Chromatographic systems with pre-detector eluent switching

• US 6,641,783 B1
• Filed: 02/08/2000
• Issued: 11/04/2003
• Est. Priority Date: 02/08/1999
• Status: Expired due to Fees

• Current Assignee: Admetric Biochem, Inc.
• Original Assignee: Admetric Biochem, Inc.
• Inventors: Lin, Sonyuan, Giles, Jeffrey, Pidgeon, Charles, Yin, Jianming, Rooke, Nadege
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): SINES, BRIAN J
• Application Number:
  US09/499,904
• Time in Patent Office: 1,365 Days
• Field of Search: 422/70, 422/82, 422/81, 422/68.1, 210/659, 210/656, 436/43
• US Class Current: 422/70
• CPC Class Codes: G01N 2030/204 Linearly moving valves, e.g. sliding valves
• CPC Class Codes: G01N 2030/328 valves, e.g. check valves of pumps
• CPC Class Codes: G01N 2030/527 sorbent material in form of a membrane
• CPC Class Codes: G01N 2030/625 by measuring reference material, e.g. carrier without sample
• CPC Class Codes: G01N 2030/628 Multiplexing, i.e. several columns sharing a single detector
• CPC Class Codes: G01N 30/06 Preparation
• CPC Class Codes: G01N 30/10 using a splitter
• CPC Class Codes: G01N 30/16 Injection G01N30/24 takes precedence
• CPC Class Codes: G01N 30/20 using a sampling valve
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/468 involving switching between different column configurations
• CPC Class Codes: G01N 30/7266 by electric field, e.g. electrospray
• CPC Class Codes: G01N 30/82 Automatic means therefor
• CPC Class Codes: G01N 30/84 Preparation of the fraction to be distributed
• CPC Class Codes: Y10T 436/11 Automated chemical analysis

Abstract

This invention relates to a high efficiency chromatographic system. More specifically, the present invention relates to a chromatographic system for determining the physicochemical properties of one or more compounds using at least two chromatographic units in eluent flow communication with one eluent analyzer via an intermediate eluent switch. The present chromatographic system allows determination of physicochemical properties through the use of multiple chromatographic units in communication with one eluent analyzer via an eluent switch.

Claims

1. A method for data acquisition by analysis of eluent streams from multiple chromatographic columns in a chromatographic system using an eluent stream analyzer having a fluid sampling port and capable of providing signals characteristic of detected chemical species in each eluent stream, said method comprising

providing a chromatoraphic system with multiple chromatograthic columns, each having an eluent stream, and an eluent switching valve having

(1) fluid input ports in fluid communication with the eluent stream from each chromatographic column and with a source of at least one indexing fluid,

(2) a fluid output port in fluid flow communication with a fluid sampling port on the eluent stream analyzer, and

(3) a valve system communicating with a programmable controller for directing aliquots of the respective eluent streams and indexing fluid in a programmed sequence through the fluid output port and toward the fluid sampling port on the eluent stream analyzer,

directing the aliquots via the valve system to the eluent stream analyzer and producing signals characteristic of detected chemical species in each aliquot, and

correlating the electronic storage of the signals from the analyzer with the programmed sequence so that analyzer signals from analysis of the aliquots of eluent of each respective column are stored in an algorithm accessible electronic storage device.

2. The method of claim 1 wherein the correlating step includes sensing aliquots of indexing fluid between each eluent stream aliquot.

3. The method of claim 1 wherein the indexing fluid comprises a liquid.

4. The method of claim 3 wherein the liquid comprises at least one analyzer detectable species.

5. The method of claim 1 wherein the indexing fluid comprises a gas.

6. The method of claim 1 wherein the indexing fluid comprises a liquid and a gas.

7. The method of claim 1 wherein the chromatographic system further comprises a pump for controlling pressure or a valve for controlling rate of flow of the respective eluent streams and indexing fluid through the valve system and toward the fluid sampling port on the eluent stream analyzer.

8. The method of claim 1 wherein the respective aliquots of indexing fluid between aliquots of the respective eluent streams are of programmably unique volumes.

9. The method of claim 1 wherein the controller for the valve system is programmed to deliver at least one aliquot of indexing fluid through the output port after each eluent stream aliquot.

10. The method of claim 1 wherein the analyzer senses the respective indexing fluid aliquots and directs the signals from the next following eluent stream aliquot to a predetermined electronic data storage register where eluent aliquot analysis signals for each respective chromatographic column is stored in an accessible format.

11. The method of claim 1 wherein the chromatographic system further comprises a flow rate detector and a flow rate controller for each chromatographic column.

19. The method of claim 1 wherein the eluent stream analyzer is selected from the group consisting of a mass spectrometer, an infra-red spectrometer, a nuclear magnetic resonance spectrometer, an ultraviolet-visible spectrometer, a fluorescence detector, an electrochemical detector and a refractive index detector.

20. The method of claim 1 wherein the signal from the analyzer is used as “

feed back”

signal to control the programmable controller.

12. A multi-column chromatographic system comprising

at least two chromatographic columns each having a mobile phase input port and an eluent stream output port;

a mobile phase delivery system in fluid flow communication with each the mobile phase input port;

an eluent stream analyzer having a fluid sampling port and capable of providing signals characteristic of chemical species in a fluid received in said sampling port;

an eluent switching valve assembly having

(1) a fluid input port positioned for fluid communication with the eluent stream from each chromatographic column and with a source of at least one indexing fluid,

(2) a fluid output port in fluid flow communication with the fluid sampling port of the eluent stream analyzer; and

(3) a valve system for directing aliquot volumes of the respective eluent streams and the indexing fluid in a programmed sequence through the fluid output port and toward the fluid sampling port on the eluent stream analyzer;

an electronic data storage device for receiving and storing signals from the eluent stream analyzer representative of analysis of eluent stream aliquots of each respective chromatographic column; and

a programmable controller (computer) including an algorithm including instructions for sensing the presence, volume or components of an indexing fluid aliquot at the fluid sampling port of the analyzer and directing signals from the analyzer for eluent stream aliquots corresponding to the respective chromatographic columns to electronic data storage registers/devices designated for data storage for the respective chromatographic columns.

13. The multi-column chromatographic system of claim 12 wherein the fluid input port on the eluent switching valve assembly is positioned for fluid communication with the eluent stream from each chromatographic column and with a pressure control source of at least one indexing liquid and at least one indexing gas.

14. The multi-column chromatographic system of claim 12 wherein the eluent stream analyzer comprises a mass spectrometer.

15. The multi-column chromatographic system of claim 12 wherein the eluent stream analyzer comprises an infra-red spectrometer.

16. The multi-column chromatographic system of claim 12 wherein the eluent stream analyzer comprises a nuclear magnetic resonance spectrometer.

17. The multi-column chromatographic system of claim 12 wherein the eluent stream analyzer comprises an ultraviolet-visible spectrometer.

18. The multi-column chromatographic system of claim 12 wherein the eluent stream analyzer is selected from the group consisting of a fluorescence detector, an electrochemical detector and a refractive index detector.

21. The multi-column chromatographic system of claim 12 wherein the signal from the analyzer is used as “

feed back”

signal to control the programmable controller.