Patent Application
20130134079
The invention relates generally to liquid chromatography and supercritical fluid chromatography. More particularly, the invention relates to the purification of a mobile phase in a liquid or supercritical fluid chromatography system.
Many materials used in solvent delivery modules for liquid chromatography (LC) systems can contribute impurities when exposed to the mobile phase. This problem is particularly evident for mobile phases containing acid modifiers. The ability to provide high purity mobile phase for LC measurements takes on increased significance as the sensitivity to impurities in LC systems increases. For example, high performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC) systems with increased detector sensitivity can be limited by impurities present in the mobile phase.
In many instances, a high purity mobile phase may be commercially available; however, the purity of the mobile phase may decrease while stored in a bottle or container. Thus the mobile phase may become sufficiently impure over time for use in performing high accuracy LC measurements.
In one aspect, the invention features a solvent delivery module for a chromatography system. The module includes a fluid path, a pump and a purification cartridge. The fluid path has a path inlet to receive a mobile phase solvent. The pump is disposed in the fluid path. The pump has a pump inlet configured to receive the mobile phase solvent and a pump outlet to provide the mobile phase solvent at an increased pressure. The purification is disposed in the fluid path and includes a packing material for removing an impurity from the mobile phase solvent. The purification cartridge has an inlet to receive the mobile phase solvent and an outlet to provide a purified mobile phase solvent.
In another aspect, the invention features a mobile phase delivery module for a chromatography system. The module includes a plurality of solvent delivery modules, a gradient proportioning valve and a pump. Each solvent delivery module includes a purification cartridge and a solvent reservoir configured to hold a mobile phase solvent. Each purification cartridge includes a packing material for removing an impurity from a respective one of the mobile phase solvents. Each purification cartridge has an inlet in communication with the solvent reservoir to receive the mobile phase solvent and an outlet to provide a purified mobile phase solvent. The gradient proportioning valve has a plurality of valve inlets and a valve outlet. Each valve inlet is in communication with the outlet of a respective one of the purification cartridges. The pump has a pump inlet that is in communication with the valve outlet and a pump outlet that provides a purified mobile phase that includes contributions of the purified mobile phase solvents from the solvent delivery modules.
In another aspect, the invention features a mobile phase delivery module for a chromatography system. The module includes a first pump having a first pump outlet to provide a first mobile phase solvent, a second pump having a second pump outlet to provide a second mobile phase solvent, a first purification cartridge, a second purification cartridge and a mixer. The first purification cartridge has an inlet in communication with the first pump outlet and has an outlet. The second purification cartridge has an inlet in communication with the second pump outlet and has an outlet. The first and second purification cartridges have packing material compositions to remove impurities from the first mobile phase solvent and the second mobile phase solvent, respectively. The mixer has a pair of inlets and an outlet. Each mixer inlet is in communication with one of the outlets of the first and second purification cartridges. The mixer outlet provides a mobile phase that includes a combination of the first and second mobile phase solvents.
In another aspect, the invention features a solvent delivery module for a chromatography system. The module includes a pump, a selectable fluid path module and a plurality of purification cartridges. The pump has a pump inlet to receive a mobile phase solvent and a pump outlet to supply a mobile phase solvent at an increased pressure. The selectable fluid path module has a module inlet in communication with the pump outlet, a module outlet and a plurality of fluid paths. One of the fluid paths is selectably configured to be in communication with the module inlet and the module outlet to receive the mobile phase solvent and to provide the mobile phase solvent, respectively. Each purification cartridge is disposed in a respective one of the fluid paths and includes a packing material for removing an impurity from the mobile phase solvent.
In yet another aspect, the invention features a solvent delivery module for a chromatography system. The module includes a solvent pump, a purge pump, a fluidic switch, a first purification cartridge and a second purification cartridge. The solvent pump has an outlet to supply a mobile phase solvent and the purge pump has an outlet to supply a purge fluid. The fluidic switch has a first fluid path and a second fluid path, and is in communication with the outlets of the solvent pump and the purge pump. The first purification cartridge is disposed in the first fluid path and includes a packing material for removing an impurity from the mobile phase solvent. The second purification cartridge is disposed in the second fluid path and includes a packing material for removing the impurity from the mobile phase solvent. The mobile phase solvent is conducted through the first purification cartridge and the purge fluid is conducted through the second purification cartridge when the fluidic switch is in a first state. The mobile phase solvent is conducted through the second purification cartridge and the purge fluid is conducted through the first purification cartridge when the fluidic switch is in a second state.
The above and further advantages of this invention may be better understood by referring to the following description in conjunction with the accompanying drawings, in which like reference numerals indicate like elements and features in the various figures. For clarity, not every element may be labeled in every figure. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention.
Reference in the specification to “one embodiment” or “an embodiment” means that a particular, feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the teaching. References to a particular embodiment within the specification do not necessarily all refer to the same embodiment.
The present teaching will now be described in more detail with reference to exemplary embodiments thereof as shown in the accompanying drawings. While the present teaching is described in conjunction with various embodiments and examples, it is not intended that the present teaching be limited to such embodiments. On the contrary, the present teaching encompasses various alternatives, modifications and equivalents, as will be appreciated by those of skill in the art. Those of ordinary skill having access to the teaching herein will recognize additional implementations, modifications and embodiments, as well as other fields of use, which are within the scope of the present disclosure as described herein.
As detector sensitivity improves, liquid chromatography (LC) and supercritical fluid chromatography (SFC) systems are increasingly limited by impurities in the mobile phase. Although high purity mobile phase solvents can be acquired or generated from a general source of mobile phase, impurities such as those introduced from a container or solvent reservoir can reduce the purity over time. According to various embodiments described herein, a solvent delivery module includes point of use purification of mobile phase solvents for LC systems such as an HPLC or a UPLC system. These solvent delivery modules can reduce or eliminate impurities in the mobile phase that cannot practically be removed by other means.
In brief overview, the solvent delivery module includes a fluid path having an inlet to receive a mobile phase solvent. A pump disposed in the fluid path increases the pressure of the mobile phase solvent. A purification cartridge in the fluid path receives the mobile phase solvent at an inlet and provides a purified mobile phase solvent at an outlet. The purification cartridge can be located on either the low pressure or high pressure side of the pump. As used herein, a purification cartridge can be an item that is easily inserted into and removed from the fluid path. Alternatively, the purification cartridge can be in the form of a column (e.g., a polishing column) that is coupled to the fluid path, for example, by fittings appropriate for high pressure fluid flow. The purification cartridge can be an item configured for routine replacement or may be provided in a regenerative form adapted for long term use. In various embodiments, a number of purification cartridges are provided so that one or more cartridges that are not in the active fluid path can be replaced or regenerated without interfering with operation utilizing another purification cartridge.
In the illustrated isocratic system 10, the purification cartridge 18 can contain the same packing material as in the analytical column 16. The purification cartridge 18 is maintained at a temperature sufficiently low as to delay the elution of the impurities on the analytical column 16 so that the impurities do not interfere with analysis. The impurities are washed off or eluted from the purification cartridge 18 either before the start of the next run or at some other desired interval. The LC system 10 can be run in a continuous regeneration mode of the purification cartridge 18 or the regeneration can be performed at a later time. At anytime the regeneration process can be accelerated by increasing the temperature of the purification cartridge 18 using the temperature control module 20.
In reversed-phase chromatography, an estimate of the temperature offset needed to separate an impurity from an analyte can be approximated by a 3% increase in the retention factor k′ for each 1° C. decrease in the temperature of the purge cartridge 18 relative to the temperature of the analytical column 16. For example, if the purification cartridge 18 and analytical column 16 are of equal size, contain a similar or identical packing material and the temperatures of the purification cartridge 18 and the analytical column 16 are maintained at 4° C. and 35° C., respectively, an increase in the retention factor k′ of about 90% is produced for the impurities on the analytical column 16. The elution time delay can be adjusted as desired by selecting or optimizing the individually controllable purification cartridge and analytical column temperatures. Preferably, active pre-column heating is used to prevent a mismatch between the analytical column temperature and the temperature of the solvent at the analytical column 16.
For the purpose of purifying mobile phase solvents, the highest capacity for impurities is typically obtained from materials having the highest specific surface area; however, porous graphitic carbon (PGC) is an exception. The retention properties of PGC such as Hypercarb® (available from Thermo Fisher Scientific of Waltham, Mass.) are unique relative to other chromatographic packing materials. PGC has higher retention for highly polar compounds than for moderately polar compounds. PGC can be more retentive for highly polar compounds than many materials having significantly higher specific surface areas. Thus PGC is a good choice for removing surfactants from aqueous mobile phases and is well suited for removing many impurities from strongly basic aqueous mobile phases (i.e., aqueous mobile phases having a pH greater than 12) due to its long term stability. For other impurities, high surface area polymer sorbents such as Oasis® hydrophilic-lipophylic-balanced (HLB) sorbent (available from Waters Corporation of Milford, Mass.) may be used.
For purification cartridges intended for use with high aqueous mobile phases (i.e., less than about 5% to 15% organic) on the low pressure side of an LC system, for example, as shown in
For purification cartridges intended for use with high aqueous mobile phases on the high pressure side of the solvent delivery pumps, such as shown in
To remove polar impurities from the numerous types of organic solvents in use today, a variety of normal phase packing materials are available for selection based on specific impurities. By way of specific examples, suitable phase packing materials include silica, alumina, zirconia, and titania. In addition, ion exchange resins can be used to remove ionic impurities.
Bead-shaped activated carbon (BAC) (available from Kureha America Inc. of New York, N.Y.) is an example of another packing material and can be used in purification cartridges to remove impurities from either water or organic solvents. BAC materials contain relatively low amounts of carbon fines but some initial shedding can occur therefore conditioning a cartridge off-line with the solvent prior to system installation is desirable. Preferably, a small guard column of the same material and particle size as the analytical column is attached at the outlet of the purification cartridge to prevent migration of the BAC fines to the inlet of the analytical column.
As described above, mobile phase impurities increasingly partition into the stationary phase of the purification cartridge 18 as the cartridge temperature decreases. As illustrated in
In an alternative embodiment, the four purification cartridges 36 are replaced by a single purification cartridge disposed between the gradient proportioning valve 38 and the mobile phase pump 40. This alternative embodiment has the advantage of reduced complexity and cost; however, the ability to isolate specific impurities according to each mobile phase solvent is sacrificed.
A control module can communicate with the selectable fluid path modules 56 via one or more control signals to configure a particular fluid path to conduct the mobile phase solvent. Alternatively, the selectable fluid path modules 56 can be manually reconfigurable. Purification cartridges 48 that are spent are taken offline (i.e., removed from the active mobile phase solvent path) and can be replaced or regenerated as described above.
The block diagram of
The mobile phase delivery module 62 is capable of operation in a LC system while regenerating a subset of the purification cartridges 48. For the illustrated state of the fluidic switches 70, a gradient separation is performed by passing a mobile phase solvent supplied by the solvent pump 66A through the upper purification cartridge 48A1 of the upper solvent delivery module 64A to the mixer 50. Similarly, a mobile phase solvent supplied by the solvent pump 66B passes through the upper purification cartridge 48B1 of the lower solvent delivery module 64B to the mixer 50. Purification cartridges 48A2 and 48B2 having reduced purification efficiency from prior use and are maintained offline. Purge fluids provided by the purge pumps 68 are passed through the offline purification cartridges 48A2 and 48B2 and on to a waste receptacle or conduit during an offline regeneration process.
In the illustrated embodiment, a temperature control module 72 adjusts the temperature of each purification cartridge 48 according to its mode of operation. For example, the online purification cartridges 48A1 and 48B1 are maintained at a lower temperature for improved purification efficiency and the offline purification cartridges 48A2 and 48B2 are maintained at a higher temperature for improved regeneration.
After extended use, the online purification cartridges 48A1 and 48B1 will accumulate impurities and become less efficient at removing impurities from the mobile phase solvents. Thus the fluidic switches 70 are changed to a complementary state in which the lower purification cartridges 48A2 and 48B2 of the solvent delivery modules 64 are place online and the upper purification cartridges 48A1 and 48B1 are taken offline for regeneration.
Various embodiments of the solvent delivery module or mobile phase delivery module, such as the embodiments described above, may be implemented in a variety of LC systems. In some embodiments, one or more of the module components are provided as part of a chip-based LC system. By way of examples, LC systems that may be adapted to include or interface with embodiments of the solvent delivery module and mobile phase delivery module include the ACQUITY® and TRIZAIC® LC/MS systems available from Waters Corporation of Milford, Mass.
While the invention has been shown and described with reference to specific embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as recited in the accompanying claims.
This application claims the benefit of the earlier filing date of U.S. Provisional Patent Application Ser. No. 61/564,117, filed Nov. 28, 2011 and titled “Mobile Phase Solvent Delivery Module,” the entirety of which is incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 61564117 | Nov 2011 | US |
