Stochastic Chromatography Retention Time Estimation

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Solution Overview

Problem

Current chromatography models are inadequate for simulating the behavior of particles in columns where operating parameters, such as temperature and phase compositions, evolve during the particle's passage, as they do not accurately account for these changes in their calculations.

Innovation Solution

A stochastic modeling approach that simulates the individual path of particles using probability laws describing their behavior in the column, allowing for the estimation of retention times and distribution based on evolving parameters like temperature and phase compositions, which can change temporally or spatially.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional chromatography models are used, then the model structure is simple, but the model cannot accurately account for parameter evolution during particle passage

Engineering Contradiction:
Improveretention time prediction accuracyVSAvoidmodel complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The chromatography column is divided into multiple discrete stages along the flow path. Each stage has its own equilibrium parameters (K values) that can vary spatially. This segmentation allows the model to capture parameter evolution without requiring continuous differential equations, thus improving accuracy while maintaining computational tractability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The model transitions from static equilibrium parameters to dynamic parameters that evolve along the column length. The equilibrium constant K becomes a function of position (K(z)), allowing the model to account for temperature gradients, mobile phase composition changes, or stationary phase degradation that occur during particle passage through the column.

Inventive Principle:
Principle #15Dynamics

2Manufacturing precision

If operating parameters are modulated to improve separation, then separation quality improves, but the model must account for temporal and spatial parameter evolution

Engineering Contradiction:
Improveseparation qualityVSAvoidmodel complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The model预先 defines the spatial distribution of equilibrium parameters K(z) before simulation. This allows the practitioner to account for anticipated temperature gradients or composition changes without requiring real-time parameter adjustment during the simulation, simplifying the computational approach while maintaining accuracy for programmed temperature ramps or gradient elution profiles.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The model explicitly incorporates changes in equilibrium parameters K along the column length to reflect operating condition variations. By allowing K to be a function of position rather than a constant, the model naturally accounts for the effects of temperature modulation, mobile phase gradient composition, or stationary phase property changes on particle retention and separation.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If the model accounts for parameter evolution during particle passage, then retention time estimation accuracy improves, but computational complexity increases

Engineering Contradiction:
Improveretention time estimation accuracyVSAvoidcomputational complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The model replaces complex continuous differential equations with a discrete stage-based computational approach. Instead of solving partial differential equations that describe continuous parameter evolution, the system uses iterative calculations over discrete stages with defined equilibrium parameters, significantly reducing computational complexity while preserving the ability to model parameter evolution effects on retention time.

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

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 method provides a more accurate modeling of chromatography columns by accounting for parameter evolution, leading to improved separation and retention time predictions, enhancing the precision of chromatogram estimation.

Implementation Method 1

The wall of the channel has a coating, called stationary phase, with which the particle has an affinity, such that the particle is capable of being momentarily adsorbed, then desorbed.

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

a particle travels through a channel, between an inlet and an outlet, being carried by a fluid, called carrier fluid

Methodology Applied
Scientific EffectAdvection: Advection

Data Source

PatentEP3133392B1Method for estimating a retention time in a chromatography column
Publication Date: 2018.06.06 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • EP3133392B1 patent drawingFigure 1
  • EP3133392B1 patent drawingFigure 2
  • EP3133392B1 patent drawingFigure 3A

AI summary

The invention is a method for estimating the retention time of a particle in a chromatography column, and more particularly in a chromatography column in which a parameter, such as temperature, is modulated. The retention time is estimated probabilistically by sequentially modeling the particle's path through the column. When this stochastic approach is applied to a set of particles of the same type, it allows for the determination of a statistical distribution of the retention time in the column.