Autosampler for liquid chromatography

Abstract

To provide an auto-sampler that, even after deep insertion of a needle into liquid, reduces the occurrence of contamination due to the liquid attached to an outer face of the needle.SOLUTION: An auto-sampler for liquid chromatography comprises: a needle 2 for sampling that has a suction port at its tip; a moving mechanism 4 that holds the needle 2 having the suction port directed vertically downward and moves it in the vertical direction; a suction mechanism 6 through the needle 2; and a control unit 10 that controls the operation of the moving mechanism 4 and the suction mechanism 6. The control unit 10 is configured to execute, during sampling of liquid in a container 16 with an open top face, lowering the needle 2 from above the container 16 to insert the tip of the needle 2 into the liquid in the container 16, sucking in a predetermined amount of liquid, raising the needle 2 from the liquid to locate the suction port above the surface of the liquid, and repeating multiple times a shake-off operation to lower and suddenly stop the needle 2 while maintaining the state where the suction port is located above the liquid surface, with a standby time between the operations in which the needle 2 is completely stopped or raised.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an autosampler for a liquid chromatograph. [Background technology]

[0002] A liquid chromatograph is equipped with an autosampler that injects a sample into a mobile phase delivered by a liquid delivery pump. The autosampler moves a needle in horizontal and vertical directions, inserts the tip of the needle into the sample in a target container, and aspirates a predetermined amount of sample from the tip of the needle. After the autosampler has finished aspirating the sample from the container, it lifts the needle above the container and then moves the needle to an injection port and injects the aspirated sample into the mobile phase (see Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2019 / 043907 [Patent Document 2] Patent No. 4296814 Summary of the Invention [Problem to be solved by the invention]

[0004] Some autosamplers (also called liquid handlers) also function as fraction collectors, which collect the fractions by dropping the eluate containing each component separated in the analytical column from a nozzle into individual collection containers. In such autosamplers, the eluate collected in the collection container may be sucked into the needle as a sample and reinjected into the mobile phase. In this case, since the top of the collection container is open, there is nothing to wipe the sample attached to the outer surface of the needle when the needle is lifted from the collection container, and the sample is likely to remain on the outer surface of the needle. If the needle with the sample attached to its outer surface is moved to another location, the sample will fall off during the needle's movement, causing contamination inside the device.

[0005] Patent Document 2 describes a method for separating liquid adhering to the outer peripheral surface of a needle-shaped member from the needle-shaped member by moving the needle-shaped member in a specific direction and colliding it with a stopper, thereby applying acceleration to the needle-shaped member in the opposite direction to the needle's movement direction, so that droplets are shaken off from the needle-shaped member. If this technology is applied to an autosampler, it is possible to shake off droplets adhering to the tip of the needle. However, when the needle is inserted deep into the liquid and sucked in, liquid is attached to the outer surface of the needle not only at the tip but also above it, and it was found that even if acceleration due to collision is applied to the needle as in Patent Document 2, some liquid may remain on the outer surface of the needle.

[0006] The present invention has been made in consideration of the above problems, and aims to provide an autosampler that can prevent contamination or fouling caused by liquid adhering to the outer surface of a needle even after the needle is inserted deep into the liquid. [Means for solving the problem]

[0007] The autosampler for liquid chromatography according to the present invention comprises a sampling needle having an intake port at its tip, a moving mechanism that holds the needle so that the intake port faces vertically downward and moves the needle at least in a vertical direction, an intake mechanism for intake of liquid through the needle, and a control unit that controls the operation of the moving mechanism and the intake mechanism, and the control unit is configured to execute the following steps in sampling liquid in a container having an open top: an insertion step of lowering the needle from above the container and inserting the tip of the needle into the liquid in the container; an intake step of aspirating a predetermined amount of the liquid through the intake port of the needle after the insertion step is completed; a lifting step of lifting the needle out of the liquid and positioning the intake port above the liquid surface of the liquid after the lifting step is completed; and a shake-off step of lowering the needle and stopping it suddenly while maintaining the intake port positioned above the liquid surface multiple times after the lifting step is completed. Effect of the Invention

[0008] According to the autosampler for liquid chromatography of the present invention, after the needle is pulled up from the liquid, the needle is lowered and suddenly stopped while maintaining the needle's intake port above the liquid surface, and this shaking-off operation is repeated multiple times, thereby effectively shaking off liquid from the outer surface of the needle that would not be shaken off in a single shaking-off operation. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a schematic diagram showing an embodiment of an autosampler. [Diagram 2] 4 is a flowchart showing an example of sampling in the embodiment. [Diagram 3] 13 is a flowchart showing an example of sampling accompanied by a shake-off operation in the embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Hereinafter, an embodiment of an autosampler for liquid chromatography according to the present invention will be described with reference to the drawings.

[0011] The autosampler 1 includes a needle 2 , a moving mechanism 4 , a syringe pump 6 , a syringe drive unit 8 , a control unit 10 , and a storage unit 12 .

[0012] Needle 2 is a sampling needle with an intake port at its tip. Moving mechanism 4 is a mechanism configured to hold needle 2 so that the intake port at its tip faces vertically downward and move it in the horizontal and vertical directions. Syringe pump 6, which is an intake mechanism, is in fluid communication with the base end of needle 2 and draws in and discharges fluid through needle 2. Syringe driving unit 8 includes a mechanism such as a stepping motor for driving syringe pump 6.

[0013] The control unit 10 controls the movement of the needle 2 and the suction and discharge of fluid by the syringe pump 6 via the needle 2 by controlling the moving mechanism 4 and the syringe driving unit 8. The control unit 10 is a function realized by software being executed in a computer circuit equipped with a central processing unit (CPU) or the like. The memory unit 12 stores settings related to the operational control of the needle 2 and the syringe pump 6 by the control unit 10. The control unit 10 controls the operational control of the needle 2 and the syringe pump 6 based on the settings stored in the memory unit 12. The memory unit 12 is a function realized by a partial storage area of ​​an information storage device such as a hard disk drive or a flash memory.

[0014] The autosampler 1 is provided with a container installation location where containers 14, 16 for containing liquids such as samples are installed. In the container installation location, a container 14 whose upper surface is sealed by a septum (hereinafter, sealed container 14) and a container 16 whose upper surface is open (hereinafter, open container 16) are installed. Examples of the sealed container 14 include a reagent container containing a reagent and a sample container containing a sample. Examples of the open container 16 include a collection container that collects eluate from an analytical column. That is, the autosampler 1 of this embodiment may have a function as a fraction collector that fractionates and collects eluate from an analytical column.

[0015] The control unit 10 is configured to execute sampling from a sealed container 14 or an open container 16 installed at a container installation location by controlling the moving mechanism 4 and the syringe driving unit 8 based on a preset analysis program. Furthermore, the control unit 10 is configured to change the operation of the needle 2 during sampling depending on whether the target container is a sealed container 14 or an open container 16.

[0016] FIG. 2 is a flowchart showing an example of an operation during sampling.

[0017] As a premise, whether or not to perform the shake-off operation during sampling is set for each container by the user, and this setting is stored in the memory unit 12. Typically, the user checks whether the target container is a sealed container 14 or an open container 16, and sets the shake-off operation not to be performed if the target container is a sealed container 14, and sets the shake-off operation to be performed if the target container is an open container 16.

[0018] When it is time to perform liquid sampling, the control unit 10 checks whether or not the shake-off operation set for the target container is to be performed (step 101). If it is set not to perform the shake-off operation for the target container (step 101: No), the control unit 10 performs sampling without the shake-off operation for shaking off the liquid adhering to the needle 2 (step 102), and if it is set to perform the shake-off operation for the target container (step 101: Yes), the control unit 10 performs sampling with the shake-off operation for shaking off the liquid adhering to the needle 2 (step 103).

[0019] Sampling without shaking off is performed as follows. First, the needle 2 is lowered vertically downward from above the target sealed container 14, causing the needle 2 to pierce the septum sealing the top surface of the sealed container 14, and the tip of the needle 2 is inserted into the liquid in the sealed container 14 to suck in the liquid from the tip of the needle 2. Thereafter, the needle 2 is raised to a predetermined height at a speed slower than the speed at which it is lowered, and completely withdrawn from the sealed container 14, and the needle 2 is moved to the next location, for example, an injection port for injecting the sample into the mobile phase. When the needle 2 is withdrawn from the sealed container 14, the liquid adhering to the outer surface of the needle 2 is wiped off by the septum.

[0020] On the other hand, when the container to be sampled is an open container 16, there is no septum to wipe off the liquid adhering to the outer surface of the needle 2 after the liquid has been sucked in, so sampling is set to be performed with a shake-off action to shake off the liquid adhering to the outer surface of the needle 2 into the same open container 16.

[0021] In the above description, the user sets whether or not to perform the shake-off operation, but the present invention is not limited to this. The control unit 10 may be configured to check whether the target container is a sealed container 14 or an open container 16 before performing sampling, and automatically determine whether or not to perform the shake-off operation.

[0022] Sampling with a shake-off operation will be described with reference to the flow chart of FIG. 3 as well as FIG.

[0023] In sampling involving a shake-off operation, the control unit 10 positions the needle 2 above the target open container 16 (step 201), and lowers the needle 2 vertically downward at a first speed to insert the tip of the needle 2 into the liquid and aspirate a predetermined amount of liquid (steps 202, 203). Thereafter, the needle 2 is raised at a second speed so that the suction port of the needle 2 is positioned above the liquid surface (204). The moving speed of the needle 2 when raising the needle 2 from the liquid (second speed) is set to reduce the liquid adhering to the outer surface of the needle 2, and is slower than the moving speed of the needle 2 when inserting the needle 2 into the liquid (first speed).

[0024] After the needle 2 is pulled up from the liquid, the needle 2 is made to wait at that position for a predetermined time (step 205). This waiting time is a time for the liquid adhering to the outer surface of the needle 2 to move toward the tip of the needle 2 by gravity. Thereafter, a shake-off operation is performed in which the needle 2 is lowered at a third speed faster than the first speed and then suddenly stopped (step 206). Due to the shake-off operation, the liquid adhering to the tip of the needle 2 is shaken off from the needle 2 and falls into the open container 16 directly below.

[0025] The number of times (2 or more) the shaking action should be performed is stored in the memory unit 12. The control unit 10 performs the number of shaking actions stored in the memory unit 12 with a waiting time in between (steps 205 to 207). The number of shaking actions may be a preset value, but may be configured so that the user can set the number of shaking actions in consideration of the viscosity of the liquid to be inhaled, etc.

[0026] Here, the shake-off operation needs to be performed while maintaining a state in which the suction port of the needle 2 is positioned above the liquid level in the container 16. The example of Fig. 3 does not include a step of raising the needle 2 between multiple shake-off operations that are performed, but if necessary to maintain a state in which the suction port of the needle 2 is positioned above the liquid level in the container 16, a step of raising the needle 2 may be performed between the shake-off operations, or the needle 2 may be raised during the waiting time.

[0027] When the preset number of shaking-off operations have been completed, the control unit 10 raises the needle 2 to a predetermined height at which the tip of the needle 2 does not interfere with each container 14, 16 even if the needle 2 is moved horizontally, and moves the needle 2 to the next location, such as an injection port (step 208).

[0028] During the standby time, other operations such as air intake can be performed.

[0029] The above-described embodiments are merely examples of the autosampler according to the present invention. The embodiments of the autosampler according to the present invention are as follows.

[0030] In one embodiment of the autosampler according to the present invention, the autosampler comprises a sampling needle having an intake port at its tip, a moving mechanism that holds the needle so that the intake port faces vertically downward and moves the needle at least in a vertical direction, an intake mechanism for intake of liquid through the needle, and a control unit that controls the operation of the moving mechanism and the intake mechanism, and the control unit is configured to perform the following steps in sampling liquid in a container having an open top: an insertion step in which the needle is lowered from above the container and the tip of the needle is inserted into the liquid in the container; an intake step in which a predetermined amount of the liquid is sucked in through the intake port of the needle after the insertion step is completed; a lifting step in which the needle is pulled up from the liquid and the intake port is positioned above the liquid surface of the liquid after the lifting step is completed; and a shake-off step in which the needle is lowered and suddenly stopped while maintaining the intake port positioned above the liquid surface after the lifting step is completed, and this shake-off operation is repeated multiple times.

[0031] In a first aspect of the embodiment, the control unit is configured to make the moving speed of the needle when descending in the shaking-off step higher than the moving speed when descending in the inserting step. With this configuration, the force of shaking off the liquid downward is greater than when the shaking-off operation is performed at a normal speed, which is the speed at which the needle is inserted into the liquid, so that the liquid is less likely to remain on the outer surface of the needle.

[0032] In a second aspect of the embodiment, the control unit is configured to lower the moving speed of the needle during the lifting step to be lower than the moving speed during the lowering step to be lower in the inserting step. With this configuration, liquid is less likely to remain on the outer surface of the needle when the needle is pulled up from the liquid. This second aspect can be combined with the first aspect.

[0033] In a third aspect of the above embodiment, the control unit is configured to provide a waiting time between the shaking-off operations when repeating the shaking-off operation in the shaking-off step. With this configuration, the liquid adhering above the tip of the needle collects at the tip of the needle during the waiting time, and the liquid that has collected at the tip of the needle is shaken off from the needle by the subsequent shaking-off operation, so that even after the needle is inserted deep into the liquid, contamination or fouling due to the liquid adhering to the outer surface of the needle is unlikely to occur.

[0034] In the third aspect, the control unit may be configured to raise the needle during the waiting time.

[0035] In the fourth aspect of the above embodiment, the device further includes a storage unit that stores the number of times of the shaking-off operation set by a user, and the control unit is configured to execute the number of times of the shaking-off operation stored in the storage unit in the shaking-off step. In this manner, the user can increase or decrease the number of times of the shaking-off operation in consideration of the viscosity of the inhalation target, etc. This third aspect can be freely combined with any of the first to third aspects. [Explanation of symbols]

[0036] 1 Autosampler 2 Needle 4 Moving mechanism 6 Syringe Pump 8 Syringe drive unit 10 Control section 12 Storage section 14 Sealed container 16 Open container

Claims

1. a sampling needle having an intake port at its tip; a moving mechanism that holds the needle so that the suction port faces vertically downward and moves the needle at least in the vertical direction; a suction mechanism for drawing liquid through the needle; A control unit that controls the operation of the moving mechanism and the suction mechanism, The control unit, in sampling the liquid in the container having an open top, an insertion step of lowering the needle from above the container and inserting the tip of the needle into the liquid in the container; an intake step of aspirating a predetermined amount of the liquid through the intake port of the needle after the insertion step is completed; a lifting step of lifting the needle out of the liquid after the suction step is completed to position the suction port above the liquid surface; a shake-off step in which, after the lifting step is completed, the needle is lowered and suddenly stopped while maintaining a state in which the suction port is positioned above the liquid surface, and the shake-off operation is repeated multiple times; is configured to run The control unit is configured to make a moving speed of the needle during ascent in the pulling-up step lower than a moving speed of the needle during descent in the inserting step.

2. 2. The autosampler according to claim 1, wherein the control unit is configured to make the moving speed of the needle when it descends in the shaking-off step higher than the moving speed of the needle when it descends in the inserting step.

3. 3. The autosampler according to claim 1, wherein the control unit is configured to provide a waiting time between the shake-off operations when repeating the shake-off operation in the shake-off step.

4. The autosampler of claim 3 , wherein the control is configured to raise the needle during the wait time.

5. A storage unit that stores the number of times the shaking-off operation is performed, the number being set by a user, 5. The autosampler according to claim 1, wherein the control unit is configured to execute the shake-off operation the number of times stored in the memory unit in the shake-off step.

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