Split-Flow Mixer Volume Offsets for Stable Chromatography Composition

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Solution Overview

Problem

Existing chromatography systems face challenges in efficiently mixing fluids with compositional disturbances, leading to interference with sample detection and increased testing time, particularly in HPLC, UPLC, and SFC systems, due to inefficiencies in current mixers that either increase volume or are prone to contamination and clogging.

Innovation Solution

A mixer design that splits fluid flow into multiple paths with predetermined volume offsets and a balanced flow restrictor system to cancel unwanted compositional ripple, using a split-flow mixer with multiple stages and recombination points to achieve efficient mixing without significant pressure drop or delay volume.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If large volume mixers are used to mix fluids effectively, then mixing effectiveness is improved, but testing time increases and throughput diminishes

Engineering Contradiction:
Improvemixing effectivenessVSAvoidtesting time
Core Design Contradiction:
Stability of the object's compositionVSLoss of time

Solution Approach 1:

The mixer divides the fluid flow into multiple parallel paths (first path, second path, third path, fourth path) with different delay volumes. Each path processes a portion of the flow simultaneously, achieving effective mixing without requiring a large overall volume, thus reducing testing time while maintaining mixing effectiveness.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from a single-volume mixing approach to a multi-path parallel processing approach. By distributing flow across multiple paths with different delay volumes and recombining them, the system achieves mixing in a dimensional space of parallel flows rather than requiring a large sequential volume, thereby reducing testing time.

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

2Stability of the object's composition

If packed-bead LC mixers are used, then mixing is achieved, but they are inefficient relative to delay volume, difficult to manufacture, and prone to contamination and clogging

Engineering Contradiction:
Improvemixing performanceVSAvoidcontamination and clogging resistance
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The invention removes the packed beads entirely from the mixing system. Instead of using packed-bead columns that are prone to contamination and clogging, the system uses open tubular paths with controlled delay volumes, eliminating the source of contamination and clogging while maintaining mixing performance through the multi-path delay mechanism.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces complex, difficult-to-manufacture packed-bead structures with simple, easily manufactured tubular paths. The mixer can be produced more cheaply and reliably without the complex packing processes required for packed-bead columns, and the simple structure is more resistant to contamination and clogging.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Manufacturing precision

If pump cycles are used to deliver precise solvent compositions, then precise composition delivery is achieved, but compositional disturbances occur at regular intervals interfering with sample detection

Engineering Contradiction:
Improvecomposition precisionVSAvoidcompositional disturbances
Core Design Contradiction:
Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The invention uses periodic delay volumes in the parallel paths that are tuned to the pump cycle frequency. The different delay volumes create phase shifts that cause the compositional disturbances from pump cycles to cancel each other out when the paths are recombined, eliminating the periodic interference while maintaining precise composition delivery.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The invention converts the harmful compositional disturbances generated by pump cycles into a beneficial cancellation effect. By designing the delay volumes to create specific phase relationships, the disturbances that would normally interfere with detection are transformed into a self-cancelling pattern, where the harmful oscillations from each path negate each other upon recombination.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

4Stability of the object's composition

If mixers with significant delay volume are used, then mixing is achieved, but throughput is reduced

Engineering Contradiction:
Improvemixing qualityVSAvoidthroughput
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The mixer segments the mixing function across multiple parallel paths rather than requiring a single large delay volume. Each path has a smaller delay volume, but the parallel arrangement achieves the same mixing quality, thereby reducing the overall delay and increasing throughput while maintaining mixing effectiveness.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS20250354964A1Equal dispersion split-flow mixer
Publication Date: 2025.11.20 WATERS TECHNOLOGY CORP
  • US20250354964A1 patent drawing
  • US20250354964A1 patent drawing
  • US20250354964A1 patent drawing

AI summary

Disclosed is a liquid chromatography system and mixer for use therein that includes a first split connected to an inlet, the first split branching the flow of fluid from the inlet into a first path and a second path; a second split connected to an outlet of the first path, the second split branching the first path into a third path and a fourth path; and a third split connected to an outlet of the second path, the third split branching the second path into a fifth path and a sixth path. The first path and the second path are offset by a first predetermined volume, the third path and the fourth path are offset by a second predetermined volume, and the fifth path and the sixth path are also offset by the second predetermined volume.