Patent Application
20230264118
The present disclosure relates to an improved column useful in chromatography, such as high performance liquid chromatography (HPLC). The improved column provides superior flow characteristics.
In separation procedures, particularly liquid chromatography, it is critical that the mobile phase and the sample undergoing analysis be delivered to the separation media uniformly throughout the cross-section of the media to ensure efficient operation of the column and to attain accurate results. In the existing columns, when fluid is introduced into the column, it has a tendency to penetrate the media to a considerable depth before spreading out, thereby reducing the efficiency and effectiveness of the media. Thus, to take full advantage of the separation media, it is desirable to construct a column that disperses the entering fluid throughout the cross-sectional area of the column and maintains a uniform flow through the media.
In an aspect, a chromatography column includes a first flow distributor, a second flow distributor different from the first flow distributor, and a media chamber having an inlet and an outlet. The first flow distributor is secured to the inlet of the media chamber and the second flow distributor is secured to the outlet of the media chamber.
In another aspect, the first flow distributor includes an opening having a first surface area and the second flow distributor includes an opening having a second surface area.
In a further aspect, the first surface area is smaller than the second surface area.
In yet another aspect, the first flow distributor includes a plurality of openings and the second flow distributor includes one opening.
In an aspect, the plurality of openings in the first flow distributor includes a sum surface area that is different from a surface area of the one opening in the second flow distributor.
In another aspect, the sum surface area of the plurality of openings in the first flow distributor is smaller than the surface area of the opening in the second flow distributor.
In a further aspect, the first flow distributor includes a first plurality of openings and the second flow distributor includes at least one opening, wherein each of the first plurality of openings includes a diameter that is smaller than a diameter of at least one opening in the second flow distributor.
In yet another aspect, the first flow distributor is a showerhead-like flow distributor and the second flow distributor is an open dispersion flow distributor.
In an aspect, a chromatography column includes a first flow distributor, a second flow distributor, and a media chamber positioned between the first flow distributor and the second flow distributor. The first flow distributor and the second flow distributor include a design that reduces a parabolic flow profile at outlet.
In another aspect, to reduce the parabolic flow profile at outlet, the first flow distributor is different from the second flow distributor.
In a further aspect, the first flow distributor includes an opening having a first surface area and the second flow distributor includes an opening having a second surface area.
In yet another aspect, the first flow distributor includes a plurality of openings and the second flow distributor includes one opening.
In an aspect, the first flow distributor includes a first plurality of openings and the second flow distributor includes at least one opening. Each of the first plurality of openings includes a diameter that is smaller than a diameter of the at least one opening in the second flow distributor.
In another aspect, the first flow distributor is a showerhead-like flow distributor and the second flow distributor is an open dispersion flow distributor.
In a further aspect, a method for reducing a parabolic flow profile in a chromatography column includes securing a first flow distributor at inlet of a media chamber and securing a second flow distributor at outlet of the media chamber, wherein the first flow distributor is different from the second flow distributor.
In yet another aspect, the first flow distributor includes an opening having a first surface area and the second flow distributor includes an opening having a second surface area, wherein the first surface area is smaller than the second surface area.
In an aspect, the first flow distributor includes a plurality of openings and the second flow distributor includes one opening.
In another aspect, the first flow distributor includes a first plurality of openings and the second flow distributor includes at least one opening, wherein each of the first plurality of openings includes a diameter that is smaller than a diameter of the at least one opening in the second flow distributor.
In a further aspect, a flow distributor includes an opening on exterior surface of the flow distributor and a plurality of channels positioned on interior surface of the flow distributor. Each of the plurality of channels on the interior surface of the flow distributor is in fluid communication with the opening on the exterior surface of the flow distributor.
In yet another aspect, each of the plurality of channels includes a first length or a second length.
Additional features and advantages of various embodiments will be set forth, in part, in the description that follows, and will, in part, be apparent from the description, or may be learned by the practice of various embodiments. The objectives and other advantages of various embodiments will be realized and attained by means of the elements and combinations particularly pointed out in the description herein.
The same part numbers designate the same or similar parts throughout the figures.
In an example (not shown in the figures), an optional fit may be inserted into each end of the media chamber 102 to compress and stabilize the separation media that is packed under high pressure in the media chamber 102. The frits inserted into each end of the media chamber 102 may also help reestablish some of the pressure lost after the packing process when the pressure is removed to complete assembly of the media chamber 102. It may be advantageous to press the frits inserted at each end of the media chamber 102 with an interference fit to seal against the inner surface of the media chamber 102 and prevent the leakage of the packed separation media from the media chamber 102.
Also shown in
In an example, the first flow distributor 106 may include any design. For example, the first flow distributor 106 may include one opening, as shown in
The chromatography column 100 may also include the second flow distributor 110 positioned at the outlet of the media chamber 102. In an example, the second flow distributor 110 can be designed to receive a second frit 108b. The second frit 108b may be the same or different from the first frit 108a or the optional frit that may have been inserted at one or both ends of the media chamber 102, as described above.
In an example, the second flow distributor 110 may include any design that is different from the design of the first flow distributor 106. For example, if the first flow distributor 106 includes a plurality of openings, as shown in
In an example, as shown in
In an example, when the first flow distributor 106 is a showerhead-like flow distributor 200, the second flow distributor 110 can be an open dispersion flow distributor 300, as shown in
In an example, when the second flow distributor 110 is the open dispersion flow distributor 300 and the first flow distributor 106 is the showerhead-like flow distributor 200, the surface area of the opening 304 of the open dispersion flow distributor 300 is larger than the sum of the surface areas of the openings 206 of the showerhead-like flow distributor 200. For example, the surface area of the opening 304 can occupy from about 99% to about 0.001% of the total surface area of the open dispersion flow distributor 300, such as from about 50% to about 90%, for example, about 80% or more. Additionally, the sum of the surface area of the openings 206 can occupy from about 0.001% to about 99% of the total surface are of the showerhead-like flow distributor 200, such as less than about 50%, or from about 0.001% to about 30%, for example, about 2% or less.
In another example, when the first flow distributor 106 is a showerhead-like flow distributor 200, the second flow distributor 110 may be a multi-hole flow distributor 350, which may include a plurality of openings 352, as shown in
In an example, when the first flow distributor 106 is a showerhead-like flow distributor 200 or an open dispersion flow distributor 300, then the second flow distributor 110 may be a new flow distributor 400, as shown in
The flow distributors 200, 300, 350, and 400 may be made of various polymer, for example, PTFE (polytetrafluoroethylene), ETFE (ethylene tetrafluoroethylene), PEEK (polyetheretherketone) or KEL-F® (polychlorotrifluoro-ethylene). In general, any non-porous parts of the flow distributors 200, 300, 350, and 400 may be made of plastics or polymer, for example, PTFE, ETFE, PEEK or KEL-F. In an example, the flow distributors 200, 300, 350, and 400 may be made of PEEK.
In summary, having a chromatography column that includes a first flow distributor 106 at its inlet that is different from a second flow distributor 110 at its outlet, unexpectedly causes a reduced parabolic flow profile at outlet.
As discussed above, the first flow distributor 106 located at the inlet of the media chamber 102 and the second flow distributor 110 located at the outlet of the media chamber 102 are different. Thus, when the first flow distributor 106 is the showerhead-like flow distributor 200, then the second flow distributor 110 may be the open dispersion flow distributor 300, the multi-hole flow distributor 350, or the new flow distributor 400. In another example, when the first flow distributor 106 is the open dispersion flow distributor 300, then the second flow distributor 110 may be the showerhead-like flow distributor 200, the multi-hole flow distributor 350, or the new flow distributor 400. In another example, when the first flow distributer 106 is the multi-hole flow distributor 350, then the second flow distributor 110 may the showerhead-like flow distributor 200, the open dispersion flow distributor 300, or the new flow distributor 400. In yet another example, when the first flow distributor 106 is the new flow distributor 400, then the second flow distributor 110 may be the showerhead-like flow distributor 200, the multi-hole flow distributor 350, or the open dispersion flow distributor 300.
In an example, the end fittings 104a, 104b may coaxially surround the flow distributors 106, 110, with the inner surface of the end fittings 104a, 104b abutting the flow distributors 106, 110. The end fittings 104a, 104b may keep the frits 108a, 108b and the flow distributors 106, 110 in place. The end fittings 104a, 104b may also compress the packed separation media and be connected to the fluid lines of a chromatographic system. In an example, each end fittings 104a, 104b may include a bore at the center of its end surface, which has threads for engaging a fluid conduit fitting (not shown).
The following examples illustrate the improved and unexpected performance of the chromatography column using the inventive flow distributor arrangement, which was tested on an Agilent 1290 Infinity II Preparative Liquid Chromatograph with a 0.3 mm flow cell using a Poroshell SB-C18 HPLC column (available from Agilent Technologies) and a UV detector set at 254 nm. The column had a diameter of 21.2 mm and a length of 50 mm and was configured with the showerhead-like flow distributor at the inlet end of the column. The second (outlet) flow distributor was changed, and the column performance was measured as Theoretical Plates (Plates) of a component peak using the European Pharmacopeia method based on the peak width at half height. Representative columns were evaluated using both an isocratic and gradient elution method.
The test was performed using naphthalene as a test probe under the following chromatographic conditions:
Mobile Phase: 60% acetonitrile/40% water (v/v)
Flow Rate: 20 mL/min.
In this test, the first (inlet) flow distributor 106 was a showerhead-like flow distributor 200, and the second (outlet) flow distributor 110 was selected from a showerhead-like flow distributor 200, an open dispersion flow dispersion 300, or a new flow distributor 400.
Table 1 shows the effect on plates when changing the second (outlet) flow distributor.
The test was performed using methylparaben as a test probe under the following chromatographic conditions.
Mobile Phase:
Gradient:
Flow Rate: 20 mL/min.
In this test, the first (inlet) flow distributor 106 was a showerhead-like flow distributor 200, and the second (outlet) flow distributor 110 was selected from a showerhead-like flow distributor 200, an open dispersion flow dispersion 300, or a new flow distributor 400.
Table 2 shows the effect on plates when changing the second (outlet) flow distributor.
Both the new and open dispersion flow distributors showed improved performance (higher plates) compared with the showerhead-like flow distributor for both the isocratic and gradient tests.
The open dispersion flow distributor demonstrated better reproducibility (lower StdDev) compared with the new flow distributor.
This disclosure is to be broadly construed. It is intended that this disclosure disclose equivalents, means, systems and methods to achieve the devices, activities and mechanical actions disclosed herein. For each device, article, method, mean, mechanical element or mechanism disclosed, it is intended that this disclosure also encompasses in its disclosure and teaches equivalents, means, systems and methods for practicing the many aspects, mechanisms and devices disclosed herein. Additionally, this disclosure is intended to encompass the equivalents, means, systems, and methods of the use of the device and/or article of manufacture and its many aspects consistent with the description and spirit of the operations and functions disclosed herein. The claims of this application are likewise to be broadly construed.
The description of the inventions herein in their many embodiments is merely exemplary in nature and, thus, variations that do not depart from the gist of the invention are intended to be within the scope of the invention. Such variations are not to be regarded as a departure from the spirit and scope of the invention.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2021/051769 | 9/23/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63085730 | Sep 2020 | US |
