster location information. This multi-functionality eliminates the need for separate fiducial systems, reducing overall system complexity while achieving both signal optimization and location tracking goals

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250111898A1Tracking and modifying cluster location on nucleotide-sample slides in real time

Publication Date: 2025.04.03 ILLUMINA INC

AI summary

This disclosure describes embodiments of methods, systems, and non-transitory computer readable media that can (i) estimate a location error for a predicted location of a cluster of oligonucleotides based on the cluster's signal and (ii) modify the predicted location of the cluster to improve signal detection and base calling on a sequencing device. For example, the disclosed systems can receive a signal from a cluster of oligonucleotides at a predicted location. The disclosed systems can further determine an intensity-value error between an intensity value and an expected intensity value for the signal at the predicted location. Based on the intensity-value error and intensity values from other locations (e.g., other clusters of oligonucleotides) within the region, the disclosed system can determine an estimated location error for the predicted location. The disclosed systems can modify the predicted location of the cluster of oligonucleotides based on the estimated location error.