Flash Chromatography Control System Gradient Calculation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Chromatography systems face challenges in adapting separation conditions from one method to another, requiring significant operator involvement and additional experimentation, especially when dealing with unknown components or those with similar retention factor values.

Innovation Solution

A method and control system for column chromatography using multi-solvent systems and solvent gradient techniques, which calculates a gradient profile based on retention factor values and solvent ratios to achieve improved separation efficiency, reducing the need for multiple TLC runs and operator intervention.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If conventional chromatography methods are used to separate components, then separation can be achieved, but significant operator involvement and additional experimentation are required to adapt separation conditions

Engineering Contradiction:
Improveautomation of separation condition transferVSAvoidtime for operator involvement and experimentation
Core Design Contradiction:
Extent of automationVSLoss of time

Solution Approach 1:

The system performs self-service by automatically calculating gradient profiles and chromatographic parameters based on TLC data without requiring operator intervention. The controller autonomously processes TLC retention factor values and solvent ratios to generate optimized separation conditions for column chromatography, eliminating the need for manual experimentation and condition adaptation.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces the manual mechanical process of operator experimentation and condition adjustment with an automated computational system. The controller uses algorithms to substitute the mechanical trial-and-error process with automatic calculation of gradient profiles based on TLC data, thereby reducing time loss and increasing automation.

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

2Manufacturing precision

If multiple TLC runs are performed to optimize separation, then acceptable separation results can be achieved, but productivity decreases due to the need for multiple runs

Engineering Contradiction:
Improveseparation qualityVSAvoidproductivity of chromatography system
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The system performs preliminary action by using TLC data to pre-calculate the optimal gradient profile and chromatographic parameters before the actual column chromatography run. This preliminary calculation based on retention factor values and solvent ratios ensures that the separation conditions are optimized in advance, eliminating the need for multiple TLC runs and thereby increasing productivity while maintaining separation quality.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by transforming TLC parameters (retention factor values and solvent ratios) into column chromatography parameters (gradient profile and flow rates). This parameter transformation allows the system to predict optimal separation conditions from preliminary TLC data, achieving high separation quality in a single run and improving overall productivity.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If isocratic elution is used in flash chromatography, then the system is simple to operate, but separation efficiency is limited for components with similar retention factor values

Engineering Contradiction:
Improveease of flash chromatography operationVSAvoidseparation resolution of components
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The system transitions from static isocratic elution to dynamic gradient elution. The controller automatically generates gradient profiles that change solvent composition over time based on TLC data, allowing the mobile phase strength to dynamically adapt during the separation process. This dynamic approach improves separation resolution for components with similar retention factors while maintaining ease of operation through automation.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent implements parameter changes by varying the solvent composition ratio throughout the chromatography run according to a pre-calculated gradient profile. Instead of maintaining constant isocratic conditions, the system dynamically adjusts the mobile phase parameters based on TLC-derived data, thereby achieving superior separation resolution while keeping the system easy to operate through automatic control.

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

Automates the transfer of separation conditions from TLC to column chromatography, enhancing separation efficiency and reducing the need for multiple runs by generating gradient profiles that optimize solvent ratios and column parameters.

Implementation Method 1

chromatography generally involves the use of one or more solvents to separate a sample composition of multiple components into individual components as a result of the solvents and the sample composition flowing around, over, or through a stationary liquid or solid phase

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

As the solvent moves past the sample composition, one or more of the components within the sample will be dissolved and carried along with the solvent upwardly along the surface of the plate

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 3

The plate is then maintained in a generally vertical orientation so that over time the solvent will move, via capillary action, upwardly through the layer of material provided on the surface of the plate

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentUS8679345B2Control system and method for flash separation
Publication Date: 2014.03.25 BIOTAGE INC
  • US8679345B2 patent drawing
  • US8679345B2 patent drawing
  • US8679345B2 patent drawing

AI summary

Provided are methods and apparatus for determining conditions for performing chromatography, particularly flash chromatography. The methods may be utilized for separating compounds in a sample in a column chromatography system. The method includes determining at least two retention factors corresponding to the TLC performance of a target compound and an adjacent compound and defining a sample loading amount and a solvent gradient profile using at least two solvents that will result in differential elution of the target and adjacent compounds from a chromatography column. The chromatography system and loading parameters may be selected to provide satisfactory separation of the target compound from adjacent compounds.