High Duty-Cycle Liquid Chromatography Using Parallel Columns

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Solution Overview

Problem

Liquid chromatography systems with low flow rates experience high downtime due to regenerative steps, leading to inefficient use of expensive mass spectrometers and increased costs, while increasing flow rates can compromise sensitivity.

Innovation Solution

A high-duty-cycle liquid chromatography system is implemented, utilizing multiple columns that alternate between productive and regeneration phases, with a single mobile phase gradient delivery pump and isocratic pump, allowing continuous gradient generation and sample analysis without the need for multiple machines, thereby reducing downtime and maintaining sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If low flow rate is used in liquid chromatography, then sensitivity is enhanced, but duty cycle decreases and machine downtime increases

Engineering Contradiction:
ImprovesensitivityVSAvoidduty cycle
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The system divides the chromatography process into two independent parallel paths: one column performs productive analysis while the other undergoes regeneration. This segmentation allows the analytical and regenerative functions to occur simultaneously in separate segments of the system, resolving the contradiction between maintaining low flow rate sensitivity and improving duty cycle.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

By implementing parallel columns where one is always in productive phase while the other regenerates, the system ensures continuous useful action. The switch between columns eliminates idle time, maintaining near-100% duty cycle while preserving the low flow rate conditions necessary for sensitivity in the productive column.

Inventive Principle:
Principle #20Continuity of useful action

2Productivity

If multiple liquid chromatography machines are used to increase throughput, then productivity improves, but device complexity and cost increase

Engineering Contradiction:
Improvesample throughputVSAvoidnumber of machines
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system merges multiple functional capabilities into a single liquid chromatography machine by incorporating parallel columns, multiple pumps, and a switching system. This allows one machine to perform the work of multiple sequential machines through parallel processing, increasing throughput while containing device complexity within a single integrated system.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The single liquid chromatography machine is designed with multi-functionality, capable of simultaneously performing sample analysis, column regeneration, and gradient preparation through its parallel architecture. This universal design eliminates the need for separate dedicated machines for different functions, improving productivity without proportionally increasing the number of machines.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Productivity

If flow rate is increased to reduce downtime, then productivity improves, but sensitivity is compromised

Engineering Contradiction:
Improveanalysis speedVSAvoidsensitivity
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system segments the flow rate requirements by applying high flow rate to the regeneration path and low flow rate to the analytical path. This segmentation allows each function to operate at its optimal flow rate independently, achieving both high productivity through fast regeneration and high sensitivity through low flow rate analysis.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system performs preliminary regeneration action on one column while the other is actively analyzing samples. This preliminary action prepares the next column in advance, ensuring immediate availability for analysis without interrupting the current productive run, thereby improving productivity without affecting the sensitivity of the active analysis.

Inventive Principle:
Principle #10Preliminary action

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

This approach significantly reduces machine downtime, laboratory overhead costs, and equipment spending while maintaining high sensitivity, enabling faster gradient generation and increased sample throughput without sacrificing separation performance.

Implementation Method 1

Liquid chromatography is an analytical chemistry technique used in the process of separating components in a mixture allowing the individual components to be identified and quantified

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

a single mobile phase gradient delivery pump, and a single isocratic pump

Methodology Applied
Scientific EffectPumping: Pump

Data Source

PatentUS20230266281A1High throughput liquid chromotography using low flowrate
Publication Date: 2023.08.24 BRIGHAM YOUNG UNIV
  • US20230266281A1 patent drawing
  • US20230266281A1 patent drawing
  • US20230266281A1 patent drawing

AI summary

A high-duty-cycle liquid chromatography system that includes two or more columns that are configured to alternatingly be in a productive phase or a regeneration phase, wherein simultaneously one of the columns is in a productive phase and the other columns are in the regeneration phase. Additionally, the system includes a mobile phase gradient delivery pump, an isocratic pump, two or more gradient storage chambers, and two or more valves that are each independently coupled to a column and a gradient storage chamber. The column in the productive phase has a solution containing a sample which is pushed through the column, collected at a detector, and analyzed. The column in the regeneration phase is being prepared for the next productive phase.