Sequencer Mask Optimization for Extended Depth of Field

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Solution Overview

Problem

Existing nucleic acid sequencers face challenges in maintaining optical signal-to-noise ratio due to point spread function degradation from defocus, which affects focus accuracy and increases noise, limiting throughput and increasing costs.

Innovation Solution

Implementing a nucleic acid sequencer with a detection system that includes an objective lens, a set of detection pixels, and a mask, such as a phase or amplitude mask, to extend the depth of field by optimizing the mask using iterative optimization steps based on discrepancies between actual and ideal point spread functions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If a conventional objective lens is used without a mask, then the device complexity is low, but the depth of field is limited and point spread function degrades with defocus

Engineering Contradiction:
Improvefocus accuracyVSAvoiddetection system complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

A mask is introduced as an intermediary optical element positioned between the objective lens and the detection pixels. This mask modifies the optical path and point spread function to extend depth of field, acting as a mediator that enables improved focus tolerance without requiring complex mechanical focusing mechanisms or multiple lenses.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The mask changes the optical parameters of the detection system by modifying the point spread function through its transmission function. This parameter change allows the system to maintain acceptable image quality over a larger range of defocus amounts, effectively extending the depth of field without altering the fundamental lens structure.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If the depth of field is extended using a mask, then the optical signal to noise ratio is improved, but the device complexity increases

Engineering Contradiction:
Improvesignal to noise ratioVSAvoiddetection system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The mask serves as a simple intermediary optical element that improves signal quality by shaping the point spread function. Rather than using complex signal processing or multiple detection systems, the mask provides a passive optical solution that enhances the optical signal to noise ratio through its spatial filtering function.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The solution replaces potential mechanical focusing adjustments with an optical mask-based approach. Instead of mechanically moving the lens or sample to achieve focus, the mask provides an optical field of view extension that maintains signal quality across a range of positions, substituting mechanical complexity with optical design.

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

3Productivity

If the depth of field is increased to +/−300 nm or greater, then the throughput is increased, but the manufacturing precision requirements for the mask increase

Engineering Contradiction:
ImprovethroughputVSAvoidmask fabrication precision
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The mask design utilizes parameter changes in the transmission function to achieve depth of field extension. By carefully designing the transmission function parameters (such as aperture size, shape, and transmission values at different radial positions), the system achieves extended depth of field while maintaining manufacturability through standard fabrication techniques.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The mask implements local quality variations through its spatially varying transmission function. Different regions of the mask have different transmission properties, with the transmission value varying as a function of radial distance from the optical axis. This local differentiation allows the mask to correct optical aberrations and extend depth of field across the field of view.

Inventive Principle:
Principle #3Local quality

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

The solution enhances focus accuracy, reduces noise, and increases throughput by extending the depth of field to greater than +/−300 nm, improving sequencing accuracy and reducing costs.

Implementation Method 1

a mask, such as a phase or amplitude mask, to extend the depth of field by optimizing the mask using iterative optimization steps based on discrepancies between actual and ideal point spread functions

Methodology Applied
Scientific EffectOptical diffraction and interference: Diffraction

Data Source

PatentUS20260023020A1Apparatus and method for extended depth of field
Publication Date: 2026.01.22 ILLUMINA INC
  • US20260023020A1 patent drawing
  • US20260023020A1 patent drawing
  • US20260023020A1 patent drawing

AI summary

A method for extending a depth of field of a nucleic acid sequencer may comprise optimization steps which are repeated one or more times, in which a result of passing light through an objective lens and a mask is compared with an ideal result, and any discrepancy is used to update the mask. Such a mask may be incorporated into a nucleic acid sequencer which adds fluorescent tags to nucleic acid sites and then detect light emitted from the fluorescent tags, thereby extending the sequencer's depth of field.