Measurement system and liquid feed control method

Through the introduction of computer control in the measurement system of the capillary electrophoresis device, optimize the number of swimming media, solve the problem of swimming medium residue, and realize the reduction of the efficient utilization and operating costs of resources.

CN119335031APending Publication Date: 2025-01-21HITACHI HIGH TECH CORP
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Patent Information

Application Number
CN202411315643.5
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2020-03-06
Publication Date
2025-01-21

AI Technical Summary

Technical Problem

After the specified number of liquid feeds in the existing capillary electrophoresis device, there are still quite a lot of swimmer media residues in the swimmer media container, resulting in waste of resources and increased operating costs.

Method used

By introducing computer control in the measurement system, according to the amount in the swimming medium container and the hypothetical delivery volume of the liquid delivery mechanism, the number of liquids that can be performed can be calculated to optimize the use of swimming media.

Benefits of technology

Effectively reduce the use of swimming medium, improve resource utilization, and reduce operating costs.

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Abstract

The invention provides a measuring system and a liquid delivery control method, which can reduce the residual amount of a swimming medium accommodated in a swimming medium container as much as possible, can be used efficiently, and can further reduce the operation cost. As an example, the present invention proposes a measurement system provided with an electrophoresis device and a computer, the electrophoresis device being provided with: an electrophoresis medium container that accommodates an electrophoresis medium; a capillary tube filled with an electrophoresis medium; a liquid feeding mechanism which feeds the swimming medium in the swimming medium container to the capillary tube; and a device control unit that controls the operation of the liquid delivery mechanism, and the computer calculates the number of times that the liquid can be delivered on the basis of the amount of the swimming medium in the swimming medium container and the assumed liquid delivery amount of the liquid delivery mechanism to the swimming medium (fig. 16).
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Description

[0001] This application is a divisional application of an invention patent application with an international application date of March 6, 2020, an international application number of PCT / JP2020 / 009879, an application number of 202080095347.2, and an invention name of “Measuring system and liquid delivery control method”. Technical Field

[0002] The invention relates to a measuring system and a liquid delivery control method. Background Art

[0003] In recent years, as an electrophoresis apparatus, a capillary electrophoresis apparatus in which a capillary is filled with a moving medium such as a polymer gel or a polymer solution has been widely used.

[0004] For example, the capillary electrophoresis device shown in Patent Document 1 has been used for a long time. Compared with the flat-plate electrophoresis device, the capillary electrophoresis device has a higher heat dissipation and can apply a higher voltage to the sample, so it has the advantage of being able to perform electrophoresis at a high speed. In addition, it has many advantages such as only a small amount of sample is required, automatic filling of the electrophoresis medium, and automatic injection of the sample, and is used for various separation analysis and determination represented by the analysis of nucleic acids and proteins.

[0005] Prior Art Literature

[0006] Patent Literature

[0007] Patent Document 1: Japanese Patent Application Publication No. 2008-8621

[0008] In the conventional capillary electrophoresis apparatus shown in Patent Document 1, a moving medium contained in a moving medium container is transported to a capillary, and when a liquid delivery operation is performed a predetermined number of times (number of liquid delivery times: set value), the moving medium container is replaced with a new one.

[0009] However, even when the predetermined number of liquid delivery times is exceeded, a considerable amount of electrophoretic medium often remains in the electrophoretic medium container that is considered to be used up. Since the electrophoretic medium is very expensive, it is desirable to use it up as much as possible to reduce running costs. Summary of the invention

[0010] Problems to be solved by the invention

[0011] In view of such a situation, the present invention provides a technology for reducing the excess amount of the eluting medium contained in the eluting medium container as much as possible and using it efficiently, thereby further reducing the running cost.

[0012] Solutions to Solve Problems

[0013] In order to solve the above-mentioned problems, for example, the structure described in the technical solution is adopted. The present invention includes a plurality of solutions to the above-mentioned problems. As an example, a measuring system is proposed, which includes an electrophoresis device and a computer, wherein the electrophoresis device includes: a moving medium container, which accommodates the moving medium; a capillary tube, which is filled with the moving medium; a liquid delivery mechanism, which delivers the moving medium in the moving medium container to the capillary tube; and a device control unit, which controls the operation of the liquid delivery mechanism, and the computer calculates the number of liquid delivery times that can be performed based on the amount of the moving medium in the moving medium container and the assumed amount of liquid delivered to the moving medium by the liquid delivery mechanism.

[0014] According to the description and drawings of this specification, further features related to the present invention will become clear. In addition, the scheme of the present invention is achieved and implemented by the combination of elements and various elements and the following detailed description and the attached technical solution. However, it should be understood that the description of this specification is only a typical example and does not limit the technical solution or application example of the present invention in any sense.

[0015] Effects of the Invention

[0016] According to the present invention, the excess amount of the phoretic medium contained in the phoretic medium container can be reduced as much as possible and used efficiently, thereby further reducing the running cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is a diagram showing a schematic configuration example of the capillary electrophoresis device 1 according to the present embodiment.

[0018] Figure 2 It is a diagram showing an example of the upper surface structure of the capillary electrophoresis device 1 according to the present embodiment.

[0019] Figure 3 It is a diagram showing a cross section taken along line AA of the capillary electrophoresis device 1 .

[0020] Figure 4 It is a diagram showing a detailed configuration example of a liquid feeding mechanism.

[0021] Figure 5 2 is a diagram showing a detailed structural example of a capillary array.

[0022] Figure 6 FIG. 1 is a diagram showing a detailed structural example of a phoretic medium container.

[0023] Figure 7 It is a diagram for explaining the details of installing the electrophoretic medium container.

[0024] Figure 8 FIG. 1 is a diagram showing a connection state between a capillary array and a phoretic medium container.

[0025] Fig. 9It is a diagram showing the details of the electrophoretic medium feeding operation (initial state).

[0026] Fig.10 It is a diagram showing the details of the electrophoretic medium feeding operation (plunger contact detection).

[0027] Fig.11 It is a diagram showing the details of the electrophoretic medium feeding operation (capillary connection).

[0028] Fig.12 It is a diagram showing the details of the electrophoretic medium feeding operation (ejection of the electrophoretic medium).

[0029] Fig.13 It is a diagram showing the details of the electrophoretic medium feeding operation (plunger contact release).

[0030] Fig.14 It is a diagram showing the details of the electrophoretic medium feeding operation (removal of residual pressure).

[0031] Fig.15 It is a diagram showing the details of the electrophoretic medium feeding operation (capillary connection release).

[0032] Fig.16 16 is a block diagram showing an example of a schematic internal structure of the capillary electrophoresis system 1600 according to the present embodiment.

[0033] Fig.17 This is a flowchart for explaining the liquid feeding frequency correction process of the first embodiment.

[0034] Fig.18 This is a flowchart for explaining the liquid feeding frequency correction process of the second embodiment.

[0035] Fig.19 It is a graph showing the relationship between the liquid delivery amount and the liquid delivery time at different liquid delivery pressures.

[0036] Fig. 20 This is a flowchart for explaining the liquid supply frequency correction processing (calculation of the current correction value of the plunger 61 + calculation of the liquid supply correction frequency) of the third embodiment.

[0037] Fig.21 This is a diagram showing the relationship (correlation: for example, proportional relationship) between the drive current and the average liquid delivery pressure.

[0038] Fig. 22 It is a graph showing the relationship (correlation) between the average liquid feeding pressure and the liquid feeding time.

[0039] Fig.23 : is a graph showing the relationship between the corrected drive current and the average liquid delivery pressure.

[0040] Fig.24This is a flowchart for explaining the liquid supply frequency correction processing (offset value calculation + liquid supply correction frequency calculation) of the fourth embodiment.

[0041] Description of reference numerals:

[0042] 1 Capillary electrophoresis device

[0043] 2 System control computer

[0044] 1600 Capillary Electrophoresis System

[0045] 1601 Device Control Unit

[0046] 1602 Motor plunger drive unit

[0047] 1603 Encoder count value monitor section

[0048] 1611 Control Department

[0049] 1612 Input and output devices

[0050] 1613 Memory

[0051] 1614 Storage Device

[0052] 1615 Communication device. DETAILED DESCRIPTION

[0053] Hereinafter, the present embodiment will be described based on the drawings. It should be noted that the drawings show specific examples based on the principle of the present embodiment, but these are for understanding the present embodiment and are not intended to limit the interpretation of the technology of the present invention.

[0054] The phoretic medium container has a syringe-like structure and is provided with a guide member for suppressing its own expansion. The guide member has high rigidity and when the phoretic medium container expands, it expands until it contacts the guide member, suppressing further expansion.

[0055] The connection between the eluting medium container and the capillary tube is as follows: a plurality of capillaries are bundled into a bundle, a capillary head with a tip pointed into a needle shape is provided, a rubber plug is provided in the eluting medium container, and the capillary head is used to penetrate the rubber plug for connection. At this time, in order to use the capillary head to suppress the expansion of the rubber plug caused by the liquid feeding pressure, the capillary head is pressed against the rubber plug.

[0056] A movable sealing component for liquid delivery is built into the syringe-structured phoretic medium container. The sealing surface of the sealing component is formed into a shape and a wall thickness that are more easily deformed by the internal pressure than the container syringe. In addition, by setting the shape of the sealing component to a concave shape facing the inside of the container and setting the front end of the concave shape as the sealing surface, an internal pressure sealing structure is formed that is further sealed when the internal pressure increases.

[0057] The feeding of the phoretic medium is performed by pressing the sealing member of the phoretic medium container from the outside. In the liquid feeding mechanism having a plunger pressing the sealing member, an encoder is provided to detect the speed change when the plunger contacts the sealing member. In addition, after the liquid is fed, since the pressure inside the phoretic medium container is kept in a state of increased pressure, the force of the sealing member returning to the original position is exerted. In this state, the plunger in contact with the sealing member is separated once. As a result, the sealing member moves in the direction of the original position, and the internal pressure of the phoretic medium container is removed.

[0058] According to the present invention, since the expansion of the eluting medium container can be suppressed, it can be a high-pressure-resistant container. Moreover, by detecting the position of the sealing member in the eluting medium container and removing the residual pressure in the eluting medium container, the remaining amount in the eluting medium container and the amount of liquid delivered can be managed. In addition, the above contents can be achieved by using an inexpensive eluting medium container with a liquid delivery function. Thus, it is possible to achieve both a reduction in running costs and an improvement in user operability.

[0059] <Device Configuration Example>

[0060] Below, use Figure 1 to Figure 7 , the structure and configuration, main component structure, installation method, etc. of the capillary electrophoresis device 1 are described.

[0061] Figure 1 1 is a diagram showing an example of the device structure of the capillary electrophoresis device 1 of the present embodiment. The present device 1 can be roughly divided into two units: an automatic sampler unit 150 located at the lower part of the device and an irradiation detection / constant temperature chamber unit 160 located at the upper part of the device. In addition, as described later, the capillary electrophoresis device 1 is also connected to a system control computer 2 that controls the device 1.

[0062] In the automatic sampler unit 150, a Y-axis driving body 85 is mounted on the sampler base 80, and can be driven along the Y-axis. A Z-axis driving body 90 is mounted on the Y-axis driving body 85, and can be driven along the Z-axis. A sample tray 100 is mounted on the Z-axis driving body 90, and the user sets a phoretic medium container 20, an anode side buffer container 30, a cathode side buffer container 40, and a sample container 50 on the sample tray 100. The sample container 50 is set on the X-axis driving body 95 mounted on the sample tray 100, and only the sample container 50 can be driven along the X-axis on the sample tray 100. A liquid delivery mechanism 60 is also mounted on the Z-axis driving body 90. The liquid delivery mechanism 60 is arranged below the phoretic medium container 20.

[0063] The irradiation detection / constant temperature bath unit 160 includes a constant temperature bath unit 110 and a constant temperature bath door 120, and can maintain a constant temperature therein. An irradiation detection unit 130 is mounted behind the constant temperature bath unit 110, and can perform detection during electrophoresis. The user sets the capillary array 10 in the constant temperature bath unit 110, and performs electrophoresis while maintaining the capillary array 10 at a constant temperature in the constant temperature bath unit 110, and performs detection using the irradiation detection unit 130. In addition, the constant temperature bath unit 110 is also equipped with an electrode 115 for reducing to GND when a high voltage for electrophoresis is applied.

[0064] As described above, the capillary array 10 is fixed to the thermostatic bath unit 110. The phoretic medium container 20, the anode buffer container 30, the cathode buffer container 40, and the sample container 50 can be driven along the YZ axis by the automatic sampler unit 150, and only the sample container 50 can be further driven along the X axis. The phoretic medium container 20, the anode buffer container 30, the cathode buffer container 40, and the sample container 50 can be automatically connected to the fixed capillary array 10 at any position by the movement of the automatic sampler unit 150.

[0065] Figure 2 1 shows a view of the capillary electrophoresis apparatus 1 viewed from the top. The anode side buffer container 30 provided on the sample tray 100 includes an anode side cleaning layer 31, an anode side electrophoresis buffer layer 32, and a sample introduction buffer layer 33. In addition, the cathode side buffer container 40 includes a waste liquid layer 41, a cathode side cleaning layer 42, and a cathode side electrophoresis buffer layer 43.

[0066] The electrophoretic medium container 20, the anode side buffer container 30, the cathode side buffer container 40, and the sample container 50 are arranged in a positional relationship as shown in the figure. Thus, the positional relationship between the anode side and the cathode side when connected to the capillary array 10 is "electrophoretic medium container 20-waste liquid layer 41", "anode side cleaning layer 31-cathode side cleaning layer 42", "anode side electrophoresis buffer layer 32-cathode side electrophoresis buffer layer 43", and "sample introduction buffer layer 33-sample container 50".

[0067] Figure 3 Shown in Figure 2 The AA cross-sectional view in FIG. 2 is a cross-sectional view taken along the line AA in FIG. The moving medium container 20 is inserted and disposed in a guide 101 embedded in the sample tray 100 . In addition, the liquid delivery mechanism 60 is configured such that a plunger 61 built into the liquid delivery mechanism 60 is located below the moving medium container 20 .

[0068] During electrophoresis, the capillary array 10 Figure 3The right side of the electrode 115 becomes the cathode side, and the left side becomes the anode side. The autosampler unit 150 moves to the position of "anode side electrophoresis buffer layer 32 - cathode side electrophoresis buffer layer 43", applies a high voltage to the capillary array 10 on the cathode side, and flows to GND via the cathode side buffer container 40 and the anode side buffer container 30 using the electrode 115, thereby performing electrophoresis.

[0069] Figure 4 Detailed diagram of the liquid delivery mechanism 60 is shown in FIG. A stepper motor 62 with a rotary encoder 63 is mounted on the liquid delivery mechanism base 70, and a drive pulley 67 is installed on the stepper motor 62. For example, the stepper motor 62 is set as a two-phase stepper motor, and the rotary encoder 63 is set to be able to count 400 per rotation. The drive pulley 67 and the driven pulley 68 are connected by a belt 69, and the driven pulley 68 and the ball screw 65 are fixed. A linear guide 66 is installed on the liquid delivery mechanism base 70 in parallel with the ball screw 65, and the linear guide 66 and the ball screw 65 are fixed by a slide 71. A detection plate 72 is installed on the slide 71, and the origin is detected by shielding the origin sensor 64 with the detection plate 72. In addition, a plunger 61 facing the same axial direction as the drive shaft is installed on the slide 71. Thus, the plunger 61 can be driven by rotating the stepper motor 62.

[0070] Figure 5 Detailed diagram of the capillary array 10 is shown in FIG. The capillary array 10 includes a capillary 11 which is a glass tube with an inner diameter of about φ50 μm, and a detection unit 12 is attached to the capillary 11. The detection unit 12 is detected by an irradiation detection unit 130. A loading head 16 and a SUS tube 17 are attached to the cathode side end of the capillary 11. The material of the loading head 16 is preferably a resin with high insulation properties and a high tracking index, such as PBT resin. A component for achieving conduction of all the SUS tubes 17 is built inside the loading head 16, and a high voltage is applied to all the SUS tubes 17 by applying a high voltage thereto. The capillaries 11 are fixed by passing through the SUS tubes 17 respectively. A plurality of capillaries 11 are gathered into one by a capillary head 13 on the anode side. The capillary head 13 includes a capillary head tip 15 formed into a needle shape at an acute angle, and a capillary head protrusion 14 which is a portion having a thicker outer diameter than the capillary head tip 15. The material of the capillary tip 13 is preferably PEEK resin or the like, which is a resin that is not easily damaged, has rigidity, and has high stability with respect to chemicals and analysis.

[0071] Although not shown in the figure, when the capillary array 10 is fixed to the thermostatic bath unit 110, the detection unit 12, the loading head 16, and the capillary head 13 are fixed respectively. The detection unit 12 is positioned with high precision so as to be in a position that can be detected by the irradiation detection unit. The loading head 16 is fixed in a manner that conducts with the portion to which the high voltage is applied when fixed. The capillary head 13 is firmly fixed in a manner that the front end 15 of the capillary head faces directly downward and can bear the load. The positional relationship between the cathode side and the anode side when fixed is a configuration in which the plurality of capillaries 11 do not overlap each other when set in the device 1.

[0072] <Example of the structure of the electrophoretic medium container>

[0073] Figure 6 Detailed diagram of the eluting medium container 20 is shown in FIG. The eluting medium container 20 has a concave seal 22 built into the syringe 21, and is sealed with a cover 24 after a rubber plug 23 is placed from above. The cover 24 is further sealed with a film 55. The material of the syringe 21 is preferably a resin that can be thin-walled, i.e., PP resin or the like. The material of the seal 22 is preferably an ultra-high molecular PE resin with excellent sliding properties that is often used in seals of fluids in sliding parts, etc. The material of the rubber plug 23 is preferably silicone rubber that is stable with respect to analysis, etc. The material of the cover 24 is preferably PC resin or the like in order to be unified with the film 55 of each container. The eluting medium 26 is sealed therein, and the air 27 that enters during sealing is sealed in a manner that accumulates in the upper part. The eluting medium 26 is sealed with a capacity that can perform 10RUN of analysis. The seal 22 can move inside the syringe 21 by applying a load from the outside.

[0074] <Installation of the Fluid Container>

[0075] Figure 7 Detailed drawings of the installation of the eluting medium container 20 are shown in FIG. When the eluting medium container 20 is set in the device 1, the film 55 attached to the cover 24 is first peeled off. Then, it is inserted into the guide 101 embedded in the sample tray 100 and fixed from above in a manner that does not float. At this time, the gap between the outer diameter of the syringe 21 and the inner diameter of the guide 101 becomes infinitely smaller. The smaller the gap, the better, but the gap is set to a gap that is not difficult to process between the outer diameter of the syringe 21 as a resin molded product and the inner diameter of the guide 101 as a machined product. Specifically, it is about 0.1 mm.

[0076] <Connection status of capillary array and moving medium container>

[0077] Figure 81 shows the connection state of the capillary array 10 and the eluting medium container 20. The eluting medium container 20 disposed on the sample tray 100 is connected to the fixed capillary array 10 by the Z-axis drive of the automatic sampler unit 150. When connected, the rubber plug 23 is penetrated by the capillary head 13 to connect. The front end 15 of the capillary head is needle-shaped, so it can also penetrate the rubber plug 23. At this time, the electrode 115 is in a positional relationship that does not contact the eluting medium container 20. The capillary head 13 has a capillary head protrusion 14 with a thickened outer diameter, and the connection is performed while pressing the upper surface of the rubber plug 23 from above by the capillary head protrusion 14. In addition, although the air 27 also enters the upper part of the eluting medium container 20, the capillary head front end 15 is configured to be located below the air 27 after insertion.

[0078] Here, the film 55 of the phoretic medium container 20 is peeled off and set, but it can also be set without peeling off the film 55 and penetrate the film 55 by the capillary head 13. In this way, although the load on the capillary head 13 increases, it is possible to prevent forgetting to peel off the film 55 and improve the workability of the user.

[0079] <Details of liquid delivery operation>

[0080] Below, use Figures 9 to 15 , the details of the liquid feeding operation of the electrophoretic medium 26 will be described.

[0081] Fig. 9 2 shows a series of operations of the injection operation of the phoretic medium 26, that is, an initial state. As described above, the phoretic medium container 20 is inserted and set in the guide 101 embedded in the sample tray 100. At this time, the plunger 61 of the liquid delivery mechanism 60 is arranged just below the phoretic medium container 20, and the seal 22 in the phoretic medium container 20 can be moved by the operation of the plunger 61.

[0082] Fig.10 2 shows a series of actions of the injection action of the phoretic medium 26, that is, the state of the contact detection of the plunger 61. First, as Fig. 9As shown, the plunger 61 of the liquid delivery mechanism 60 is brought into contact with the seal 22 in the eluting medium container 20 to detect its position. The stepping motor 62 of the liquid delivery mechanism 60 is driven by a weak driving current, and the stepping motor 62 is decoupled at the time of contact with the seal 22. In order to reduce the load on the seal 22, the driving current of the stepping motor 62 is adjusted so that the thrust of the plunger 61 at this time is about 10N. The decoupling of the stepping motor 62 at this time is detected by using the rotary encoder 63, so as to detect the contact of the plunger 61. By performing the contact position detection of the plunger 61, the amount of the eluting medium 26 in the eluting medium container 20 can be accurately grasped, which is used for the management of the liquid delivery amount and the leakage detection. After the contact detection of the plunger 61, the plunger 61 is excited with a current larger than the current during the driving, and is maintained at the position of contact with the seal 22. The current value during the excitation is preferably a current value that maintains the same thrust as the pressure generated when the eluting medium 26 is transported as much as possible.

[0083] Fig.11 1 shows a series of actions of the electrophoretic medium 26 injection action, that is, the state in which the capillary head 13 is connected. The capillary head 13 is connected to the electrophoretic medium container 20 by the action of the Z-axis driving body 90 of the automatic sampler unit 150. As described above, the sharp tip 15 of the capillary head is used to penetrate the rubber plug 23 in the electrophoretic medium container 20 and connect. The plunger 61 of the liquid feeding mechanism 60 is mounted on the Z-axis driving body 90 of the automatic sampler unit 150, so the plunger 61 is connected in a state of contact with the seal 22. In addition, as described above, the connection is performed while pressing the rubber plug 23 from above by the capillary head protrusion 14. At this time, the capillary head 13 is inserted into the electrophoretic medium container 20 in a state of being sealed by the rubber plug 23. As a result, a volume change occurs in the electrophoretic medium container 20, and the pressure in the electrophoretic medium container 20 increases, but since the seal 22 is suppressed by the plunger 61, the seal 22 does not work.

[0084] Fig.12 2 shows a series of actions of the electrophoretic medium 26 injection operation, that is, a diagram of the electrophoretic medium 26 injection state. After the capillary head 13 is connected, the plunger 61 is driven by the liquid delivery mechanism 60, thereby the sealing member 22 is operated, and the volume in the electrophoretic medium container 20 is changed to transport. At this time, the electrophoretic medium container 20 becomes high pressure, and each component of the electrophoretic medium container 20 expands. Since the rigidity of the electrophoretic medium container 20 is low at this time, the expansion amount is large and becomes unstable. Therefore, due to the expansion of the electrophoretic medium container 20, the airtightness of the electrophoretic medium 26 is greatly affected.

[0085] Therefore, the expansion of the syringe 21 is suppressed by the guide 101. In addition, the expansion of the rubber plug 23 is suppressed by the capillary head 13. In addition, since the shape of the seal 22 is a concave shape, the seal 22 becomes a shape that is further sealed when it expands under internal pressure. By forming the seal 22 in a shape and strength that is easier to expand than the syringe 21 in advance, the influence caused by the expansion of the syringe 21 can also be reduced. Specifically, the wall thickness of the syringe 21 is set to 1 mm, and the wall thickness of the seal 22 is set to about 0.6 mm, and the expansion coefficient is set to be different.

[0086] This reduces the effect of expansion on airtightness. However, no matter how much the expansion is reduced, it cannot be eliminated. The uneven expansion affects the management of the liquid delivery volume.

[0087] Therefore, first, the stepper motor 62 is driven with a driving current that becomes the pressure required for liquid delivery, and the plunger 61 is driven. The pressure required for this liquid delivery is set to 3 MPa. In order to generate this pressure, the driving current of the stepper motor 62 is adjusted so that the thrust of the plunger 61 becomes 75 N. As a result, although the inside of the eluting medium container 20 expands, the stepper motor 62 loses step at the time when the internal pressure increases by the required pressure amount. At this time, since the eluting medium container 20 is fully expanded, the loss of step is detected by the rotary encoder 63. Even after the loss of step is detected, the stepper motor 62 continues to drive while losing step. Since the eluting medium 26 is gradually delivered to the capillary 11, the plunger 61 is gradually driven. Then, after it is detected that the eluting medium container 20 is fully expanded, the amount of the plunger 61 driven is detected by the rotary encoder 63, and the amount corresponding to the required eluting medium 26 is delivered to the capillary 11. By adopting such a liquid delivery method, the amount of liquid delivery can be managed without being affected by the expansion of the eluting medium container 20.

[0088] Fig.13 and Fig.14 FIG. 2 shows a series of actions of the phoretic medium 26 injection action, that is, a detailed diagram of the residual pressure removal action in the phoretic medium container 20. Fig.12 As shown in FIG. 1 , the plunger 61 of the liquid delivery mechanism 60 is lowered to release the contact with the seal 22. After the liquid delivery is completed, the interior of the eluting medium container 20 still maintains a state of increased pressure. However, by this action, Fig.13 As shown, the seal 22 is pushed back by the pressure inside the phoretic medium container 20, and the residual pressure inside the phoretic medium container 20 is removed.

[0089] Fig.15Detailed diagrams of a series of actions including the injection action of the electrophoretic medium 26, namely, the action of disconnecting the capillary head 13 are shown in FIG. The connection between the capillary head 13 and the electrophoretic medium container 20 is disconnected by the action of the Z-axis driving body 90 of the automatic sampler unit 150. At this time, since the residual pressure in the electrophoretic medium container 20 is removed by the previous action, there is no need to worry about the electrophoretic medium 26 scattering when the connection between the capillary head 13 and the electrophoretic medium container 20 is disconnected. Through the above actions, the electrophoretic medium 26 is transported to the capillary 11.

[0090] <Example of the internal structure of a capillary electrophoresis system>

[0091] Fig.16 1 is a block diagram showing an example of a schematic internal structure of a capillary electrophoresis system 1600 according to the present embodiment. The capillary electrophoresis system 1600 includes a capillary electrophoresis apparatus 1 and a system control computer 2 .

[0092] The capillary electrophoresis apparatus 1 includes, as an internal structure related to the operation, a device control unit 1601 for controlling the entire capillary electrophoresis apparatus 1, a motor-plunger driving unit 1602 for driving the motor and the plunger 61, and an encoder count value monitoring unit 1603 for monitoring the encoder and its count value. The internal structure of the apparatus may also include various other components.

[0093] The system control computer 2 comprises: a control unit (e.g., composed of a processor) 1611, which performs various operations related to the liquid delivery correction control processing based on the flowchart (each embodiment) described later, generates a command signal and sends it to the capillary electrophoresis device; an input-output device 1612, which is composed of a keyboard, a mouse, various switches or buttons, etc., for example, an input unit for inputting instructions by a user or receiving signals from the outside (via a communication device 1615) and transferring them to the control unit 1611, and an output unit for outputting processing results (printouts, screen displays, etc.); a memory 1613, which stores, for example, various programs, various parameters and various data for executing the processing of embodiments 1 to 4 described later; a storage device 1614, which stores, for example, data related to the processing results; and a communication device 1615, which communicates with the outside and the capillary electrophoresis device 1, receives instructions or sends processing results, etc. to the outside and the capillary electrophoresis device 1.

[0094] The control unit 1611 of the system control computer 2, for example, performs a liquid delivery number management process for managing the number of liquid delivery times (counting the number of liquid delivery times) of the eluting medium, a liquid delivery time monitoring process, a eluting medium remaining amount calculation process, a liquid delivery number correction process, a liquid delivery amount and deviation calculation process, a liquid delivery amount correction process, a liquid delivery pressure calculation process, and a liquid delivery pressure correction process based on the information sent from the capillary electrophoresis device 1 (for example, the encoder count value), and sends the calculated control values ​​(instructions) such as the liquid delivery amount and the driving current to the device control unit 1601 of the capillary electrophoresis device 1 (for example, via the communication device 1615). The device control unit 1601 controls the motor plunger drive unit 1602, the encoder count value monitor unit 1603, etc. in response to the instructions sent from the system control computer 2. It should be noted that in Fig.16 In the embodiment, the system control computer 2 and the device control unit 1601 are depicted as different components, but the device control unit 1601 may be provided in the system control computer 2, and the control unit (processor) 1611 may also perform the functions of the device control unit 1601. Fig.16 In the embodiment, the device control unit 1601 may be included in the system control computer 2 (in this case, referred to as the device control unit 1601'), or may be Fig.16 In this case, the device control unit 1601' or the control unit 1611 in the system control computer 2 directly controls the motor plunger driving unit 1602 and the encoder count value monitoring unit 1603 to obtain the encoder count value.

[0095] The following describes the liquid delivery correction control process according to Examples 1 to 4. Fig.16 The system control computer 2 and the device control unit 1601 are described as different components, but as mentioned above, the device control unit 1601 can also be set in the system control computer 2. Therefore, in this case, the device control unit 1601 is replaced by the system control computer 2 or the control unit 1611, etc.

[0096] <Details of liquid delivery calibration control processing>

[0097] The capacity of the moving medium container 20 can usually be converted into a count value of the rotary encoder (for example, 4000 counts). In addition, the minimum amount of liquid that must be delivered to the capillary (liquid delivery amount setting value) is predetermined, and this value is notified to the device control unit 1601 of the capillary electrophoresis device 1 from the system control computer 2 as an indication amount (for example, 100 counts). On the other hand, in the capillary electrophoresis device 1, a slightly larger liquid delivery amount (assumed liquid delivery amount (worst value): for example, 200 counts) is set (used) in consideration of the deviation of the device and the moving medium container, and the minimum number of liquid delivery times (assumed liquid delivery times) is obtained by dividing the total amount of the moving medium contained in the moving medium container 20 (4000 counts) by the count value corresponding to the assumed liquid delivery amount. In addition, in the conventional capillary electrophoresis device, one moving medium container 20 is used up when the assumed number of liquid delivery times (minimum number of liquid delivery times: for example, 20 times) is completed. That is, for example, when the actual average value of the liquid delivery amount per time is 150 counts when liquid delivery control is performed with the liquid delivery amount setting value (e.g., 100 counts), no further liquid delivery operation will be performed regardless of the remaining amount of the electrophoretic medium contained therein. However, this will waste the expensive electrophoretic medium and become a major cause of increasing running costs. For example, if the number of counts is 130 (actual value) in one liquid delivery and 170 (actual value) in another liquid delivery, if the average liquid delivery amount is 150 counts, it will become 3000 counts in 20 liquid delivery operations, and the remaining amount of 1000 counts will be wasted.

[0098] The processing of each embodiment described below relates to a technology that can eliminate such waste of the bouncing medium as much as possible and efficiently utilize the expensive bouncing medium.

[0099] <Example>

[0100] Example 1

[0101] Embodiment 1 relates to the following processing: calculating the remaining amount of the electrophoretic medium after the assumed number of liquid feeding operations is completed, and correcting the number of liquid feeding operations based on the remaining amount (calculating the number of additional liquid feeding operations). Fig.17 The flowchart of FIG. 1 illustrates its contents. Fig.17 This is a flowchart for explaining the liquid feeding frequency correction process of Example 1. Each step will be described below.

[0102] (i) Step 1701

[0103] The control unit 1611 of the system control computer 2, for example, responds to an instruction from a user (operator) to start liquid delivery, and sends a command to the capillary electrophoresis device 1 to start the liquid delivery operation. In response to the command, the device control unit 1601 of the capillary electrophoresis device 1 controls the motor plunger drive unit 1602 and the encoder count value monitor unit 1603 to perform the liquid delivery operation of the phoretic medium. In addition, the device control unit 1601 notifies the control unit 1611 of the actual encoder count value (indicating the position of the plunger 61) at the end of one liquid delivery operation. It should be noted that, when performing one liquid delivery operation, the device control unit 1601 controls the motor plunger drive unit 1602 to move the position of the plunger 61 until the encoder count value becomes the liquid delivery amount setting value (for example, 100 counts). Thus, although the encoder count value (liquid delivery amount setting value: for example, 100 counts) in one liquid delivery is predetermined, the encoder count value indicating the actual position of the plunger 61 may not become the setting value (100 counts) due to the structural reasons of the plunger 61. Therefore, the actual liquid delivery amount of each time is deviated. That is, although the encoder count value indicating the position of the plunger 61 is electrically controlled so as to become an amount equivalent to the liquid delivery amount setting value, the actual position of the plunger 61 at the end of the liquid delivery operation may not become an amount equivalent to the liquid delivery amount setting value.

[0104] When the liquid feeding operation of the assumed liquid feeding number (the minimum liquid feeding number: for example, 20 times) is completed, the control unit 1611 calculates the total encoder count value when the assumed liquid feeding number (the minimum liquid feeding number) is completed based on the encoder count value (actual value) of each time notified by the device control unit 1601. Then, the control unit 1611 subtracts the total encoder count value when the assumed liquid feeding number (the minimum liquid feeding number) is completed from the encoder count value (for example, 4000 counts) of the capacity of the floating medium container 20 to calculate the remaining amount (count value) of the floating medium.

[0105] (ii) Step 1702

[0106] The control unit 1611 determines whether the remaining amount (count value) calculated in step 1701 is greater than the assumed liquid supply amount (worst value) for each time. If the remaining amount is less than the assumed liquid supply amount (if it is No in step 1702), the process moves to step 1705. If the remaining amount is greater than the assumed liquid supply amount (if it is Yes in step 1702), the process moves to step 1705.

[0107] (iii) Step 1703

[0108] Since the set value of the liquid delivery amount (for example, 100 counts) may not be guaranteed with this margin, the control unit 1611 determines that the number of liquid delivery times should not be corrected.

[0109] (iv) Step 1704

[0110] The control unit 1611 outputs a warning (for example, a warning display) urging replacement of the flowing medium container 20. For example, the warning display is displayed on a display screen of a display device constituting the input / output device.

[0111] (v) Step 1705

[0112] This margin can ensure the set value of the liquid delivery amount for one time (for example, 100 counts), and therefore the control unit 1611 determines that the number of liquid delivery times must be corrected.

[0113] (vi) Step 1706

[0114] The control unit 1611 calculates the number of corrections by dividing the remaining amount (count value) calculated in step 1701 by the assumed liquid delivery amount (worst value: for example, 200 counts). For example, when the remaining amount is 1100 counts, 1100÷200=5···100, indicating that at least five more deliveries are possible.

[0115] (vii) Step 1707

[0116] For example, the control unit 1611 displays the number calculated in step 1706 on the display screen, notifies the user of the additional number of liquid supply times (corrected liquid supply times), and in response to the liquid supply start instruction from the user, sends a command to the device control unit 1601 to start the liquid supply operation.

[0117] (viii) Step 1708

[0118] When the liquid delivery is completed to the limit (corresponding to the additional liquid delivery number obtained by calibration), the control unit 1611 terminates the liquid delivery of the moving medium contained in the moving medium container 20. Then, the process transfers to step 1704, and a warning is output to urge the moving medium container to be replaced with a new one.

[0119] It should be noted that in step 1708, when the liquid delivery action corresponding to the calibration number is completed, the remaining amount can be calculated again to determine whether liquid delivery is possible.

[0120] Example 2

[0121] In Example 1, the assumed liquid delivery volume (worst case value: for example, 200 counts) (set to a fixed value) when delivering with the minimum number of liquid delivery times is used to calculate the corrected liquid delivery times based on the remainder, but in Example 2, the average value and deviation (standard deviation) of the actual liquid delivery volume are calculated after delivering with the minimum number of liquid delivery times, and the corrected liquid delivery times (additional liquid delivery times) are calculated based on the corrected assumed liquid delivery volume (variable worst case value) and the remainder calculated based on this. Fig.18This is a flowchart for explaining the liquid feeding frequency correction process according to Embodiment 2. Each step will be described below.

[0122] (i) Step 1801

[0123] When the liquid feeding operation of the assumed liquid feeding number (minimum liquid feeding number) according to the liquid feeding amount setting value (e.g., 100 counts) is completed, the control unit 1611 calculates the total encoder count value when the assumed liquid feeding number (minimum liquid feeding number) is completed based on the encoder count value (actual value) of each time notified by the device control unit 1601. Then, the control unit 1611 subtracts the total encoder count value when the assumed liquid feeding number (minimum liquid feeding number) is completed from the encoder count value of the capacity of the floating medium container 20 (e.g., 4000 counts) to calculate the remaining amount (count value) of the floating medium.

[0124] (ii) Step 1802

[0125] The control unit 1611 calculates an average value of the liquid delivery amount from the liquid delivery amount for each liquid delivery, and calculates a deviation (for example, a standard deviation, a dispersion) based on the average value.

[0126] (iii) Step 1803

[0127] The control unit 1611 calculates the corrected assumed liquid supply amount (variable worst value) in consideration of the deviation calculated in step 1802. For example, it can be calculated by the corrected assumed liquid supply amount = the average value of the actual liquid supply amount + 3σ (σ: represents the standard deviation). For example, if the average value of the actual liquid supply amount of the assumed liquid supply number (the minimum liquid supply number: for example, 20 times) is 120 counts and the standard deviation σ is 10 counts, the corrected assumed liquid supply amount becomes 150 counts. The corrected assumed liquid supply amount is calculated using the actual value based on the assumed liquid supply number, so that compared with the fixed assumed liquid supply amount (1 time amount), the assumed liquid supply amount (1 time amount) that matches the actual liquid supply action can be obtained.

[0128] (iv) Step 1804 to Step 1810

[0129] The processing from step 1804 to step 1810 is the same as Fig.17 Steps 1702 to 1708 are the same, so detailed description is omitted. However, the "liquid delivery amount per time" or "assumed liquid delivery amount" mentioned after step 1802 is replaced by the "corrected assumed liquid delivery amount" calculated in step 1803.

[0130] Example 3

[0131] Example 3 is a technology that utilizes the correlation between liquid feeding time and liquid feeding pressure and controls the driving current of the plunger 61 based on the measured liquid feeding time, thereby adjusting the pressing force of the plunger 61 and suppressing the variation in the liquid feeding amount.

[0132] (Calibration of liquid delivery times)

[0133] Fig.19 is a graph showing the relationship between the liquid delivery amount and the liquid delivery time at different liquid delivery pressures. Fig.19 It can be seen that if the liquid feeding pressure (pressure applied to the plunger 61) is small (for example, in the case of 2MPa), the deviation of the liquid feeding amount becomes smaller, but the liquid feeding time is required, and the deviation of the liquid feeding time also becomes larger. In addition, it can be seen that if the liquid feeding pressure becomes larger (for example, in the case of 5MPa, 5.5MPa), the deviation of the liquid feeding time becomes smaller, but the deviation of the liquid feeding amount becomes larger. Therefore, if a more appropriate liquid feeding pressure is set (for example, in the case of 3.5Pa (relatively appropriate)), the deviation of the liquid feeding time and the deviation of the liquid feeding amount are both within an appropriate range. Therefore, the driving current of the driving plunger 61 is controlled in a manner that the liquid feeding action can be performed at a more appropriate liquid feeding pressure. Fig. 20 This is a flowchart for explaining the liquid supply frequency correction processing (calculation of the current correction value of the plunger 61 + calculation of the liquid supply correction frequency) according to the third embodiment.

[0134] (i) Step 2001

[0135] The control unit 1611 completes the liquid supply operation for a presumed number of liquid supply operations (minimum number of liquid supply operations: for example, 20 times) according to the liquid supply volume setting value (for example, 100 counts). In addition, the control unit 1611 measures the time taken for the liquid supply operation for each liquid supply operation.

[0136] (ii) Step 2002 to Step 2004

[0137] The processing from step 2002 to step 2004 is the same as Fig.18 Steps 1801 to 1803 are the same, so detailed description is omitted.

[0138] (iii) Step 2005

[0139] The control unit 1611 calculates the average value of the measured liquid delivery times each time the liquid is delivered.

[0140] (iv) Step 2006

[0141] The control unit 1611 estimates the liquid delivery pressure based on the average liquid delivery time calculated in step 2002, and calculates a correction value of the drive current of the plunger 61 so that the liquid delivery time falls within a predetermined threshold range. The calculation process of the correction value of the drive current will be described in detail below.

[0142] First, if Fig.21 As shown in FIG. 1 , it can be seen that there is a correlation (for example, a proportional relationship) between the driving current and the average liquid delivery pressure. Fig. 22 As shown in FIG. 1 , it can be seen that there is also a correlation between the average liquid delivery pressure and the liquid delivery time. Therefore, the system control computer 2 maintains the same Fig.21 and Fig. 22 The table or information of the corresponding correlation straight line and correlation curve is referred to when calculating the correction value of the driving current.

[0143] Specifically, first, the control unit 1611 refers to Fig. 22 (Apply the average liquid delivery time to the approximate curve) and estimate the liquid delivery pressure value based on the average liquid delivery time calculated in step 2002. For example, when the driving current value of the plunger 61 is set to 0.5A and the plunger 61 generates a pressure of 3.5MPa to perform the liquid delivery operation, the average liquid delivery time is 80s. Fig. 22 , the estimated liquid delivery pressure is about 5MPa (it should be noted that the approximate curve y = -5.963x 3 +91.001x 2 -480.7x+956.81 The average liquid delivery time (y) is applied to 80s to obtain the average liquid delivery pressure (x). However, this estimated result shows that the actual assumed liquid delivery pressure value (3.5MPa) produces a liquid delivery pressure of 5MPa at a drive current setting value of 0.5A due to the change in the liquid delivery pressure. In other words, it is determined that the current value is too high when the drive current setting value is 0.5A (resulting in an excessively high liquid delivery pressure).

[0144] Therefore, the relationship between the driving current and the average liquid delivery pressure is corrected ( Fig.21 : y = 10.454x - 1.8413). However, the driving current and the liquid delivery pressure are proportional, and the inclination does not change even if there is a deviation. Therefore, the setting value of 0.52A and the estimated liquid delivery pressure are used to correct the Fig.21 The intercept of the equation shown is (-1.8413). That is, intercept = y-10.454x = 5-10.454×0.52 = -0.227. Therefore, the relationship between the corrected drive current and the average liquid delivery pressure (correction relationship) is y = 10.454x-0.436. According to this correction relationship ( Fig.23The relationship between the corrected driving current and the average liquid delivery pressure is shown in Figure 2), and when calculating the current value at which the liquid delivery pressure becomes 3.5 MPa, 3.5 = 10.454x - 0.436, x = 0.356514253 = 0.377 [A]. Therefore, if the current setting value is changed to 0.377 A, the liquid delivery pressure can be properly controlled. In addition, if the corrected current value is used for liquid delivery, the liquid delivery time is controlled to fall within the range of the above-mentioned threshold value (for example, 100 s to 150 s).

[0145] Furthermore, the control unit 1611 can adjust the relationship between the liquid delivery amount and the liquid delivery time according to different liquid delivery pressures ( Fig.19 ) to estimate the deviation of the liquid delivery amount, so the set value of the liquid delivery amount and the assumed liquid delivery amount can be recalculated based on the deviation of the liquid delivery amount (corrected set value of the liquid delivery amount and assumed liquid delivery amount). In addition, the control unit 1611 can use the corrected set value of the liquid delivery amount and the assumed liquid delivery amount to instruct the device control unit 1601 to perform a liquid delivery operation (additional liquid delivery) for the remaining amount.

[0146] (v) Step 2007 to Step 2013

[0147] The processing from step 2002 to step 2004 is the same as Fig.18 Steps 1804 to 1810 ( Fig.17 However, when the control unit 1611 performs the liquid delivery operation corresponding to the calculated correction number, the driving current of the plunger 61 is set to the corrected current value (for example, 0.377A as described above).

[0148] (Others: Modifications, etc.)

[0149] (i) in Fig. 20 In the processing shown, the assumed liquid delivery volume taking into account the deviation is calculated (corrected assumed liquid delivery volume: initially 200 counts → 125 counts after correction), and the additional liquid delivery number (corrected liquid delivery number) is calculated (corresponding to Example 2), but it is also possible to ignore the deviation and use a fixed assumed liquid delivery volume to calculate the corrected liquid delivery number (additional liquid delivery number), and execute the liquid delivery action corresponding to this number (corresponding to Example 1).

[0150] (ii) The above-mentioned plunger 61 current correction value calculation process (steps 2005 and 2006) can be applied independently as a control of the capillary electrophoresis apparatus 1 even without being combined with the liquid feeding frequency correction process. Fig. 20In the embodiment, in steps 2001 and 2002, the current correction value is calculated after the minimum number of liquid delivery times (for example, 20 times) is completed, but when the calculation process of the drive current correction value of the plunger 61 is performed independently, steps 2005 and 2006 can be performed before the minimum number of liquid delivery times is reached (that is, even when the number of liquid delivery times has not reached 20 times). Thus, the plunger 61 of the capillary electrophoresis apparatus 1 can be operated at an appropriate current value, and the deviation of the liquid delivery amount can be suppressed.

[0151] Example 4

[0152] Example 4 involves the following technology: the average value of the actual liquid supply volume is calculated based on the displacement of the position of the plunger 61, the liquid supply volume setting value is automatically adjusted, and the assumed liquid supply volume (worst value) is replaced by the average value of the actual liquid supply volume (corrected assumed liquid supply volume), and the remaining amount of the electrophoretic medium is divided by the corrected assumed liquid supply volume, thereby calculating the correction number (additional liquid supply number).

[0153] (Calibration of liquid delivery times)

[0154] Fig.24 This is a flowchart for explaining the liquid supply frequency correction processing (offset value calculation + liquid supply correction frequency calculation) according to Embodiment 4. Each step will be described below.

[0155] (i) Step 2401

[0156] The control unit 1611 performs a liquid delivery operation for a predetermined number of times (minimum number of times: for example, 20 times) according to the liquid delivery amount setting value (for example, 100 counts). In addition, the control unit 1611 may also measure the time taken for the liquid delivery operation for each liquid delivery.

[0157] (ii) Step 2402

[0158] When the liquid supply operation of the assumed number of liquid supply times (the minimum number of liquid supply times: for example, 20 times) is completed, the control unit 1611 calculates the overall encoder count value when the liquid supply is completed (for example, 20 times of liquid supply are completed) based on the encoder count value (actual value) of each time notified by the device control unit 1601. Then, the control unit 1611 calculates the average value of the liquid supply amount based on the total amount of liquid supply.

[0159] (iii) Step 2403

[0160] The control unit 1611 compares the average value of the liquid supply amount calculated in step 2402 (e.g., 160 counts) with the liquid supply amount setting value (e.g., 100 counts), and calculates an offset value of the liquid supply amount (average value-setting value=160-100=60 counts).

[0161] (iv) Step 2404

[0162] The control unit 1611 subtracts the offset value calculated in step 2403 from the initial value of the liquid delivery amount setting value (e.g., 100 counts), corrects (adjusts) the liquid delivery amount setting value (corrects the liquid delivery amount setting value), and resets the fixed assumed liquid delivery amount to the average value of the actual liquid delivery amount (e.g., 160 counts as described above). However, the corrected liquid delivery amount setting value is subject to a condition that the minimum required liquid delivery amount that must be ensured is greater than a predetermined amount. When the calculated setting value is less than the required liquid delivery amount, the offset value may be adjusted to achieve the required liquid delivery amount.

[0163] (v) Steps 2405 and 2406

[0164] The control unit 1611 sends an instruction to restart the liquid delivery of the eluting medium to the device control unit 1601 of the capillary electrophoresis device 1, and subtracts the overall encoder count value when the assumed liquid delivery number (minimum liquid delivery number) is completed from the encoder count value of the capacity of the eluting medium container 20 (for example, 4000 counts) to calculate the remaining amount (count value) of the eluting medium.

[0165] (vi) Step 2407 to Step 2413

[0166] The processing from step 2407 to step 2413 is the same as Fig.17 Steps 1702 to 1708 are the same, so their description is omitted.

[0167] (Others: Modifications, etc.)

[0168] (i) In the above-mentioned processing, the correction number (additional number of liquid supply) corresponding to Example 1 is calculated, but the deviation of the actual liquid supply amount can also be calculated corresponding to Example 2, and the correction number (additional number of liquid supply) can be calculated based on the corrected assumed liquid supply amount taking into account the deviation.

[0169] In addition, the processing contents of Example 3 may be added to the processing of Example 4. In this case, as described in Example 3, the liquid feeding pressure is estimated based on the average liquid feeding time of the assumed number of liquid feeding times (for example, 20 times), and the correction value (corrected driving current value) of the driving current of the plunger 61 is calculated based on this, and when the liquid feeding is additionally performed, the plunger 61 is driven with the calculated corrected driving current value.

[0170] (ii) In addition, the above-mentioned process of automatically adjusting the set value of the liquid delivery amount (steps 2401 to 2405) can be applied independently as a control of the capillary electrophoresis apparatus 1 even if it is not combined with the liquid delivery frequency correction process. Fig.24In the embodiment, the process of adjusting the set value of the liquid delivery amount is performed after the minimum number of liquid delivery times (for example, 20 times) is completed (step 2401), but in the case where this process is performed independently, steps 2402 to 2405 can be performed before the minimum number of liquid delivery times is reached (that is, even if the number of times is not reached 20 times). That is, the "minimum number of liquid delivery times" in step 2401 can be replaced with "predetermined number of times (less than the minimum number of liquid delivery times)" to perform the process of adjusting the set value of the liquid delivery amount. In addition, the set value of the liquid delivery amount adjusted in the liquid delivery action of the next new liquid delivery medium container after the currently used liquid delivery medium container is used up can also be used. In this way, the liquid delivery amount for one time can be appropriately determined (not too much, not too little), and the deviation of the liquid delivery amount can be suppressed.

[0171] Summary

[0172] (i) According to the first embodiment, the following processing is involved: the remaining amount of the electrophoretic medium after the assumed number of liquid feeding operations is completed is calculated, and the number of liquid feedings is corrected based on the remaining amount (the number of additional liquid feedings is calculated). That is, according to the first embodiment, a capillary electrophoresis system (measurement system: hereinafter referred to as "system") is proposed, which calculates the possible number of liquid feedings based on the amount of electrophoretic medium in the electrophoretic medium container and the assumed liquid feeding amount of the electrophoretic medium based on the liquid feeding mechanism. By configuring such a system, the electrophoretic medium contained in the electrophoretic medium container can be used efficiently, and the running cost can be reduced.

[0173] For example, the above-mentioned assumed liquid delivery amount of the electrophoretic medium indicates the assumed liquid delivery amount determined in consideration of the deviation of the liquid delivery amount based on the electrophoretic device and / or the electrophoretic medium container. At this time, the system calculates the possible liquid delivery times indicating the number of times that additional liquid delivery can be performed based on the remaining amount of the electrophoretic medium after the specified number of liquid delivery actions (for example, the minimum number of liquid delivery times: 20 times) are completed and the assumed liquid delivery amount, and instructs the electrophoretic device to perform the liquid delivery action corresponding to the possible liquid delivery times. It should be noted that the calculation of the possible liquid delivery times can be set to be performed when the remaining amount of the electrophoretic medium is greater than the assumed liquid delivery amount. In this way, the remaining amount of the electrophoretic medium contained in the electrophoretic medium container can be minimized from being used up.

[0174] (ii) According to the second embodiment, after liquid is sent at the minimum number of times, the average value and the deviation (standard deviation) of the actual liquid sending amount are calculated, and the corrected liquid sending number (additional liquid sending number) is calculated based on the corrected assumed liquid sending amount (variable worst value) and the margin calculated based on the calculated amount. In this way, the additional possible number of liquid sendings (corrected liquid sending number) can be obtained more accurately, so that the electrophoretic medium can be used more efficiently.

[0175] (iii) According to Example 3, the fact that the liquid delivery time and the liquid delivery pressure are correlated is utilized, and the driving current of the plunger 61 is controlled based on the measured liquid delivery time, thereby adjusting the pressing force of the plunger 61 and suppressing the deviation of the liquid delivery amount. That is, the system measures the filling time of the electrophoretic medium into the capillary, and based on the filling time and the relationship between the filling time and the liquid delivery pressure ( Fig. 22 ), detects the change in liquid delivery pressure, and changes the liquid delivery pressure. More specifically, the system changes the liquid delivery pressure by changing the driving current of the plunger of the liquid delivery mechanism. Thereby, the pressing force of the plunger 61 can be appropriately adjusted, and in particular, the deviation of the liquid delivery amount when the liquid delivery time is shorter than the specified liquid delivery time (when it is outside the range of the threshold of the specified liquid delivery time) can be suppressed. Moreover, by controlling the capillary electrophoresis device 1 in a manner that can perform the liquid delivery action of the number of times that can be delivered under the changed liquid delivery pressure, the delivery action to the capillary can be performed stably (the liquid delivery amount is stable).

[0176] In addition, the system corrects the target liquid supply amount during liquid supply control, that is, the liquid supply amount setting value and the assumed liquid supply amount based on the changed liquid supply pressure, thereby appropriately determining the corrected liquid supply number (additional liquid supply number).

[0177] It should be noted that the main technical idea of ​​Example 3 is not to correct the number of liquid delivery times (calculate the additional number of liquid delivery times based on the margin), but to change the liquid delivery pressure by adjusting the driving current of the plunger 61. Based on this premise, it must be understood that the technology of Example 3 (processing of changing the liquid delivery pressure) can also be applied to Example 1 and Example 2.

[0178] (iv) According to Example 4, the average value of the actual liquid delivery amount is calculated based on the displacement of the position of the plunger 61, the liquid delivery amount setting value is automatically adjusted, and the assumed liquid delivery amount (worst value) is replaced by the average value of the actual liquid delivery amount (corrected assumed liquid delivery amount), thereby dividing the remaining amount of the electrophoretic medium by the corrected assumed liquid delivery amount to calculate the correction number (additional liquid delivery number). That is, the system corrects the liquid delivery amount setting value based on the actual liquid delivery amount, which is the offset value relative to the target liquid delivery amount when performing liquid delivery control, that is, the liquid delivery amount setting value, and controls the electrophoretic device in a manner of performing liquid delivery operation according to the corrected liquid delivery amount. As a result, the electrophoretic medium can be transported with the liquid delivery control value corresponding to the actual liquid delivery status, and the electrophoretic medium can be used more efficiently. In addition, the system calculates the average liquid delivery amount in a specified number of liquid delivery times based on the actual liquid delivery amount, sets the average liquid delivery amount as the assumed liquid delivery amount, and controls the liquid delivery operation of the electrophoretic medium.

[0179] It should be noted that the main technical idea of ​​Example 4 is not to correct the number of liquid delivery times (calculate the additional liquid delivery times based on the remaining amount), but to correct the liquid delivery amount setting value. Based on this premise, it must be understood that the technology of Example 4 (processing of changing the liquid delivery pressure) can also be applied to Example 1 and Example 2.

[0180] (v) The functions of each embodiment can also be implemented by the program code of the software. In this case, a storage medium recording the program code is provided to a system or device, and the computer (or CPU, MPU) of the system or device reads the program code stored in the storage medium. In this case, the program code read from the storage medium itself implements the functions of the aforementioned embodiments, and the program code itself and the storage medium storing the program code constitute the present invention. As a storage medium for supplying such a program code, for example, a floppy disk, CD-ROM, DVD-ROM, hard disk, optical disk, magneto-optical disk, CD-R, magnetic tape, non-volatile memory card, ROM, etc. are used.

[0181] In addition, based on the instructions of the program code, the OS (operating system) etc. operating on the computer may perform part or all of the actual processing, and the functions of the aforementioned embodiments may be realized through the processing. In addition, after the program code read from the storage medium is written into the memory on the computer, the CPU etc. of the computer may perform part or all of the actual processing based on the instructions of the program code, and the functions of the aforementioned embodiments may be realized through the processing.

[0182] Furthermore, the program code of the software that implements the functions of each embodiment can also be distributed via the network and stored in a storage means such as a hard disk or memory of the system or device or a storage medium such as CD-RW or CD-R. When in use, the computer (or CPU, MPU) of the system or device reads and executes the storage means and the program code stored in the storage medium.

[0183] Finally, it should be understood that the processes and techniques described herein are not essentially related to any specific device, and can be installed by any corresponding combination of components. In addition, various types of general-purpose equipment can be used in accordance with the teachings described herein. It can be seen that building a dedicated device is beneficial for executing the steps of the method described herein. In addition, various inventions can be formed by appropriate combinations of multiple constituent elements disclosed in the embodiments. For example, several constituent elements can also be deleted from all constituent elements shown in each embodiment. Furthermore, the constituent elements of different embodiments and embodiments can also be appropriately combined. Although the present invention is described in relation to specific examples, these descriptions are not intended to be limited in all viewpoints but to be explained. For those skilled in the art, it should be clear that there are multiple combinations of hardware, software and firmware corresponding to the implementation of the present invention. For example, the described software can be installed by a wide range of programs or scripting languages ​​such as assemblers, C / C++, perl, Shell, PHP, Java (registered trademark).

[0184] Furthermore, in the above-mentioned embodiments and examples, control lines and information lines are shown as parts that are considered necessary for explanation, and not all control lines and information lines are necessarily shown in the product. All structures may be connected to each other.

[0185] In addition, for those with common knowledge in the art, other implementations of the present invention will become clear based on the description and embodiments of the present invention disclosed herein. The various schemes and / or components of the described embodiments can be used alone or in any combination in a computerized storage system having the function of managing data. The description and specific examples are only typical contents, and the scope and spirit of the present invention are shown in the above technical solutions.

Claims

1. A measuring system comprising an electrophoresis device and a computer, wherein: The electrophoresis device comprises: a phoretic medium container, which contains a phoretic medium; a capillary tube, which is filled with the phoretic medium; a liquid delivery mechanism for delivering the electrophoretic medium in the electrophoretic medium container to the capillary tube; as well as a device control unit, which controls the operation of the liquid delivery mechanism, The computer measures the filling time of the electrophoretic medium into the capillary, detects a change in the liquid feeding pressure based on the filling time and a relationship between the filling time and the liquid feeding pressure, and changes the liquid feeding pressure.

2. The measuring system according to claim 1, wherein: The computer changes the liquid delivery pressure by changing a driving current of a plunger of the liquid delivery mechanism.

3. The measuring system according to claim 1, wherein: The computer instructs the device control unit to execute a liquid delivery operation for a predetermined possible number of liquid deliveries at the changed liquid delivery pressure.

4. The measuring system according to claim 1, wherein: The computer corrects a target liquid supply amount during liquid supply control, i.e., a liquid supply amount setting value, and a hypothetical liquid supply amount determined in consideration of a variation in the liquid supply amount of the electrophoresis device and / or the mobilization medium container, based on the changed liquid supply pressure.

5. A liquid delivery control method for controlling the delivery of a mobilization medium from a mobilization medium container to a capillary in an electrophoresis device, wherein: The liquid delivery control method comprises: A computer controlling the operation of the electrophoresis device measures the filling time of the capillary tube with the electrophoretic medium; and The computer detects a change in the liquid delivery pressure based on the filling time and a relationship between the filling time and the liquid delivery pressure, and changes the liquid delivery pressure.

Citation Information

Patent Citations

  • Capillary electrophoresis apparatus

    JP2008008621A