Liquid distributor and collector for chromatography columns

Abstract

DISTRIBUTOR AND LIQUID COLLECTOR FOR CHROMATOGRAPHY COLUMNS. The present invention relates to a column liquid distributor or collector for fluid chromatography, preferably with a round base, particularly suitable for columns with a large diameter in relation to the height of the filling.

Description

Descriptive Report of the Invention Patent for "DISTRIBUTOR AND COLLECTOR OF LIQUIDS FOR CHROMATOGRAPHY COLUMNS". The present invention relates to a liquid distributor or collector for columns for fluid chromatography, which is particularly suitable for columns with a large cross-sectional area relative to the packing height. Liquid distributors or collectors are used in column chromatography to uniformly distribute or collect liquids in the circulating cross-sections. This is a necessary condition to achieve the desired separation capability. In order to accommodate, within a column, the quantities of adsorbent necessary for the purification of increasingly larger feed volumes, developments in chromatography are moving towards larger column diameters, since the column length is limited upwards due to pressure loss and the need for the shortest possible residence or processing time. Furthermore, in order to achieve good separation yields in these columns with a large cross-sectional area relative to the packing height, new distributors or liquid collectors are needed for uniform distribution. Liquid distributors or collectors with fractional construction are known (WO 03 / 005018 A1, WO 02 / 093159 A2, WO 98 / 55198), in which the inlet or outlet occurs through a central opening, with a narrow slit between the opening and the filling to ensure uniform distribution. In increasingly larger cross-sections of circulation, the uniformity of distribution decreases due to the different lengths of the circulation path (from the opening to the middle or from the opening to the edge of the cross-section of the filling). Another design consists of distributing or collecting the liquid through several openings for filling (WO 89 / 11901, WO 99 / 48599). Ideally, uniform distribution is achieved here so that each opening corresponds to an equal volume flow and every flow path corresponds to an equal residence time. Constructively, this is achieved by maintaining the same distance as well as the same flow resistance (pressure loss) for the circulation channels. With an increasing number of openings (> 32), it is no longer possible to meet all criteria simultaneously. This results in either solutions with complex circulation channel geometries or, on the other hand, geometries that only guarantee uniform distribution for a given volume stream. An approved principle for distributing liquids between a large number of openings with increasing cross-sectional circulation cuts provides for the use of branched circulation channels based on symmetrical T-shaped distributors (US 4537217, WO 99 / 48599). This principle ensures, through the same length and geometric similarity of the circulation channels, the same resistance and thus equal volume flows and equal residence times.With increasing flow cross-sections, however, not all of the above-mentioned criteria regarding flows for any cross-section shapes can be simultaneously met: equal lengths of circulation channels and equal flow resistances with large flow cross-sections can only be achieved with square flow cross-sections (US 4537217), while the same volume flow distribution at the openings through exact geometric distribution (WO 99 / 48599) can only be achieved by complex, three-dimensional flow channel arrangements. A design for liquid distributors or collectors for chromatography columns that have a large diameter relative to the filling height, considering the residence time of the liquid in the circulation channels, is not yet known. Thus, based on the state of the art, the task is to provide a liquid distributor or collector that can also be used for large cross-sectional flow and that, through uniform distribution, ensures the condition for good separation capacity, that does not suffer limitations in relation to its shape, and that is as simple as possible to manufacture. This task is handled by the liquid distributor or collector. According to the invention, in addition to circulation channels with a symmetrical T-shaped distribution, i.e., in each case with equal length and cross-sectional area, circulation channels with asymmetrical T-shaped forms are employed, i.e., the lengths and cross-sectional areas of the circulation channels may have different sizes. The arrangement and proportion of the circulation channels may be chosen in such a way that the passage from the inlet to all outlets or from all inlets to the outlet of the liquid distributor or collector takes the same amount of time. Here, the mass flows, which are pooled at each opening by the arrangement and proportion of the circulation channels, should be as uniform in volume as possible. By employing equal flow passage duration as a normative criterion for the uniform distribution of liquid across the flow cross-section, a liquid distributor or collector is available that has a large number of openings and can therefore accommodate many flow cross-sections. It can be simply manufactured in a flat pattern and produced as a molded piece, and is not restricted by the shape of its base, thus allowing it to be round and scaled to any diameter in most chromatography columns. This enables a transition from laboratory scale to industrial production scale. Chromatography columns made using the liquid distributor or collector according to the invention, compared to traditional chromatography columns of the same geometry under the same operating conditions, have the advantage of better separation. The uniform distribution of liquids in large cross-sections in the liquid distributor and collector according to the invention is achieved by the greatest possible number of equidistant openings. Here, an opening of 50 to 5000, preferably 200 to 800, particularly preferably 300 to 400 square millimeters of cross-sectional surface area is provided for filling the column. The liquid distributor and collector according to the invention is, Furthermore, it is characterized by the fact that the connected liquid passages (circulation channels) are arranged in a plane, the base of which can be any shape, preferably round or rectangular, particularly preferred round. The liquid distributor or collector according to the invention can be made of metal, glass, or any suitable synthetic material (e.g., polycarbonate, polyester, polymethyl methacrylate), preferably metal, particularly corrosion-resistant metal, herein most particularly preferred stainless steel. For manufacturing the liquid distributor or collector according to the invention, the circulation channels can be produced by machine processing (e.g., drilling, milling) on ​​the workpiece; the liquid distributor or collector can also be produced by casting (e.g., glass or synthetic material). The liquid distributor or collector may consist of several correspondingly machined parts (for example by fusion, welding, gluing or bolting) or it may consist of a single piece. In a particularly preferred process for preparing the liquid distributor or collector according to the invention, a single piece of stainless steel is provided with the corresponding circulation channels and openings by fusion and perforation. The arrangement and dimensions of the circulation channels for the liquid distributor or collector according to the invention are determined as follows: To determine the optimal cross-sectional flow surface, which may contain an opening of the distributor or liquid collector, in the laboratory and / or pilot scale, a pulse is fed into several columns with different cross-sections under the same conditions, and the chromatogram provided by a detector is evaluated in relation to retention time, number of steps, symmetry, and maximum dissolution. From this series, the largest current surface still capable of satisfactory separation is chosen as the ideal cross-sectional flow surface. Based on the cross-sectional flow surface quotient The ideal number of openings required for the distributor or liquid collector results from the column filling rate in proportion to the production and the ideal cross-sectional area of ​​the stream evaluated in the laboratory. The openings of the liquid collector or distributor are arranged equidistantly above the cross-sectional flow predicted by the production ratio of the column to be used. The isolated openings are connected to each other by circulation channels that form a network of symmetrical T-shaped collectors. Here, neighboring openings or channels are connected, in each case, by a channel. The position of the circulation channels, as well as the dimensions (height and width) of the isolated circulation channels, are adjusted in a first approximation based on empirical considerations and values, so that approximately the same residence time is associated with the flow path for each opening, resulting in lanes with flow channel segments of equal length and equal cross-sectional surface area, as well as lanes with circulation channels of divergent length and / or cross-sectional surfaces.Additionally, the volume flows conjugated to the isolated openings should be as similar as possible. This design for residence time and volume flow occurs, for example, with the aid of numerical flow simulation, but other approximation and simulation processes are also possible. Thus, in the first approximation, for example, the residence times and volume flows can be determined on the basis of mass and energy balance or impulse for a one-dimensional current along a streamline between individually chosen cross-sectional sections of the current. A computerized model of the liquid distributor or collector is developed, and the residence times and volume flows are determined based on a flow simulation. By varying the model geometries, the geometry of the liquid distributor or collector can be determined in such a way that the conditions mentioned above are met.As a rule, several iteration cycles are required, ideally at least 2. The liquid distributor or collector is then tested by e- Further improvements to the geometry are potentially possible. Analogously to the procedure in the laboratory or pilot model, pulses are fed to the columns. From the chromatograms, retention times, number of steps, symmetries, and maximum dissolutions are determined and compared with the values ​​of the laboratory or pilot model. Color tests are also possible, i.e., the advancement of a colored liquid front in the distributor, filling, and collector, when the piece is made of a transparent material. With a given number of openings, while maintaining the original size proportions of the circulation channels, the liquid distributor or collector can be scaled to any technically useful diameter. Here, the defined measurements for a given liquid distributor or collector are provided for the circulation channels; that is, both the intervals between the openings and the lengths and width of the circulation channels are maintained in the main geometric arrangement with a factor that leads to the desired size. Due to limitations in construction and finishing, slight practical variations in the execution of the theoretical layout are possible. The liquid distributor or collector according to the invention can be used for the preparation of any chromatography columns for liquid chromatography (LC), supercritical fluid chromatography (SFC) and high-performance liquid chromatography (HPLC), preferably in chromatography columns with large diameters compared to the packing height, which in turn can be used in analytical and preparative chromatography and in process chromatography, in elution chromatography, adsorption chromatography (LSC) and displacement chromatography, in chiral chromatography, normal phase chromatography, reverse phase chromatography (RPC), ion exchange chromatography (IEC), ion pair chromatography (IPC), ion exclusion chromatography, gel permeation chromatography (GPC) or gel filtration chromatography (GFC) or side exclusion chromatography (SEC), hydrophobic reverse effect chromatography (HIC), hydroxyapatite chromatography, affinity chromatography,a) immobilized metal affinity (IMAC) and both in batch chromatography and in Continuous processes such as ring chromatography and simulated-moving-bed (SMB) chromatography are preferred. Its use is especially favored in preparative chromatography, particularly chiral, normal-phase, reversed-phase (RPC), ion-exchange (IEC), gel permeation (GPC), hydrophobic inverse-effect (HIC), hydroxyapatite, affinity, and immobilized metal affinity (IMAC) chromatography, and in both batch and continuous processes, with simulated-moving-bed (SMB) chromatography being particularly preferred. These columns and their use in analytical and preparative chromatography are also objects of the present invention. The use of a frit, preferably made of metal, ceramic, synthetic material, glass, preferably sintered metals and metal fabrics, particularly multi-layered metal fabrics (nominal width 5 to 500 micrometers) also with wide-pore drainage fabrics (nominal width 0.5 to 5 mm), can further improve the uniform distribution of the liquid distributor and collector. The liquid distributor and collector according to the invention can also be employed for other applications requiring a uniform distribution of liquid through a given number of openings on a surface on which, for example, receptacles belonging to the openings are also arranged. It is possible to use it for sample application, for example in high-speed screening. The invention is further illustrated by way of example through the figures, without, however, limiting its application. It is shown: Figure 1 - the side of the liquid distributor or collector facing the filling column. Figure 2 - the side of the liquid distributor or collector away from the packing column, with inlet or outlet channels and circulation channels. Figure 1 shows the side of the liquid distributor or collector column facing the filling column. Ninety-six equidistant openings are visible, symmetrically arranged across the circular cross-section. The openings are circular. Figure 2 shows the side of the liquid distributor or collector column distant from the filling column with a central inlet or outlet. The circulation channels are represented in symmetrical and asymmetrical T-shaped configurations. The filling openings in the column are located, in each case, at the ends of the Ts.

Claims

CLAIMS 1. Liquid distributor and collector for chromatography columns with at least one liquid inlet or liquid outlet opening and connected liquid passages (circulation channels) between the inlet or outlet opening and openings arranged equidistantly from the column packing, characterized in that the same time is required for the passage from the inlet to the outlet of the distributor or collector through the different liquid passages (circulation channels).

2. Liquid distributor and collector according to claim 1, characterized in that the mass streams corresponding to each opening are as uniform as possible.

3. Liquid distributor and collector according to claim 1 or 2, characterized in that a portion of the connected liquid passages (circulation channels) has a symmetrical T-shaped distribution form, and another portion has asymmetrical T-shaped forms.

4. Liquid distributor and collector according to one of claims 1 to 3, characterized in that each opening has a cross-sectional area of ​​50-5000 square millimeters for the column filling.

5. Liquid distributor and collector according to one of claims 1 to 4, characterized in that the connected liquid passages (channels) are arranged in a plane.

6. Liquid dispenser and collector according to one of claims 1 to 5, characterized in that the base of the dispenser or collector is round or rectangular.

7. Process for preparing a liquid distributor or collector according to claim 1, wherein a piece of metal or synthetic material is provided with connected liquid passages (circulation channels) and openings by machine processing, characterized in that a numerical flow simulation is used to place the circulation channels at equal residence times and equal volume currents.

8. Chromatography columns containing the liquid distributor or collector according to claim 1.

9. Use of the liquid distributor and collector according to one of claims 1 to 7 or of the chromatography columns according to claim 8, for analytical as well as preparative chromatography.

10. Use of a frit for improving the uniform distribution of the liquid distributor and collector according to one of claims 1 through 7.