JP6365323B2 - Auto sampler - Google Patents

Description

  The present invention relates to an autosampler that introduces a sample into an analysis flow path of a liquid chromatograph.

  As an autosampler that automatically collects a sample in a liquid chromatograph and introduces it into an analysis channel, a sampling channel with a needle for collecting the sample and a sample loop for holding the sample collected, a needle And a switching valve having a plurality of ports to which an analysis flow path leading to an analysis column and a detector is connected, respectively. There is one that switches the flow path configuration (see Patent Document 1). The switching valve is provided with an injection port to which a sampling channel is connected by inserting a needle tip.

  The switching valve of such an autosampler is configured to switch whether or not the sampling channel is interposed between the liquid feeding device and the analytical column when the needle tip is inserted into the injection port.

  When collecting a sample, the sampling flow path should not be interposed between the liquid delivery device and the analytical column, the sampling flow path and the syringe pump are connected, and the tip of the needle is inserted into the sample container and the syringe is inserted. By inhaling the pump, the sample is sucked from the tip of the needle and held in the sample loop.

  When introducing the sample collected by the above sampling operation into the analysis channel, insert the tip of the needle into the injection port and switch the switching valve so that the sampling channel is interposed between the liquid delivery device and the analysis column. Then, the sample held in the sample loop is introduced into the analysis flow path by the mobile phase from the liquid feeding device. The sample introduced into the analysis channel is separated for each component in the analysis column and detected by a detector.

JP 2005-265805 A

  In the above autosampler, for example, when the sample is inhaled by moving the needle to the sample container, the tip of the needle is inserted into the injection port until just before that, and the sampling channel is interposed between the liquid delivery device and the analysis column. In such a state, since the mobile phase from the liquid delivery device was fed through the sampling flow path at a high pressure, a compressed mobile phase exists in the sampling flow path. When the needle is pulled out from the injection port in this state, there is a problem that the mobile phase is ejected from the tip of the needle and the inside of the apparatus is soiled.

  Therefore, an object of the present invention is to prevent liquid from being ejected from the tip of a needle when the needle is pulled out from an injection port.

  One embodiment of the autosampler according to the present invention includes a sampling flow path, a needle drive mechanism, an injection port, a switching mechanism, and a pressure release operation unit. The sampling flow path has a needle for sucking a sample from a sample container containing the sample at one end and a sample loop for holding the sample sucked through the needle. The needle drive mechanism moves the needle. The injection port is connected to the sampling channel by inserting the needle tip. When the needle tip is inserted into the injection port, the switching mechanism has a state in which a sampling flow path is interposed between the liquid feeding device for feeding the mobile phase and the analysis column for separating the sample for each component. The system including the sampling flow path is switched to an open system or a closed system in a state where the sampling flow path is not interposed between the liquid delivery device and the analysis column. The pressure release operation unit controls the operation of the needle drive mechanism and the switching mechanism, so that the needle tip is withdrawn from the injection port after the sampling channel is interposed between the liquid delivery device and the analysis column. Until the pressure in the sampling channel returns to atmospheric pressure by switching the switching mechanism so that the sampling channel is not interposed between the liquid delivery device and the analytical column, and the system including the sampling channel is an open system The standby pressure release operation is executed.

  In one embodiment of the autosampler according to the present invention, the needle tip is injected after the state where the sampling channel is interposed between the liquid feeding device and the analysis column by controlling the operation of the needle driving mechanism and the switching mechanism. Before being withdrawn from the port, the pressure in the sampling channel is changed by switching the switching mechanism so that the sampling channel is not interposed between the liquid delivery device and the analytical column, and the system including the sampling channel is opened. Since the pressure release operation part that performs the pressure release operation that waits until the pressure returns to the atmospheric pressure is provided, the pressure in the sampling flow path is returned to the atmospheric pressure before the needle tip is pulled out from the injection port, and the needle tip is When it is pulled out from the injection port, it can prevent the mobile phase from being ejected from the tip of the needle. .

It is a flow-path block diagram of the liquid chromatograph provided with the autosampler of one Example. It is a block diagram which shows an example of the control system of the Example. It is a block diagram which shows the other example of the control system of the Example. It is a flowchart which shows an example of operation | movement of the Example. It is a flow-path block diagram at the time of the pressure release operation | movement of the Example. It is a flow-path block diagram at the time of the sampling operation | movement of the Example. It is a block diagram which shows the further another example of the control system of the Example.

  The time required for the pressure in the sampling flow path to return to atmospheric pressure due to the pressure release operation depends on the pressure in the sampling flow path immediately before the pressure release operation. It takes a long time for the internal pressure to return to atmospheric pressure, and if the pressure in the sampling channel is low, the pressure in the sampling channel can be returned to atmospheric pressure in a short time. Nevertheless, if the pressure release operation is executed for a uniform time, the pressure release operation may be performed longer than necessary, in which case the analysis efficiency decreases.

  Therefore, the pressure release operation unit further includes a pressure release time setting unit that sets the execution time of the pressure release operation based on the liquid supply pressure of the mobile phase of the liquid delivery device immediately before the pressure release operation is performed, and the pressure release operation unit is a pressure release operation. Is preferably executed for the time set by the pressure release time setting unit. As a result, the time required for the pressure release operation can be made according to the pressure in the sampling flow path immediately before, and the analysis efficiency can be improved.

  As a preferred embodiment of the above case, the pressure release time setting unit further includes a pressure release time information holding unit that holds pressure release time information defined in advance with respect to the relationship between the liquid feeding pressure and the execution time of the pressure release operation. , The pressure of the liquid delivery device is taken in before the pressure release operation is executed, and the execution time of the pressure release operation based on the taken-in liquid supply pressure and the pressure release time information held in the pressure release time information holding unit Can be mentioned.

  In addition to a control unit that controls the needle drive mechanism and the switching mechanism, there may be a system controller that performs information communication with the control unit. In such a case, a pressure release time setting unit may be provided in the system controller.

  The switching mechanism can be constituted by two switching valves. In this case, the first switching valve, which is one of the switching valves, includes a sampling port to which the other end of the sampling channel is connected, a syringe port to which a syringe pump that sucks and discharges liquid is connected, an injection port, a mobile phase A mobile phase supply port to which a liquid supply device for supplying liquid is connected, and an analysis port to which a flow path leading to an analysis column is connected, and the mobile phase supply port and the analysis port are connected between the sampling port and the syringe port Switching between a sampling mode and a mobile phase supply port and an injection mode connecting between an injection port and an analysis port. As the second switching valve, which is the other switching valve, a system including a sampling flow path configured when the tip of the needle is inserted into the injection port and the first switching valve is in the loading mode is an open system or a sealed system. One that switches to one of the systems is mentioned.

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

  First, the liquid chromatograph provided with the autosampler of one Example is demonstrated using FIG.

  The liquid chromatograph includes an autosampler 1, a liquid feeding device 19, an analysis column 22, and a detector 24. The autosampler 1 is provided with a first switching valve 2 and a second switching valve 4 as a switching mechanism for switching the flow channel configuration of the liquid chromatograph.

  The first switching valve 2 is a rotary type high pressure valve having six ports. The first switching valve 2 includes a port “a” (sampling port) to which the sampling flow path 10 is connected, a port “b” (mobile phase supply port) to which the mobile phase liquid supply flow path 19 is connected, and the analysis column 22. A port “c” (analysis port) to which an analysis flow path 8 leading to one end is connected, an injection port “d”, and a port “e” to which a flow path 14 leading to a port “h” of the second switching valve 4 described later is connected. ”And six ports“ f ”(syringe port) to which the syringe flow path 12 leading to the syringe pump 13 is connected.

  The second switching valve 4 includes ports “g”, “h”, “i”, “j”, and “k”. Among these ports, the port “g” is connected to the syringe pump 13 via the syringe flow path 32, the port “h” is connected to the port “e” of the first switching valve 2 via the flow path 14, The port “k” is connected to the cleaning port 36 via the flow path 34. Further, a flow path 38 for supplying a cleaning liquid is connected to the port “i”.

  The liquid feeding device 19 includes a liquid feeding pump 20 and sends the mobile phase to the autosampler 1 side through the mobile phase supply channel 6. The other end of the analysis column 22 is connected to the detector 24 via a pipe. The analytical column 22 is accommodated in a column oven 23, and its temperature is controlled to be constant.

  The sampling flow path 10 includes a sampling needle 16 at the tip and a sample loop 18 that holds a sample sucked from the tip of the needle 16. The needle 16 is moved in the horizontal direction and the vertical direction by the needle driving mechanism 17 and accesses the sample container 30 installed in the injection port d of the first switching valve 2 and the sample rack 28.

  The syringe pump 13 has two suction / discharge ports, and the syringe flow path 12 is connected to one of the suction / discharge ports, and the flow path 32 is connected to the other. The cleaning flow path 32 is connected to the port “g” of the second switching valve 4.

  In the first switching valve 2, the port “a” is adjacent to the ports “b” and “f”, the port “c” is adjacent to the ports “c” and “d”, and the port “e” is the port “d”. And “f”. The first switching valve 2 is configured to switch the connection between adjacent ports, and connects the ports “a” and “b”, “c” and “d”, and “e” and “f”. (State in FIG. 1; hereinafter referred to as injecting mode), and states in which ports “a” and “f”, “b” and “c”, and “d” and “e” are connected (FIG. 5 and FIG. 5). The state is switched to one of the states shown in FIG.

  The second switching valve 4 is switched according to when the sample is sucked, when the cleaning liquid is sucked and discharged, and when the pressure of the sampling channel 10 is released.

  When the sample is inhaled from the sample container 30, the second switching valve 4 is brought into a state where the ports “g” and “k” are not communicated. At this time, by setting the first switching valve 2 in the loading mode and communicating between the ports “a” and “f”, the syringe pump 13 communicates with the tip of the needle 16, and the syringe pump 13 passes through the needle 16. The sample can be inhaled (see FIG. 6).

  At the time of suction / discharge of the cleaning liquid, first, the ports “i” and “h” of the second switching valve 4 are connected to each other, and the first switching valve 2 is set to the injection mode between the ports “e” and “f”. Is communicated between the syringe pump 13 and the flow path 38 for supplying the cleaning liquid. In this state, the syringe pump 13 is driven to suck, whereby the cleaning liquid is sucked into the syringe pump 13. Thereafter, in the second switching valve 4, the ports “g” and “k” are connected to each other, the port “h” is closed, and the cleaning liquid is discharged from the syringe pump 13. The cleaning liquid is sent to the cleaning port 36.

  When releasing the pressure in the sampling flow path 10, the second switching valve 4 communicates between the ports “g” and “k” and closes the port “h”. At this time, the first switching valve 2 is set to the loading mode to allow communication between the ports “a” and “f” and between “d” and “e”, so that the sampling channel 10 is released into the atmosphere. The pressure in the sampling flow path 10 decreases to the atmospheric pressure with time (see FIG. 5).

  An example of the control system in this embodiment will be described with reference to FIG.

  The autosampler 1, the liquid feeding device 19, the column oven 23, and the detector 24 are connected to a common system controller 48, and these operations are centrally managed by the system controller 48. A general-purpose personal computer can be used in place of the system controller 48.

  The autosampler 1, the liquid feeding device 19, the column oven 23, and the detector 24 are each provided with a control unit for controlling the operation of the operation module provided therein. In FIG. Only the control unit 40 and the control unit 42 of the autosampler 1 are shown, and the other control units are not shown. The control unit provided in the autosampler 1, the liquid feeding device 19, the column oven 23, and the detector 24 performs information communication with the system controller 48 and outputs a signal based on information given from the system controller 48. Give to each module. Each of the control units is realized by a combination of an arithmetic processing device such as a CPU and a storage device storing a predetermined program.

  The controller 40 controls the operation of the liquid feeding pump 20 so that the mobile phase is fed at a preset flow rate. The liquid feeding device 19 is provided with a pressure sensor 21 (not shown in FIG. 1) that detects the liquid feeding pressure of the mobile phase.

  In the autosampler 1, the control unit 42 that controls the operations of the first switching valves 2 and 4, the syringe pump 13, and the needle driving unit 17 includes a sampling operation unit 43, an injection operation unit 44, a pressure release operation unit 45, a pressure release time. A setting unit 46 and a pressure release time information holding unit 47 are provided. The sampling operation unit 43, the injection operation unit 44, the pressure release operation unit 45, and the pressure release time setting unit 46 are functions realized when the arithmetic processing unit executes a program stored in the storage device that constitutes the control unit 42. It is. The pressure release time information holding unit 47 is a storage area provided in the storage device constituting the control unit 42.

  The sampling operation unit 43 is configured to execute a sampling operation in which a sample is sucked from the tip of the needle 16 and held in the sample loop 18 in response to a sampling operation start signal given from the system controller 48. In the sampling operation, the first switching valve 2 is set to the loading mode to connect between the sampling flow path 10 and the syringe flow path 12, and the second switching valve 4 is rotated 30 degrees so that the ports “g” and “k” The tip of the needle 16 is inserted into the sample container 30 and the syringe pump 13 is driven in the suction direction to remove the sample in the sample container 30 from the tip of the needle 16. Inhale (see Figure 6).

  The injection operation unit 44 is configured to execute an injection operation for introducing the sample held in the sample loop 18 by the sampling operation into the analysis flow path 8. In the injection operation 44, after the above sampling operation, as shown in FIG. 1, the tip of the needle 16 is inserted into the injection port “d” of the first switching valve 2, and the first switching valve 2 is placed in the loading mode. The sampling channel 10 is connected between the mobile phase supply channel 6 and the analysis channel 8, and the sample held in the sample loop 18 by the mobile phase from the liquid feeding device 19 is analyzed. To introduce.

  The pressure release operation unit 45 performs a pressure release operation for returning the pressure in the sampling flow path 10 to the atmospheric pressure before the needle 16 is pulled out from the injection port “d”, for example, before the above-described sampling operation is performed. It is configured. The needle 16 is inserted into the injection port “d” of the first switching valve 2 until immediately before the sampling operation is performed, and the mobile phase from the liquid feeding device 19 often flows through the sampling flow path 10 (FIG. 1). State). Thereafter, when the sampling operation is executed, the first switching valve 2 is switched to the loading mode, and the needle 16 moves to the sample container 30 to be in the state of FIG. 6, but the first switching valve 2 is switched to the loading mode. When the needle 16 is pulled out from the injection port “d” immediately after the injection, liquid is ejected from the needle 16 due to the pressure in the sampling channel 10 being the liquid supply pressure of the liquid supply device 19.

  Therefore, as shown in FIG. 5, as the pressure release operation, before the needle 16 is pulled out from the injection port “d”, the second switching valve 4 is connected to the ports “g” and “k”. At the same time, the first switching valve 2 is switched to the loading mode and waits for a preset time as the pressure release time. As described above, the sampling channel 10 communicates with the cleaning port 36 opened to the atmosphere via the syringe channel 12, the syringe pump 13, the cleaning channel 32 and the channel 34 by setting the state of FIG. 5. Then, the pressure in the sampling channel 10 is released over time and returns to atmospheric pressure.

  The atmosphere release time setting unit 46 is configured to set the execution time of the pressure release operation, that is, the time to wait in the state shown in FIG. 5 (pressure release time). The time from when the state in FIG. 5 is reached until the pressure in the sampling flow path 10 returns to atmospheric pressure is the pressure in the sampling flow path 10 immediately before the flow path configuration is switched to the state in FIG. It depends on the liquid feeding pressure of the liquid device 19. The correlation between the liquid feeding pressure of the liquid feeding device 19 and the time required for the pressure in the sampling flow path 10 to return to atmospheric pressure is obtained in advance by experiment, and the correlation data is used as pressure release time information to release the pressure. A time information holding unit 47 is provided. The atmospheric release time setting unit 46 sets the pressure release time based on the liquid delivery pressure of the liquid delivery device 19 and the atmospheric release time information held in the atmospheric release time information holding unit 47.

  Note that the information related to the liquid supply pressure of the liquid supply device 19 may be taken into the control unit 42 from the system controller 48, or as shown in FIG. 3, the control unit of the liquid supply device 19 40 may be taken into the control unit 42.

  As shown in FIG. 7, the system controller 48 has functions (pressure release time setting unit 46 a and pressure release time information holding unit 47 a) for setting the pressure release time according to the liquid supply pressure of the liquid supply device 19. You may let them. These functions may be provided on the liquid delivery device 19 side.

  The air release time setting unit 46 may further set the air release time in consideration of the inner diameter and length of the sample loop 18 and the type of mobile phase (compression rate, viscosity, etc.). In that case, the correlation between the time until the pressure in the sampling channel 10 returns to the atmospheric pressure, the inner diameter and length of the sample loop 18, and the type of mobile phase is also stored in the atmosphere release time information holding unit 47 as atmosphere release time information. The atmosphere release time setting unit 46 is prepared on the basis of information such as the solution delivery pressure of the solution delivery device, the inner diameter and length of the sample loop 18 provided from the system controller 48, the type of mobile phase, and the atmosphere release time information. Set the air release time.

  Next, an example of the operation of this embodiment will be described with reference to the flowchart of FIG. 4 together with FIGS. 1, 2, 5, and 6. FIG.

  Before execution of the sampling operation, the needle 16 is inserted into the injection port “d”, and the first switching valve 2 is in the injection mode (this state is referred to as a standby state). When the control unit 42 of the autosampler 1 receives a sampling operation start signal from the system controller 48, the control unit 42 takes in information on the liquid supply pressure of the liquid supply device 19, and supplies the liquid supply pressure and pressure release time information holding unit 47. The pressure release time is set based on the pressure release time information held in the.

  After setting the pressure release time, the first switching valve 2 is switched to the loading mode, the sampling channel 10 and the syringe channel 12 are connected, and the second switching valve 4 is connected between the ports “g” and “k”. Is connected (see FIG. 5) and waits until the set pressure release time elapses. Thereby, the pressure in the sampling flow path 10 returns to atmospheric pressure.

  After the above pressure release operation is completed, the second switching valve 4 is switched to a state where the ports “g” and “k” are blocked, and the needle 16 is moved to the position of the predetermined sample container 30 to move the tip. And inhale the sample (see FIG. 6). After inhaling the sample, the needle 16 is inserted into the injection port “d”, the first switching valve 2 is switched to the injection mode (see FIG. 1), and held in the sample loop 18 by the mobile phase from the liquid delivery device 19. The prepared sample is introduced into the analysis channel 8. The sample introduced into the analysis flow path 8 is separated for each component in the analysis column 22 and detected by the detector 24. Thus, a series of operations from sampling for one sample to analysis of the sample is completed.

  When the inner and outer surfaces of the needle 16 are cleaned after the separation analysis of the sample in the analysis flow path 8 is completed, the first switching valve 2 is switched to the loading mode again, the needle 16 is moved to the cleaning port 36 and the needle 16 is moved. Clean the inner and outer surfaces of the. When the needle 16 is pulled out from the injection port “d”, a pressure release operation in the sampling flow path 10 is required as in the case immediately before the sampling operation. After the inner and outer surfaces of the needle 16 are cleaned, the needle 16 is inserted into the injection port “d” again, and the first switching valve 2 is switched to the injection mode to return to the standby state (see FIG. 1).

DESCRIPTION OF SYMBOLS 1 Autosampler 2 1st switching valve 4 2nd switching valve 6 Mobile phase supply flow path 8 Analysis flow path 10 Sampling flow path 12 Syringe flow path 14, 34, 38 flow path 16 Needle 18 Sample loop 19 Liquid supply apparatus 20 Liquid supply Pump 21 Pressure sensor 22 Analysis column 23 Column oven 24 Detector 28 Rack 30 Sample container 32 Washing channel 36 Washing port 40, 42 Control unit 43 Sampling operation unit 44 Injection operation unit 45 Pressure release operation unit 46 Pressure release time setting unit 47 Pressure release information holding unit 48 System controller

Claims (4)

A sampling flow path having a needle for inhaling the sample from a sample container containing the sample at one end and a sample loop for holding the inhaled sample through the needle;
A needle drive mechanism for moving the needle;
An injection port connected to the sampling flow path by inserting the needle tip;
When the tip of the needle is inserted into the injection port, the sampling flow path is not interposed between the liquid feeding device for feeding the mobile phase and the analysis column for separating the sample for each component. A switching mechanism for switching the system including the sampling flow path to an open system or a closed system in a state where the sampling flow path is not interposed between the liquid delivery device and the analysis column, while switching to any state of the state,
By controlling the operation of the needle driving mechanism and the switching mechanism, the needle tip is withdrawn from the injection port after the sampling flow path is interposed between the liquid feeding device and the analysis column. The pressure in the sampling channel is switched by switching the switching mechanism so that the sampling channel is not interposed between the liquid delivery device and the analysis column, and the system including the sampling channel is an open system. A pressure release operation unit that executes a pressure release operation that waits until the pressure returns to atmospheric pressure,
A pressure release time setting unit that sets an execution time of the pressure release operation based on a liquid supply pressure of the liquid supply device immediately before the pressure release operation is performed,
The autosampler configured to perform the pressure release operation for a time set by the pressure release time setting unit . A pressure release time information holding unit for holding pressure release time information defined in advance with respect to a relationship between the liquid feeding pressure and the execution time of the pressure release operation;
The pressure release time setting unit captures the liquid supply pressure of the liquid supply device before the pressure release operation is performed, and the pressure release held by the received liquid supply pressure and the pressure release time information holding unit The autosampler according to claim 1 , wherein an execution time of the pressure release operation is set based on time information. A control unit for controlling the needle driving mechanism and the switching mechanism;
A system controller that performs information communication with the control unit,
Autosampler of claim 1 or 2, wherein the pressure release time setting section is provided in the system controller. The switching mechanism is
A sampling port to which the other end of the sampling channel is connected, a syringe port to which a syringe pump for sucking and discharging liquid is connected, the injection port, and a mobile phase supply port to which a liquid feeding device for supplying a mobile phase is connected An analysis port to which a flow path leading to the analysis column is connected, and a loading mode for connecting between the sampling port and the syringe port and connecting between the mobile phase supply port and the analysis port; A first switching valve that connects between the sampling port and the mobile phase supply port and switches between an injection mode that connects between the injection port and the analysis port;
A second system that switches the system including the sampling channel configured when the tip of the needle is inserted into the injection port and the first switching valve is in the loading mode to either an open system or a closed system. The autosampler according to any one of claims 1 to 3 , further comprising a switching valve.

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