JP2018124143A - Filter unit for chromatographic column liquid feeding system - Google Patents

Abstract

PROBLEM TO BE SOLVED: To suppress the occurrence of unevenness of a liquid component supplied to a chromatography column in a filter unit and also to suppress bacteria breeding and insolubilization and precipitation of the liquid component in a liquid feeding system.SOLUTION: Disclosed is a filter unit which is used in a solution feeding system to a chromatography column. In a disc filter unit 40, the diameter of a disc filter 44 is 1-3 times the diameter of a raw water inlet 41 or a filtered water outlet 46. The thickness of the disc filter 44 is 0.5-5 mm.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a filter unit used in a liquid feeding system to a chromatography column used in a separation and purification process of pharmaceuticals, fine chemicals, functional components, and the like, and more particularly to a space-saving and efficient filter unit.

  2 and 3 show an example of a liquid feeding system to a chromatography column. In FIG. 2, in the liquid feeding system 10, the solvent 1 and the stock solution sample 2 are fed by the pumps 3 and 4, merged and mixed by the in-line mixer 5, and the suspended components are removed by the line filter 6. The sorting control device 13 receives the signal from the detector 12 supplied to the column 11 and switches between opening and closing of the automatic ball valves 14 and 15, thereby sorting a predetermined portion of the predetermined mobile phase into the fraction tanks 16 and 17.

  FIG. 3 shows a system in which the solvent 1 and the sample 2 are combined after being sequentially passed through the in-line mixer 5 and the line filter 6, respectively. Other configurations are the same as those in FIG. When there are a plurality of types of solvents (buffers) and stock solutions, they are independently passed through the solvent line 7 and the stock solution line 8. While the liquid flow is stopped, the stock solution line 8 is extruded and replaced with a solvent.

  In FIGS. 2 and 3, the solvent 1 and the stock solution sample 2 are each one kind, but may be plural kinds.

  In a conventional liquid feeding system to a chromatographic column, a line filter unit 20 for general industrial use as shown in FIG. The line filter unit 20 includes a stock solution inlet 21 for performing filtration, a cylindrical main body 22 into which the stock solution flows, a perforated cylindrical inner cylinder 27 attached coaxially to the main body 22, and an inner cylinder 27. A filter 23 that filters the undiluted solution attached so as to cover the holes, a flange 24 that opens / closes the main body 22 when the filter 23 is attached or removed, a filtrate outlet 25 that removes the filtrate of the filter 23, It comprises a lid 26 that closes one end side of the inner cylinder 27 so that the stock solution does not flow into the filtrate flow path from the opposite side of the filtrate outlet 25 of the inner cylinder 27.

  Patent Document 1 describes an inline filter in which a stock solution inlet is provided on a side surface of a main body.

  By the way, in the liquid feeding system to the chromatography column used in the separation and purification process of pharmaceuticals, fine chemicals, functional components, etc., the plug flow supplied to the chromatography after the line filter is inhibited by diffusion, resulting in uneven liquid components. It is important to prevent the target component from being purified and recovered with high purity and high recovery rate, and to prevent the occurrence of miscellaneous bacteria growth, insolubilization and precipitation of the liquid component in the liquid feeding system. It is a requirement. A review of the system from this point of view revealed that there was room for improvement in the line filter.

  That is, in the conventional filter unit structure, liquid retention may occur as described below, and this liquid retention may cause the above problem.

  The processing amount of the filter is determined by considering the flow resistance and filtration area load, and the design processing amount (L / m / piece) is determined. Therefore, it is necessary to increase the number of filters attached to the filter unit as the processing amount increases. There is. As a method for installing filters when increasing the number of filters, there are a method of connecting filters in series, a method of arranging them in parallel, and a method of combining both methods.

  In the method in which the filters are connected in series, the flow rate near the stock solution inlet is fast, so that the stock solution is not easily developed to the opposite side of the stock solution inlet for the filter near the stock solution inlet. In other words, liquid retention tends to occur on the opposite side of the stock solution inlet.

  In the method of arranging filters in parallel, when filters are arranged in parallel in a unit, a gap is created between adjacent filters, and the stock solution is flowed at a high flow rate in the direction perpendicular to the filter surface (in the major axis direction of the main body). When this is caused to flow in, this gap becomes a liquid retention region (due to the generation of vortex flow), which hinders rapid development of the stock solution on the filter surface.

  Therefore, it is conceivable to apply a disk filter unit instead of a conventional filter as an inline filter used in the liquid feeding system. The disc filter unit for general industrial use has a simple structure and is easy to maintain. Therefore, it may be applicable as an in-line filter used in a liquid feeding system.

  As an example, a vertical sectional perspective view of the disk filter unit 30 is shown in FIG.

  The disk filter unit 30 includes a main body upper 32 having an inlet 31 for raw water to be filtered, a raw water flow path 33 in which raw water flowing from the inlet 31 is developed on the filter filtration surface, a disk filter 34 for filtering the raw water, a disk A filtered water flow path 35 for collecting the filtered water of the filter 34, a main body lower 37 having a filtered water outlet 36 for taking out the filtered water, and opening / closing the main body upper 32 and the main body lower 37 when the filter 34 is attached or removed. A clamp 38 as a fastener to be clamped, and an O-ring 39 for sealing the mating surfaces of the main body upper 32 and the main body lower 37.

  The diameters of the raw water inlet 31 and the filtered water outlet 36 are selected so that the water flow resistance becomes a certain value or less by engineering calculation from the flow rate. That is, the larger the flow rate, the larger the diameter of the inlet 31 and the outlet 36, and the smaller the flow rate, the smaller the diameter of the inlet 31 or the outlet 36.

  In general industrial applications, the disk filter unit is applied for the purpose of obtaining filtered water by filtering a suspended component having a relatively high concentration of a certain size or more contained in raw water with a disk filter. In this case, since the raw water contains a relatively high concentration of suspended components, the filtered components adhere to and accumulate on the filtration surface of the filter, the filtration resistance increases, and the amount of filtered water per unit time gradually decreases. . When the specified amount of filtered water per unit time cannot be obtained, stop the raw water flow, remove the clamp, separate the upper and lower parts of the main unit, take out the filter and clean it, or replace it with a new filter. Exchange. Next, the disk filter unit is assembled, and the flow of raw water is resumed. If the filter diameter is small and the filter filtration area is small, the frequency of cleaning or replacement of the filter increases. Therefore, a filter having a filter diameter that is about 10 to 20 times larger than the diameter of the raw water inlet or the filtered water outlet is usually used.

  However, in the disk filter unit for general industrial use, the water flow LV at the center (near the raw water inlet and the filtrate water outlet) of the filter increases, while the water flow LV increases as the distance from the center approaches the periphery. Since it becomes smaller and diffusion occurs and liquid retention tends to occur, the risk of liquid retention still cannot be eliminated even if a general disk filter unit is used as it is.

JP 2000-205208 A

  The present invention suppresses the occurrence of unevenness of liquid components supplied to a chromatography column in a filter unit for a liquid feeding system to a chromatography column used in separation and purification processes of pharmaceuticals, fine chemicals, functional components, etc. It is an object of the present invention to provide a filter unit capable of suppressing the propagation of various bacteria in the liquid feeding system and insolubilization and precipitation of liquid components.

  The filter unit of the present invention is a filter unit used in a liquid feeding system to a chromatography column, and is characterized in that the filter diameter is a disk filter unit having 1 to 3 times the raw water inlet diameter or the filtrate outlet diameter. .

  In one aspect of the present invention, the raw water inlet diameter is greater than or equal to the filtered water outlet diameter.

  In one embodiment of the present invention, the filter has a thickness of 0.5 to 5 mm.

  In one aspect of the present invention, the pipe diameter of the supply-side pipe of the liquid-feeding system and the raw water inlet diameter of the filter unit are the same diameter, or the pipe diameter of the liquid-feeding system is increased to increase the supply pipe of the liquid-feeding system. And a tapered throttle tube between the raw water inlet of the filter unit.

  In one aspect of the present invention, the pipe diameter of the discharge side pipe of the liquid feeding system and the filtered water outlet diameter of the filter unit are made the same diameter, or the pipe diameter of the liquid feeding system is made smaller to reduce the filtered water of the filter unit. A tapered throttle pipe is interposed between the outlet and the discharge pipe of the liquid feeding system.

  Raw water (raw solution sample) or pure water or sterile water (solvent) that is passed through a liquid feeding system to a chromatography column used in the separation and purification process of pharmaceuticals, fine chemicals, functional components, etc., is separated into solid-liquid separation, for example, Since it is centrifuged, there are almost no suspended components. Therefore, the filtration area of the disk filter is smaller than that of a disk filter for general industrial use. Based on this knowledge, the present invention optimizes the diameter of the disk filter in terms of chemical engineering.

  The filter unit of the present invention uses a disk filter with an appropriately reduced filter diameter, thereby preventing stagnation of raw water and filtered water in the filter unit and enabling a rapid flow. Thereby, the nonuniformity of the liquid component supplied to the chromatography is suppressed, and the accuracy of separation and purification is increased. Moreover, it becomes possible to suppress miscellaneous bacteria propagation and insolubilization and precipitation of liquid components in the liquid feeding system by preventing the stay.

  In addition, separation and purification of pharmaceuticals, fine chemicals, and functional components are performed in a clean room, but the clean room ensures and maintains cleanliness and cannot be unnecessarily large. However, since the disk filter unit is miniaturized according to the present invention, the liquid feeding system is miniaturized and installation in a clean room with limited space becomes easy.

  In the present invention, if the filtrate outlet diameter is larger than the raw water inlet diameter, turbulent flow is generated and diffusion is likely to be induced.In the present invention, the filtrate outlet diameter is the same as the raw water inlet diameter or A small diameter is preferable. In addition, since the risk of contamination increases as the sealing pipe increases when the throttle pipe is interposed, it is preferable that the filtered water outlet diameter and the raw water inlet diameter are the same.

  In the filter unit of the present invention, since the disc filter diameter is relatively small, the liquid flow rate in the filter is increased and the liquid flow resistance is increased. Therefore, it is conceivable to increase the thickness of the disk filter in order to increase the mechanical strength of the disk filter. However, if the filter thickness is large, diffusion of target components occurs in the filter, and chromatographic separation with good purity and recovery cannot be achieved. . Therefore, in the present invention, the thickness of the disk filter is preferably small from the viewpoint of chromatographic accuracy, and is preferably 5 mm or less, particularly 3 mm or less. For manufacturing reasons, the thickness of the disc filter is preferably 0.5 mm or more, particularly 1 mm or more.

  Make the pipe diameter of the supply system piping equal to the diameter of the raw water inlet of the filter unit, or increase the pipe diameter of the liquid supply system to increase the supply pipe of the liquid supply system and the raw water inlet of the filter unit. By interposing the tapered throttle tube between them, it is possible to suppress the formation of a liquid retention region at the connection portion between the filter unit and the pipe of the liquid feeding system. Also, make the pipe diameter of the discharge side pipe of the liquid feeding system and the filtered water outlet diameter of the filter unit the same diameter, or make the pipe diameter of the liquid feeding system smaller to reduce the filtered water outlet of the filter unit and the liquid feeding system. By interposing a tapered throttle pipe between the pipe and the discharge pipe, it is possible to suppress the formation of a liquid retention region at the connection portion between the filter unit and the pipe of the liquid feeding system.

It is sectional drawing of the disc filter unit which concerns on embodiment. It is a block diagram of the liquid feeding system to a chromatography column. It is a block diagram of the liquid feeding system to a chromatography column. It is sectional drawing of the conventional line filter unit. It is sectional drawing of the conventional disc filter unit. It is sectional drawing of the disc filter unit which concerns on embodiment. It is a chromatogram which shows the result of an Example. It is a chromatogram which shows the result of an Example.

  An example of the present invention is shown in FIG. The disk filter unit 40 includes a main body upper 42 having an inlet 41 for raw water to be filtered, a raw water flow path 43 through which raw water flowing from the raw water inlet 41 develops on a filter filtration surface, a disk filter 44 for filtering raw water, A filtered water passage 45 for collecting the filtered water of the filter 44, a main body lower 47 having a filtered water outlet 46 for taking out the filtered water, and opening / closing the main body upper 42 and the main body lower 47 when the filter 44 is attached or removed. And a clamp 48 as a fastener for sealing, and an O-ring 49 for sealing the mating surfaces of the main body upper 42 and the main body lower 47. Since any member can be used in the same operation as conventional general-purpose products, there is an advantage that the user is not burdened with learning or proficiency of operation in application.

  On the other hand, by optimizing the filter diameter based on fluid engineering grounds, the diameter of the raw water inlet or filtered water outlet selected so that the water flow resistance is below a certain level calculated from the flow rate can be reduced. The filtered water was prevented from staying and a rapid flow was possible. In this embodiment, the diameter of the disk filter 44 is 1 to 3 times, preferably 1 to 2 times the diameter of the raw water inlet 41.

  In another embodiment of the present invention, the diameter of the disk filter 44 is 1 to 3 times, preferably 1 to 2 times, the diameter of the filtered water outlet 47.

  In this way, by reducing the diameter of the disk filter 44 (in other words, the filtration area) optimally, the disk filter unit 40 is reduced to 1/3 to 1/20 of the disk filter unit 30 of FIG. This can also contribute to the downsizing of the liquid feeding unit.

  In the present invention, as shown in FIG. 6, the diameter of the supply-side piping 51 of the liquid feeding system is the same as the diameter of the raw water inlet 41 of the filter unit 40 (FIG. 6 (a)), or the liquid feeding system. The diameter of the pipe 53 may be made larger so that a tapered throttle pipe 54 is interposed between the supply pipe 53 of the liquid feeding system and the raw water inlet 41 of the filter unit 40 (FIG. 6B).

  Further, the diameter of the discharge side pipe 52 of the liquid feeding system and the diameter of the filtered water outlet 46 of the filter unit 40 are made the same diameter (FIG. 6A), or the diameter of the pipe 55 of the liquid feeding system is made smaller. Then, a configuration in which a tapered throttle pipe 56 is interposed between the filtered water outlet 46 of the filter unit 40 and the discharge pipe 55 of the liquid feeding system (FIG. 6B) may be adopted.

  For filters and filter units that are suitable for use in a liquid delivery system to a chromatographic column, it is desirable to minimize the accumulation of liquid (liquid retention) and the diffusion of components for separation and purification. In comparison, it is important to set the filter diameter to an appropriate ratio without increasing the filter diameter as in water treatment applications, and it is also necessary to optimize the filter thickness. That is, if the thickness of the filter is too thick, the components for separation and purification will diffuse in the filter layer, and chromatographic separation with good purity and recovery will not be possible. The proper filter thickness is preferably 5 mm or less, although it depends on the flow rate, filter pore diameter and material.

  As a material of the disk filter, for example, polypropylene (PP), polyvinylidene fluoride, polyether ether ketone (PEEK), Teflon (PTFE), SUS316, SUS316L, Hastelloy, or the like is used.

  In the present invention, since a disk filter unit is used, a plurality of filters cannot be used in parallel in multiple stages as in the conventional filter. Therefore, although it depends on the pipe diameter, it is suitably applied to a liquid feeding system for a relatively medium / small chromatography column in which the linear flow velocity (LV) in the pipe of the liquid feeding system is about 2 m / s or less. The

  As described above, it is desirable that the filter unit suitable for use in the liquid feeding system to the chromatography column should minimize the accumulation of liquid (liquid retention) and the diffusion of the separation / purification target component. In addition to making the diameter of the raw water inlet 41 of the unit equal to the diameter of the filtrate outlet 46, the diameters of the raw water inlet 41 and filtrate outlet 46 and the pipe of the liquid feed system (after unifying the diameter of each pipe of the liquid feed system) It is more desirable to make it equal to the diameter.

  The disk unit structure in which the raw water inlet diameter and filtered water outlet diameter are made equal and the filter diameter is changed from 1 to 18 times the raw water inlet or filtered water outlet diameter is spiked from the raw water inlet by numerical mechanics analysis method. We simulated the time change of the dyes coming out from the exit. In this analysis example, the raw water inlet diameter was 7.5 mm and the raw water flow rate was 7 L / min. Examples of analysis results are shown in FIGS.

  As shown in FIGS. 7 and 8, when the disk filter diameter is about 1 to 2 times the raw water inlet diameter, the dye outflow curve at the disk filter unit outlet has a sharp shape, and the retention in the disk filter unit is However, when the disk filter diameter is about three times the raw water inlet diameter, the shape of the dye outflow curve begins to become less sharp, that is, begins to become broad, Since the shape becomes extremely broad at 6 times and 18 times, there is a noticeable stagnation in the disk filter unit, that is, the fluid does not flow uniformly on the filter filtration surface and is wasted. I understand that.

30, 40 Disc filter unit 31, 41 Raw water inlet 34, 44 Disc filter 36, 46 Filtration water outlet

Claims (5)

  A filter unit used in a liquid feeding system to a chromatography column, wherein the filter diameter is a disk filter unit having a filter diameter of 1 to 3 times the raw water inlet diameter or filtered water outlet diameter. Filter unit.   2. The filter unit for a chromatography column liquid feeding system according to claim 1, wherein the raw water inlet diameter is equal to or larger than the filtrate water outlet diameter.   The filter unit for a chromatography column liquid feeding system according to claim 1 or 2, wherein the filter has a thickness of 0.5 to 5 mm.   The pipe diameter of the supply side pipe of the liquid feeding system and the raw water inlet diameter of the filter unit are set to the same diameter in any one of claims 1 to 3, or the pipe diameter of the liquid feeding system is made larger to send the liquid. A filter unit for a chromatography column liquid feeding system, wherein a tapered throttle tube is interposed between a supply pipe of the liquid system and a raw water inlet of the filter unit.   In any one of Claims 1-4, the pipe diameter of the discharge side piping of a liquid feeding system and the filtrate water outlet diameter of a filter unit are made into the same diameter, or the direction of the piping diameter of a liquid feeding system is made small. A filter unit for a chromatography column liquid feeding system, wherein a tapered throttle tube is interposed between a filtrate outlet of the filter unit and a discharge pipe of the liquid feeding system.

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