Autosampler

Abstract

This autosampler comprises needle cleaning units (12, 14) that each have an internal space for accommodating a cleaning liquid with which to clean a needle (2) inserted into the space, and a control unit (46) configured to control sampling mechanisms (2, 4, 6). The control unit (46) is configured to perform: as a needle cleaning operation for cleaning the needle (2), an outer surface cleaning step in which the needle (2) is inserted into the space of the needle cleaning unit (12) and the outer surface of the needle (2) is cleaned with the cleaning liquid, and a cleaning liquid suction step in which the cleaning liquid in the needle cleaning unit (12) is suctioned from the tip of the needle (2) by means of a pump (6); and, after the outer surface cleaning step and the cleaning liquid suction step are completed, a cleaning liquid discharge step for discharging the cleaning liquid from the tip of the needle (2).

Description

Autosampler

[0001] The present invention relates to an autosampler that injects a sample into a mobile phase flowing through an analysis channel in a liquid chromatograph.

[0002] A general autosampler for a liquid chromatograph fluidly connects a pump to a needle that moves three-dimensionally, sucks a sample from the tip of the needle, and then injects the sucked sample into the mobile phase flowing toward the separation column. In such an autosampler, in order to prevent contamination of liquids such as the sample, it is necessary to wash the inner and outer surfaces of the needle after the sample injection is completed (see Patent Documents 1 and 2).

[0003] Japanese Patent Application Laid-Open No. 2004-271241 International Publication No. 2015 / 189927

[0004] Generally, the outer surface of the needle is washed by immersing the needle in a container storing the cleaning liquid, and the inner surface of the needle is washed by fluidly connecting a pump that has sucked the cleaning liquid to the proximal end side of the needle and sending the cleaning liquid toward the tip of the needle to discharge the cleaning liquid from the tip of the needle. In ultra-high-speed continuous analysis that completes one analysis in 1 minute or less, it is desired to complete the cleaning operation in a short time in order to improve the throughput. However, when performing the inner surface cleaning of the needle that supplies the cleaning liquid from the proximal end side of the needle, an operation is required to replace the cleaning liquid remaining in the needle or in the flow path leading to the needle with the mobile phase, and there is a limit to shortening the time required for cleaning the inner and outer surfaces of the needle.

[0005] The present invention has been made in view of the above problems, and an object thereof is to enable the cleaning of the inner and outer surfaces of the needle to be completed in a short time.

[0006] The autosampler according to the present invention is an autosampler comprising a sampling mechanism having a three-dimensionally moving sampling needle and a pump that sucks in and discharges fluid through the needle, and configured to inject the sample collected by the sampling mechanism into a mobile phase flowing toward a separation column of a liquid chromatograph, comprising: a needle cleaning unit having a space for containing a cleaning solution inside, into which the needle is inserted and the needle is cleaned with the cleaning solution; and a control unit configured to control the sampling mechanism, wherein the control unit is configured to perform a needle cleaning operation for cleaning the needle, which includes an outer surface cleaning step in which the needle is inserted into the space of the needle cleaning unit and the outer surface of the needle is cleaned with the cleaning solution, and a cleaning solution suction step in which the cleaning solution in the needle cleaning unit is sucked in from the tip of the needle using the pump, and after the outer surface cleaning step and the cleaning solution suction step are completed, a cleaning solution discharge step in which the cleaning solution is discharged from the tip of the needle.

[0007] According to the autosampler of the present invention, the needle cleaning operation includes an external cleaning step in which the needle is inserted into the space within the needle cleaning section and the external surface of the needle is cleaned with a cleaning solution, and a cleaning solution suction step in which the cleaning solution in the needle cleaning section is sucked in from the tip of the needle using a pump. After the external cleaning step and the cleaning solution suction step are completed, a cleaning solution discharge step is performed in which the cleaning solution is discharged from the tip of the needle. As a result, the cleaning of the inner and outer surfaces of the needle can be completed in a short time.

[0008] This is a schematic diagram showing one embodiment of an autosampler. This is a flowchart illustrating an example of the operation during analysis in the same embodiment. This is a flowchart illustrating an example of the needle cleaning operation in the same embodiment.

[0009] Hereinafter, an embodiment of the autosampler according to the present invention will be described with reference to the drawings.

[0010] The autosampler 1 mainly comprises a needle 2, a sampling channel 4, a metering pump 6, a first switching valve 8, a second switching valve 10, a first needle cleaning port 12, a second needle cleaning port 14, a drain port 15, an injection port 20, and a control unit 46.

[0011] Needle 2 is a sampling needle that moves three-dimensionally in the horizontal and vertical directions with its tip pointed vertically downward by a moving mechanism (not shown). One end of the sampling channel 4 is fluid-connected to the base end of needle 2. The other end of the sampling channel 4 is connected to the port (6) of the first switching valve 8. Needle 2 is fluid-connected to the metering pump 6 via the first switching valve 8 and the second switching valve 10, allowing for the intake and discharge of fluid from its tip. Needle 2, sampling channel 4, and metering pump 6 constitute a sampling mechanism for performing sampling.

[0012] The first switching valve 8 is a multi-port valve equipped with six connection ports, (1) to (6). The connection ports (1) to (6) of the first switching valve 8 are evenly arranged counterclockwise on the same circumference. The first switching valve 8 can be switched between two states: one in which connection ports (1)-(2), (3)-(4), and (5)-(6) are connected, and the other in which ports (1)-(6), (2)-(3), and (4)-(5) are connected.

[0013] The connection port (1) of the first switching valve 8 is fluidly connected to the common port (0) of the second switching valve 10 via the flow path 16. A drain flow path 18 leading to a drain is fluidly connected to the connection port (2) of the first switching valve 8, an injection port 20 is fluidly connected to the connection port (3), a separation flow path 24 leading to a separation column is fluidly connected to the connection port (4), and a mobile phase supply flow path 22 leading to a liquid transfer pump is fluidly connected to the connection port (5).

[0014] The second switching valve 10 is equipped with one common port (0) and connection ports (1) to (4). The connection ports (1) to (4) of the second switching valve 10 are arranged counterclockwise on the same circumference, and the common port (0) is located at the center of the circumference where the connection ports (1) to (4) are located. The switching valve 30 can fluidly communicate any one of the connection ports (1) to (4) with the common port (0), and can also be configured to have fluid communication between connection ports (1) and (2), between connection ports (2) and (3), or between connection ports (3) and (4).

[0015] A fluid channel 26 leading to the main suction / discharge port at the tip of the metering pump 6 is fluidly connected to connection port (1) of the second switching valve 10, a fluid channel 28 leading to the bottom of the second cleaning port 14 is fluidly connected to connection port (2), a fluid channel 32 leading to three cleaning fluid containers each containing cleaning fluids R0 to R2 is fluidly connected to connection port (3), and a fluid channel 27 leading to the sub-suction / discharge port of the metering pump 6 is fluidly connected to connection port (4).

[0016] The first cleaning port 12 and the second cleaning port 14 have a space inside for containing cleaning fluid and constitute a needle cleaning section for cleaning the needle 2 with cleaning fluid by inserting the needle 2 from the top surface.

[0017] A cleaning fluid container for storing cleaning fluid R3 is fluidly connected to the bottom of the first cleaning port 12 via a flow path 40. A pump 42 for pumping up the cleaning fluid R3 and supplying it to the first cleaning port 12 and an on / off valve 44 for opening and closing the flow path 40 are provided on the flow path 40.

[0018] A pump 30 is provided in the flow path 28 leading to the bottom of the second cleaning port 14 to pump up one of the cleaning liquids R0 to R2 and supply it to the cleaning port 14 when the flow path 28 is fluidly connected to the flow path 32 by the second switching valve 10 (when fluid communication is established between connection ports (2) and (3)). On the flow paths leading to the containers storing the cleaning liquids R0 to R2, on-off valves 34, 36, and 38 are provided, respectively.

[0019] Furthermore, the cleaning solutions R0 to R2 can also be drawn in from the sub-inlet / outlet of the metering pump 6 by ensuring fluid communication between the connection ports (3) and (4) of the second switching valve 10.

[0020] In this embodiment, a cleaning solution R3 (first cleaning solution) with high cleaning power is used in the first cleaning port 12, and one of the cleaning solutions R0 to R2 is used in the second cleaning port 14. R0 is the cleaning solution with the weakest cleaning power among R0 to R3, and R3 is the cleaning solution with the strongest cleaning power among R0 to R3. R0 is a cleaning solution having the same or a similar composition as the composition of the mobile phase used in the analysis at the start of the analysis, and is used as a rinsing solution. For example, if the mobile phase used in the analysis is a mixture of water and an organic solvent, and the composition of the mobile phase in the analysis gradually increases from a state of 100% water to a state where the concentration of the organic solvent increases, then the cleaning solution R0 may be water.

[0021] The drain port 15 is a port for receiving the waste liquid discharged from the needle 2 and discharging it into the drain.

[0022] The control unit 46 controls the operation of the moving mechanism for moving the needle 2, the metering pump 6, the first switching valve 8, the second switching valve 10, pumps 30 and 42, and the on / off valves 34, 36, 38, and 44, and is configured to perform a sample injection operation into the mobile phase flowing into the separation channel 24 and a needle cleaning operation after the sample injection operation, according to preset analysis conditions. The control unit 46 is a function realized by the execution of control software in a computer circuit equipped with a CPU (Central Processing Unit) and an information storage device.

[0023] An example of the operation during analysis realized by the control unit 46 will be explained using the flowchart in Figure 2 along with Figure 1.

[0024] When the analysis system, including the autosampler 1, is ready for analysis, the metering pump 6 is connected to the sampling channel 4 (as shown in Figure 1) at the time the analysis is to begin, and the sample in the sample container placed in a predetermined position is drawn in through the tip of the needle 2 and held in the needle 2 and the sampling channel 4 (step 101).

[0025] Next, the tip of the needle 2 is inserted into the injection port 20 (step 102), and the state of the first switching valve 8 is switched to a state that allows fluid communication between connection ports (3)-(4) and connection ports (5)-(6) so that the sampling channel 4 is interposed between the mobile phase supply channel 22 and the separation channel 24. As a result, the mobile phase supplied through the mobile phase supply channel 22 flows through the sampling channel 4 and the needle 2, and the sample held in the needle 2 and the sampling channel 4 is injected into the mobile phase heading toward the separation channel 24 (step 103). The injected sample is introduced into the separation channel 24 together with the mobile phase.

[0026] After the introduction of the sample into the separation channel 24 is complete, the first switching valve 8 is switched, disconnecting the needle 2 and the sampling channel 4 from the mobile phase supply channel 22 and the separation channel 24, and the needle cleaning operation is performed (step 104). During the needle cleaning operation, the inner and outer surfaces of the needle 2 and the inner surface of the sampling channel 4 are cleaned. Details of the needle cleaning operation will be described later. The needle cleaning operation is performed during the analysis of the sample. If there is another sample to be analyzed, after the analysis and needle cleaning operation of the currently running sample are completed, steps 101 to 103 are repeated for the next sample.

[0027] As described above, after introducing a sample into the separation channel 24, a needle cleaning operation is performed until the analysis of that sample is completed. However, if the time required for the needle cleaning operation is long, and the analysis time for the sample is short, a waiting time for the needle cleaning operation will occur between the completion of the analysis of one sample and the start of the analysis of the next sample, which may reduce the throughput in continuous analysis. Therefore, it is desirable to complete the needle cleaning operation in a short time.

[0028] Figure 3 is a flowchart showing an example of a needle cleaning operation that can be performed in a short amount of time.

[0029] Before performing this needle cleaning operation, the cleaning solution R0 is placed in the second cleaning port 14. After drawing a predetermined amount of air from the tip of the needle 2 (step 201), the needle 2 is inserted into the second cleaning port 14 and the outer surface of the needle 2 is cleaned by immersing the needle 2 in the cleaning solution R0 (step 202).

[0030] While the needle 2 is immersed in the cleaning solution R0, a predetermined amount of the cleaning solution R0 is drawn in as a rinse solution from the tip of the needle 2 (step 203: rinse solution drawing step). Since air is drawn in from the tip of the needle 2 before it is immersed in the cleaning solution R0, when the cleaning solution R0 is drawn in from the tip of the needle 2, the mobile phase present in the needle 2 and the sampling channel 4 is prevented from mixing with the cleaning solution R0 by diffusion.

[0031] Next, the needle 2 is withdrawn from the second cleaning port 14, and a predetermined amount of air is drawn in through the tip of the needle 2 (step 204: air intake step). Then, the needle 2 is inserted into the first cleaning port 12, and the outer surface of the needle 2 is cleaned by immersing the needle 2 in the cleaning solution R3 (step 205: outer surface cleaning step).

[0032] While the needle 2 is immersed in the cleaning solution R3, a predetermined amount of cleaning solution R3 is drawn in from the tip of the needle 2 (Step 206: Cleaning solution drawing step). The amount of cleaning solution R3 drawn in during the cleaning solution drawing step is an amount that allows the cleaning solution R3 to reach the position in the sampling channel 4 where the sample drawn in from the tip of the needle 2 in the most recent sample injection reached, and is preferably an amount greater than or equal to the amount of the most recent sample injection. Since air is drawn in from the tip of the needle 2 before the needle 2 is immersed in the cleaning solution R3, when the cleaning solution R3 is drawn in from the tip of the needle 2, mixing of the drawn-in cleaning solution R3 and the previously drawn-in cleaning solution R0 by diffusion is prevented.

[0033] While the needle 2 is inserted into the first cleaning port 12, the pump 42 may continuously supply cleaning fluid R3 to the first cleaning port 12 and discharge cleaning fluid R3 from the first cleaning port 12, thereby continuously replacing the cleaning fluid R3 in the first cleaning port 12. By continuously supplying clean cleaning fluid R3 from the bottom side of the first cleaning port 12, not only can the cleaning efficiency of the outer surface of the needle 2 be improved, but clean cleaning fluid can also be reliably drawn in from the tip of the needle 2 during the cleaning fluid suction step (step 206), thereby improving the cleaning efficiency of the inner surface of the needle 2.

[0034] After the external cleaning process of the needle 2 and the cleaning solution suction process at the first cleaning port 12 are completed, the needle 2 is moved to the drain port 15, and cleaning solution R3, air, cleaning solution R0, and air are discharged sequentially from the tip of the needle 2 at the drain port 15 (step 207: cleaning solution discharge process).

[0035] Through the cleaning solution suction step (step 206) and cleaning solution discharge step (step 207) described above, any sample remaining on the inner surface of the needle 2 and the inner surface of the sampling channel 4 is removed by the cleaning solution R3, which has strong cleaning power. Furthermore, in the cleaning solution discharge step (step 207), after the cleaning solution R3, a rinsing solution R0 is discharged from the tip of the needle 2, so that any cleaning solution R3 remaining on the inner surface of the needle 2 and the inner surface of the sampling channel 4 is washed away by the cleaning solution R0, preventing the cleaning solution R3 from being introduced into the separation channel 24 together with the mobile phase.

[0036] After the above cleaning fluid discharge process is completed, the needle 2 is inserted into the second cleaning port 14 and immersed in the cleaning fluid R0 to wash away the cleaning fluid R3 adhering to the outer surface of the needle 2 (step 208).

[0037] The needle cleaning operation described above is just one example, and parts of the process may be modified, or steps may be omitted or added as needed. For example, the step of immersing the needle 2 in the cleaning solution R0 at the second cleaning port 14 (step 202) may be omitted, and only the rinsing solution suction step (step 203) may be performed at the second cleaning port 14. Alternatively, the cleaning solution R0 may be continuously supplied to the second cleaning port 14 while the needle 2 is immersed in the cleaning solution R0 at the second cleaning port 14. Furthermore, during the cleaning solution discharge step, the needle 2 may be inserted into the injection port 20, and cleaning solution R3, air, cleaning solution R0, and air may be discharged sequentially from the tip of the needle 2 to the injection port 20.

[0038] The embodiments described above are merely examples of embodiments of the autosampler according to the present invention. Embodiments of the autosampler according to the present invention are as follows.

[0039] One embodiment of the autosampler according to the present invention is an autosampler comprising a sampling mechanism having a three-dimensionally moving sampling needle and a pump that sucks in and discharges a fluid through the needle, and configured to inject a sample collected by the sampling mechanism into a mobile phase flowing toward a separation column of a liquid chromatograph, comprising: a needle cleaning section (12, 14) having a space for containing a cleaning solution, into which the needle is inserted and the needle is cleaned with the cleaning solution; and a control unit configured to control the sampling mechanism, wherein the control unit is configured to perform a needle cleaning operation for cleaning the needle, which includes an outer surface cleaning step in which the needle is inserted into the space of the needle cleaning section and the outer surface of the needle is cleaned with the cleaning solution, and a cleaning solution suction step in which the cleaning solution in the needle cleaning section is sucked in from the tip of the needle using the pump, and after the outer surface cleaning step and the cleaning solution suction step are completed, a cleaning solution discharge step in which the cleaning solution is discharged from the tip of the needle.

[0040] In the first embodiment of the above-described embodiment, a drain for receiving waste liquid is further provided, and the control unit is configured to discharge the cleaning liquid from the tip of the needle to the drain during the cleaning liquid discharge step.

[0041] In the second embodiment of the above-described embodiment, an injection port is provided that is fluidly connected to the analysis channel, and the control unit is configured to discharge the cleaning solution from the tip of the needle to the injection port during the cleaning solution discharge step. With this configuration, not only the inner surface of the needle but also the inside of the injection port can be cleaned.

[0042] In a third aspect of the above embodiment, the needle cleaning unit comprises a first cleaning port containing a first cleaning solution and a second cleaning port containing a second cleaning solution, wherein the second cleaning solution has a lower cleaning effect than the first cleaning solution. The control unit performs the external cleaning step and the cleaning solution suction step in the first cleaning port, and before performing the external cleaning step, it performs a rinsing solution suction step in which the second cleaning solution contained in the second cleaning port is suctioned from the tip of the needle as a rinsing solution, and after the rinsing solution suction step, it performs an air suction step in which air is suctioned from the tip of the needle. In the cleaning solution discharge step, the first cleaning solution, air, and the second cleaning solution are discharged from the tip of the needle. In this embodiment, after the first cleaning solution is discharged from the tip of the needle in the cleaning solution discharge step, any remaining first cleaning solution in the needle can be washed away by the second cleaning solution, thus preventing the first cleaning solution from mixing with the mobile phase and affecting the analysis. This third embodiment can be combined with the first or second embodiment described above.

[0043] In the first aspect of the third embodiment described above, the second cleaning solution is a liquid having the same or similar composition as the mobile phase flowing through the analysis channel at the start of the analysis. In this embodiment, even if the second cleaning solution remains in the needle, the influence of the analysis by the second cleaning solution is reduced because the second cleaning solution has the same or similar composition as the mobile phase.

[0044] In the second aspect of the third aspect described above, in the rinsing liquid suction step, the control unit is configured to suck the second rinsing liquid from the tip of the needle while immersing the needle in the second rinsing liquid in the second rinsing port. With such an aspect, when sucking the second rinsing liquid from the tip of the needle, the outer surface of the needle can be pre-rinsed with the second rinsing liquid, and the cleaning efficiency of the needle is improved. This second aspect can be combined with the first aspect described above.

[0045] In the third aspect of the third aspect described above, the control unit is configured to suck air from the tip of the needle before the rinsing liquid suction step. With such an aspect, since an air layer is interposed between the second rinsing liquid sucked in the rinsing liquid suction step and the mobile phase existing in the needle, the second rinsing liquid is prevented from being mixed with the mobile phase existing in the needle by diffusion. This third aspect can be combined with the first aspect and / or the second aspect described above.

[0046] In the fourth aspect of the third aspect described above, in the outer surface cleaning step, the first cleaning port is configured to continuously discharge the first cleaning liquid in contact with the needle from the space while supplying the first cleaning liquid to the internal space. With such an aspect, not only can a non-contaminated cleaning liquid be continuously supplied to the first cleaning port, improving the cleaning efficiency of the outer surface of the needle, but also a non-contaminated cleaning liquid can be reliably sucked from the tip of the needle in the cleaning liquid suction step, thereby improving the cleaning efficiency of the inner surface of the needle. This fourth aspect can be combined with the first aspect, the second aspect, and / or the third aspect described above.

[0047] 1. Autosampler 2. Needle 4. Sampling flow path 6. Metering pump 8. First switching valve 10. Second switching valve 12. First cleaning port 14. Second cleaning port 15. Drain port 20. Injection port 30, 42. Pump 34, 36, 38, 44. On-off valve 46. Control unit

Claims

1. An autosampler comprising a sampling mechanism having a three-dimensionally moving sampling needle and a pump for drawing in and discharging fluid through the needle, configured to inject a sample collected by the sampling mechanism into a mobile phase flowing toward a separation column of a liquid chromatograph, the autosampler comprising: a needle cleaning unit having a space for containing a cleaning solution, into which the needle is inserted and the needle is cleaned with the cleaning solution; and a control unit configured to control the sampling mechanism, wherein the control unit is configured to perform a needle cleaning operation for cleaning the needle, which includes an external cleaning step of inserting the needle into the space of the needle cleaning unit and cleaning the outer surface of the needle with the cleaning solution, and a cleaning solution suction step of drawing in the cleaning solution from the tip of the needle through the needle using the pump, and after the external cleaning step and the cleaning solution suction step are completed, a cleaning solution discharge step of discharging the cleaning solution from the tip of the needle.

2. The autosampler according to claim 1, further comprising a drain for receiving waste liquid, wherein the control unit is configured to discharge cleaning liquid from the tip of the needle to the drain in the cleaning liquid discharge step.

3. The autosampler according to claim 1, further comprising an injection port fluid-connected to the analysis channel, wherein the control unit is configured to discharge the cleaning solution from the tip of the needle to the injection port during the cleaning solution discharge step.

4. The autosampler according to claim 1, wherein the needle cleaning unit comprises a first cleaning port for containing a first cleaning liquid and a second cleaning port for containing a second cleaning liquid, the second cleaning liquid being a liquid with a lower cleaning effect than the first cleaning liquid, and the control unit is configured to perform the external cleaning step and the cleaning liquid intake step in the first cleaning port, and before performing the external cleaning step, to perform a rinsing liquid intake step in which the second cleaning liquid contained in the second cleaning port is drawn in as a rinsing liquid from the tip of the needle, and after the rinsing liquid intake step, to perform an air intake step in which air is drawn in from the tip of the needle, and in the cleaning liquid discharge step, the first cleaning liquid, air, and the second cleaning liquid are discharged from the tip of the needle.

5. The autosampler according to claim 4, wherein the second washing solution is a liquid having the same or similar composition as the mobile phase flowing through the analysis channel at the start of analysis.

6. The autosampler according to claim 4, wherein the control unit is configured to draw in the second cleaning solution from the tip of the needle while immersing the needle in the second cleaning solution in the second cleaning port during the rinsing solution suction step.

7. The autosampler according to claim 4, wherein the control unit is configured to draw air from the tip of the needle before the rinse liquid suction step.

8. The autosampler according to claim 4, wherein the first cleaning port is configured to continuously discharge the first cleaning liquid that has come into contact with the needle from the internal space while supplying the first cleaning liquid to the internal space during the external cleaning process.

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