JP4597841B2 - Feed pump - Google Patents

Description

  The present apparatus relates to a liquid feed pump, and more particularly, to a liquid feed pump used in an apparatus for analyzing a liquid sample.

  An example of a liquid sample analyzer is a liquid chromatograph mass spectrometer (LC / MS) in which a liquid chromatograph (LC) and a mass spectrometer (MS) are connected.

  In this liquid chromatograph mass spectrometer, peak parking is used in order to acquire a lot of sample structure information.

  This peak parking means that when the sample peak elutes from the separation column and is detected by MS, the LC flow rate is instantaneously lowered, and at a normal flow rate, the sample peak eluting over about 1 minute takes longer. The elution is continued for a period of time.

This is because it is possible to perform more MS ⁿ analysis of the sample components, an effective technique In structural analysis of unknown compounds.

  In order to perform this peak parking, the flow rate must be reduced immediately after the peak is detected. Therefore, for example, Patent Document 1 describes a split-type technique.

  That is, in the split method, two types of lengths of resistance piping for controlling the flow rate of the pump are prepared, and the flow rate is changed by switching them according to the flow rate.

  On the other hand, there is a technique described in Patent Document 2 as a splitless liquid feed pump. In the technique described in Patent Document 2, the first plunger and the second plunger are connected in series via a check valve, and bubbles are discharged. It is filled and fed at a low flow rate by the second plunger to perform steady operation.

  In this splitless type pump, even if the pumping speed of the pumping plunger is lowered during pumping, the flow rate does not drop immediately due to the pressure remaining in the pump generated by the previous pumping, Poor follow-up of flow rate to pump operation.

  In particular, in a low flow rate liquid feed pump, the effect of the remaining pump pressure is large, and it is impossible to execute peak parking.

  For this reason, in order to perform peak parking with a splitless type liquid feed pump, as described in Patent Document 3, in addition to the liquid feed pump, a second dedicated to low flow rate liquid feed such as a syringe pump is used. A liquid pump is required.

US Pat. No. 6,315,905 B1 JP 2004-137974 A US Patent 6858435B2 Specification

  However, since the split flow system has a configuration in which the flow rate of the pump is changed by the resistance piping, the pressure applied to the resistance piping fluctuates due to clogging of the thin resistance piping, and even when the same resistance piping is used, the flow rate Reproducibility and flow accuracy were low.

  In addition, in the case of the splitless system, as described above, in addition to the first liquid feed pump, a second liquid feed pump dedicated to low flow rate liquid supply is necessary, which increases the price and increases the size of the apparatus. There is a problem.

  An object of the present invention relates to a liquid feed pump capable of performing a peak parking operation with a single pump while being a splitless system with high flow accuracy.

  In the low flow rate liquid feeding pump of the present invention, two plungers having different uses for pressurization and stable liquid feeding are connected in series, and switching means for opening and closing between these plungers, and operations of the two plungers and the switching means are operated. Control means for controlling.

  Then, the control means opens the switching means during liquid feeding by the stable liquid feeding plunger to lower the liquid feeding pressure, then closes the switching means and repressurizes to the target pressure value by the pressure plunger.

  Further, in the low flow rate liquid feeding pump of the present invention, the control means sets the flow path of the switching means, feeds the liquid from the discharge portion of the stable liquid feeding plunger, and according to the flow rate lowering command, After switching the flow path, lowering the feeding pressure of the plunger for stable liquid feeding and operating the pressurizing plunger so that the discharge pressure of the plunger for stable liquid feeding becomes the target pressure, the flow of the switching means It switches to a path | route, and the plunger for stable liquid feeding is operated so that it may liquid-feed with the flow volume value of the said flow volume fall command.

  Further, the low flow rate liquid feed pump of the present invention includes a pressure sensor for detecting the liquid feed pressure from the discharge portion of the stable liquid feed plunger, and the control means switches the flow path of the switching means according to the flow rate lowering command. In addition, the liquid feeding pressure detected by the pressure sensor is stored, and the stable liquid feeding plunger is operated so as to feed the liquid at the flow rate value of the flow rate lowering command. Then, in accordance with the flow rate recovery command that is output thereafter, the flow path of the switching means is switched, and the pressurizing plunger is operated so that the discharge pressure of the stable liquid supply plunger becomes the stored liquid supply pressure. Thereafter, when the stored liquid supply pressure is reached, the flow is switched to the flow path of the switching means so that the discharge flow rate of the plunger for stable liquid supply becomes the flow rate when the flow rate lowering command is output.

  The liquid feeding pump is used in a liquid chromatograph apparatus. When the detector of the liquid chromatograph is a mass analyzer, the flow rate reduction command is output from the mass analyzer to the control means when the mass analyzer detects a specific ion, and the flow rate recovery command is When the analyzer finishes detecting a specific ion, it is output to the control means.

  According to the present invention, it is possible to realize a liquid feed pump capable of performing a peak parking operation with a single pump while being a splitless system with high flow accuracy.

  In addition, according to the present invention, the flow rate can be changed instantaneously with the liquid feed pump alone.

  Moreover, peak parking is possible in the liquid chromatograph using the liquid feed pump of the present invention.

Embodiments of the present invention will be described below with reference to the accompanying drawings.
FIG. 1 is a schematic configuration diagram when a liquid feed pump according to an embodiment of the present invention is applied to a liquid chromatograph mass spectrometer.

  In FIG. 1, a low flow rate liquid feeding pump 4 includes a pressurizing plunger 1, a stable liquid feeding plunger 2, a switching valve 3 for switching connection and separation between these plungers 1 and 2, and a stable liquid feeding plunger 2. And a pressure sensor 17 for detecting the liquid feeding pressure. This pump 4 is a pump for feeding the liquid 5.

  In addition, the liquid chromatograph mass spectrometer includes a pump 8 having a function of feeding a plurality of solvents 6 and 7 while mixing them while changing their composition over time, and a mixed solution sent by the pump 8. The two loops 9 and 10 are alternately filled with a 10-way valve 11 connected to the low-flow rate pump 4 and pumped out by the low-flow rate pump 4.

The liquid chromatograph mass spectrometer is connected to a 10-way valve 11, an injector 12 for introducing a sample into the liquid flow path, a column 13 for separating the sample from the liquid from the injector 12, and the separation column 13. A mass spectrometer (MS) 14 capable of performing MS ¹ and MS ⁿ analysis by ionizing the separated sample.

  Further, the liquid chromatograph mass spectrometer includes a mass spectrometer 14, a pressure plunger 1, a stable liquid feeding plunger 2, a switching valve 3, a 10-way valve 11, and a controller 15 that controls the operation of the pump 8.

  The controller 5 is supplied with the detected pressure value of the pressure sensor 17 and the analysis output value of the mass spectrometer 14.

  The operator sets the flow rate and target pressure of the pump 4 and the flow rate and gradient program of the pump 8 in the controller 15 in advance.

  When the operator instructs the start of liquid feeding via a keyboard, a display screen, or the like, the pump 4 and the pump 8 start liquid feeding simultaneously. At the start of liquid feeding, the flow path of the switching valve 3 in the pump 4 is the dotted flow path of FIG. 1, the discharge part of the plunger 1 and the suction part of the plunger 2 are connected, and the suction part of the plunger 1 and the liquid 5 are connected. The flow path with the accommodated container is in a separated state.

  The pressurizing plunger 1 feeds and pressurizes the liquid at a flow rate as high as 50 times the set flow rate of the pump 4 until the target pressure set by the operator is reached. When the liquid supply pressure from the discharge portion of the plunger 2 reaches the target pressure, the switching valve 3 switches to the solid line flow path in FIG. 1, and the discharge portion of the plunger 1 and the suction portion of the plunger 2 are separated. The flow path between the suction portion and the container in which the liquid 5 is stored is connected, and the stable liquid feeding plunger 2 starts liquid feeding at the set flow rate. At this time, the pressurizing plunger 1 sucks the liquid 5 into the plunger 1.

  FIG. 2 shows the flow rate change with respect to the liquid feeding time when the liquid feeding is started by the stable liquid feeding plunger 2 at a set flow rate of 200 nL / min. The flow rate can reach the set flow rate of 200 nL / min in about 5 seconds from the start of liquid feeding by the sequence of performing stable liquid feeding after the pressure liquid feeding (0 to 5 seconds) of the above-described pressurizing plunger 1. .

  Next, when the operator instructs the start of analysis, the sample is introduced into the flow path by the injector 12, and at the same time, the pump 8 starts the gradient liquid feeding. The 10-way valve 11 switches the flow path indicated by the dotted line and the flow path indicated by the solid line in FIG. 1 at regular intervals, and separates the gradient solution sent by the pump 8 at a flow rate sent from the pump 4. Send to 13. The sample sent to the separation column 13 is separated for each component and sequentially mass separated by the MS 14.

  FIG. 3 shows a total ion chromatogram obtained by measuring a protein digest sample at 200 nL / min using the system according to the embodiment of the present invention without performing peak parking. Each peak in FIG. 3 shows a single peptide component.

Next, a case where peak parking is performed at 20 nL / min only for the elution time of peak A in order to perform MS ⁿ analysis in detail for the component of peak A in FIG. 3 will be described with reference to the flowchart in FIG. 4.

In step S1 of FIG. 4, in advance operator, in addition to the analysis conditions described above, the mass number of the target component A ions desired to MS ⁿ analysis in detail by the peak parking, the flow rate of 20 nL / min Peak Parking Set in controller 15.

  When the analysis is started, the controller 15 monitors ions detected by the MS 14 in step S2. When the mass spectrometer 14 detects ions of the target component A set by the operator (the mass spectrometer 14 outputs a flow rate reduction command to the controller 15), the controller 15 causes the MS 14 to convert the target component A in step S3. The liquid feeding pressure of the pump 4 at the time of detection is stored.

  At this time, since the pump 4 is executing the gradient liquid feeding made by the pump 8, the mixing ratio of the solvents 6 and 7 is different from that at the start of the liquid feeding. Accordingly, the liquid supply pressure is different from the target pressure at the start of liquid supply.

  Subsequently, in step S4, the controller 15 switches the valve 3 to the dotted line flow path of FIG. 1 and connects the flow paths of the plungers 1 and 2.

  Thereby, the liquid feeding pressure in the plunger 2 is released to the plunger 1, the liquid feeding pressure of the pump 4 becomes substantially equal to the atmospheric pressure, the flow rate of the pump 4 decreases to near 0 nL / min, and the liquid feeding is stopped. The execution of the gradient program of the pump 8 is temporarily stopped.

  The pump 8 that has suspended the gradient program continues to feed the pump 8 while maintaining the mixing ratio of the solvents 6 and 7 at that time.

  Next, in step S5, the controller 15 re-pressurizes the plunger 1 to start peak parking liquid supply from the liquid supply pressure of the pump 4 stored at the start of peak parking based on the flow ratio before and after peak parking. Calculate the pressure.

  For example, when peak parking is performed by reducing the flow rate (flow rate value of the flow rate lowering command) to 20 nL / min during liquid feeding at a flow rate of steady liquid feeding of 200 nL / min and a liquid feeding pressure of 8.0 MPa, The target pressure is 0.8 MPa, which is 1/10 of 8.0 MPa.

  Then, repressurization is performed by the plunger 1 in step S6 so as to achieve the calculated target pressure. When the target pressure is reached, in step S7, the controller 15 switches the valve 3 to the solid line flow path of FIG. 1 and separates the flow paths of the plungers 1 and 2.

  The plunger 2 feeds liquid at a flow rate of 20 nL / min during peak parking.

  During peak parking, a mixed solvent having the same composition is sent to the column 13 at an extremely low flow rate. The peak of the target component A that the MS 14 starts to detect at the start of peak parking is maintained for about 10 minutes.

  In peak parking at a flow rate of 20 nL / min, it is maintained for about 10 minutes. However, in the case of normal liquid feeding of 200 nL / min instead of peak parking, elution is completed in about 1 minute.

  When the target component is completely eluted, the set ions are not detected by the MS 14 (a flow rate recovery command is output to the controller 15). At this time, in step S8, the controller 15 switches the valve 3 to the dotted line flow path of FIG. 1 and connects the flow paths of the plungers 1 and 2.

  Thereby, the pressure of the plunger 2 is released to the plunger 1 and the liquid feeding of the pump 4 is stopped. At the same time, the controller 15 resumes the gradient program of the pump 8.

  Next, in step S <b> 9, the controller 15 sets the liquid feeding pressure 8.0 MPa before peak parking stored at the start of peak parking as the target pressure, and repressurizes with the plunger 1.

  When the target pressure is reached, the controller 15 switches the valve 3 to the solid line flow path of FIG. 1 and separates the flow paths of the plungers 1 and 2 in step S10. Then, the plunger 2 starts liquid feeding at a normal flow rate of 200 nL / min before peak parking. In this way, peak parking ends.

  FIG. 5 is a total ion chromatogram obtained by an embodiment of the present invention. The total ion chromatogram shown in FIG. 5 shows the result of peak parking at a flow rate of 20 nL / min for the peak of A in the same sample as the total ion chromatogram shown in FIG.

  As described above, in the present invention, the pressurizing plunger 1 and the stable liquid feeding plunger 2 of the low flow rate liquid feeding pump 4 are connected in series via the flow path switching valve 3, and this flow path switching valve is connected. 3, the pressure plunger 1 and the stable liquid feeding plunger 2 are connected and separated, and the liquid feeding pressure is controlled to perform peak parking.

  Therefore, according to the present invention, it is possible to execute the peak parking operation with the single pump 4 while using the splitless method with high flow accuracy.

  In addition, although the example mentioned above is an example at the time of applying this invention to a liquid chromatograph mass spectrometer, not only a liquid chromatograph mass spectrometer but also a peak parking, for example, a liquid using a UV detector The present invention can also be applied to a liquid feed pump used in a liquid sample analyzer such as a chromatograph.

It is a schematic block diagram at the time of applying the liquid feeding pump which is one Embodiment of this invention to a liquid chromatograph mass spectrometer. It is a figure which shows the flow volume change with respect to liquid feeding time when liquid feeding is started with the plunger for stable liquid feeding. It is a graph which shows the total ion chromatogram of the protein digest sample when not performing peak parking. 5 is an operation flowchart of peak parking according to an embodiment of the present invention. It is a graph which shows the total ion chromatogram of the protein digest sample when peak parking is performed by one Embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Plunger for pressurization 2 Plunger for stable liquid feeding 3 Flow path switching valve 4 Low flow rate liquid feeding pump 5 Solvent for low flow rate liquid feeding pump 6, 7 Solvent for gradient pump 8 Gradient pump 9, 10 10-way valve loop 11 10-way valve 12 Injector 13 Separation column 14 Mass spectrometer 15 Controller 17 Pressure sensor

Claims (7)

Low flow rate having two plungers having different uses for pressurization and stable liquid feeding connected in series, switching means for opening and closing between these plungers, and control means for controlling the operation of the two plungers and the switching means In the liquid feed pump,
The control means opens the switching means to lower the liquid feeding pressure during liquid feeding by the stable liquid feeding plunger, then closes the switching means again, and re-applies to the target pressure value by the pressure plunger. A liquid feed pump characterized by changing the flow rate by applying pressure. In a liquid feed pump that delivers liquid at a low flow rate,
A first plunger for pressurization;
A second plunger for stable liquid feeding;
A first flow path for connecting the flow path of the liquid to be fed and the suction section of the first plunger, and separating the discharge section of the first plunger and the suction section of the second plunger; A switching valve that separates the flow path of the liquid to be performed and the suction part of the first plunger and switches the second flow path that connects the discharge part of the first plunger and the suction part of the second plunger; ,
A control unit for controlling operations of the first plunger, the second plunger, and the switching valve;
A liquid feed pump comprising: In the liquid feeding pump according to claim 2,
The control unit sets the switching valve to the first flow path, sends liquid from the discharge section of the second plunger, and switches the switching valve to the first flow path according to a flow rate lowering command. Then, after lowering the liquid feeding pressure of the second plunger and operating the first plunger so that the discharge pressure of the second plunger becomes the target pressure, the switching valve is switched to the second flow path, A liquid feed pump, wherein the second plunger is operated so as to feed liquid at a flow rate value of the flow rate reduction command. In the liquid feeding pump according to claim 3,
A pressure sensor for detecting a liquid feeding pressure from the discharge portion of the second plunger, and the control unit detects the pressure by the pressure sensor before switching the switching valve to the first flow path in accordance with the flow rate lowering command. The liquid supply pressure is stored, and the switching valve is set to the second flow path in accordance with the flow rate recovery command output after the second plunger is operated so that the liquid is supplied at the flow rate value of the flow rate reduction command. When the first plunger is operated so that the discharge pressure of the second plunger becomes the memorized liquid feeding pressure, and when the memorized liquid feeding pressure is reached, the switching valve is set to the first flow path. A liquid feed pump that switches and operates the second plunger so that the discharge flow rate of the second plunger becomes the flow rate when the flow rate lowering command is output. Connected to the first liquid feeding pump, the second liquid feeding pump for mixing and feeding a plurality of solvents having different compositions while changing the mixing ratio, and the first liquid feeding pump and the second liquid feeding pump. Multi-way switching means, a sample introduction part for introducing a sample into the liquid from the multi-way flow switching means , a separation column for separating the mixed sample supplied from the sample introduction part for each component, and the separation column A liquid chromatograph apparatus comprising: a detector that detects a sample component separated by the above; and a controller that controls the operation of the first and second liquid feeding pumps, the multi-way flow switching means, the sample introduction unit, and the detector. In
The first liquid feed pump is
A first plunger for pressurization;
A second plunger for stable liquid feeding;
A first flow path for connecting the flow path of the liquid to be fed and the suction section of the first plunger, and separating the discharge section of the first plunger and the suction section of the second plunger; A switching valve that separates the flow path of the liquid to be performed and the suction part of the first plunger and switches the second flow path that connects the discharge part of the first plunger and the suction part of the second plunger ; ,
The liquid chromatograph is characterized in that the controller controls operations of the first plunger, the second plunger, and the switching valve . The liquid chromatograph apparatus according to claim 5, wherein
The first liquid feeding pump includes a pressure sensor that detects a liquid feeding pressure from the discharge portion of the second plunger, and the control unit sets the switching valve as a first flow path, Liquid is fed from the discharge part of the plunger, and the liquid feeding pressure is stored as detected by the pressure sensor in accordance with the flow rate lowering command. Then, the switching valve is switched to the first flow path and the second plunger is fed. After the hydraulic pressure is lowered and the first plunger is operated so that the discharge pressure of the second plunger becomes the target pressure, the switching valve is switched to the second flow path, and the flow rate value of the flow rate reduction command is set. The second plunger is operated so that the liquid is fed, and the switching valve is switched to the second flow path according to the flow rate recovery command that is output thereafter, and the discharge pressure of the second plunger is stored in the memory. When the first plunger is operated so as to become the liquid pressure and the stored liquid supply pressure is reached, the switching valve is switched to the first flow path, and the discharge flow rate of the second plunger is changed to the flow rate reduction command. A liquid chromatograph device, wherein the second plunger is operated so as to have a flow rate when is output. The liquid chromatograph apparatus according to claim 6, wherein
The detector is a mass analyzer, and the flow rate reduction command is output from the mass analyzer to the control unit when the mass analyzer detects a specific ion, and the flow rate recovery command is A liquid chromatograph apparatus, wherein the analyzer outputs the specific ions when the detection of specific ions is completed.

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