US 6,309,541 B1Granted

Apparatus and method for multiple channel high throughput purification

AssigneeOntogen Corporation

InventorsRomaine Maiefski, Don Wendell, William C. Ripka, Jonathan D. Krakover

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Abstract

A multiple channel high throughput purification system for purifying a plurality of samples, preferably four or more samples from a chemical library. The high throughput purification uses chromatography, and more preferably, super critical fluid chromatography. Four parallel channels are provided in this system and coupled to a common analyzer and computer. The four channels direct the selected sample flow through a separator, such as an SFC column, a detector, such as a UV detector, to detect peaks within the sample flow, and a micro sample valve that splits a sampling of the flow to an analyzer, such as a mass spectrometer. The system also utilizes unique back pressure regulator assemblies and pressure relief assemblies to maintain a selected pressure within the purification channel. While the sample flow continues, the mass spectrometer simultaneously analyzes the sampling to determine if a target compound is within the sample portion. A fraction collection valve directs sample portions to one of two fraction collectors such as a microtiter plate. The purified target compounds are collected in one microtiter plate and the other non-desirable peaks are collected in a second microtiter plate in corresponding wells. In the supercritical fluid chromatography purification system, an expansion chamber is provided to condense the vaporous sample flow before the purified compounds are added to the particular well of the microtiter plate. A fraction collection assembly is used that automates the use of disposable expansion chambers for depositing the samples in the microtiter plates.

Claims29

Dependent claims

A multiple channel, high throughput supercritical fluid chromatographic purification system for substantially simultaneously purifying multiple samples from a chemical library, each of the samples being separable into first and second components comprising:

a sample analyzer that analyzes selected sample characteristics;
a first purification channel coupled to the sample analyzer, the first purification channel including;
a first chromatographic sample separation device positioned to separate a first sample flow into first and second sample components;
a first detector positioned to detect the first and second components in the first sample flow;
a first flow diverting device moveable to direct a sampling of the first sample component to the analyzer and the remainder of the first sample portion flows along a first flow path away from the diverting first flow device;
a first collector positioned to receive at least a portion of the first or second sample component of the first sample the sample analyzer identified as having selected sample characteristics;
a second collector positioned to receive remaining components of the first sample not having the selected sample characteristics;
and
a second purification channel coupled to the sample analyzer, the second purification channel including:
a second chromatographic separation device positioned to receive a second sample flow for separation into the first and second components of the second sample flow;
a second detector positioned to detect the first and second components of the second sample flow;
a second flow diverting device moveable to direct a sampling of the first or second components to the analyzer and a remainder of the second sample portion flows along a second flow path away from the flow diverting device;
a third collector positioned to receive at least a portion of the first or second sample components of the second sample having the selected sample characteristics;
and
a fourth collector positioned to receive remaining components of the second sample not having the selected sample characteristics.

12 more elements

A multiple channel, high throughput purification system for substantially simultaneously purifying at least two samples from a chemical library, comprising:

a controller;
a sample analyzer coupled to the controller, the analyzer being configured to determine whether the first sample has selected sample characteristics;
at least two purification channels coupled to the common sample analyzer, each purification channel including:
a separation device positioned to receive a sample flow containing the sample and to separate the sample into first and second sample components spaced apart from each other in the first sample flow;
a detector coupled to the separation device, the detector being positioned to receive the sample flow from the separation device, the detector configured to detect at least the sample component within the first sample flow;
a flow sampling device positioned to receive the sample flow from the detector, the flow sampling device being moveable between open and closed positions, in the open position the flow sampling device directs a sampling of the sample component to the analyzer and a remainder of the first sample flows along a flow path past the flow splitting device, and in the closed position the device blocks the sample flow from passing to the analyzer;
a flow directing valve in fluid communication with the flow path and positioned to receive the sample, the flow directing valve being movable to a first position to direct the sample portion in a first direction if the analyzer has determined that the sample component has the selected sample characteristics, and the flow directing valve being movable to a second position to direct the sample portion in a second direction if the analyzer has determined that the sample component does not have the first selected sample characteristics;
a first collector positioned to receive the sample components that have the selected sample characteristics from the flow directing devices when the flow directing devices are in the first position;
and
a second collector and positioned to receive the sample components that do not have the selected sample characteristics when the first flow directing devices are in the second position.

7 more elements

A multiple channel, high throughput purification system for substantially simultaneously purifying at least two samples from a chemical library, comprising:

a sample analyzer configured to determine whether a sample portion passing therethrough has selected sample characteristics;
at least two purification channels coupled to the common sample analyzer and configured to simultaneously carry a respective sample flow, each purification channel including:
a sample separation device configured to separate a selected sample into first and second sample components spaced apart from each other in the respective sample flow;
a detector coupled to the sample separation device, the detector being configured to detect at least one sample component within the respective sample flow;
a flow sampling device positioned to receive the respective sample flow from the detector, the flow sampling device being moveable to direct a sampling of the sample component to the analyzer and a remainder of the respective sample flow continues along the respective flow path;
a first collector positioned to receive the sample components that have the selected sample characteristics from the flow directing devices when the flow directing devices are in the first position;
and
a second collector and positioned to receive the sample components that do not have the selected sample characteristics when the first flow directing devices are in the second position.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/430,194Filed 29 Oct 1999
Granted: 30 Oct 2001
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

B01D 15/08
Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor: selective adsorption, e.g. chromatography
B01D 15/102
Characterised by constructional or operational features: process control, e.g. determination or optimization of process parameters; Programmable…
B01D 15/1885
Using two or more columns: placed in parallel
B01D 15/40
Characterised by the separation mechanism: using supercritical fluid as mobile phase or eluent