US 6,508,938 B2Granted

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.

Claims44

Dependent claims

A method of substantially continuous, multiple channel high throughput supercritical fluid chromatography purification of at least first and second samples from a chemical library to provide corresponding array-to-array mapping of purified components, comprising purifying the first sample along a first channel by:

chromatographically separating the first sample into first and second sample portions;
spacing the first and second sample portions apart from each other along at least a portion of a first fluid path;
moving the first and second sample portions along the first fluid path;
detecting the first sample portion along the first fluid path;
removing a first sampling from the first sample portion;
directing the first sampling to an analyzers with a the remainder of the first sample portion continuing along the first fluid path;
analyzing the first sampling with the analyzer;
determining from the first sampling if the first sample portion has first selected sample characteristics;
collecting the first sample portion in a first collector if the first sample portion has the selected sample characteristics;
collecting the first sample portion in a second collector if the first sample portion does not have the selected characteristics;
and
purifying the second sample along a second channel substantially simultaneously with the purifying of the first sample, purifying the second sample including:
chromatographically separating the second sample into third and fourth sample portions;
spacing the third and fourth sample portions apart from each other along at least a portion of a second fluid path;
moving the third and fourth sample portions along the second fluid path;
detecting the third sample portion along the second fluid path;
removing a second sampling from the third sample portion;
directing the second sampling to the analyzer with a remainder of the third sample portion continuing along the second fluid path;
analyzing the second sampling with the analyzer;
determining from the second sampling if the third sample portion has second selected sample characteristics;
collecting the third sample portion in a third collector if the third sample portion has the second selected sample characteristics;
and
collecting the third portion in the a fourth collector if the third portion does not have the second selected sample characteristics.

20 more elements

The method of multiple channel high throughput purification of multiple samples from a chemical library, comprising of separating and purifying the components of each sample along a first channel by:

moving the first sample to be separated into components along the first fluid path which passes through a separation medium that results in differential passage times through the separation media for the various components of the first sample;
detecting individual components of the first sample as the first sample travels along the first fluid path;
identifying the components as associated with the first channel;
sampling each component and sending a sample to a common analyzer with its channel identifier;
determining if the analyzed sample meets the first selected sample characteristics;
if the detected component of this first sample meets the selected sample characteristics a control valve is activated to allow collection of this first component in a first collector associated with the first channel;
if the detected component of this first sample does not meet the selected sample characteristics a control valve is activated to direct the collection of these components to a second collector associated with the first channel;
moving the second sample to be separated into components along the second fluid path which passes through a separation medium that results in differential passage times for the various components of the second sample;
detecting individual components of the second sample as it travels along the second fluid path and identifying these components as associated with the second channel;
sampling each component and sending such sample to a common analyzer with its channel identifier;
determining if the analyzed sample meets the second selected sample characteristics;
if the detected component of this second sample meets the selected sample characteristics a control valve is activated to allow collection of this second component in a first collector associated with the second channel;
if the detected component of this second sample does not meet the selected sample characteristics the control valve is activated to direct the collection of these components to a second collector associated with the second channel;
moving the third sample to be separated into components along the second fluid path which passes through a separation medium that results in differential passage times for the various components of the third sample;
detecting individual components of the third sample as it travels along the third fluid path and identifying these components as associated with the third channel;
sampling each component and sending such sample to a common analyzer with its channel identifier;
determining if the analyzed sample meets the third selected sample characteristics;
if the detected component of this third sample meets the selected sample characteristics a control valve is activated to allow collection of this third component in a first collector associated with the third channel;
if the detected component of this third sample does not meet the selected sample characteristics the control valve is activated to direct the collection of these components to a second collector associated with the third channel;
moving the fourth sample to be separated into components along the fourth fluid path which passes through a separation medium that results in differential passage times for the various components of the fourth sample;
detecting individual components of the fourth sample as it travels along the fourth fluid path and identifying these components as associated with the fourth channel;
sampling each component and sending such sample to a common analyzer with its channel identifier;
determining if the analyzed sample meets the fourth selected sample characteristics;
if the detected component of this fourth sample meets the selected sample characteristics a control valve is activated to allow collection of this fourth component in a first collector associated with the fourth channel;
if the detected component of this fourth sample does not meet the selected sample characteristics the control valve is activated to direct the collection of these components to a second collector associated with the fourth channel.

22 more elements

A method of multiple channel high throughput purification of multiple samples from a chemical library, comprising:

moving a first sample to be separated into components along a first fluid path;
separating the first sample into a plurality of components that are spaced apart from each other in the first fluid path;
detecting components of the first sample as the first sample travels along the first fluid path;
identifying the components of the first sample associated with the first channel;
sampling each component of the first sample and sending the sampling to a common analyzer;
analyzing each sampling from a component of the first sample with the common analyzer;
determining if the analyzed sampling from a component of the first sample meets first selected sample characteristics;
collecting the component of the first sample in a first collector if the analyzed sampling from the component first sample meets the first selected sample characteristics;
collecting the component of the first sample in a second collector if the analyzed sampling of from the first component does not meet the first selected sample characteristics;
moving a second sample to be separated into components along a second fluid path simultaneously as the first sample is moving through the first fluid path;
separating the second sample into a plurality of components that are spaced a pair from each other in the second fluid path;
detecting components of the second sample as the second sample travels along the second fluid path;
identifying the components of the second sample associated with the second channel;
sampling each component of the second sample and sending the sampling to the common analyzer;
analyzing each sampling from a component of the second sample with the common analyzer;
determining if the analyzed sampling from a component of the second sample meets second selected sample characteristics;
collecting the component of the second sample in the first collector if the analyzed sampling from the component second sample meets the second selected sample characteristics;
collecting the component of the second sample in the second collector if the analyzed sampling of from the second component does not meet the second selected sample characteristics.

15 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/825,564Filed 2 Apr 2001 · division
Priority: 29 Oct 1999
Published: US 2001/0013494 A116 Aug 2001
Granted: 21 Jan 2003
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

Family

Application09/430,194Parent of this division · filed 29 Oct 1999
US 2001/0013494 A1Pre-grant publication · published 16 Aug 2001
US 6,309,541 B1Parent of this division
US 6,508,938 B2This patent

From the US filing history. Foreign family members aren’t listed.

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