JP4470797B2 - Automatic sample introduction device - Google Patents

Description

  The present invention relates to an automatic sample introduction device (auto sampler) for introducing a sample into an analyzer such as a liquid chromatograph.

  The automatic sample introduction device is a device for sucking a sample solution from sample bottles arranged in a sample rack and injecting the sample solution into a flow path of the analyzer. As a sample injection method in such an automatic sample introduction apparatus, a total injection method for injecting the entire amount of the aspirated sample liquid into the flow channel, and a partial injection method for injecting a part of the aspirated sample liquid into the flow channel (See Non-Patent Document 1).

  In the total volume injection method, a sampling loop with a sampling needle at the tip is connected to a metering pump to suck a predetermined amount of sample liquid, and then the sampling needle is inserted into an injection port (injection port) connected upstream such as a column. In addition, by switching the flow path and connecting the sampling loop downstream of the liquid chromatograph mobile phase pump, etc., the entire amount of the sample liquid filled in the sampling loop is supplied to the injection port. To be injected. On the other hand, in the partial injection method, a sample liquid is sucked by a sampling needle provided in a flow channel independent of a flow channel (mobile phase flow channel) through which a mobile phase flows, and a part thereof is injected into an injection port. .

  The above-mentioned total injection method has the advantages of low sample loss and excellent injection accuracy and injection linearity. However, because of its structure, it is suitable for sample handling such as pretreatment such as sample concentration, dilution, and mixing. Not. On the other hand, in the partial injection method, since the sampling needle is outside the mobile phase flow path, the needle can be moved and the sample can be measured even during analysis. Although it is suitable for parallel control analysis in which samples are injected into a plurality of systems provided, there is a problem that measurement accuracy is inferior to that of the full-volume injection method due to many operation steps during sample weighing.

Shimadzu Corporation, "HPLC / LCtalk46 TEC Autosampler Injection Method (Comparison between Full Volume Injection Method and Partial Injection Method)", [online], [Search April 4, 2005], Internet <URL: http : //www.an.shimadzu.co.jp/support/lib/lctalk/46/46tec.htm>

  Thus, since these two injection methods have advantages and disadvantages, it is desirable to use them according to the purpose of analysis. However, in general, an automatic sample introduction apparatus has a greatly different apparatus configuration depending on the sample injection method, and is controlled by a control program corresponding to each injection method. Therefore, only one type of injection method is used in one apparatus. I couldn't.

  Therefore, the problem to be solved by the present invention is to provide an automatic sample introduction device capable of injecting a sample by a plurality of methods with one device.

An automatic sample introduction device according to the present invention made to solve the above problems is an automatic sample introduction device for automatically supplying a sample to an analysis device.
a) Sample capable of switching the flow path configuration corresponding to two or more sample injection methods among all injection methods, partial injection methods, and injection methods capable of injecting the entire amount and cleaning the sampling loop with a plurality of cleaning liquids An introduction,
b) channel configuration determination means for determining the current channel configuration of the sample introduction unit;
c) Based on an injection operation control subroutine that describes the operation content of each step related to sample injection, and an injection operation control routine that describes the entire sample injection operation by a combination of the injection operation control subroutine, the sample introduction unit is Injection operation control means for controlling;
In the injection operation control means, the injection operation control routine appropriately calls an injection operation control subroutine corresponding to the current flow path configuration of the sample introduction unit determined by the flow path configuration determination means, It is characterized in that an appropriate injection operation is controlled according to the flow path configuration.

  The flow path configuration determining means includes a sensor or the like for detecting the current flow path configuration in the sample introduction unit, and automatically determines the current flow path configuration based on a detection signal from the sensor or the like. Alternatively, the current flow path configuration may be determined based on the information input to the operator regarding the current flow path configuration. In the latter case, as a method for the operator to input information on the current flow path configuration, for example, a method of operating a mechanical switch provided in the sample introduction unit or a main body of the automatic sample introduction device A method using a console provided, an input unit of a personal computer connected to an automatic sample introduction device, or the like can be used.

  According to the automatic sample introduction device of the present invention having the above configuration, the flow channel configuration of the sample introduction unit is changed according to the analysis purpose and the like, and an appropriate subroutine corresponding to the current flow channel configuration of the sample introduction unit is combined. Thus, since a series of sample injection operations can be controlled, it is possible to inject samples by a plurality of methods with one apparatus.

Hereinafter, the best mode for carrying out the present invention will be described using embodiments.
[Example]
1 to 3 show a schematic configuration of the automatic sample introduction device of the present embodiment. The automatic sample introduction device of the present embodiment introduces a sample into the liquid chromatograph analyzer, and includes a sample introduction unit 10 that performs a sample introduction operation, a control unit 20 that controls the sample introduction unit 10, and The console 30 includes an operation key for inputting a flow path configuration of the sample introduction unit 10 and other conditions to the control unit 20 and a display for displaying predetermined information.

  The control unit 20 controls each component of the sample introduction unit 10 based on a predetermined program, and is configured by a microcomputer including a CPU and a storage device that stores firmware including the program.

  The sample introduction unit 10 includes a sample rack 11 for arranging vials containing sample liquids, a metering pump 12 for measuring sample liquids and performing suction and discharge operations, and sampling for sucking the sample liquids and the like. A needle 13, a sampling loop 14 for holding the sucked sample liquid, an injection port 15 for introducing the sample liquid into the mobile phase, and a cleaning port 16 for cleaning the sampling needle 13, the sampling loop 14, and the like are provided. Of these, those other than the sample rack 11 are connected to one of the two rotary valves 17 and 18 by a detachable tube-like pipe made of synthetic resin.

  The rotary valves 17 and 18 include a drive source such as a stepping motor, and can switch the communication state of each flow path connected to the valve by rotating a rotating member (rotor) in the valve. In the automatic sample introduction apparatus of this embodiment, of the two rotary valves, the high pressure flow path side valve (high pressure valve) 17 is a 6-port 2-position valve, and the low pressure flow path side valve (low pressure valve) 18 is a rotor. It can be used as both a 6-port 2-position valve and a 6-position valve by exchanging the components.

  Further, in the liquid chromatograph analyzing apparatus of the present embodiment, in addition to the flow path including the rotary valves 17 and 18, the outside of the needle comprising a cleaning liquid container, a liquid feeding pump, a needle cleaning port, and a pipe connecting them. A cleaning channel 19 is provided.

  The automatic sample introduction apparatus of the present embodiment does not change the components of the sample introduction unit 10 as described above, but only changes the piping connection between the components and replaces some parts of the rotary valve. A flow path configuration corresponding to the three sample injection methods of “total injection method”, “partial injection method”, and “injection method capable of cleaning the sampling loop with a plurality of cleaning solutions”. It is. Hereinafter, the flow path configuration and operation in each injection method will be described.

1. Total Volume Injection Method FIG. 1 is a schematic flow path configuration diagram when using the total volume injection method. Each of the high-pressure valve 17 and the low-pressure valve 18 is a 6-port 2-position valve, and the communication state between adjacent ports can be switched by rotating the rotor.

  A port a of the high-pressure valve 17 has a liquid feeding pump 41 connected to the mobile phase solution reservoir 40, a port b has a sampling loop 14 with a sampling needle 13, a port c has a metering pump 12, and a port d Is connected to the port g of the low-pressure valve 18, the port e is connected to the injection port 15, and the port f is connected to the column. The port d of the high pressure valve 17 is stored in the port g of the low pressure valve 18, the metering pump 12 is stored in the port i, the cleaning port 16 is stored in the port j, the drain is stored in the port k, and the cleaning liquid is stored in the port l. Each reservoir 50 is connected.

  In the flow path configuration as described above, when the sample is injected, first, the high pressure valve 17 and the low pressure valve 18 are set to the state shown in FIG. 1A (load state). Thereby, the sampling loop 14 and the metering pump 12 are connected via the high pressure valve 17 and the low pressure valve 18. Subsequently, the sampling needle 13 is moved to the position of a predetermined sample bottle on the sample rack 11, and a predetermined amount of sample liquid is sucked by the metering pump 12 and filled in the sampling loop 14.

  Next, the sampling needle 13 is moved to the injection port 15, and the high pressure valve 17 is brought into the state shown in FIG. 1B (injection state). As a result, a flow path is formed in which the mobile phase fed by the liquid feed pump 41 reaches the column via the sampling loop 14, and the sample filled in the sampling loop 14 enters the column via the injection port 15. be introduced. As described above, when the sample is injected by this method, the entire amount of the sample sucked by the needle 13 is introduced into the column, so that high measurement accuracy can be obtained.

2. Injection method capable of injecting the entire volume and washing the sampling loop with multiple cleaning solutions When performing pretreatment such as dilution before injecting the sample into the mobile phase, these samples can be handled by handling the sample solution and the diluted solution. When mixing is performed, it is necessary to clean the inside of the sampling needle 13 and the inside of the sampling loop 14. However, in the case of the total injection method as described above, when the inside of the needle 13 is cleaned with the cleaning liquid, the inside of the sampling loop 14 is filled with the cleaning liquid, and a part of this cleaning liquid is injected into the mobile phase flow path. There is a fear. Moreover, when the compositions of the cleaning liquid and the mobile phase are different, it is difficult to sufficiently clean the inside of the needle 13. In view of this, a sample pretreatment by enabling the sampling needle 13 and the sampling loop 14 to be cleaned with a plurality of liquids in the full volume injection method is shown below.

  An outline of the flow path configuration in this method is shown in FIG. In this system, the low-pressure valve 18 is a 6-position valve that can selectively communicate the common port m with any of the other ports g to l by rotation of the rotor.

  The port a of the high-pressure valve 17 has a liquid feeding pump 41 connected to the mobile phase solution reservoir 40, the port b has a sampling loop 14 having the sampling needle 13, and the port c has a port k of the low-pressure valve 18. The injection port 15 is connected to the port e, the column is connected to the port f, and the port d is closed. Further, the reservoir 50 storing the cleaning liquid A is stored in the port g of the low pressure valve 18, the reservoir 60 storing another type of cleaning liquid B is stored in the port h, the metering pump 12 is stored in the port i, and the cleaning is performed in the port j. The port 16 is connected to the port k, the port c of the high-pressure valve 17, and the port l is connected to the mobile phase solution reservoir 40. A plurality of sample liquids and The mobile phase solution can be sucked.

  In the flow path configuration as described above, the operation in the case of performing pretreatment by dilution of the sample and introduction into the mobile phase will be described. First, a sample bottle containing a sample solution in advance on the sample rack 11, a reagent bottle containing a diluent for diluting the sample solution, and a mixing bottle used when mixing the sample solution and the diluent (Empty bottles) are arranged as many as the number of samples to be analyzed. Subsequently, the high pressure valve 17 is set to the load state shown in FIG. 2A, and the common port m and the port k of the low pressure valve 18 are communicated. Thereby, the sampling loop 14 and the metering pump 12 are connected via the high pressure valve 17 and the low pressure valve 18. In this state, the sampling needle 13 is inserted into the sample bottle, and a predetermined amount of sample liquid is sucked. Then, the needle 13 is moved to the position of the predetermined mixing bottle, and the sucked sample liquid is discharged to the mixing bottle.

  Thereafter, the common port m of the low-pressure valve 18 is communicated with the port g, and the cleaning liquid A is sucked into the metering pump 12. Subsequently, after moving the needle 13 to the cleaning port 16, the common port m and the port k of the low-pressure valve 18 are communicated, and the suctioned cleaning liquid A is discharged to the cleaning port 16 via the sampling loop 14 and the sampling needle 13. To wash. Similarly, the mobile phase solution stored in the mobile phase solution reservoir 40 is sucked into the metering pump 12 and discharged from the needle 13, thereby replacing the needle 13 and the sampling loop 14 with the mobile phase solution, and then sampling. The needle 13 is moved to the washing port of the needle outside washing channel 19 to wash the outside of the needle 13.

  Similarly to the above, a predetermined amount of the diluted solution is sucked from the reagent bottle and discharged to the mixing bottle, and the sample liquid and the diluted solution in the mixed bottle are sucked and discharged several times by the sampling needle 13 to mix them. . When the mixed sample is introduced into the mobile phase flow path, the mixed solution is sucked from the mixing bottle, the sampling needle 13 is moved to the injection port 15, and the high-pressure valve 17 is brought into the injection state shown in FIG. To do. As a result, a flow path is formed in which the mobile phase fed by the liquid feed pump 41 reaches the column via the sampling loop 14, and the pretreated sample filled in the sampling loop 14 passes through the injection port 15. Introduced into the column.

  As described above, according to this method, the sampling needle 13 and the sampling loop 14 can be cleaned with a plurality of cleaning liquids, and the inside of the flow path can be replaced with a solution having the same composition as the mobile phase. It is possible to inject the entire amount of the sample even in the analysis that needs to be performed.

3. Partial Injection Method FIG. 3 shows an outline of the flow channel configuration when a sample is introduced by the partial injection method. In this configuration, unlike the above-described two systems, the needle 13 is configured independently from the mobile phase flow path. Both the high-pressure valve 17 and the low-pressure valve 18 are 6-port 2-position valves. A port a of the high-pressure valve 17 has a liquid feed pump 41 connected to the mobile phase solution reservoir 40, a port b has an upstream side of the sampling loop 14, a port c has a drain, and a port d has an injection port 15. , A downstream side of the sampling loop 14 is connected to the port e, and a column is connected to the port f. Further, the reservoir 50 storing the cleaning liquid is connected to the port h of the low-pressure valve 18, the metering pump 12 is connected to the port i, and the pipe including the sampling needle 13 is connected to the port j, and the other ports are closed. Has been.

  In introducing the sample liquid in the above-described flow path configuration, first, the high pressure valve 17 is set to the load state shown in FIG. 3A, and the low pressure valve 18 is set to the state where the ports i and j are communicated. . As a result, the sampling loop 14 becomes independent from the mobile phase flow path, and the sampling needle 13 and the metering pump 12 communicate with each other. In this state, the sampling needle 13 is inserted into the sample bottle, and the metering pump 12 sucks the sample solution. Subsequently, the needle 13 is inserted into the injection port 15 to fill the sampling loop 14 with a predetermined amount of sample. Next, the high-pressure valve 17 is switched to the injection state shown in FIG. Thereby, a flow path is formed in which the mobile phase fed by the liquid feed pump 41 reaches the column via the sampling loop 14, and the sample liquid filled in the sampling loop 14 is introduced into the column.

  As described above, the sample introduction unit 10 according to the automatic sample introduction device of the present embodiment can construct a plurality of flow path configurations corresponding to the different sample injection methods as described above in one device. It has become.

  Next, the configuration of firmware incorporated in the control unit 20 according to the automatic sample analyzer of the present embodiment will be described with reference to FIG. The firmware communicates with the kernel unit 100 responsible for basic functions such as initialization and IO access, an interrupt processing routine 110 for executing interrupt processing such as time measurement, and a personal computer connected to the main body of the automatic sample introduction apparatus. The communication control unit 120 for controlling, the console processing routine 130 for performing screen display processing, input processing, and the like on the console 30 provided in the apparatus main body, and the operation of the sample introduction unit 10 as described above are controlled. The sequence control unit 140 is provided.

  The sequence control unit 140 controls an injection operation control routine 141 and an injection operation control subroutine 142 for controlling the sample injection operation by the sample introduction unit 10 and temperature control of the sample rack 11 by a Peltier element (not shown). The temperature control routine 145 is incorporated.

  The injection operation control subroutine 142 describes the operation of each step relating to sample injection (needle movement, sample suction / discharge, switching of each valve, etc.). A plurality of different subroutines are provided. The injection operation control routine 141 describes the flow of the entire sample injection operation, and a command for reading out the subroutine 142 corresponding to the situation is described for each step of the injection operation. Therefore, by changing the combination of the subroutines 142 called in the injection operation control routine 141, different injection operations corresponding to the respective flow path configurations can be realized.

  The temperature adjustment control routine 145 controls the Peltier element based on the temperature of the sample rack 11 read by the temperature reading unit 147, and executes a predetermined process described in the error control routine 148 when an error occurs. To do.

  When the sample is introduced using the automatic sample introduction apparatus of the present embodiment, the pipe connection is changed or the rotary valve parts are changed according to the analysis purpose, etc. A corresponding flow channel configuration is constructed, and the flow channel configuration (or injection method) is input to the control unit 20 using the operation keys of the console 30 or the input unit of a personal computer connected to the automatic sample introduction device. In the control unit 20, a subroutine 142 corresponding to the input flow path configuration is appropriately called according to the injection operation control routine 141. The motor output unit 143 executes a predetermined operation by controlling the output to the motor provided in the drive unit for moving the rotary valves 17 and 18 and the needle 13 in accordance with the instruction described in the subroutine 142. To do. At this time, the current operation state of the rotary valve 17 and the needle 13 is detected by a sensor (not shown) provided in the sample introduction unit 10, and these operations are feedback-controlled based on the detection signal.

  As described above, the automatic sample introduction device according to the present embodiment enables a desired flow path configuration to be constructed by rearranging pipes and parts as necessary, and a series of firmware incorporated in the device by a combination of subroutines. By adopting a configuration that realizes the injection operation, it is possible to inject a sample by a plurality of methods with one apparatus.

The figure which shows the flow-path structure in the case of using the whole quantity injection | pouring method in the automatic sample introduction apparatus which concerns on one Example of this invention, (a) Load state (b) Injection state. The figure which shows the flow-path structure in the case of using the injection method which can inject | pour the whole quantity and can wash | clean a sampling loop with a some washing | cleaning liquid in the automatic sample introduction apparatus which concerns on the Example, (a) Load state (b) Injection Status. The figure which shows the flow-path structure in the case of using a partial injection system in the automatic sample introduction apparatus which concerns on the Example, (a) Load state (b) Injection state. The block diagram which shows the structure of the firmware in the automatic sample analyzer which concerns on the Example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... Sample introduction part 11 ... Sample rack 12 ... Metering pump 13 ... Sampling needle 14 ... Sampling loop 15 ... Injection port 16 ... Washing port 17 ... High pressure valve 18 ... Low pressure valve 19 ... Needle outer washing flow path 20 ... Control part 30 ... Console 40 ... Mobile phase solution reservoir 41 ... Feed pump 50, 60 ... Cleaning liquid reservoir 100 ... Kernel unit 110 ... Interrupt processing routine 120 ... Communication control unit 130 ... Console processing routine 140 ... Sequence control unit 141 ... Injection operation control Routine 142 ... Injection operation control subroutine 143 ... Motor output unit 144 ... Sensor reading unit 145 ... Temperature control routine 146 ... Peltier control unit 147 ... Temperature reading unit 148 ... Error control routine

Claims (1)

In an automatic sample introduction device for automatically supplying a sample to an analyzer,
a) Sample capable of switching the flow path configuration corresponding to two or more sample injection methods among all injection methods, partial injection methods, and injection methods capable of injecting the entire amount and cleaning the sampling loop with a plurality of cleaning liquids An introduction,
b) channel configuration determination means for determining the current channel configuration of the sample introduction unit;
c) Based on an injection operation control subroutine that describes the operation content of each step related to sample injection, and an injection operation control routine that describes the entire sample injection operation by a combination of the injection operation control subroutine, the sample introduction unit is Injection operation control means for controlling;
In the injection operation control means, the injection operation control routine appropriately calls an injection operation control subroutine corresponding to the current flow path configuration of the sample introduction unit determined by the flow path configuration determination means, An automatic sample introduction device that controls an appropriate injection operation according to a flow path configuration.

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