Flow Cell Multi-Layer Stack Patterning for Paired-End Sequencing

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Solution Overview

Problem

Current sequencing technologies face challenges in efficiently patterning flow cell surfaces for simultaneous paired-end sequencing, which affects the accuracy and throughput of nucleic acid sequencing.

Innovation Solution

A multi-layer stack comprising a transparent base support, a patterned sacrificial layer, and a transparent layer with functionalized layers and primer sets is used to develop a flow cell for simultaneous paired-end sequencing. This involves selective etching, photoresist development, and the application of functionalized layers to create a patterned surface for sequencing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional single-layer patterning methods are used for flow cell surface preparation, then the manufacturing process is simpler, but the precision and accuracy of simultaneous paired-end sequencing is compromised

Engineering Contradiction:
Improvepatterning precisionVSAvoidmulti-layer stack complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The flow cell surface is divided into multiple functional layers (base support layer, sacrificial layer, functionalized layer, and optional transparent layer) that can be independently patterned and processed. Each layer serves a specific function in the sequencing process, allowing precise control over primer attachment regions and flow cell geometry while maintaining manufacturing feasibility through modular fabrication approaches.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from conventional single-layer two-dimensional patterning to multi-layer three-dimensional structuring. By adding vertical dimensionality with stacked layers at different heights and optical properties, the system achieves superior patterning precision for simultaneous paired-end sequencing while managing complexity through systematic layer design and selective etching processes.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Productivity

If multi-layer stack with sacrificial layers is used for simultaneous paired-end sequencing, then sequencing accuracy and throughput are improved, but the manufacturing process becomes more complex

Engineering Contradiction:
Improvesequencing throughputVSAvoidfabrication ease
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

Sacrificial layers are pre-patterned into the multi-layer stack structure before final functional layer deposition. These preliminary structures guide subsequent processing steps and enable precise positioning of sequencing features. The sacrificial materials are temporarily incorporated to facilitate manufacturing, then selectively removed to create the final functional geometry, thereby improving sequencing throughput while managing fabrication complexity through staged processing.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Sacrificial layers serve as intermediary structures during manufacturing that temporarily hold or define the geometry of the final device. These intermediary elements enable complex multi-layer patterning by providing temporary structural support and alignment references during fabrication, then are selectively removed to reveal the final functional structure optimized for high-throughput simultaneous paired-end sequencing.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If selective etching and photoresist development are used for precise patterning, then the positioning accuracy of primer sets is improved, but the manufacturing time and process complexity increase

Engineering Contradiction:
Improveprimer set positioning accuracyVSAvoidmanufacturing cycle time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

Conventional mechanical or manual patterning methods are replaced with photoresist-based photolithography and selective chemical etching processes. Light-sensitive photoresist materials are applied to the multi-layer stack, exposed through photomasks to define precise primer attachment regions, then developed chemically to create accurate patterns. This substitution of mechanical processes with optical and chemical processes achieves superior positioning accuracy for primer sets while reducing manual intervention and improving repeatability.

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

Solution Approach 2:

The invention utilizes changes in material properties during processing, particularly the solubility transitions of photoresist materials upon light exposure and the selective etch rates of different layer materials. By controlling exposure parameters, development conditions, and etch chemistry, precise patterning is achieved in optimized time cycles. Parameter optimization across multiple processing steps enables high-precision primer set positioning while managing overall manufacturing cycle time through efficient process sequencing.

Inventive Principle:
Principle #35Parameter changes

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 described method enables efficient patterning of flow cell surfaces, facilitating simultaneous paired-end sequencing and improving the accuracy and throughput of nucleic acid sequencing processes.

Implementation Method 1

utilizing the multi-layer stack to develop a negative photoresist through the portion of the transparent base support to define an insoluble negative photoresist at a predetermined region of the multi-layer stack

Methodology Applied
Scientific EffectPhotoresist development: Photopolymerisation

Implementation Method 2

selectively etching a multi-layer stack including a patterned resin layer positioned over a sacrificial layer positioned over a transparent base support, thereby exposing a portion of the transparent base support

Methodology Applied
Scientific EffectSelective etching: Ablation

Data Source

PatentUS12298665B2Flow cells and methods for making the same
Publication Date: 2025.05.13 ILLUMINA INC
  • US12298665B2 patent drawing
  • US12298665B2 patent drawing
  • US12298665B2 patent drawing

AI summary

An example flow cell includes a multi-layer stack including a transparent base support; a patterned sacrificial layer over the transparent base support; and a transparent layer over the patterned sacrificial layer. The flow cell further includes first and second functionalized layers over different portions of the transparent layer, wherein at least one of the first and second functionalized layers aligns with a pattern of the patterned sacrificial layer; and first and second primer sets respectively attached to the first and second functionalized layer.