Control system and method for flash separation
AssigneeBiotage AB
InventorsJeffrey Horsman, John Bickler
Life of this patent
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Abstract
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.
Claims34
A method of separating compounds in a sample using a column chromatography system, the method comprising:
- receiving data input sufficient for determining;
- at least two retention factors (Rf) corresponding to a primary compound and a secondary compound exposed to an initial solvent system;
- and
- a proportion of each solvent in the initial solvent system;
- generating a solvent ratio profile based on the received inputs including;
- a starting point corresponding to a starting solvent ratio;
- an ending point corresponding to an ending solvent ratio;
- and
- a transitional phase during which the solvent ratio increases from the starting solvent ratio to the ending solvent ratio;
- and
- introducing separation solvent system having the starting solvent ratio at a solvent flow rate into an upstream end of a chromatography column having a column volume;
- introducing a sample including the primary compound and the secondary compound into an upstream end of a chromatography column;
- varying the solvent ratio of the separation solvent system being introduced into the upstream end of the chromatography column in accord with the solvent ratio profile;
- and
- carrying at least the primary compound to a downstream end of the chromatography column.
A method of controlling a column chromatography system, the method comprising:
- conducting a TLC separation on a sample composition using a solvent system to determine a first retention factor (Rf1) corresponding to a primary compound and a second retention factor (Rf2) corresponding to a secondary compound;
- applying a system algorithm to the first and second retention factors to calculate a first elution column volume (CV1) for the primary compound and a second elution column volume (CV2) for the secondary compound;
- determining a Δ column volume (ΔCV) from the first and second elution column volumes;
- and
- projecting a target sample mass as a function of the ΔCV and a column configuration.
A method of controlling a column chromatography system, the method comprising:
- determining a first retention factor (Rf1) corresponding to a primary compound and a second retention factor (Rf2) corresponding to an adjacent secondary compound in a base solvent system;
- applying a system algorithm to calculate a first elution column volume (CV1) for the primary compound and a second elution column volume (CV2) for the secondary compound from the first and second retention factors;
- determining a Δ column volume (ΔCV) from the first and second elution column volumes;
- and
- projecting a column selection as a function of the ΔCV and a proposed sample load.
A chromatography system comprising:
- a first solvent supply operatively connected to a chromatography column;
- a second solvent supply operatively connected to the chromatography column;
- a controller operatively connected to the first and second solvent supplies for delivering a flow of a solvent system to an inlet for the chromatography column in accord with a predetermined solvent gradient, wherein the flow of the solvent system through the chromatography column will separate components from a sample composition;
- and
- a collection apparatus operatively connected to an outlet from the chromatography column for collecting designated portions of the solvent system flow exiting the column,
- wherein the controller also determines a target sample mass as a function of chromatography column parameters.
Dependencies are inferred from the claim text.