Flow Cell Integrated Manifold Reduces Reagent Cross-Contamination

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Solution Overview

Problem

Existing microfluidic devices face challenges in minimizing reagent cross-contamination and achieving efficient flush efficiency due to high external common line swept volumes and non-planar flow paths, which require excessive reagent volumes for flushing, leading to dead areas and increased reagent consumption.

Innovation Solution

A flow cell design with an integrated manifold section and detection section, where the manifold section has a smaller swept volume compared to the detection section, and both are in the same plane, reducing dead areas by using acute angle junctions and minimizing external common lines, allowing for efficient reagent flow and reduced flush volumes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If an external common line is used to route reagents from the rotary valve to the flow cell, then reagent selection and routing flexibility is improved, but the swept volume of the common line becomes high (two or more times the swept volume of the flow cell), requiring excessive flushing reagent volume

Engineering Contradiction:
Improvereagent selection and routing flexibilityVSAvoidflushing reagent volume
Core Design Contradiction:
Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The patent merges the external common line with the flow cell by integrating the manifold section directly into the flow cell structure. This eliminates the separate external common line and its associated swept volume, while maintaining the ability to route multiple reagents through a single common path to the detection section.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent extracts the common line functionality from the external routing system and relocates it within the flow cell structure. The manifold section is integrated into the flow cell, removing the need for a separate external common line and reducing the overall flushed volume required.

Inventive Principle:
Principle #2Taking out (Extraction)

2Adaptability or versatility

If the common line includes fittings, manifolds, layers, and materials to connect to the flow cell and rotary valve, then connection flexibility is improved, but sharp bends in the flow path are created (e.g., at right angles or greater), contributing to dead areas

Engineering Contradiction:
Improveconnection flexibilityVSAvoiddead areas with slow flow
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent merges the connection components (fittings, manifolds) directly into the flow cell structure, eliminating the need for external connections with sharp bends. The manifold section is integrated into the flow cell body, creating smooth, continuous flow paths without right-angle bends or dead areas.

Inventive Principle:
Principle #5Merging (Combining)

3Adaptability or versatility

If reagent wells are positioned at a different level than the flow cell, then spatial arrangement flexibility is improved, but the external common line must adjust for this difference, creating sharp bends and dead areas

Engineering Contradiction:
Improvespatial arrangement flexibilityVSAvoiddead areas from level changes
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent merges the reagent well positioning with the flow cell structure by integrating the manifold section directly into the flow cell. This eliminates the need for external common lines to bridge level differences, creating a planar flow path without sharp bends or dead areas while maintaining spatial flexibility through the integrated design.

Inventive Principle:
Principle #5Merging (Combining)

4Reliability

If a high flush factor (5 to 10 times the swept volume) is used to achieve predetermined flush efficiency, then cross-contamination is minimized, but reagent consumption increases significantly

Engineering Contradiction:
Improvecross-contamination preventionVSAvoidreagent consumption
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent merges the common line with the flow cell structure, reducing the total swept volume that requires flushing. This integration eliminates dead areas and reduces the flush factor needed to achieve the same flush efficiency, thereby reducing reagent consumption while maintaining cross-contamination prevention.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent changes the geometric parameters of the flow path by integrating the manifold section into the flow cell, creating a more efficient flow path with smaller swept volume. This parameter change reduces the flush factor from 5-10 times to approximately 2.5 times the swept volume, significantly reducing reagent consumption while maintaining flush efficiency.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS11951477B2Flow cell with integrated manifold
Publication Date: 2024.04.09 ILLUMINA INC
  • US11951477B2 patent drawing
  • US11951477B2 patent drawing
  • US11951477B2 patent drawing

AI summary

An example method includes connecting a flow cell to an instrument. The flow cell includes a flow channel including a manifold section having a manifold section swept volume and a detection section having a detection section swept volume. A ratio of the detection section swept volume to manifold section swept volume is at least 10 to 1. A first reagent is pumped through the flow channel. A first chemical reaction is performed between the first reagent and analytes positioned in the detection section. A subsequent reagent is pumped through the flow channel to flush out the remaining reagent. A concentration of at least 99.95 percent of reagent positioned in the detection section is the subsequent reagent, after pumping a total volume of the subsequent reagent through the flow channel that is equal to or less than 2.5 times a total swept volume of the manifold section plus the detection section.