Patent Application
20170010243
Liquid chromatography systems are used to separate and analyze components of sample mixture. These systems use pumps to pass pressurized solvent and the sample through a column filled with a sorbent which is used to separate components of the sample. Typically a liquid sample passes over a solid adsorbent material packed into a column with a liquid solvent. Different components of the sample interact differently with the adsorbent material. If a component has a weak interaction with the adsorbent material, it flows through the column relatively quickly. If the component has a strong interaction, it flows through the column relatively slowly. Accordingly, different components flow through the column at varying speeds, separating from one another so that they may be analyzed and collected.
Different types of liquid chromatography systems employ different column types that utilize different injection ports. For example, a flash chromatography system typically uses a type of column and a corresponding injection port that are configured for operation under relatively low pressures (0-200 psi). In contrast, a preparative chromatography system uses a type of column and a corresponding injection port that are configured for operation under relatively high pressures (0-5,000 psi).
The apparatus and methods described herein provide for selection of a column in a multiple column chromatographic system. In one embodiment, apparatus and methods described herein provide for selectively switching between columns within a multiple column chromatographic system. The types of columns within the multiple column chromatographic system may be configured for operation under the same or different chromatographic conditions.
The following presents a simplified summary in order to provide a basic understanding of some aspects of the claimed subject matter. This summary is not an extensive overview. It is not intended to identify key/critical elements or to delineate the scope of the claimed subject matter. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is presented later.
A chromatographic apparatus and an associated method includes a first chromatographic column configured to perform a first type of chromatography as well as a second chromatographic column configured to perform a second type of chromatography. The first type of chromatography and second type of chromatography may be the same or different. In one embodiment, the first type of chromatography to be performed in the first chromatographic column is flash chromatography, and the second type of chromatography to be performed in the second chromatographic column is preparatory chromatography. Other types of chromatography which may be performed in at least one of the first or second chromatographic columns of the multiple column chromatographic system, include, but are not limited to, analytical chromatography, flash chromatography, preparatory chromatography, supercritical fluid chromatography and liquid chromatography.
The apparatus further includes a pump upstream of the columns that is configured to be in selective fluid communication with either the first chromatographic column or the second chromatographic column. A means of switching between the first chromatographic column and the second chromatographic column is disposed upstream of the first chromatographic column and the second chromatographic column and downstream of the pump. In one embodiment, a single multiport primary valve is disposed upstream of the first chromatographic column and the second chromatographic column and downstream of the pump. The primary value may have at least 3 ports. In one embodiment, the primary value has at least 4 ports. In a preferred embodiment, the primary value has from 4 to 16 ports. The primary valve selectively switches between a first position in which the pump is in fluid communication with a first path that includes the first chromatographic column and a second position in which the pump is in fluid communication with a second path that includes the second chromatographic column. Advantageously this single valve switch system provides a much simpler and faster method for switching between columns and/or chromatographic modes than prior art systems which require complex, error-prone multiple configuration changes to achieve the same result.
It is also within the scope of this invention that the means of switching between a first position in which the pump is in fluid communication with a first path that includes the first chromatographic column and a second position in which the pump is in fluid communication with a second path that includes the second chromatographic column is accomplished using two or more valves actuated simultaneously.
The apparatus also includes a first and a second sample injection port associated with said first and second columns, respectively, and at least one detector downstream of said columns. The apparatus is configured such that flow from the column in the selected path goes to said at least one detector without passing through the other column.
The following description may be understood when read in conjunction with the appended drawings. For purposes of illustrating the multiple column chromatographic system and methods of use, there is shown in the drawings exemplary constructions of this system and method; however, the system and method is not limited to the specific methods and instrumentalities disclosed. In the drawings:
The various aspects of the subject matter described herein are now described with reference to the drawings. It should be understood, however, that the drawings and detailed description relating thereto are not intended to limit the claimed subject matter to the particular form disclosed. Rather, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the claimed subject matter.
The following description relates to a liquid chromatography apparatus 10 such as that shown in
A primary valve 18 is disposed upstream of the first chromatographic column 12 and the second chromatographic column 14 and downstream of the pump 16. The primary valve 18 may be a six-port valve. With reference to
The apparatus also includes a first sample injection port 24 associated with the first chromatographic column 12 and a second sample injection port 34 associated with the second chromatographic column 14. Different types of injection ports provide for different types of sample loading into a column. For example, for both of the first and second chromatographic columns 12, 14, a secondary valve may be used for direct injection, solid loading, or both direct injection and solid loading into the column. Such valves may be supplied by Rheodyne (Idex) in Rohnert Park, Calif. or Valco in Houston, Tex.
Each column 12, 14 is in selective fluid communication with a detector 40 and, optionally, a fraction collector 42. Collector 42 may be omitted if the apparatus 10 is intended only for analysis and not collection. Both the detector 40 and the fraction collector 42 are disposed downstream of the first and second chromatographic columns 12, 14. Together, the detector 40 and the fraction collector 42 are configured to analyze and collect at least one fraction of a sample S1, S2 that passes through either the first or second path. Specifically, the apparatus is configured such that flow from the column 12 or 14 in the selected path 22 or 32 goes to said at least one detector 40 without passing through the other column 12 or 14, respectively.
When the apparatus 10 is in flash mode, the primary valve 18 is in its first position 20 (shown in
As shown in
As the sample S1 flows through the first column 12, different fractions F1A, F1B of the sample interact differently with the adsorbent material. A fraction P1A with a weak interaction with the adsorbent material flows through the first column 12 relatively quickly, while a fraction F1B with a strong interaction flows through the column relatively slowly. Accordingly, fractions F1A, F1B, disposed in solvent, flow from the first column 12 at different times. From the first column 12, these fractions F1A, F1B, along with solvent, are routed back to the primary valve 18 to the detector 40 and collector 42 which ate disposed downstream of the first column 12 and the primary valve 18 when the primary valve is in its first position 20. When the primary valve 18 is in its first position 20, the second column 14 is not in fluid communication with either the pump 16 or the detector 40 and collector 42.
Detector 40 may be a non-destructive detector such an ultraviolet light detector, an optical absorbance detector, a refractive index detector (RID), a fluorescence detector (FC), chiral detector (CD), or a conductivity detector. Other types of detectors, including destructive detectors, may be used instead of or in addition to a non-destructive detector. For example, an evaporative light scattering detector, a mass spectrometer (MS), a condensation nucleation light scattering detector (CNLSD), and a corona discharge detector. Multiple non-destructive and/or destructive detectors may be used in apparatus 10. Destructive detectors may be used in conjunction with a shuttle valve such that only a portion of the sample is removed from the sample stream and destroyed.
When the apparatus 10 is in preparative mode, the primary valve 18 is in its second position 30 (shown in
As shown in
Similar to the process described above, as the sample S2 through the second column 14, different fractions F2A, F2B of the sample interact differently with the adsorbent material. A fraction F2A with a weak interaction with the adsorbent material flows through the second column 14 relatively quickly, while a fraction F2A, F2B with a strong interaction flows through the column relatively slowly. Accordingly, fractions F2A, F2B, disposed in solvent, flow from the second column 14 at afferent times. From the second column 14, these fractions F2A, F2B, along with solvent, are routed back to the primary valve 18 to the detector 40 and collector 42 which are disposed downstream of the second column 14 and the primary valve 18 when the primary valve is in its second position 30. Detector 40 and collector 42 are more fully described in relation to Example 1. When the primary valve 18 is in its second position 30, the first column 12 is not in fluid communication with either the pump 16 or the detector 40 and collector 42.
Primary valve 18 may be configured to switch between the first position 20 and the second position 30 in various ways. For example, primary valve 18 may be manually actuated between positions 20, 30. Alternatively, primary valve 18 may be automatically actuated using a control system 100.
Control system 100 includes sensors disposed throughout apparatus 10 that are configured to identify and set the position of primary valve 18. For example, control system 100 uses sensors configured to read RFID tags or bar codes on columns 12, 14. Other identification tags may also be used, such as QR codes. In conjunction with the sensors, control system 100 can determine whether a flash or preparative column is installed in the apparatus and the operating parameters associated with an installed column. Control system 100 may connect to a network, such as the internet, to determine operating parameters associated with the installed column. The network may also be used to control the apparatus 10 remotely and/or to report results of a run. Control system 100 may also include a user interface (not shown) to display operating parameters of the system and to accept user input regarding whether to process a sample using flash or preparative modes.
Optionally, with reference to U.S. Application No. 61/938,508 filed Feb. 11, 2014, which is hereby incorporated in its entirety herein, control system 100 be used to control other aspects of apparatus 10. For example, the positions of secondary valves 26, 36, may be controlled using sensors to determine if the secondary valves 26, 36 have been sufficiently primed with solvent and a sample S1, S2. Operating speed of pump 16 may also be controlled based on readings from pressure sensors 102, 104.
As the foregoing illustrates, the present invention is directed to a multiple column chromatographic system and methods of use. Changes may be made to the embodiments described above without departing from the broad inventive concepts thereof. Accordingly, the present invention is not limited to the particular embodiments disclosed, but is intended to cover all modifications that are within the spirit and scope of the invention as defined by the appended claims.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US15/15469 | 2/11/2015 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 61938563 | Feb 2014 | US |
