Control method of an automatic analysis device

By employing a multi-sample port switching valve and sample loop control method in the automated analysis device, the cleaning and sample introduction processes were optimized, solving the problems of complex structure and low productivity in the existing technology, and achieving simplification of the device and improvement of measurement accuracy.

CN115516319BActive Publication Date: 2025-12-16HITACHI HIGH TECH CORP
View PDF 4 Cites 0 Cited by

Patent Information

Application Number
CN202180033108.9
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2020-05-29
Filing Date
2021-05-19
Publication Date
2025-12-16
Estimated Expiration
2041-05-19

AI Technical Summary

Technical Problem

Existing automated analysis devices suffer from complex structures and difficulty in shortening cleaning and sample introduction processes when handling batch operations in a fully automated manner, resulting in insufficient productivity and measurement accuracy.

Method used

An automated analysis device with a switching valve and sample loop featuring multiple sample ports is employed. By adjusting the driving parameters of the syringe and the state of the switching valve, the sample introduction and cleaning processes are optimized, including efficient switching between the syringe and the sample loop and precise control of the cleaning solvent.

Benefits of technology

The automated analysis device has been simplified in structure and maintenance-free, and the cleaning and sample introduction processes have been shortened, which has improved productivity and measurement accuracy, and ensured the reproducibility and accuracy of the analysis results.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN115516319B_ABST
    Figure CN115516319B_ABST
Patent Text Reader

Abstract

In a control method of an automatic analysis device provided with a sample loop connecting between two of a plurality of sample ports connected to a switching valve, there are a step of adjusting a drive parameter of a syringe in accordance with viscosity of a sample obtained in advance, a step of switching the switching valve to a first state in which a carrier and the syringe are conducted without passing through the sample loop, a step of driving the syringe based on the drive parameter to introduce and conduct the sample into the carrier, a step of switching the switching valve to a second state in which the syringe and the sample loop are conducted, and a step of driving the syringe based on the drive parameter to conduct the sample to the sample loop. Thus, robustness, productivity, and measurement accuracy can be improved.
Need to check novelty before this filing date? Find Prior Art

Description

TECHNICAL FIELD

[0001] The present application relates to a control method of an automatic analysis device. BACKGROUND

[0002] A liquid chromatograph mass spectrometer (HPLC / MS) is a device that combines a liquid chromatograph (HPLC) and a mass spectrometer (MS). In the liquid chromatograph mass spectrometer (HPLC / MS), separation based on the chemical structure and physical properties of a measurement target substance by the liquid chromatograph (HPLC) and separation based on the mass of the measurement target substance by the mass spectrometer (MS) are combined, whereby each component in a sample can be qualitatively and quantitatively analyzed. By virtue of such advantages of the liquid chromatograph mass spectrometer (HPLC / MS), for example, even in a case where a measurement target substance is metabolized in vivo and mixed with a plurality of similar substances like a pharmaceutical in a biological sample, qualitative and quantitative analysis of the measurement target substance can be performed, and application to the field of clinical examination is expected. In examination centers, university hospitals, and the like, the liquid chromatograph mass spectrometer (HPLC / MS) is used to perform examinations such as immunosuppressants, anticancer agents, neonatal metabolic abnormality examinations, and TDM (Therapeutic Drug Monitoring). Pretreatment is performed by a check kit or a manual method, and the sample is supplied to the liquid chromatograph mass spectrometer (HPLC / MS). Verification (validity examination) of each examination method is performed under the responsibility of each examination institution, and the examination results are ensured. Since the pretreatment process is complicated, depending on the proficiency of an examination technician, there can be a deviation in the examination results. In addition, in the pretreatment and measurement by the liquid chromatograph mass spectrometer (HPLC / MS), there is a possibility that an adverse situation in the examination results due to human error can occur. Therefore, from the pretreatment to the liquid chromatograph mass spectrometer (HPLC / MS), an automatic analysis device capable of automatically processing batch processes is required to be developed in the field of clinical examination.

[0003] As a mode of the autosampler used for introducing a sample to the liquid chromatograph (HPLC), for example, there are a Partial-Loop-Injection mode or a Direct-Injection mode. The Partial-Loop-Injection mode, for example, introduces a sample in a sample loop connected between two ports by the amount of drive of a syringe connected to a 6-port 2-position high-pressure valve. The Partial-Loop-Injection mode has a feature of excellent handling because of a relatively simple structure. On the other hand, the Direct-Injection mode, for example, has a configuration in which a mobile phase discharged from a pump passes through a sample loop and a carrier. In the Partial-Loop-Injection mode, since it is possible to use all of the sample sucked by the syringe, there is no waste of the sample. However, in the Direct-Injection mode, it is not possible to use all of the sample sucked by the syringe, and thus there is a waste of the sample. In addition, the Direct-Injection mode must be a configuration in which a joint portion of the carrier and the 6-port 2-position high-pressure valve is maintained at a high pressure in order to avoid leakage of the sample, and thus the configuration is relatively complex. In view of such circumstances, the Partial-Loop-Injection mode is mainly used as a mode of the autosampler suitable for an automatic analysis device capable of fully automatically processing batch processes.

[0004] For example, in Patent Literature 1, there is disclosed an analysis device including an injection valve including a sample loop, having an output port in fluid communication with an LC column and an input port in fluid communication with a mobile phase supply line, a sample pump, at least two standard supply sources associated with at least two pharmaceuticals, and a selection valve connecting the sample pump in a flow fluid and selectable manner to at least two pharmaceutical manufacturing process lines associated with the at least two standard supply sources, the sample injection valve, and the at least two pharmaceuticals.

[0005] In addition, in Patent Literature 2, there is disclosed a sample injection method for a liquid chromatograph in which a piston of a metering syringe is pulled, a sample is sucked in an intermediate portion of a suction tube connected to the metering syringe via air, then, by switching a valve, a sample loop connected between a mobile phase pump and a column of the liquid chromatograph is separated from the connection, the sample loop is connected with the intermediate portion of the suction tube therebetween, then, the piston of the metering syringe is pressed, the sample liquid in the suction tube on the metering syringe side is introduced into the sample loop in a set amount, then, the valve is switched to the original state, thereby connecting the sample loop between the mobile phase pump and the column, and the sample liquid in the sample loop is injected into the column.

[0006] Further, in Patent Document 3, a method for transferring a liquid sample by a valve having at least two positions is disclosed, which includes a stage of passing the sample through a valve in a first direction of a first position, switching the valve at a second position, and passing at least a part of the sample through the valve at the second position.

[0007] Prior Art Documents

[0008] Patent Documents

[0009] Patent Document 1: Japanese Patent Application Laid-Open (JP-A) No. 2011-513732

[0010] Patent Document 2: Japanese Patent Application Laid-Open (JP-A) No. H02-132369

[0011] Patent Document 3: Japanese Patent Application Laid-Open (JP-A) No. H02-176538 SUMMARY

[0012] Problems to be Solved by the Invention

[0013] In an automatic sampler suitable for an automatic analysis device capable of handling batch processes fully automatically, as to robustness, "simplification of structure" and "maintenance-free" are required, as to productivity, "shortening of a washing process" and "shortening of a sample introduction process" are required, and as to measurement accuracy, "optimization of a washing process" and "optimization of a sample introduction process" are required.

[0014] However, in the prior art described in Patent Document 1 described above, a structure of only one pump (corresponding to a syringe for transporting a sample) is disclosed, and the washing process and the sample introduction process cannot be performed in parallel, and thus it is difficult to achieve "shortening of a washing process" and "shortening of a sample introduction process" in productivity.

[0015] Further, in the prior art described in Patent Document 2 described above, since the sample is temporarily compressed and then returned to the original state, air bubbles generated by an air layer and residual air in the sample at that time are mixed into the sample. If air bubbles are introduced into the sample loop, the analysis accuracy decreases, and thus it is difficult to achieve "optimization of a washing process" and "optimization of a sample introduction process" in measurement accuracy.

[0016] Further, in the prior art described in Patent Document 3 described above, a structure in which backlash of a driving mechanism of a syringe is taken into consideration. Therefore, if realization of "shortening of a washing process" and "shortening of a sample introduction process" in productivity is intended, it is necessary to shorten the time of each process, and it is difficult to eliminate air bubbles generated by backlash. If air bubbles are mixed, the analysis accuracy decreases, and thus it is difficult to achieve "optimization of a washing process" and "optimization of a sample introduction process" in measurement accuracy.

[0017] The present application has been achieved in view of the above-described circumstances, and has an object to provide a control method of an automatic analysis device capable of improving robustness, productivity, and measurement accuracy.

[0018] Means for solving the problem

[0019] The present application includes a plurality of means for solving the above-described problem, and if one example is cited, it is a control method of an automatic analysis device having: a switching valve having a plurality of sample ports, selectively switching conduction and shutoff between each of the plurality of sample ports; a sample loop connected between two sample ports of a first sample port and a second sample port among the plurality of sample ports of the switching valve; a syringe connected to a third sample port of the switching valve different from the first sample port and the second sample port; and a carrier connected to a fourth sample port of the switching valve different from the first sample port to the third sample port, and immersed in a test sample housed in a test sample container, the control method of the automatic analysis device having: a step of adjusting a drive parameter of the syringe according to viscosity of the test sample obtained in advance; a step of switching the switching valve to a first state in which the carrier and the syringe are conducted without passing through the sample loop; a step of driving the syringe based on the drive parameter, introducing and introducing the test sample through the carrier; a step of switching the switching valve to a second state in which the syringe and the sample loop are conducted; and a step of driving the syringe based on the drive parameter and introducing the test sample to the sample loop.

[0020] Effects of the invention

[0021] According to the present application, with respect to robustness, "simplification of structure" and "maintenance-free" can be achieved, with respect to productivity, "shortening of cleaning process" and "shortening of test sample introduction process" can be achieved, and with respect to measurement accuracy, "optimization of cleaning process" and "optimization of test sample introduction process" can be achieved. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 is a diagram schematically showing the entire structure of the automatic analysis device, and is a diagram in which a functional section as an automatic sampler is extracted and shown together with the associated structure.

[0023] Figure 2 is a diagram schematically showing the electric drive system including the regenerative braking system of the electric drive dump truck of the first embodiment.

[0024] Figure 3 is a diagram schematically showing an example of the structure of the power conversion module.

[0025] Figure 4is a diagram showing an example of the operation of the bypass device.

[0026] Figure 5 is a functional block diagram schematically showing the processing function of the control device of the first embodiment.

[0027] Figure 6 is a diagram schematically showing the structure of the injection valve, and is a diagram showing the case of switching to position A.

[0028] Figure 7 is a diagram schematically showing the structure of the injection valve, and is a diagram showing the case of switching to position B, respectively.

[0029] Figure 8 is a diagram schematically showing the structure of the cleaning tank, and is a diagram showing an example of the structure of the cleaning tank.

[0030] Figure 9 is a diagram schematically showing the structure of the cleaning tank, and is a diagram showing another example of the structure of the cleaning tank.

[0031] Figure 10 is a diagram schematically showing the structure of the electromagnetic valve, and is a diagram showing the electromagnetic valve connected to the cleaning pump.

[0032] Figure 11 is a diagram schematically showing the structure of the electromagnetic valve, and is a diagram showing the electromagnetic valve connected to the injector.

[0033] Figure 12 is a timing chart showing an example of the operation of the functional section of the automatic sampler as the automatic analysis device.

[0034] Figure 13 is a diagram showing an example of the relationship between time and the injection speed, and is a diagram showing the case where the injection speed is constant as time elapses.

[0035] Figure 14 is a diagram showing an example of the relationship between time and the injection speed, and is a diagram showing the case where the injection speed changes as a rectangular function (non-linear) as time elapses.

[0036] Figure 15 is a diagram showing an example of the relationship between time and the injection speed, and is a diagram showing the case where the injection speed changes non-linearly as time elapses.

[0037] Figure 16 is a diagram showing an example of the relationship between time and the injection speed, and is a diagram showing the case where the injection speed decreases linearly as time elapses.

[0038] Figure 17is a graph showing an example of the relationship between time and injector drive speed, and is a graph showing a case where the injector drive speed decreases in a rectangular function (non-linear) as time elapses.

[0039] Figure 18 is a graph showing an example of the relationship between pressure and injector drive speed, and is a graph showing a case where the injector drive speed is constant according to the change in pressure.

[0040] Figure 19 is a graph showing an example of the relationship between pressure and injector drive speed, and is a graph showing a case where the injector drive speed changes in a rectangular function (non-linear) according to the change in pressure.

[0041] Figure 20 is a graph showing an example of the relationship between pressure and injector drive speed, and is a graph showing a case where the injector drive speed changes non-linearly according to the change in pressure.

[0042] Figure 21 is a graph showing an example of the relationship between pressure and injector drive speed, and is a graph showing a case where the injector drive speed decreases linearly according to the change (increase) in pressure.

[0043] Figure 22 is a graph showing an example of the relationship between pressure and injector drive speed, and is a graph showing a case where the injector drive speed decreases in a rectangular function (non-linear) according to the change (increase) in pressure. DETAILED DESCRIPTION

[0044] Hereinafter, an embodiment of the present application will be described with reference to the drawings.

[0045] Figure 1 is a graph schematically showing the overall structure of the automatic analyzer of the present embodiment, and is a graph showing the functional section as an automatic sampler together with the associated structure.

[0046] Further, in the present embodiment, a sample subjected to pretreatment such as purification / concentration by a pretreatment section not shown in the automatic analyzer is housed in a sample container 108 (described later) and is transferred to a suction position of a carrier 109 (described later). The purification / concentration in the pretreatment section in the present embodiment employs, for example, a method using magnetic beads. The functional group bonded to the surface of the magnetic beads can be any one of a reverse phase mode, a normal phase mode, a molecular weight fractionation mode, a HILIC mode, and an antigen-antibody reaction mode. In addition, in the purification / concentration in the pretreatment section, in addition to the magnetic beads, solid phase extraction, liquid / liquid extraction, slow protein treatment, and the like can be used.

[0047] In Figure 1In this embodiment, the automatic analysis device has an injection valve 101, a sample loop 102, a syringe 103, a gear pump 104, a system water container 105, a purge pump 106, a purge tank 107, a sample container 108, a shipper 109, a solenoid valve 111, a delivery pump 112, a separation column 113, a detector 114, and a control device 115.

[0048] The injection valve 101 has a plurality of sample ports and is a switching valve that selectively switches the conduction (flow) and the cutoff between the respective plurality of sample ports. In this embodiment, a case where a valve having 6-port 2-position high-pressure function with a pressure resistance of 100 MPa is used is exemplified.

[0049] Figure 6 and Figure 7 is a diagram schematically showing the structure of the injection valve, Figure 6 is a diagram showing a case where it is switched to one position, Figure 7 is a diagram showing a case where it is switched to the other position.

[0050] In Figure 6 and Figure 7 , the injection valve 101 has a plurality of (6 in this embodiment) sample ports 101a to 101f, the sample port 101a is connected to the delivery pump, the sample port 101b is connected to one end of the sample loop 102 (described later), the sample port 101c is connected to the shipper 109, the sample port 101d is connected to the syringe 103 via the solenoid valve 111, the sample port 101e is connected to the other end of the sample loop 102 (described later), and the sample port 101f is connected to the separation column 113.

[0051] The valve head of the injection valve 101 is rotated to two positions to switch the flow path of the slit groove provided in the stator inside, thereby connecting either of the sample ports adjacent in the circumferential direction and cutting off the other, and thereby selectively switching the conduction and the cutoff between the sample ports. Specifically, in the position shown in Figure 6 (hereinafter referred to as position A), the sample port 101a and the sample port 101b, the sample port 101c and the sample port 101d, and the sample port 101e and the sample port 101f are respectively conducted, the delivery pump 112, the sample loop 102, and the separation column 113 are connected, and the shipper 109 and the syringe 103 (solenoid valve 111) are connected. In addition, in the position shown in Figure 7 (hereinafter referred to as position B), the sample port 101a and the sample port 101f, the sample port 101b and the sample port 101c, and the sample port 101d and the sample port 101e are respectively conducted, the delivery pump 112 and the separation column 113 are connected, and the shipper 109 and the sample loop 102 and the syringe 103 (solenoid valve 111) are connected.

[0052] In a state where the injection valve 101 is switched to the position A, the flow path from the liquid feeding pump 112 is connected, and thus liquid feeding is performed under a high pressure condition of, for example, 100 MPa at the maximum. In addition, in a state where the injection valve 101 is switched to the position B, the syringe 103 or the gear pump 104 of the rear stage of the syringe 103 is connected, and thus liquid feeding is performed under a low pressure condition of, for example, 1 MPa or less (for example, 300 KPa) at the maximum. Therefore, in a case where the injection valve 101 is switched from the position A to the position B, the flow path inside the injection valve 101 (including the sample loop 102) changes from the high pressure to the low pressure. On the other hand, in a case where the injection valve 101 is switched from the position B to the position A, the flow path inside the injection valve 101 (including the sample loop 102) changes from the low pressure to the high pressure. That is, the position of the sample and the cleaning liquid of the flow path inside the injection valve 101 including the sample loop 102 moves each time the position of the injection valve 101 is switched and the pressure changes. This change affects the measurement accuracy.

[0053] The sample loop 102 is a pipe whose accuracy is managed. In the present embodiment, for example, the material of the sample loop 102 is stainless steel (SUS), and a pipe having an inner diameter of 0.3 mm, an outer diameter of 1 / 16 inch, a length of 283 mm, and a volume of 20 μL is used as the sample loop 102. In addition, the material can be a material other than SUS, for example, a material obtained by coating a fused quartz with PEEK (Polyethertherketone), a material obtained by coating a fused quartz with PEEK, PTFE (Polytetrafluoroethylene), PFA (Perfluoroalkoxyalkane), or the like. In addition, the size of the pipe can be appropriately changed according to the measurement conditions. The inner diameter accuracy has a tolerance of ±30% at the maximum, and a tolerance of 27.32 μL at the maximum is generated in the 20 μL sample loop. For example, in the present embodiment, liquid feeding under 444 μL / min is considered, and thus an error of 3.7 seconds at the maximum is generated. The tolerance of the inner diameter of the sample loop 102 affects the measurement accuracy.

[0054] The syringe 103 has a not-illustrated stepping motor, and is driven by pulse control of the stepping motor. In the present embodiment, for example, the inner diameter of the syringe 103 is 23.8 mm, the length is 85 mm, and the plunger capacity is 723 μL. In addition, the syringe 103 can be configured to be driven by a servo motor, in addition to being driven by the stepping motor. In a case where the syringe 103 is driven by the servo motor, an encoder (rotation detector) is used to perform feedback control with respect to the motor driver.

[0055] A gear pump 104 is positioned after the syringe 103 and functions to supply system water (in this case, pure water) contained in the system water container 105 to the syringe 103 and the flow path preceding the syringe 103. A two-way solenoid valve (not shown) is positioned between the syringe 103 and the system water container 105. The supply of system water from the system water container 105 to the syringe 103 is controlled by the opening / closing of this two-way solenoid valve. The pressure of the system water supplied by the gear pump 104 is, for example, 300 kPa. Furthermore, the discharge pressure (pressure value) of the system water from the gear pump 104 is adjusted according to the pressure resistance of the two-way solenoid valve 111 positioned preceding the gear pump 104.

[0056] The cleaning pump 106 is, for example, a diaphragm pump. The flow path of the cleaning pump 106 is connected to the solenoid valve 110. Upstream of the cleaning pump 106 is a low-pressure 3-way solenoid valve (not shown), which is connected to three cleaning solvents (solvent SA: ultrapure water, solvent SB: acetonitrile, and solvent SC: methanol). The solenoid valve can be switched based on the cleaning conditions set by the user for each component to be measured, thereby changing the cleaning solvent. The cleaning pump 106 performs cleaning within the piping flow path and inside the transporter 109 by discharging the cleaning solvent. Additionally, the cleaning pump 106 supplies cleaning solvent to the cleaning tank 107 via the solenoid valve 110.

[0057] The cleaning tank 107 is a cleaning tank that cleans the outside of the carrier 109 by immersing the carrier 109 in cleaning solvent accumulated at the cleaning port.

[0058] Figure 8 and Figure 9 It is a diagram that roughly shows the structure of the cleaning tank. Figure 8 This is a diagram illustrating an example of the structure of a cleaning tank. Figure 9 These are diagrams illustrating other examples of the structure of a cleaning tank.

[0059] like Figure 8 As shown, the cleaning tank 107 has a cleaning solvent discharge port 107a and a cleaning port 107b. Additionally, in Figure 8 In the middle, the cleaning tank 107A has a cleaning solvent discharge port 107a and two cleaning ports 107c and 107d for organic solvents and water.

[0060] like Figure 8 As shown in the cleaning tank 107, when cleaning port 107b is in position 1, the normally closed side of solenoid valve 110 is connected to cleaning port 107b. Three cleaning solvents (SA, SB, SC) connected upstream of cleaning pump 106 via a low-pressure 3-way solenoid valve (not shown) are switched and supplied to cleaning port 107b. On the other hand, as... Figure 9In the case where the number of the cleaning ports 107c, 107d is two as shown in the cleaning tank 107A, the normally closed side of the electromagnetic valve 110 is connected to the cleaning port 107c for the organic solvent. Three kinds of cleaning solvents (SA, SB, SC) connected to the upstream of the cleaning pump 106 via a 3-way electromagnetic valve of low pressure, not shown, are switched to be supplied to the cleaning port 107c.

[0061] The sample container 108 is a cup which is precision-managed. In the present embodiment, for example, as the sample container 108, a sample cup of which material is PTFE, lower inner diameter is 5 mm, upper inner diameter is 6 mm, height is 26 mm, and volume is 250 μL is used. The sample container 108 is held in a sample cup holding position, not shown. In the sample container 108, for example, a sample containing a measurement target component which is refined / concentrated by a magnetic bead using a pretreatment section is housed. In the sample which is refined / concentrated using a magnetic bead, there is a possibility that a minute magnetic bead remains, and if the minute magnetic bead is attracted / discharged by the carrier 109, there is a possibility that the flow path piping, the injection valve 101, the separation column 113, or the detector 114 is clogged or contaminated. Therefore, in the present embodiment, the volume of the sample containing the measurement target component which is refined / concentrated by the pretreatment section is calculated from the measurement conditions of the pretreatment section, and the carrier lowering amount is changed according to the calculated volume so that only the upper clear supernatant can be attracted by the carrier 109. In addition, by providing a magnet on the entire inner side of the sample cup holding position, the minute magnetic bead is collected on the wall surface of the sample container 108, and the mixing of the minute magnetic bead at the time of attraction / discharging by the carrier 109 is prevented.

[0062] In the present embodiment, the carrier 109 is, for example, made of stainless steel (SUS: Steel Use Stainless), and a piping of which inner diameter is 0.3 mm, outer diameter is 1 / 16 inch, length is 20 mm, and volume is 1.41 μL is used. On the inner side of the carrier 109, a ground surface finish is implemented in order to reduce carryover. In the connection portion of the carrier 109 and the piping, a fitting corresponding to zero dead volume is used in order to prevent dead volume. Thereby, the reduction of sample diffusion and carryover can be achieved.

[0063] The electromagnetic valve 111 is, for example, a diaphragm type 3-way electromagnetic valve.

[0064] Figure 10 and Figure 11 is a diagram schematically showing the structure of the electromagnetic valve, Figure 10 is a diagram showing the electromagnetic valve connected to the cleaning pump, Figure 11 is a diagram showing the electromagnetic valve connected to the syringe.

[0065] As Figure 10As shown, solenoid valve 110 has a common port (COM), a normally open port (NO), and a normally closed port (NC). The common port (COM) of solenoid valve 110 is connected to the flow path of cleaning pump 106, the normally open port (NO) is connected to solenoid valve 111, and the normally closed port (NC) is connected to cleaning tank 107. During cleaning inside piping, sample loop 102, injection valve 101, transporter 109, etc., solenoid valve 110 is controlled by connecting the flow paths of the normally open port and the common port. Furthermore, when supplying cleaning solvent from cleaning pump 106 to cleaning tank 107, it is controlled by connecting the flow path of the normally closed port and the common port.

[0066] like Figure 11 As shown, solenoid valve 111 has a common port (COM), a normally open port (NO), and a normally closed port (NC). The common port (COM) of solenoid valve 110 is connected to injection valve 101, the normally open port (NO) is connected to syringe 103, and the normally closed port (NC) is connected to solenoid valve 110. Solenoid valve 111 is controlled by connecting the flow path of the normally open port to the common port when using syringe 103 for suction / discharge or when receiving liquid from gear pump 104. Additionally, it is controlled by connecting the flow path of the normally closed port to the common port when supplying cleaning solvent from cleaning pump 106. Furthermore, during cleaning inside tubing, sample loop 102, injection valve 101, transporter 109, etc., the normally open valve of solenoid valve 110 is opened.

[0067] The delivery pump 112 has a two-plunger structure and is driven reciprocally by pulse control, thereby continuously delivering the delivery solvent at high pressure (e.g., 100 MPa). In this embodiment, the delivery pump 112 is composed of two pumps, A and B (not shown), and the delivery is performed by changing the ratio of pump A and pump B according to the gradient conditions set by the user for each analyte component. The delivery solvent delivered from pumps A and B is mixed by a mixer (not shown) in a subsequent stage. The solvent ratio of each pump A and B of the delivery pump 112 can be changed by a low-pressure solenoid valve (not shown) according to the mixing conditions set by the user for each analyte component. In this embodiment, a case using six delivery solvents is illustrated (solvent SA: ultrapure water, solvent SB: acetonitrile, solvent SC: methanol, solvent VB1: formic acid (1 mol / L), solvent VB2: ammonia (1 mol / L), solvent VB3: ammonium acetate (1 mol / L)). Six solvents are mixed through a low-pressure solenoid valve and fed into pumps A and B, with gradient delivery based on the change in the ratio of pumps A and B.

[0068] The separation column 113 is, for example, filled with a packing material having an inner diameter of 1.0 mm, a length of 50 mm, and a particle size of 2.6 mm. In the present embodiment, a case where a reverse phase mode is used in the separation mode of the separation column 113 is exemplified. Furthermore, the separation mode of the separation column 113 is not limited to the reverse phase mode, and, for example, a forward mode, a molecular weight fractionation mode, a HILIC mode, an antigen-antibody reaction mode, or the like can be used.

[0069] The detector 114 is a mass spectrometer, for example, using a triple quadrupole mass spectrometer. The triple quadrupole mass spectrometer has a feature of excellent quantification. Furthermore, the mass spectrometer can not be a triple quadrupole mass spectrometer (Triple Q-MS), but can be an ion trap type mass spectrometer (Iontrap-MS), a time of flight type mass analyzer (TOF-MS). In addition, the detector 114 can not be a mass spectrometer, but can be a diode array detector, a UV detector, a trend detector.

[0070] The control device 115 is a device that controls the operation of the entire automatic analysis device including the functional sections of the automatic sampler, and is, for example, a PC (Personal Computer), a driver for the automatic analysis device, or the like. The control device 115 has a storage section that stores programs, various settings, information required for other analysis (for example, physical property information (viscosity and the like) of a sample), and the like, a control section that performs an operation of a control signal or the like using the programs and the like stored in the storage section, a signal output section that outputs a control signal to each section of the automatic analysis device and drives the same, and the like, and controls the operation of the automatic analysis device on the basis of an instruction and information from an input device not shown.

[0071] Figure 12 is a timing chart indicating an example of the operation of the functional sections of the automatic sampler as the automatic analysis device in the present embodiment.

[0072] As shown in Figure 12 , the operation of the functional sections of the automatic sampler as the automatic analysis device is constituted by, for example, 13 processes: an in-carrier cleaning process (step S1), an out-of-carrier cleaning process (step S2), a flow path purging process (step S3), a carrier movement to a starting position process (step S4), an air suction process (step S5), a sample suction process (step S6), a sample transfer process (step S7), a backflush process (step S8), an injection valve switching process (step S9), a sample introduction to a sample loop process (step S10), a sample introduction to a separation column process (step S11), a sample exclusion from the sample loop process (step S12), and a syringe movement to a starting position process (step S13).

[0073] After the sample cup in which the sample refined / concentrated by the magnetic beads using the pretreatment section is transferred, an in-carrier cleaning process (step S1) is performed. At this time, the carrier 109 is positioned at a start position. The start position of the carrier 109 is above the sample suction port. The carrier 109 is rotated in the θ direction (direction around the vertical axis) and rotated to above the cleaning solvent discharge port 107a of the cleaning tank 107 (107A). Thereafter, the carrier 109 is lowered in the Z direction (vertical axis direction) into the cleaning solvent discharge port 107a (in-cleaning position). The solvent used in the cleaning in the carrier 109 is selected from system water or any one of a plurality of cleaning solvents connected upstream of the cleaning pump 106 according to the object substance to be measured. In the case of cleaning in the carrier 109 with system water, the 2-way electromagnetic valve (not shown) between the injector 103 and the system water container 105 is switched to the open (OPEN) side, and the system water of the system water container 105 is delivered in the flow path to perform the cleaning in the carrier 109. On the other hand, in the case of cleaning in the carrier 109 with a cleaning solvent connected via a 3-way electromagnetic valve downstream of the cleaning pump 106, any one of the solvent SA (ultra-pure water), the solvent SB (acetonitrile), and the solvent SC (methanol) is selected, and the electromagnetic valve 111 is switched to the normally closed port and the common port to be conducted, and the selected cleaning solvent is delivered in the flow path to perform the cleaning in the carrier 109. The time of the in-carrier cleaning process (step S1) is, for example, 9 seconds.

[0074] The outer container cleaning process (step S2) is performed after the inner container cleaning process (step S1) is completed. The container 109 is returned to the initial position in the Z direction. Thereafter, the container 109 is rotated in the θ direction, and the rotation is moved to above the cleaning port 107b (in the case of the cleaning tank 107A, the cleaning ports 107c, 107d) of the cleaning tank 107. In the case of the cleaning tank 107, the rotation is moved to above the cleaning port 107b at 1, and in the case of the cleaning tank 107A, the rotation is moved to above one of the cleaning ports 107c, 107d determined according to the measurement target. Thereafter, the container 109 is lowered in the Z direction into the cleaning port 107b (107c, 107d) (outer cleaning position), and the outer cleaning of the container 109 is performed by moving up and down a plurality of times. During the outer cleaning of the container 109, the replacement of the cleaning solvent of the cleaning port 107b (107c, 107d) of the cleaning tank 107 (107A) is performed. The solvent used in the outer cleaning of the container 109 is selected from any one of the three kinds of cleaning solvents located upstream of the cleaning pump 106 according to the measurement target substance. The cleaning solvents connected via the three solenoid valves downstream of the cleaning pump 106 are the solvent SA (ultra-pure water), the solvent SB (acetonitrile), and the solvent SC (methanol), and any one of these solvents is selected, and the solenoid valve 110 is switched in a manner in which the normally closed port is conducted with the common port, and the selected cleaning solvent is sent in the flow path and supplied to the cleaning port 107b (107c, 107d) of the cleaning tank 107 (107A). The time of the outer container cleaning process (step S2) is, for example, 3 seconds.

[0075] The flow path purging process (step S3) is performed after the outer container cleaning process (step S2) is completed. The container 109 is returned to the initial position in the Z direction. Thereafter, the container 109 is rotated in the θ direction, and the rotation is moved to above the cleaning solvent discharge port 107a. Thereafter, the container 109 is lowered in the Z direction to the discharge position of the cleaning solvent. The solvent used in the cleaning in the container 109 is selected to be the system water or the cleaning solvent connected to the upstream of the cleaning pump 106 according to the measurement target substance. In the case of performing the cleaning with the system water, the non-illustrated two-way solenoid valve between the syringe 103 and the system water container 105 is switched in a manner in which the normally closed port is conducted with the common port, and the system water is sent in the flow path and performs the cleaning in the container 109. On the other hand, in the case of performing the cleaning with the cleaning solvent connected by the non-illustrated three-way solenoid valve upstream of the cleaning pump 106, any one of the solvent SA (ultra-pure water), the solvent SB (acetonitrile), and the solvent SC (methanol) is selected, and the solenoid valve 111 is switched in a manner in which the normally closed port is conducted with the common port, and the selected cleaning solvent is sent in the flow path and performs the cleaning in the container 109. The time of the flow path purging process (step S3) is, for example, 4 seconds.

[0076] The moving process of the carrier to the initial position (step S4) is performed after the flow path purging process (step S3) is completed. The carrier 109 is returned to the initial position in the Z direction. The carrier 109 is rotated in the θ direction and rotated above the initial position. The time of the moving process of the carrier to the initial position (step S4) is, for example, 1 second.

[0077] The air suction process (step S5) is performed after the moving process of the carrier to the initial position (step S4) is completed. The electromagnetic valve 111 is switched so that the normally open port is communicated with the common port, and the injector 103 is driven to suck air. In the present embodiment, the injector 103 is driven by 20 pulse amounts, and 4 μL of air is sucked. During the air suction process (step S5), the carrier 109 is lowered to the sample suction position in the Z direction. The time of the air suction process (step S5) is, for example, 1 second. In this way, by sucking air, air can be interposed between the solution in the flow path and the sample, and diffusion of the sample to the solution is reduced. Therefore, the analysis accuracy, specifically, the reproducibility is improved.

[0078] The sample suction process (step S6) is performed after the air suction process (step S5) is completed. The injector 103 is driven to suck the sample. In the present embodiment, the injector 103 is driven by 175 pulse amounts, and 35 μL of the sample is sucked. The time of the sample suction process (step S6) is, for example, 5 seconds.

[0079] Figures 13-17 is a graph showing an example of the relationship between time and the injector driving speed. In addition, Figures 18-22 is a graph showing an example of the relationship between pressure and the injector driving speed.

[0080] The sample which becomes the analysis object of the automatic analysis device is, for example, a biological sample, and is serum, crystal, urine, biological tissue, and the like. In addition, in the automatic analysis device, in addition to the biological sample, there are a calibration sample, a quality control (QC) sample, and the like. In the present embodiment, the calibration sample and the QC sample are dissolved in a 30% methanol solution. The sample is refined / concentrated by the pretreatment section using a magnetic bead, and the sample container 108 containing the sample is transferred to the sample cup holding section which is a functional section of the automatic sampler in the automatic analysis device. Since the viscosity of the transferred sample differs depending on the sample, the introduction position of the sample to the sample loop 102 differs in the parameters of the same injector driving. In addition, in the case of a sample having a relatively high viscosity, the pressure in the flow path rises, and an air pocket is generated, and air is generated in the flow path. That is, the analysis accuracy is deviated. The deviation of the analysis accuracy described here is mainly a decrease in the reproducibility. Therefore, in the present embodiment, the injector driving speed is changed depending on the viscosity of the sample.

[0081] Figure 13 is a graph showing an example of the relationship between time and the injection speed, and shows a case where the injection speed is constant over time. In addition, Figure 14 is a graph showing an example of the relationship between time and the injection speed, and shows a case where the injection speed changes in a rectangular function (non-linear) over time. In addition, Figure 15 is a graph showing an example of the relationship between time and the injection speed, and shows a case where the injection speed changes non-linearly over time. In addition, Figure 16 is a graph showing an example of the relationship between time and the injection speed, and shows a case where the injection speed decreases linearly over time. In addition, Figure 17 is a graph showing an example of the relationship between time and the injection speed, and shows a case where the injection speed decreases in a rectangular function (non-linear) over time. In addition, in Figures 13-17 , the relationship between time and the injection speed in the case of a sample with relatively high viscosity is shown by a solid line, and the relationship between time and the injection speed in the case of a sample with relatively low viscosity is shown by a broken line. That is, the injection speed is set to be faster in the case of a sample with relatively high viscosity than in the case of a sample with relatively low viscosity. In this way, by previously acquiring the sample to be fed to the pretreatment section and the parameter (viscosity) of the pretreatment section, and adjusting the injection speed in accordance with the viscosity, it is possible to stabilize the introduction of the sample to the introduction position of the sample loop 102 at all times, and to improve the analysis accuracy.

[0082] In addition, even if the injection speed is adjusted in accordance with the pressure value in the flow path, the same effect can be obtained. Therefore, a case where the adjustment of the injection speed is fed back while monitoring the pressure in the flow path is shown.

[0083] Figure 18 is a graph showing an example of the relationship between pressure and the injection speed, and shows a case where the injection speed is constant in accordance with the change in pressure. In addition, Figure 19 is a graph showing an example of the relationship between pressure and the injection speed, and shows a case where the injection speed changes in a rectangular function (non-linear) in accordance with the change in pressure. In addition, Figure 20 is a graph showing an example of the relationship between pressure and the injection speed, and shows a case where the injection speed changes non-linearly in accordance with the change in pressure. In addition, Figure 21 is a graph showing an example of the relationship between pressure and the injection speed, and shows a case where the injection speed decreases linearly in accordance with the change (increase) in pressure. In addition, Figure 22 is a graph showing an example of the relationship between pressure and the injection speed, and shows a case where the injection speed decreases in a rectangular function (non-linear) in accordance with the change (increase) in pressure. In addition, in Figures 18-22The relationship between the pressure and the injector drive speed in the case of a sample with relatively high viscosity is indicated by a solid line, and the relationship between the pressure and the injector drive speed in the case of a sample with relatively low viscosity is indicated by a dashed line. That is, the injector drive speed is set to be faster in the case of a sample with relatively high viscosity than in the case of a sample with relatively low viscosity. In this way, by monitoring the pressure in the flow path and adjusting the injector drive speed in accordance with the pressure, the introduction of the sample into the sample loop 102 can be stabilized at all times, and the analysis accuracy can be improved. Furthermore, the method of detecting the pressure in the flow path can be considered variously, but in the present embodiment, a case in which the injector 103 detects the pressure in the flow path based on the drive load is exemplified. Alternatively, the function of detecting the pressure in the flow path can be provided separately.

[0084] The sample transfer process (step S7) is performed after the sample suction process (step S6) is completed. The carrier 109 is returned to the start position in the Z direction. Next, the injector 103 is driven to suck air. In the present embodiment, the injector 103 is driven for 150 pulse counts, and 30 μL of air is sucked. The time of the sample transfer process (step S7) is, for example, 4 seconds. The sample transfer process (step S7) is performed so as to achieve "shortening of the sample introduction time", and the injector drive speed is set to be faster than in other processes. In the case where the injector drive speed is fast, the adjustment is performed in such a manner that the injector drive amount is appropriately set, due to the influence of the pressure loss in the flow path. As the adjustment parameter of the injector drive amount, a field in which the adjustment parameter can be input to the software screen is provided. Preferably, an automatic adjustment function can also be provided in accordance with the analysis accuracy in the case of analyzing the calibration sample. In this case, specifically, the injector drive parameters are each changed by 1 pulse, and the parameter of the injector drive amount with the highest peak intensity is adopted.

[0085] The backflush process (step S8) is performed after the sample transfer process (step S7) is completed. The backflush process (step S8) is a process in which, by the injector drive until the sample transfer process (step S7), the injector drive amount is returned to the discharge side in the Z direction in order to decompress the pressure applied to the flow path, and thereby decompresses. In the present embodiment, the injector is driven for 5 pulse counts, and 1 μL of air is discharged. The time of the backflush process (step S8) is, for example, 1 second.

[0086] The injection valve switching process (step S9) is performed after the backflush process (step S8) is completed.

[0087] Figure 2 is a diagram in which the functional section as the automatic sampler and the associated structure in the overall structure of the automatic analysis device are extracted and schematically indicated, and is a diagram indicating the case of the injection valve switching process. That is, Figure 2Figure 2 shows a state in which the injection valve 101 is switched from position A to position B, and the state in which the shipper 109, the sample loop 102, and the electromagnetic valve 111 are connected. The time for the injection valve switching process (step S9) is, for example, 0.2 seconds.

[0088] The sample introduction process to the sample loop (step S10) is performed after the injection valve switching process (step S9) is completed.

[0089] Figure 3 and Figure 4 is a diagram that extracts and schematically shows the functional section as an automatic sampler and the associated structure in the overall structure of the automatic analysis device, Figure 3 is a diagram showing the case of the sample introduction process to the sample loop (press-in method), Figure 4 is a diagram showing the case of the sample introduction process to the sample loop (introduction method).

[0090] As shown in Figure 3 , in the sample introduction process to the sample loop (step S9) of the press-in method, the syringe 103 is driven to discharge the sample to the sample loop 102. In this embodiment, the syringe 103 is driven by 50 pulse amounts, and 10 μL of the sample is discharged to the sample loop 102. That is, the syringe 103 is driven in the direction in which the sample is pressed into the sample loop 102, and the sample introduction is performed. The time for the sample introduction process to the sample loop (step S10) is, for example, 6 seconds.

[0091] As shown in Figure 4 , in the sample introduction process to the sample loop (step S9) of the introduction method, the syringe 103 is driven to introduce the sample into the sample loop 102. In this embodiment, the syringe 103 is driven by 50 pulse amounts, and 10 μL of the sample is introduced into the sample loop 102. That is, the syringe 103 is driven in the direction in which the sample is introduced into the sample loop 102, and the sample introduction is performed. The time for the sample introduction process to the sample loop (step S10) is, for example, 6 seconds.

[0092] Further, in the sample introduction process to the sample loop (step S10), the sample is quantified by two methods that can adjust the sample introduction amount to the sample loop 102, that is, the "Partial Loop Injection method" in which the sample is quantified according to the syringe drive amount (the sample loop capacity > the sample introduction amount to the sample loop corresponding to the syringe drive amount), and the "Full Loop Injection" in which the sample is quantified with the sample loop capacity (the sample loop capacity ≤ the sample introduction amount to the sample loop corresponding to the syringe drive amount).

[0093] Further, in the sample introduction into the sample loop process (step S10), the injector drive speed can be appropriately set according to the viscosity of the sample and the monitored pressure value, so that the analysis accuracy is improved.

[0094] Further, in the injection valve switching process (step S9), the pressure around the sample loop 102 is switched from high pressure to low pressure, so that the pressure is released and the sample before and after the sample loop 102 is moved. Therefore, the parameter of the injector drive amount in the sample introduction into the sample loop process (step S10) varies according to the "Partial Loop Injection mode", "Full Loop Injection", and the set value of the injection volume. The variation amount can adjust the parameter of the injector drive amount according to whether the user values the reproducibility of the analysis accuracy or the deviation from the true value. This is provided with a field in which the analysis value mode can be input in the software screen, so that the user can set the analysis value mode. Preferably, the automatic adjustment function can also be set according to the analysis value mode when the calibration sample is analyzed. In this case, specifically, the injector drive parameters are each varied by 1 pulse, and in the case of valuing the reproducibility of the analysis accuracy, the deviation of the peak intensity is adopted, and in the case of valuing the deviation from the true value, the parameter of the injector drive amount at which the peak intensity is highest. The items of the analysis value mode also consider productivity, sample consumption, and the like in addition to the above.

[0095] The sample introduction into the separation column process (step S11) is performed after the sample introduction into the sample loop process (step S10) is completed.

[0096] Figure 5 is a diagram that extracts and schematically represents the functional part as an automatic sampler and the associated structure in the overall structure of the automatic analyzer, and is a diagram that shows the case of the sample introduction into the separation column process.

[0097] As shown in Figure 5 , in the sample introduction into the separation column process (step S11), the position of the injection valve 101 is switched from position B to position A, and the liquid delivery pump 112, the sample loop 102, and the separation column 113 are connected. The time of the sample introduction into the separation column process (step S11) is, for example, 0.2 seconds.

[0098] The sample removal from the sample loop process (step S12) is performed after the sample introduction into the separation column process (step Sll) is completed. The carrier 109 is raised in the Z direction to the initial position. Thereafter, it is rotated to above the washing solvent discharge position. The injector 103 is driven in the discharge direction by the initial position + number of pulses. In the present embodiment, during the period from the washing process from the carrier (step S1) to the sample introduction into the separation column process (step Sll), the injector is driven by the amount of 50 pulses (the amount of 10 μL) in addition to the injector movement amount, and waste liquid is discharged to the washing solvent discharge position of the washing tank 107. The time of the sample removal from the sample loop process (step S12) is, for example, 4 seconds.

[0099] The injector movement to the initial position process (step S13) is performed after the sample introduction into the separation column process (step Sll) is completed. The injector position is moved to the initial position. The injector movement to the initial position process (step S13) is started at the same time as the sample removal from the sample loop process (step S12). The time of the injector movement to the initial position process (step S13) is, for example, 1 second.

[0100] In the present embodiment configured as above, it is possible to improve the robustness, the productivity, and the measurement accuracy. That is, with respect to the robustness, it is possible to achieve "simplification of the structure" and "maintenance-free", with respect to the productivity, it is possible to achieve "shortening of the washing process" and "shortening of the sample introduction process", and with respect to the measurement accuracy, it is possible to achieve "optimization of the washing process" and "optimization of the sample introduction process".

[0101] With respect to the "simplification of the structure" in the robustness, in the present embodiment, the "Partial Loop injection method" is adopted, and therefore it is not necessary to maintain high pressure (for example, 100 MPa) as in the "Direct Injection method", it is possible to form a structure that does not include a fitting for high pressure, and it is possible to simplify the configuration. Further, since the configuration in which the pump, the valve, and the carrier are connected with the shortest flow path length and the flow path inner diameter, it is possible to further simplify the configuration.

[0102] Further, with respect to the "maintenance-free" in the robustness, with the achievement of the "simplification of the structure", it is possible to operate in a state in which the frequency of maintenance is very low. That is, for example, the frequency of periodic maintenance by a service person can be once a year.

[0103] Further, with respect to the "shortening of the washing process" in the productivity, with the achievement of the "simplification of the structure", it is possible to use the driving time of the washing pump and the gear pump used in the washing process in the shortest possible manner. That is, in order to suppress the carryover, the gear pump that supplies the washing pump and the system water without performing washing by suction / discharge of the injector is provided, and by optimizing the driving timing of these pumps, it is possible to achieve shortening of the washing time.

[0104] Further, regarding the "shortening of the sample introduction step" in productivity, shortening of the time of sample introduction is achieved by minimizing the length of the pipe between the syringe for sucking / discharging the sample and the carrier of the sample suction port in the sample cup, the inner diameter of the pipe, and the volume inside the pipe. For example, in the present embodiment, sample introduction every 36 seconds can be achieved.

[0105] Further, regarding the "optimization of the cleaning step" in measurement accuracy, instead of performing cleaning after sample introduction by the automatic sampler mounted on the HPLC as usual, the cleaning step is allocated to the first half of the series of sample introduction steps, and cleaning can be performed immediately before the sample is introduced. Thus, the mixing of air inside the flow path under low pressure conditions, and the mixing of air bubbles due to pressure fluctuation caused by switching from high pressure from the liquid feed pump to low pressure from the syringe at the time of switching of the injection valve can be reduced. That is, even if air bubbles are mixed, bubble removal is performed before the sample introduction operation is started.

[0106] Further, regarding the "optimization of the sample introduction step" in measurement accuracy, shortening in productivity (for example, sample introduction including the cleaning step every 36 seconds) can be achieved by shortening the length of the pipe between the syringe for sucking / discharging the sample and the carrier of the sample suction port in the sample cup, and the volume inside the pipe. Further, by changing the driving parameters of the syringe according to the physical properties of the sample, such as viscosity and solvent composition, high-precision measurement can be performed. Further, by performing the "optimization of the cleaning step" and the "optimization of the sample introduction step", regarding measurement accuracy, the precision (for example, CV 5%) and the accuracy (for example, 10%) required in an automatic analysis device for clinical examination can be achieved. Further, regarding carryover, 0.001% can also be achieved.

[0107] <Notes>

[0108] Further, the present application is not limited to the above-described embodiments, and various modifications, combinations thereof within the scope of the gist thereof are included. Further, the present application is not limited to having all the structures described in the above-described embodiments, and a structure in which a part of the structures is deleted is also included. Further, each of the above-described structures, functions, and the like can be implemented by a part or all of them, for example, by an integrated circuit design or the like. Further, each of the above-described structures, functions, and the like can be implemented by software by a processor interpreting and executing a program implementing each function.

[0109] Explanation of Reference Signs

[0110] 101… injection valve, 101a-101f… sample ports, 102… sample loop, 103… injector, 104… gear pump, 105… system water container, 106… purge pump, 107, 107A… purge tank, 107a… purge solvent discharge port, 107b… purge port, 107c… purge port, 107d… purge port, 108… sample container, 109… carrier, 110, 111… solenoid valves, 112… delivery pump, 113… separation column, 114… detector, 115… control device.

Claims

1. A control method for an automatic analysis device, characterized in that, The automatic analysis device includes: A switching valve having multiple sample ports selectively switches the conduction and cutoff between the multiple sample ports; A sample loop is connected between the first sample port and the second sample port among the multiple sample ports of the switching valve. A syringe connected to a third sample port of the switching valve, which is different from the first and second sample ports; as well as The transporter, which is connected to a fourth sample port of the switching valve (different from the first to third sample ports), is immersed in the sample contained in the sample container. The control method of the automatic analysis device has the following characteristics: The process of adjusting the driving parameters of the syringe based on the viscosity of the sample obtained in advance; The process of switching the switching valve to a first state in which the transporter and the syringe are not connected via the sample loop; The process of driving the syringe based on the driving parameters to introduce and import the sample via the transporter; The process of switching the switching valve to a second state in which the syringe and the sample loop are connected; as well as The process of driving the syringe based on the driving parameters and introducing the sample into the sample loop. In the process of adjusting the driving parameters of the syringe, the driving speed of the syringe is adjusted as the driving parameters of the syringe. The driving parameters of the syringe are adjusted so that the driving speed of the syringe changes linearly as the driving time of the syringe passes, and the higher the viscosity of the sample, the faster the driving speed of the syringe.

2. A control method for an automatic analysis device, characterized in that, The automatic analysis device includes: A switching valve having multiple sample ports selectively switches the conduction and cutoff between the multiple sample ports; A sample loop is connected between the first sample port and the second sample port among the multiple sample ports of the switching valve. A syringe connected to a third sample port of the switching valve, which is different from the first and second sample ports; as well as The transporter, which is connected to a fourth sample port of the switching valve (different from the first to third sample ports), is immersed in the sample contained in the sample container. The control method of the automatic analysis device has the following characteristics: The process of adjusting the driving parameters of the syringe based on the viscosity of the sample obtained in advance; The process of switching the switching valve to a first state in which the transporter and the syringe are not connected via the sample loop; The process of driving the syringe based on the driving parameters to introduce and import the sample via the transporter; The process of switching the switching valve to a second state in which the syringe and the sample loop are connected; as well as The process of driving the syringe based on the driving parameters and introducing the sample into the sample loop. In the process of adjusting the driving parameters of the syringe, the driving speed of the syringe is adjusted as the driving parameters of the syringe. The driving parameters of the syringe are adjusted such that the driving speed of the syringe changes non-linearly as the driving time of the syringe passes, and the higher the viscosity of the sample, the faster the driving speed of the syringe.

3. A control method for an automatic analysis device, characterized in that, The automatic analysis device includes: A switching valve having multiple sample ports selectively switches the conduction and cutoff between the multiple sample ports; A sample loop is connected between the first sample port and the second sample port among the multiple sample ports of the switching valve. A syringe connected to a third sample port of the switching valve, which is different from the first and second sample ports; as well as The transporter, which is connected to a fourth sample port of the switching valve (different from the first to third sample ports), is immersed in the sample contained in the sample container. The control method of the automatic analysis device has the following characteristics: The process of adjusting the driving parameters of the syringe based on the viscosity of the sample obtained in advance; The process of switching the switching valve to a first state in which the transporter and the syringe are not connected via the sample loop; The process of driving the syringe based on the driving parameters to introduce and import the sample via the transporter; The process of switching the switching valve to a second state in which the syringe and the sample loop are connected; as well as The process of driving the syringe based on the driving parameters and introducing the sample into the sample loop. In the process of adjusting the driving parameters of the syringe, the driving speed of the syringe is adjusted as the driving parameters of the syringe. The driving parameters of the syringe are adjusted so that the driving speed of the syringe changes linearly according to the pressure of the syringe, and the higher the viscosity of the sample, the faster the driving speed of the syringe.

4. A control method for an automatic analysis device, characterized in that, The automatic analysis device includes: A switching valve having multiple sample ports selectively switches the conduction and cutoff between the multiple sample ports; A sample loop is connected between the first sample port and the second sample port among the multiple sample ports of the switching valve. A syringe connected to a third sample port of the switching valve, which is different from the first and second sample ports; as well as The transporter, which is connected to a fourth sample port of the switching valve (different from the first to third sample ports), is immersed in the sample contained in the sample container. The control method of the automatic analysis device has the following characteristics: The process of adjusting the driving parameters of the syringe based on the viscosity of the sample obtained in advance; The process of switching the switching valve to a first state in which the transporter and the syringe are not connected via the sample loop; The process of driving the syringe based on the driving parameters to introduce and import the sample via the transporter; The process of switching the switching valve to a second state in which the syringe and the sample loop are connected; as well as The process of driving the syringe based on the driving parameters and introducing the sample into the sample loop. In the process of adjusting the driving parameters of the syringe, the driving speed of the syringe is adjusted as the driving parameters of the syringe. The driving parameters of the syringe are adjusted so that the driving speed of the syringe changes non-linearly according to the pressure of the syringe, and the higher the viscosity of the sample, the faster the driving speed of the syringe.

5. The control method for the automatic analysis device according to any one of claims 1 to 4, characterized in that, In the process of driving the syringe based on the driving parameters and introducing the sample into the sample loop, the sample is introduced into the sample loop from the upstream side of the switching valve through the syringe.

6. The control method for the automatic analysis device according to any one of claims 1 to 4, characterized in that, In the process of driving the syringe based on the driving parameters and introducing the sample into the sample loop, the sample is pushed back from the downstream side of the switching valve and introduced into the sample loop by the syringe.

7. The control method for the automatic analysis device according to any one of claims 1 to 4, characterized in that, In the process of driving the syringe based on the driving parameters and introducing the sample into the sample loop, the driving parameters of the syringe are adjusted according to whether the amount of the sample introduced into the sample loop is less than the capacity of the sample loop.

8. The control method for the automatic analysis device according to any one of claims 1 to 4, characterized in that, The driving parameters of the syringe are adjusted according to the pressure loss of the flow path obtained in advance.

Citation Information

Patent Citations

  • Sample injecting method for liquid chromatograph

    JP1990132369A

  • Push loop liquid sampling

    JP1990176538A

  • Chromatographic monitoring and control of multiple process streams

    JP2011513732A

  • Liquid sample movement

    EP0360604A2