Column filling system, column filling method, and program

Abstract

According to the present invention, filling work is controlled so as to evaluate the performance of a column during filling with a filler, or so as to improve the performance of the column during filling. This column filling system includes one or more computers that execute: filling processing for delivering a solvent in order to fill a chromatographic column with slurry containing a filler from the upstream side of the column; and discharge pressure control, in the filling processing, for controlling a discharge pressure for delivering the solvent, in accordance with the flow rate of the solvent flowing out from the downstream side of the column.

Description

Column packing system, column packing method and program

[0001] The present disclosure relates to a column packing system, a column packing method, and a program.

[0002] Conventionally, packing devices for liquid chromatography columns packed using the wet slurry method have been proposed. For example, a packing device has been proposed that includes a control mechanism that linearly and / or stepwise changes the pump flow rate and / or downstream pressure over time, and a pump that can linearly and / or stepwise change the flow rate and / or downstream pressure (Patent Document 1). In this packing device, the pump operates according to a time-dependent program of flow rate and / or pressure preset in the control mechanism. Another proposed column packing method involves placing a packing material dispersed in a predetermined solvent at a fixed ratio in a packing container connected to a liquid chromatography column, and then pumping the packing material using a pump (Patent Document 2). In this column packing method, the upper pressure limit of the pump is increased in a gradient manner over time in accordance with the length of the column being packed. Also proposed is a column manufacturing device that includes a tube, a packing material supply mechanism that is disposed at one end of the tube and fills the tube with a packing material slurry prepared by dispersing a packing material in a solvent, and a packing control means that is disposed at the other end of the tube and maintains the flow rate and pressure of the packing material slurry at predetermined flow rates and pressures during packing (Patent Document 3).

[0003] JP-A-59-028660 JP-A-2-078954 International Publication No. 2015 / 186183

[0004] Conventionally, column performance evaluation was performed after packing, and could not be judged during packing. Furthermore, if a column was judged to be unacceptable, not only was the work required for manufacturing the column wasted, but post-processing of the column was required, resulting in inefficiency. The present disclosure aims to provide a technique for evaluating column performance during packing, or for controlling the packing operation to improve column performance during packing.

[0005] The present disclosure can be realized by the following aspects. (Aspect 1) A column packing system including one or more computers that perform a packing process in which a slurry containing a packing material is packed into a chromatographic column from the upstream side of the column by pumping a solvent therethrough, and a discharge pressure control process in which a discharge pressure for pumping the solvent is controlled in accordance with the flow rate of the solvent flowing out of the downstream side of the column. (Aspect 2) The column packing system according to Aspect 1, in which the packing process includes gradually increasing the discharge pressure, and in the discharge pressure control, the one or more computers change a rate at which the discharge pressure is gradually increased in accordance with the flow rate of the solvent flowing out of the downstream side of the column. (Aspect 3) The column packing system according to Aspect 2, in which in the discharge pressure control, the one or more computers change a rate at which the discharge pressure is gradually increased in accordance with the difference between the amount of the solvent flowing out of the downstream side of the column per unit time and a predetermined target. (Aspect 4) In the control of the discharge pressure, the one or more computers change the length of the unit time when detecting a pulsation in which the flow rate of the solvent flowing out from the downstream side of the column per unit time. (Aspect 5) The column packing system according to Aspect 3, comprising one or more computers that perform a packing process of filling a chromatographic column with a slurry containing a packing material from the upstream side of the column by sending a solvent, and evaluating the performance of the column after packing based on the flow rate of the solvent flowing out from the downstream side of the column.

[0006] The content of the means for solving the problem can be provided as a device such as a computer, a system including multiple devices, a method executed by one or more computers, or a program executed by one or more computers. A recording medium storing the program may also be provided.

[0007] According to the disclosed technology, it is possible to provide a technology for evaluating the performance of a column during packing with a packing material, or for controlling the packing operation so as to improve the performance of the column during packing.

[0008] FIG. 1 is a diagram illustrating an example of a filling system according to a first embodiment. FIG. 2 is a diagram illustrating the relationship between filling pressure and the amount of solvent flowing out of a column according to a comparative example. FIG. 3 is a diagram illustrating the relationship between the pump pressure increase rate during filling and column performance. FIG. 4 is a process flow diagram illustrating an example of a filling process. FIG. 5 is a diagram illustrating a filling process. FIG. 6 is a diagram illustrating an example of an allowable range of deviation from a reference value. FIG. 7 is a diagram illustrating a change in the discharge pressure increase rate. FIG. 8 is a diagram illustrating an example of a filling system according to a second embodiment. FIG. 9 is a diagram illustrating an example of a filling system according to a third embodiment. FIG. 10 is a diagram illustrating an example of a filling system according to a fourth embodiment. FIG. 11 is a diagram illustrating an example of a filling system according to a fifth embodiment. FIG. 12 is a diagram illustrating an example of a filling system according to a sixth embodiment. FIG. 13 is a diagram illustrating an example of a filling system according to a seventh embodiment. FIG. 14 is a diagram illustrating an example in which the magnitude relationship between a predetermined reference value for the amount of solvent outflow and a mass flow rate based on a measurement value acquired from a measuring instrument is reversed.

[0009] Hereinafter, an embodiment will be described with reference to the drawings.

[0010] <Embodiment 1> Fig. 1 is a diagram illustrating an example of a filling system. The filling system 10 of Fig. 1 is a system for filling a column 20 used in a column chromatograph with a filler by a wet method. The column 20 is, for example, a stainless steel tube. The column 20 is, for example, a chiral column used in high-performance liquid chromatography (HPLC), but is not limited thereto. The filler is a general filler that can hold a sample to be measured and perform optical separation. The filling system 10 includes a pump 1, a first container 2, a packer 3, a second container 4, a measuring instrument 5, and a control device 6.

[0011] The first container 2 is a container for containing the organic solvent to be delivered in the filling process. The first container 2 is, for example, a glass bottle, and contains the solvent therein. The inside of the first container 2 may be pressurized. The first container 2 and the pump 1 are connected by a pipe. The pipe is made of, for example, resin, but the material is not particularly limited.

[0012] The pump 1 draws up the solvent from the first container 2 and delivers it to the packer 3. The pump 1 is, for example, an air pressure amplification type filling pump, and may be connected to a nitrogen cylinder or compressor for driving it. The pump 1 gradually increases the discharge pressure to a set value and can maintain the set value by feedback control, for example, PID control. Furthermore, the pump 1 according to this embodiment is capable of changing the rate of change when increasing the discharge pressure, for example, in response to a signal from the control device 6. The pump 1 and the packer 3 are connected by piping. The piping is made of, for example, stainless steel, but the material is not particularly limited.

[0013] The packer 3 is a tool used to pack a packing material into the column 20 by a wet method. The packer 3 is fixed in a predetermined position using a tripod, a dedicated stand, or the like. The packer 3 is connected to one end of the column 20 via an attachment. A user prepares a slurry containing a packing material using a solvent and loads the slurry into the packer 3. The pump 1 then pumps the solvent contained in the first container 2, and the resulting liquid pressure causes the slurry loaded into the packer 3 to pack the column 20. During loading, the pressurized solvent flows out from the other end of the column 20 opposite the end connected to the packer 3.

[0014] The second container 4 is a container such as a measuring cylinder for receiving the solvent flowing out of the column 20. The second container 4 is made of, for example, resin, but the material is not particularly limited. The weighing device 5 is a weight measuring device such as a platform scale. The weighing device 5 outputs the measured weight to the control device 6, for example, as a digital signal.

[0015] The control device 6 is a computer such as a PC (Personal Computer) or a PLC (Programmable Logic Controller), and includes an arithmetic unit 61, a storage device 62, and an input / output interface (IF) 63. The arithmetic unit 61 is a processor such as a CPU (Central Processing Unit) that executes programs to perform various processes according to the embodiment. Specifically, the arithmetic unit 61 controls the discharge pressure of the pump 1 based on the solvent outflow rate obtained from the meter 5. The storage device 62 is at least one of a main storage device such as a RAM (Random Access Memory) or a ROM (Read Only Memory), and an auxiliary storage device (secondary storage device) such as a HDD (Hard-Disk Drive), an SSD (Solid State Drive), or a flash memory. The main storage device temporarily stores programs read by the arithmetic unit 61 and provides a working area for the arithmetic unit 61. The auxiliary storage device stores programs executed by the arithmetic unit 61 and other data. The storage device 62 is assumed to have stored in advance information indicating packing conditions (control profile) for each combination of, for example, the type and particle size of the packing material and the size (inner diameter and length) of the column. The control profile includes information specifying a predetermined target value for the solvent outflow rate that changes over time and a method for changing the discharge pressure of the pump 1 when the solvent outflow rate deviates from the target value. The input / output IF 63 continuously acquires information indicating weight from the weighing device 5. The input / output IF 63 also outputs a signal for controlling the discharge pressure of the pump 1 based on the processing of the calculation device 61. The input / output IF 63 may also include a user interface, such as a touch panel, keyboard, or pointing device.

[0016] After packing, the user removes the column 20 from the packer 3 and attaches an end cap to the end of the column 20, completing the column as a product.

[0017] FIG. 2 illustrates the relationship between the packing pressure and the amount of solvent flowing out of the column in a comparative example. In the upper graph of FIG. 2 , the solid line indicates the process value (MPa) of the pump discharge pressure. The dashed line indicates the solvent flow rate per unit time measured using the measuring device 5 during packing for a column determined to have insufficient performance in post-manufacturing evaluation. The dashed-dotted line indicates the solvent flow rate (g / s) measured using the measuring device 5 during packing for a column determined to have sufficient performance in post-manufacturing evaluation. In the comparative example, the pump 1 gradually increases the discharge pressure from the start of packing until a predetermined time t2, and then performs PID control to maintain a constant pressure. At t1, immediately after packing of the packer-containing slurry into the column 20 begins, a relatively large amount of solvent flows out to pump the slurry. Subsequently, when a cake layer forms in the column 20, pressure loss occurs due to accumulated packing particles, and the amount of solvent flowing out decreases.

[0018] The performance of a column can be evaluated, for example, by peak symmetry. Peak symmetry is an index represented by the symmetry coefficient (tailing coefficient). The symmetry coefficient is calculated based on the shape of the peak after loading a sample into the column. Specifically, the symmetry coefficient is calculated by dividing the peak width at 1 / 20 of the peak height by twice the length of the rising side of the peak from the apex. That is, a coefficient of 1.0 indicates that the areas before and after the peak are symmetrical. Furthermore, a coefficient greater than 1.0 indicates tailing, and a coefficient less than 1.0 indicates leading. For example, if the coefficient is within a predetermined allowable range above and below 1.0, the column performance can be determined to be sufficient. Peak symmetry can vary depending on the quality of the packing operation.

[0019] In these comparative examples, the inventors of the present application discovered a relationship between column performance and solvent outflow. For example, as the flow rate of the solvent flowing out of the column increases, the symmetry coefficient decreases. The lower part of Figure 2 schematically illustrates the assumed state of packing particles within a column. The schematic diagram enclosed by the dashed line represents an example of a column evaluated as having insufficient performance. A column evaluated as having insufficient performance is one in which the packing density is inappropriate. For example, if the density is insufficient, the solvent pumped by Pump 1 easily passes through the gaps between the particles, resulting in a relatively large amount of solvent flowing out of the column outlet. The schematic diagram enclosed by the dashed line represents an example of a column evaluated as having sufficient performance. A column evaluated as having sufficient performance is one in which the particles are packed at an appropriate density, a predetermined pressure loss occurs when Pump 1 pumps the solvent, and the solvent flows out of the column outlet at a predetermined flow rate.

[0020] Such differences in column performance can occur even when the profile of the pressure increase rate of the pump 1 is the same. Therefore, in the present disclosure, column performance is evaluated based on the flow rate of the solvent flowing out of the column during packing, or the conditions of the packing operation are changed during packing to improve column performance. That is, a target solvent outflow rate is determined in advance, and column performance is evaluated during packing based on the deviation between the actual outflow rate and the target. Furthermore, if the deviation between the actual outflow rate and the target is greater than a predetermined standard, the rate of change of the discharge pressure of the pump 1 (pressure increase rate) is changed to improve column performance.

[0021] FIG. 3 illustrates the relationship between the pressure increase rate of the pump 1 during filling and the performance of the column 20. The upper graph in FIG. 3 shows the pressure P (MPa) on the vertical axis and the elapsed time T (sec.) on the horizontal axis. The example in FIG. 3 also includes a period in which the discharge pressure of the pump 1 is gradually increased after the pump 1 is activated, and is controlled to remain constant after reaching a predetermined pressure P1. The solid line indicates the reference set value of the pressure increase rate, and shows an example in which the discharge pressure of the pump 1 is increased to P1 at the same rate until time t3 after the start of filling. The dashed line indicates an example in which the pressure increase rate is increased at time t1 during filling, with the discharge pressure reaching P1 at time t2. The dashed line indicates an example in which the pressure increase rate is decreased at time t1 during filling, with the discharge pressure reaching P1 at time t4. The lower graph in FIG. 3 shows the integrated solvent outflow rate W (g) on ​​the vertical axis and the elapsed time T (sec.) on the horizontal axis. The solid, dashed, and dashed lines represent the integrated solvent outflow volume when packed at the corresponding pressure increase rates shown in the upper graph. The symmetry factor of the column measured after packing was 1.02 for the reference pressure increase rate shown by the solid line, 1.10 for the increased pressure increase rate shown by the dashed line, and 0.98 for the decreased pressure increase rate shown by the dotted line. Thus, during packing of the column, increasing the pressure increase rate of Pump 1 shifted the peak symmetry toward tailing, whereas decreasing the pressure increase rate of Pump 1 shifted the peak symmetry toward leading. Furthermore, increasing the pressure increase rate of Pump 1 resulted in a slightly smaller solvent outflow volume than the reference, whereas decreasing the pressure increase rate of Pump 1 resulted in a slightly larger solvent outflow volume than the reference. When multiple components were detected, the chromatogram contained multiple peaks, and the symmetry factor could be calculated for each peak. Even when multiple peaks were present, the symmetry of each of the multiple peaks similarly changed with changes in the pressure increase rate of Pump 1.

[0022] Based on the above preliminary measurement results, a profile that serves as a reference for the pressure increase rate used to control pump 1, a reference value for the amount of solvent outflow from the outlet of column 20 and the allowable range for deviation from the reference value, and an algorithm for changing the pressure increase rate in the event of deviation from the allowable range are set.

[0023] <Filling Process> Figure 4 is a process flow diagram showing an example of the filling process. The filling process is started, for example, by a user's operation on the control device 6 or the like. First, the meter 5 starts measuring the amount of solvent outflow (Figure 4: S1). Note that the measurement may be started by a user's operation on the meter 5, or the meter 5 may start the measurement in cooperation with the control device 6. The meter 5 outputs the accumulated amount of solvent outflow. Furthermore, after S1, the control device 6 continuously acquires measured values ​​from the meter 5.

[0024] After S1, the arithmetic unit 61 of the control device 6 operates the pump 1 and increases the discharge pressure of the pump 1 based on the initial control profile (S2 in FIG. 4). FIG. 5 is a diagram for explaining the filling process. (1) in the upper part of FIG. 5 shows an example of a control profile. In the graph of FIG. 5 (1), the horizontal axis represents time T (sec.) and the vertical axis represents pressure P (MPa). The initial control profile gradually increases the discharge pressure of the pump 1 to P1 in proportion to the elapsed time from the start of filling to time t6. Furthermore, after time t6, PID control is performed to maintain the pressure at a constant P1. Note that after time t6, the pressure may be controlled to a constant value until filling is completed, or may include control that changes the pressure in proportion to the elapsed time or in stages.

[0025] (2) shown in the middle of Figure 5 shows an example of information continuously transmitted from the measuring device 5 to the control device 6. In the graph of Figure 5 (2), the horizontal axis indicates time T (sec.) and the vertical axis indicates the outflow amount W (g) of solvent obtained from the measuring device 5 at each time point. After the measuring device 5 starts measuring the outflow amount of solvent in S1, the control device 6 obtains the measured value shown in Figure 5 (2) from the measuring device 5.

[0026] After S2, the calculation device 61 uses the measurement value acquired from the measuring device 5 to calculate the solvent outflow rate (i.e., the moving average of the solvent outflow rate) in the most recent unit time (FIG. 4: S3). The unit time can be any length, for example, 1 second. In this step, the mass flow rate is calculated. Furthermore, the timing for executing this step may be one or more predetermined time points, such as t3 in FIG. 5. In (3) shown in the lower part of FIG. 5, the horizontal axis represents time T (sec.) and the vertical axis represents the most recent outflow rate w (g) per second. The solid line in FIG. 5 (3) represents the mass flow rate based on the measurement value acquired from the measuring device 5. That is, the value represented by the solid line at the time of processing is calculated in S3. The dashed line in FIG. 5 (3) represents a predetermined reference value for the solvent outflow rate. As described above, the reference value for the solvent outflow rate is predetermined based on the measurement results of the solvent outflow rate during packing of a column that is determined to have sufficient performance after packing.

[0027] After S3, the calculation device 61 determines whether the solvent outflow rate calculated in S3 deviates from a predetermined standard (S4 in FIG. 4). As described above, a threshold value representing the allowable range of deviation of the solvent outflow rate from the standard value is also predefined. FIG. 6 is a diagram illustrating an example of the allowable range of deviation from the standard value. The table in FIG. 6 includes attributes of "judgment time," "standard value," and "allowable range." The allowable range includes an "upper limit" and a "lower limit." The "judgment time" field stores information representing the timing of the judgments in S3 and S4, for example, the elapsed time from the start of operation of the pump 1. The "standard value" field stores, for example, the standard value of the solvent outflow rate indicated by the dashed line in FIG. 5(3). The "allowable range" field stores upper and lower limits indicating the allowable range of deviation from the standard value. When such conditions are set, in S4, if the difference Δw between the mass flow rate shown by the solid line in Figure 5 (3) and the reference value shown by the dashed line (for example, Δw3 at time t3 in Figure 5 (3) and Δw4 at time t4 in Figure 5 (3)) is outside the range from the lower limit value to the upper limit value, it is determined that there has been a deviation from the predetermined reference value.

[0028] If it is determined in S4 that the flow rate has deviated from the reference value (S4: YES), the calculation device 61 changes the increase rate (pressure increase speed) of the discharge pressure of the pump 1 (FIG. 4: S5). In this step, the changed increase rate is determined based on the difference Δw between the flow rate per unit time based on the measured value and the reference value. That is, the slope of the set value of the pressure increase period shown in FIG. 5(1) is changed. For example, if the difference Δw is larger than the allowable range, the symmetry coefficient is predicted to be smaller than the appropriate range (i.e., the product acceptance standard). Therefore, in S4, the pressure increase speed is changed to increase the symmetry coefficient. Furthermore, the degree of change can be determined in proportion to the magnitude of the difference Δw.

[0029] FIG. 7 is a diagram illustrating a change in the discharge pressure increase rate. The graph in FIG. 7 shows an example of changing the control profile. In the graph in FIG. 7, the horizontal axis represents time T (sec.) and the vertical axis represents pressure P (MPa). The thin dashed line represents the initial control profile (set value (target value, set-point variable, SV) in PID control), which is the same as that in FIG. 5(1). The thick dashed line represents the set value after changing the pressure increase rate at t3. The solid line represents the measured pressure increase rate (process variable, PV). For example, if it is determined that the difference Δw between the flow rate per unit time based on the measured value and the reference value at t3 is greater than the upper threshold Δw31, the pressure increase rate is changed to be increased according to the magnitude of the difference Δw, as shown in FIG. 7(1).

[0030] The changed boost rate may be determined using, for example, the SV and PV in PID control. For example, at time t3 in Figure 7(1), the changed boost rate may be determined so that it has a slope equal to the ratio of the difference between SV (P1) at t6 and PV (P2) at t3 to the difference between t6 and t3 (i.e., (P1-P2) / (t6-t3)), and control may be performed based on the SV based on this.

[0031] For example, when using an air-pressure amplification filling pump, pulsation, in which the flow rate of the solvent discharged by the pump 1 repeatedly increases and decreases, may occur. Therefore, it is preferable to set the unit time (the interval (window) in the moving average) in advance to a length that does not cause pulsation. Furthermore, if pulsation occurs during the filling process, the above-mentioned unit time may be lengthened to reduce the effect of pulsation. In this case, the reference value compared with the flow rate per unit time is also increased according to the unit time. Note that pulsation can be detected based on the fluctuations in the flow rate at each of t1 to t6 in FIG. 7, for example.

[0032] The determination in S4 may be based not only on deviation from the standard at one time point but also on deviation from the standard at multiple time points. For example, it may be determined that deviation from the standard has occurred when deviation from the standard exceeds a threshold value on either the upper or lower side at all of multiple predetermined time points.

[0033] After S5, or if it is determined in S4 that the pressure has not deviated from the standard (S4: NO), the calculation device 61 determines whether the pump 1 has reached a predetermined pressure (FIG. 4: S6). In this step, it is determined whether the target pressure set in the initial control profile (P1 in the examples of FIGS. 5(1) and 7(1)) has been reached. Note that this step may be determined by the pump 1 rather than the control device 6. If it is determined that the predetermined pressure has not been reached (S6: NO), the process returns to S3 and is repeated.

[0034] When the process is repeated and it is determined at t4 that the difference Δw between the flow rate per unit time based on the measured value and the reference value is smaller than the lower limit threshold Δw42, the set value may be changed to decrease the pressure increase rate depending on the magnitude of the difference Δw, for example, as shown in Figure 7 (2).

[0035] On the other hand, if it is determined in S6 that the predetermined pressure has been reached (S6: YES), the calculation device 61 controls the discharge pressure of the pump 1 based on a predetermined profile (FIG. 4: S7). In this step, the target pressure (P1 in the example of FIG. 5(1)) set in the initial control profile is maintained. Note that this step may be performed by the pump 1 instead of the control device 6. Thereafter, for example, after a predetermined time has elapsed since the start of filling, the pump 1 stops operating, and the process of filling the column 20 with the packing material is completed.

[0036] According to the above-described packing process, the performance of the manufactured column can be evaluated based on the difference between the target flow rate of the solvent flowing out during packing. If the difference is greater than a threshold, the column performance can be improved by changing the rate at which the discharge pressure of the pump 1 is increased.

[0037] Second Embodiment FIG. 8 is a diagram showing an example of a filling system 10A according to a second embodiment. Note that components identical to those in the first embodiment are denoted by corresponding reference numerals, and descriptions thereof will be omitted. In the example of FIG. 8, the filling system 10A does not include a control device 6. Furthermore, in the filling system 10A, the pump 1A controls the discharge pressure for delivering the solvent in accordance with the flow rate of the solvent flowing out from the downstream side of the column 20. That is, the pump 1A includes a computer including a calculation device for controlling the discharge pressure of the pump 1A, a storage device for storing information used in processing, and an input / output interface for acquiring information from the measuring device 5. Even with this configuration, the performance of the column being manufactured can be evaluated or the column performance can be improved during filling.

[0038] Third Embodiment FIG. 9 is a diagram illustrating an example of a filling system 10B according to a third embodiment. Note that components identical to those in the first embodiment and the like are denoted by corresponding reference numerals, and descriptions thereof will be omitted. In the example of FIG. 9 , the filling system 10B does not include a control device 6. The filling system 10B also includes a control valve 7 between the pump 1 and the packer 3, and a regulator 8 between the meter 5 and the control valve 7. The regulator 8 acquires the flow rate of the solvent flowing from the downstream side of the column 20 from the meter 5 and controls the control valve 7 according to the acquired flow rate, thereby changing the discharge pressure at which the pump 1 delivers the solvent to the packer 3. That is, the regulator 8 functions as a computer including a calculation device for controlling the discharge pressure, a storage device for storing information used in processing, and an input / output interface for acquiring information from the meter 5. Even with this configuration, the performance of the column being manufactured can be evaluated or improved during packing.

[0039] Fourth Embodiment FIG. 10 is a diagram illustrating an example of a filling system 10C according to a fourth embodiment. Note that components identical to those in the first embodiment are denoted by corresponding reference numerals, and descriptions thereof will be omitted. In the example of FIG. 10 , the filling system 10C includes a control device 6, which is a PLC, and the control device is communicatively connected to a server 9 via a communication network N. When the storage capacity of the storage device 62 of the PLC (control device 6) is limited, information acquired from the measuring device 5 and operation logs related to the control of the pump 1 are transmitted from the control device 6 to the server 9 and stored in the server 9. Note that the communication network N includes, for example, an Internet Protocol (IP) network, and devices connected to the network can communicate based on a predetermined communication protocol. Part of the network may be a telephone network (landline telephone network or mobile communication network), an ad hoc network, an intranet, a virtual private network (VPN), a local area network (LAN), a wireless LAN (Wireless LAN), a wide area network (WAN), or the Internet.

[0040] Alternatively, the server 9 may be connected to the pump 1 and the measuring device 5 via a communication network N and a control device 6 such as a PLC, thereby providing control of the above-described filling process on the cloud. Even with this configuration, it is possible to evaluate the performance of the column being manufactured or improve the performance of the column during filling.

[0041] Fifth Embodiment FIG. 11 is a diagram illustrating an example of a filling system 10D according to a fifth embodiment. Note that components identical to those of the first embodiment and the like are denoted by corresponding reference numerals, and description thereof will be omitted. In the example of FIG. 11 , the filling system 10D includes a reading device 11 connected to a control device 6. The reading device is capable of reading identification information 201, such as a one-dimensional code (barcode), a two-dimensional code, or a wireless tag (IC tag, RFID (Radio Frequency Identification) tag). The column 20 is also provided with the identification information 201. The identification information 201 includes, for example, information indicating the column type. Meanwhile, the storage device 62 of the control device 6 stores, in association with the information indicating the column type, a profile serving as a reference for the pressure increase rate of the pump 1 to be applied to the column, a reference value for the solvent outflow rate from the outlet of the column 20 and a tolerance for deviation from the reference value, and an algorithm for changing the pressure increase rate when the tolerance is exceeded. Before the filling process, the arithmetic unit 61 of the control unit 6 acquires information indicating the type of column 20 via the reading unit 11, and during the filling process, performs an operation according to the type of column 20. This configuration can prevent incorrect operation settings when manufacturing multiple types of columns. Note that the filling system 10D may not include the reading unit 11, and may instead allow the user to select from settings for each column type stored in advance in the storage unit 62.

[0042] Sixth Embodiment FIG. 12 is a diagram showing an example of a filling system 10E according to a sixth embodiment. Note that components identical to those of the third embodiment and the like are denoted by corresponding reference numerals, and description thereof will be omitted. In the example of FIG. 12, the filling system 10E includes a combination of a control valve 7, a packer 3, a column 20, a second container 4, a measuring device 5, and a controller 8, which are connected in parallel, and each of which performs feedback control of the control valve 7. This configuration allows for efficient production of the column 20. Note that, not limited to the third embodiment, the first, second, fourth, or fifth embodiments may also be configured to pack the columns 20 connected in parallel. Furthermore, three or more columns 20 may also be connected in parallel and packed.

[0043] Seventh Embodiment FIG. 13 is a diagram showing an example of a filling system 10F according to a seventh embodiment. Note that components identical to those of the third embodiment and the like are designated by corresponding reference numerals, and description thereof will be omitted. In the example of FIG. 13 , multiple columns 20 are connected in series via connecting pipes 21, and solvent is allowed to flow from the leading column 20 to the second container 4. Furthermore, the control valve 7 is feedback-controlled based on the flow rate of the solvent flowing from the leading column 20. Even with this configuration, columns 20 can be efficiently manufactured. Note that, not limited to the third embodiment, the first, second, fourth, fifth, or sixth embodiments may also be configured to pack columns 20 connected in series. Furthermore, three or more columns 20 may also be connected in series and packed.

[0044] <Modifications> The configurations and combinations thereof in each embodiment are merely examples, and additions, omissions, substitutions, and other modifications of the configurations are possible as appropriate without departing from the spirit of the present disclosure. The present disclosure is not limited by the embodiments, but only by the scope of the claims. Furthermore, each aspect disclosed in this specification can be combined with any other feature disclosed in this specification.

[0045] At least some of the functions of the control device 6 shown in Figure 1 may be distributed and implemented among multiple devices. The filling process shown in Figure 4 may be performed in a different order or in parallel, as long as the results are the same. For example, S1 and S2 may be interchanged or performed simultaneously. The table shown in Figure 6 is an example of a database, and may be properly normalized to store information separately in multiple tables, or may be denormalized to store additional information collectively in a single table.

[0046] Furthermore, instead of the mass flow rate of the solvent flowing out of the column 20, the volume flow rate may be used for processing.

[0047] Furthermore, in the packing process of the above-described embodiment, it is also possible to perform only the performance evaluation of the column 20 without changing the discharge pressure of the pump 1. It is also useful to determine the pass / fail of the column 20 after manufacturing without performing a performance evaluation again, or to simply screen the column 20 for which performance evaluation should be performed by sampling.

[0048] FIG. 14 is a diagram illustrating an example in which the magnitude relationship between a predetermined reference value for the solvent outflow rate and a mass flow rate based on a measurement value acquired from the measuring device 5 is reversed. In FIG. 14, the horizontal axis represents time T (sec.) and the vertical axis represents the most recent outflow rate w (g) per second. The solid line in FIG. 14 represents the mass flow rate based on a measurement value acquired from the measuring device 5. The dashed line in FIG. 14 represents the predetermined reference value for the solvent outflow rate. The arrows indicate the magnitude of the difference. For example, when the slurry concentration is low, the initial flow rate tends to be relatively fast and the final flow rate tends to be slow. Conversely, when the slurry concentration is high, the initial flow rate tends to be relatively slow and the final flow rate tends to be fast. Against this background, in the example shown in FIG. 14, the magnitude relationship between the predetermined reference value for the solvent outflow rate, indicated by the dashed line, and the mass flow rate based on a measurement value acquired from the measuring device 5, indicated by the solid line, is reversed between time t3 and time t4. In FIG. 14, the difference Δw when the measured value is lower than the reference value is indicated by a negative sign.

[0049] In such a case, for example, in steps S4 and S5 of FIG. 3 , the increase rate of the secondary pressure may be changed using the difference Δw at multiple time points. For example, the trend of the mass flow rate based on measurements obtained from the measuring device 5, shown by the solid line in FIG. 14 , is continuously monitored and compared with the trend of a predetermined reference value of the solvent outflow rate, shown by the dashed line. That is, rather than independently determining whether the value is within the allowable range at a predetermined time point as shown in FIG. 5(3) or FIG. 6 , the difference Δw at multiple time points is comprehensively evaluated. In this case, the timing (e.g., time point, interval, total number, etc.) for monitoring the difference Δw can be set as appropriate. While the example in FIG. 14 illustrates the period from time t0 to time t8, the timing is not particularly limited. Furthermore, evaluation using multiple difference Δw may involve, for example, accumulating multiple difference Δws and determining whether the integrated value of the difference Δw deviates from a reference allowable range. Furthermore, evaluation using multiple differences Δw may involve determining an approximate formula using multiple measured values ​​for Figure 14 or other graphs (e.g., graphs of outflow volume (g) or flow rate (g / s)), and then changing the rate of increase in the discharge pressure of the pump 1 by taking into account the predicted future differences. Alternatively, for example, using the maximum and minimum values, inflection points, or singular points of each curve in Figure 14 or other graphs as a reference, the reference graph and a graph based on measured values ​​may be synchronized, and then the difference Δw may be calculated. Furthermore, when the magnitude relationship between the reference value of the solvent outflow volume and the mass flow rate based on the measured values ​​is reversed, different methods of changing the rate of increase in the discharge pressure of the pump 1 may be applied before and after this.

[0050] The present disclosure also includes a method and a computer program for executing the above-described process, and a computer-readable recording medium having the program recorded thereon. The recording medium having the program recorded thereon enables the above-described process by causing a computer to execute the program.

[0051] Here, a computer-readable recording medium refers to a recording medium that stores information such as data and programs electrically, magnetically, optically, mechanically, or chemically and can be read by a computer. Among such recording media, those that can be removed from a computer include flexible disks, magneto-optical disks, optical disks, magnetic tapes, memory cards, etc. Furthermore, recording media that are fixed to a computer include HDDs, SSDs (Solid State Drives), ROMs, etc.

[0052] 10: Filling system 1: Pump, 2: First container, 3: Packer, 4: Second container, 5: Measuring device, 6: Control device (computer), 61: Arithmetic device, 62: Storage device, 63: Input / output interface (IF) 20: Column

Claims

1. A column filling system including one or more computers that perform a filling process of filling a column for chromatography with a slurry containing a packing material by feeding a solvent from an upstream side of the column, and a discharge pressure control of controlling a discharge pressure for feeding the solvent according to a flow rate of the solvent flowing out from a downstream side of the column in the filling process.

2. The column filling system according to claim 1, wherein the filling process includes gradually increasing the discharge pressure, and in the discharge pressure control, the one or more computers change a rate of gradually increasing the discharge pressure according to a flow rate of the solvent flowing out from a downstream side of the column.

3. The column filling system according to claim 2, wherein in the discharge pressure control, the one or more computers change a rate of gradually increasing the discharge pressure according to a difference between an amount of the solvent flowing out per unit time from a downstream side of the column and a predetermined target.

4. The column filling system according to claim 3, wherein in the discharge pressure control, when the one or more computers detect a pulsation in which the flow rate of the solvent flowing out from a downstream side of the column per unit time increases or decreases, the one or more computers change a magnitude of the unit time.

5. A column filling system including one or more computers that perform a filling process of filling a column for chromatography with a slurry containing a packing material by feeding a solvent from an upstream side of the column, and evaluating a performance of the column after filling based on a flow rate of the solvent flowing out from a downstream side of the column in the filling process.

6. A column filling method in which one or more computers perform a filling process of filling a column for chromatography with a slurry containing a packing material by feeding a solvent from an upstream side of the column, and a discharge pressure control of controlling a discharge pressure for feeding the solvent according to a flow rate of the solvent flowing out from a downstream side of the column in the filling process.

7. A program for causing one or more computers to perform a filling process of filling a column for chromatography with a slurry containing a packing material by feeding a solvent from an upstream side of the column, and a discharge pressure control of controlling a discharge pressure for feeding the solvent according to a flow rate of the solvent flowing out from a downstream side of the column in the filling process.

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