JP2011107004A - Mobile phase mixing apparatus for high performance liquid chromatograph and control method of the apparatus - Google Patents

Abstract

【Task】
Provided is a mobile phase mixing apparatus that does not require replacement of a liquid feed pump when installing a mobile phase mixing apparatus in HPLC, and that can perform recycling analysis even when a mobile phase mixing apparatus is used.
[Solution]
By connecting the mobile phase outlet of the mobile phase mixer for HPLC to the mobile phase inlet of the HPLC liquid pump and operating the HPLC liquid pump, the solvent sucked from the plurality of solvent suction pipes is mixed with a mixer. A mobile phase mixing device for HPLC that mixes to produce a mobile phase having a predetermined composition and supplies it to a liquid feed pump, wherein the electromagnetic valve open / close control in the electromagnetic valve open / close control device depends on the solvent composition of the mobile phase Set the open / close time ratio of each solenoid valve and repeat a certain amount of each solvent to the mixer by repeating the cycle that all the solenoid valves installed for each solvent that constitutes the mobile phase open and close once. While supplying, it controls so that the cycle number per unit time is proportional to the flow rate of a mobile phase.
[Selection] Figure 1

Description

  The present invention relates to a mobile phase mixing apparatus used in a high performance liquid chromatograph (hereinafter also referred to as HPLC) and a control method of the apparatus.

  The mobile phase used in HPLC analysis usually consists of a mixture of several solvents. The mobile phase is generally prepared in advance prior to analysis. The mobile phase is prepared by weighing and mixing each solvent. The amount of mobile phase required until the end of all analyzes differs depending on the analysis conditions, the number of repetitions, reproducibility, etc., and is not determined before analysis. Therefore, the mobile phase may become insufficient during the analysis, or the mobile phase may remain after the analysis is completed. If the mobile phase runs out during the analysis, the mobile phase must be prepared again, which is complicated. In addition, analysis results may not be stable due to mobile phase preparation errors. On the other hand, this problem does not occur if a sufficient amount of mobile phase is prepared for the amount of mobile phase required for analysis. However, the mobile phase remaining after the end of the analysis is often discarded, and the solvent constituting the mobile phase is wasted.

  In order to solve the above problem, a mobile phase mixing apparatus exemplified below is used. FIG. 8 is an explanatory diagram showing an example of the configuration of an HPLC having a conventional mobile phase mixing apparatus.

  First, the structure of HPLC which has the conventional mobile phase mixing apparatus for HPLC is demonstrated.

  In FIG. 8, 800 is a HPLC having a conventional HPLC mobile phase mixing apparatus, and a conventional HPLC mobile phase mixing apparatus is surrounded by a one-dot chain line.

  Reference numerals 801 a to c denote solvent storage tanks, and different solvents 803 a to 803 c are stored therein. Near the inner bottoms of the solvent storage tanks 801a to 801c, one ends of solvent suction pipes 805a to 805c are arranged, respectively, so that the solvents 803a to 803c inside can be sucked. The other ends of the solvent suction tubes 805a to 805c are connected to the inlets of the electromagnetic valves 807a to 807c, respectively. The solenoid valves 807a to 807c are connected to the solenoid valve opening / closing control device 811 by wiring 809, and the opening / closing of the solenoid valves is controlled by electric signals from the solenoid valve opening / closing control device 811. One ends of the pipes 813a to 813c are connected to the outlets of the solenoid valves 807a to 807c, respectively. The other ends of the pipes 813a to c are connected to the respective inlets of the flow path junction 815. The flow path merging section 815 is a member that joins the pipes 813a to 813c and joins the pipe 817, and uses a four-way joint or the like. The outlet of the flow path junction 815 is connected to one end of the pipe 817. The other end of the pipe 817 is connected to the inlet (suction side) of the liquid feed pump 823 constituting the HPLC, and the outlet (discharge side) of the liquid feed pump 823 is connected to one end of the pipe 825. The liquid feeding pump 823 is connected to the electromagnetic valve opening / closing control device 811 by a wiring 809, and the operating state of the liquid feeding pump 823 is output to the electromagnetic valve opening / closing control device 811. The other end of the pipe 825 is connected to the inlet of the mixer 827.

  The mixer 827 usually has an actual volume of several mL, where each of the solvents 803a-c is temporarily retained and mixed. As the mixer 827, a stainless steel pressure-resistant container provided with a solvent inlet and a solvent outlet is filled with a large number of glass beads (spherical) having a diameter of several millimeters, and the gap formed by the glass beads makes stainless steel. An example of the mixer is that a complicated flow path is formed in a pressure-resistant container. In this mixer, the solvent flowing in from the solvent inlet moves through a complicated flow path formed by glass beads filled in the pressure resistant container toward the solvent outlet. Since the actual capacity of the mixer is much larger than the capacity of the pipe, each solvent that continuously flows into the mixer is mixed in the mixer. Such a mixer needs to be mixed while pumping each solvent into the complex flow path by the liquid feed pump 823, and therefore, it is interposed on the downstream side (discharge port side) of the pump as shown in FIG. .

  The outlet of the mixer 827 and the inlet of the sample introduction device 831 are connected via a pipe 829, and the outlet of the sample introduction apparatus 831 and the inlet of the column 835 are connected by a pipe 833. The outlet of the column 835 and the inlet of the detector 839 are connected by a pipe 837. One end of a pipe 841 is connected to the outlet of the detector 839, and the other end is inserted into the collection tank 847.

  Next, the case where HPLC analysis is performed using HPLC having a conventional mobile phase mixer for HPLC will be described.

  The respective solvents 803a to 803c constituting the mobile phase are sucked from the solvent suction pipes 805a to 805c by the liquid feed pump 823, respectively, and sent to the electromagnetic valves 807a to 807c. The electromagnetic valves 807a to 807c are connected to the electromagnetic valve opening / closing control device 811 via a wiring 809, and the opening / closing of the valves is controlled. When the electromagnetic valve 807a is open, the solvent 803a is sucked from the solvent suction pipe 805a by the liquid feed pump 823, and sent to the flow path junction 815 via the electromagnetic valve 807a and the pipe 813a. The solvent 803 a that has exited the flow path junction 815 reaches the liquid feed pump 823 via the pipe 817. Thereafter, the solvent 803 a is sent to the mixer 827 via the pipe 825.

  Even when the electromagnetic valve 807b or 807c is open, the solvents 803b and 803c are sent to the mixer 827 as described above.

  Each of the solvents 803a to 803c (hereinafter also simply referred to as a mobile phase) mixed by the mixer 827 is sent to the sample introduction device 831 via the pipe 829. The sample (containing a plurality of components) introduced from the sample introduction device 831 is sent to the column 835 through the pipe 833 together with the mobile phase.

  Each component in the sample is eluted from the column 835 at different rates due to the difference in partition coefficient between the mobile phase and the stationary phase of the packing material packed in the column 835. The mobile phase containing each component eluted according to the distribution coefficient exits the column 835 and is sent to the detector 839 via the pipe 837, where each component is detected. The mobile phase containing each component detected by the detector 839 is sent to the recovery tank 847 via the pipe 841, and the recovered liquid 845 is recovered here. The recovered liquid 845 is usually a waste liquid, or the eluted components are collected for each holding time by using a fraction collector (not shown).

  The solenoid valves 807a to 807c are controlled by the solenoid valve opening / closing control device 811 so that when one solenoid valve is open, the other two solenoid valves are closed. Only the solvent belonging to the flow path in which the electromagnetic valve is open is sucked from the solvent storage tank by the liquid feeding pump 823. Open / close control of each solenoid valve is performed in units of time. For example, when preparing a mobile phase in which the mixing ratio (volume) of the solvents 803a / 803b / 803c is 5/2/1, each of the solenoid valves 807a to 807c has the solenoid valve 807a set according to the setting of the solenoid valve opening / closing control device 811. The cycle is opened for 5 unit times, then the solenoid valve 807b is opened for 2 unit hours, and then the solenoid valve 807c is opened for 1 unit time.

  However, in the plunger type pump generally used for HPLC, soaking of the solvent from the pump inlet side and discharging of the solvent to the pump outlet side are alternately repeated, so-called pulsating flow is generated. Increasing the number of plungers tends to eliminate this pulsating flow, but it is difficult to eliminate it completely. If the solenoid valve is opened while the liquid feed pump is performing a suction operation, the solvent is sucked from the solvent storage tank. On the other hand, the solvent is not sucked even if the electromagnetic valve is opened while the liquid feed pump is performing the discharge operation. Unless the timing of opening and closing of the solenoid valve is matched with the suction-discharge cycle of the liquid feed pump, the amount of each solvent sucked from the solvent storage tank varies from time to time. Therefore, the solvent composition of the prepared mobile phase is not constant (Patent Document 1). Therefore, the conventional mobile phase mixing apparatus is designed integrally with the liquid feed pump. Therefore, when a mobile phase mixing apparatus is incorporated in an HPLC other than the HPLC designed for the above purpose, it is necessary to replace the liquid feeding pump, which increases the price.

  Recycle analysis using HPLC is widely used in the fields of organic purification and analytical chemistry because sample components that are difficult to isolate can be accurately isolated. However, when the above mobile phase mixing apparatus is used, the recycling analysis cannot be performed for the reason described below.

  In FIG. 9, 900 is a recycle HPLC having a conventional mobile phase mixing apparatus. 901a to 901c are solvent storage tanks, and different solvents 903a to 903c are stored in the respective tanks. Near the inner bottoms of the solvent storage tanks 901a to 901c, one ends of solvent suction pipes 905a to 905c are arranged, respectively, so that the internal solvents 903a to 903c can be sucked. The other ends of the solvent suction tubes 905a to 905c are connected to the inlets of the electromagnetic valves 907a to 907c, respectively. The solenoid valves 907a to 907c are connected to the solenoid valve opening / closing control device 911 by wiring 909, and the opening / closing of each solenoid valve is controlled by an electrical signal from the solenoid valve opening / closing control device 911. One ends of the pipes 913a to 913c are connected to the outlets of the electromagnetic valves 907a to 907c. The other ends of the pipes 913a to 913c are connected to the respective inlets of the flow path junction 915. The outlet of the flow path junction 915 is connected to one end of the pipe 917. The other end of the pipe 917 is connected to the port 919a of the recycle switching valve 919. The port 919b of the recycle switching valve 919 and the inlet (suction side) of the liquid feed pump 923 are connected by a pipe 921, and the outlet (discharge side) of the liquid feed pump 923 and the inlet of the mixer 927 are connected by a pipe 925. The liquid feeding pump 923 is connected to the electromagnetic valve opening / closing control device 911 by a wiring 909, and the operating state of the liquid feeding pump 923 is output to the electromagnetic valve opening / closing control device 911. The mixer 927 has the same structure as the mixer 827 described above. The outlet of the mixer 927 and the inlet of the sample introduction device 931 are connected via a pipe 929, and the outlet of the sample introduction device 931 and the inlet of the column 935 are connected by a pipe 933. The outlet of the column 935 and the inlet of the detector 939 are connected by a pipe 937. One end of a pipe 941 is connected to the outlet of the detector 939, and the other end of the pipe 941 is connected to the port 919 c of the recycle switching valve 919. One end of a pipe 943 is connected to the port 919d of the recycle switching valve 919, and the other end is inserted into the collection tank 947.

  When the recycle switching valve 919 is allowed to flow between the ports 919a and 919b, between the ports 919b and 919c, and between the ports 919a and 919d, it cannot flow between the ports 919c and 919d. It is configured as follows. Further, when the flow between the ports 919a and 919b, the flow between the ports 919a and 919d, and the flow between the ports 919c and 919d are enabled, the flow between the ports 919b and 919c is not allowed to flow. ing.

  Next, a case where HPLC analysis is performed using a recycle HPLC having a conventional mobile phase mixer for HPLC will be described. This recycling analysis is not actually performed for the following reasons.

  The solvents 903a to 903c constituting the mobile phase are sucked from the solvent suction pipes 905a to 905c by the liquid feed pump 923, and sent to the electromagnetic valves 907a to 907c. The electromagnetic valves 907a to 907c are connected to the electromagnetic valve opening / closing control device 911 by wiring 909, and the opening / closing of the valves is controlled. When the electromagnetic valve 907a is open, the solvent 903a is sucked from the solvent suction pipe 905a by the liquid feed pump 923, and sent to the flow path junction 915 via the electromagnetic valve 907a and the pipe 913a. The solvent 903 a exiting the flow path junction 915 reaches the liquid feed pump 923 via the pipe 917, the recycle switching valve 919, and the pipe 921. At this time, the recycle switching valve 919 can flow between the flow paths of the ports 919a and 919b. Thereafter, the solvent 903 a is sent to the mixer 927 via the pipe 925. Even when the electromagnetic valve 907b or 907c is open, the solvents 903b and 903c are sent to the mixer 927 as described above.

  The method of electromagnetic valve opening / closing control by the electromagnetic valve opening / closing control device 911 is the same as in the case of FIG.

  Each of the solvents 903 a to 903 c (hereinafter also simply referred to as a mobile phase) mixed by the mixer 927 is sent to the sample introduction device 931 via the pipe 929. The sample (containing a plurality of components) introduced from the sample introduction device 931 is sent to the column 935 through the pipe 933 together with the mobile phase.

  Each component in the sample is eluted from the column 935 at different rates due to the difference in partition coefficient between the mobile phase and the stationary phase of the packing material packed in the column 935. The mobile phase containing each component eluted according to the distribution coefficient exits the column 935 and is sent to the detector 939 via the pipe 937, where each component is detected. The mobile phase containing each component detected by the detector 939 is collected or recycled through the pipe 941.

  When the mobile phase containing each component is recovered, the recycle switching valve 919 is switched to allow the flow between the pipe 941 and the pipe 943. On the other hand, the flow between the pipe 941 and the pipe 921 is blocked. As a result, the mobile phase containing each component is sent from the pipe 941 to the pipe 943, and the mobile phase containing each component is sent to the recovery tank 947, where the recovered liquid 945 is recovered. The recovered liquid 945 is usually a waste liquid, or the eluted components are collected every holding time by using a fraction collector (not shown) or the like.

  If the mobile phase containing each component is not sufficiently separated, the mobile phase containing each component is recycled.

  When the mobile phase containing each component is recycled, the recycle switching valve 919 is switched to allow flow between the pipe 941 and the pipe 921. On the other hand, the flow between the pipes 941 and 943 is blocked. As a result, the recycle flow comprising the recycle switching valve 919, the pipe 921, the liquid feed pump 923, the pipe 925, the mixer 927, the pipe 929, the sample introduction device 931, the pipe 933, the column 935, the pipe 937, the detector 939, and the pipe 941. A road is constructed. The mobile phase containing each component circulates in this recycling channel. However, a mixer 927 is interposed in the recycle channel. For this reason, when the mobile phase containing each component is circulated in the recycling flow path, each component once separated is diffused and mixed by the mixer 927. Therefore, when a conventional mobile phase mixing apparatus is used, a recycling analysis cannot be performed.

JP 2005-156218 A

  The present invention has been made in view of the above circumstances, and the object of the present invention is that it is not necessary to replace the liquid feeding pump when installing the mobile phase mixing apparatus in the HPLC, and the mobile phase mixing apparatus is used. Is to provide a mobile phase mixing apparatus capable of performing a recycle analysis. Another object of the present invention is to provide a method for controlling opening and closing of a solenoid valve used in the mobile phase mixing apparatus.

  As a result of earnestly examining the above problems, the present inventor has used a mixer that can efficiently mix the solvent even if it is inserted upstream of the liquid feed pump, and the opening / closing cycle of the electromagnetic valve can The present inventors have found that the above problem can be solved by changing the flow rate according to the flow velocity, and have completed the present invention.

  The present invention for solving the above problems is described below.

[1]
An HPLC mobile phase mixing device connected to an HPLC liquid feed pump and supplying a mobile phase having a predetermined composition to the liquid feed pump,
(A) a mixer having a mobile phase outlet connected to a mobile phase inlet of an HPLC liquid feed pump;
(B) a plurality of solvent suction tubes that suck solvent from one end and supply solvent from the other end to the mixer inlet;
(C) an electromagnetic valve that is interposed in each of the solvent suction tubes and opens and closes by an electrical signal;
(D) a solenoid valve opening / closing control device that controls opening and closing of the plurality of solenoid valves;
Consists of
By connecting the mobile phase outlet of the mobile phase mixer for HPLC to the mobile phase inlet of the HPLC liquid pump and operating the HPLC liquid pump, the solvent sucked from the plurality of solvent suction pipes is mixed with a mixer. A mobile phase mixing device for HPLC, which mixes to produce a mobile phase of a predetermined composition and supplies it to a feed pump,
The electromagnetic valve opening and closing control in the electromagnetic valve opening and closing control device,
Set the open / close time ratio of each solenoid valve according to the solvent composition of the mobile phase,
By repeating a cycle in which all the solenoid valves installed for each solvent constituting the mobile phase are opened and closed once, a certain amount of each solvent is repeatedly supplied to the mixer,
A mobile phase mixing apparatus for HPLC, comprising a solenoid valve control device having means for controlling the number of cycles per unit time to be proportional to the flow rate of the mobile phase.

  The above-described invention includes a configuration to which the following configuration [2] is added.

[2]
The mixer
(A) A cylindrical main body having both ends closed and an inlet portion into which each solvent is introduced and an outlet portion that flows out after the introduced solvent is mixed;
(B) a plurality of partition walls formed at predetermined intervals perpendicular to the axial direction along the axial direction of the cylindrical main body,
In the mixer [1], the plurality of partition walls have a through hole formed at one position in the center of the partition wall or at a plurality of positions on the periphery of the partition wall, and these partition walls are alternately arranged in the cylindrical main body. The HPLC mobile phase mixing apparatus described.

[3]
A method for controlling a mobile phase mixer for HPLC, which prepares a mobile phase of a predetermined composition by sequentially sucking a solvent from a plurality of solvent storage tanks by a liquid feed pump and mixing the mixture by sending it to a mixer,
The solvent composition of the mobile phase is controlled by the suction time of each solvent sucked from each solvent storage tank,
While repeating the cycle in which all the solvents constituting the mobile phase are sucked once each time,
A method for controlling a mobile phase mixing apparatus for HPLC, wherein the number of cycles per unit time is proportional to the flow rate of the liquid feeding pump.

  The HPLC mobile phase mixing apparatus of the present invention can be attached to the HPLC using the HPLC pump without replacing the existing HPLC liquid feeding pump. That is, it can be easily attached to an existing HPLC apparatus.

  The mobile phase mixer for HPLC of the present invention is controlled so as to change the open / close cycle of the solenoid valve in accordance with the flow rate of the liquid feed pump. As a result, a mobile phase having a constant composition can be produced regardless of the flow rate of the liquid feed pump.

  In the HPLC mobile phase mixing apparatus of the present invention, the mixer is interposed upstream of the liquid feed pump. Therefore, when performing the recycling analysis, the sample does not pass through the mixer, so that the once separated sample is not remixed by the mixer. Therefore, highly accurate analysis is possible in the recycling analysis.

It is explanatory drawing which shows an example of the flow-path structure of the mobile phase mixing apparatus for HPLC of this invention, and the recycle HPLC in which it was incorporated. 2 (a) is a perspective view and 2 (b) is an exploded view showing an example of the configuration of a mixer used in the present invention. It is explanatory drawing which shows the flow path of the mixer of FIG. 4a to 4c are top views showing the top shapes of the spacers 211a to 211c, respectively. 5a to 5c are perspective views showing the shapes of the spacers 211a to 211c, respectively. 6a to 6c are cross-sectional views of the spacers 211a to 211c along the lines aa, bb, and cc in FIGS. 5a to 5c, respectively. It is explanatory drawing which represents notionally the presence state of the solvent in piping at the time of sending each solvent to a mixer with the opening / closing control method of the solenoid valve of this invention. It is explanatory drawing which shows an example of the flow-path structure of HPLC incorporating the conventional mobile phase mixing apparatus for HPLC. It is explanatory drawing which shows an example of the flow path structure of the recycle HPLC incorporating the conventional mobile phase mixing apparatus for HPLC.

  Hereinafter, the mobile phase mixer for HPLC of the present invention and the recycle HPLC in which it is incorporated will be described.

  First, the configuration of the HPLC mobile phase mixing apparatus of the present invention and the recycle HPLC in which it is incorporated will be described. FIG. 1 is an explanatory diagram showing an example of the configuration of a mobile phase mixing apparatus for HPLC of the present invention and a recycle HPLC in which the apparatus is installed.

  In FIG. 1, reference numeral 100 denotes an HPLC in which the HPLC mobile phase mixing apparatus of the present invention is incorporated, and the HPLC mobile phase mixing apparatus of the present invention is surrounded by an alternate long and short dash line.

  101a-c are solvent storage tanks, and different solvents 103a-c are stored therein. Near the inner bottoms of the solvent storage tanks 101a to 101c, one ends of solvent suction pipes 105a to 105c are arranged, respectively, so that the solvents 103a to 103c inside can be sucked. The other ends of the solvent suction pipes 105a to 105c are connected to the inlets of the electromagnetic valves 107a to 107c, respectively. The electromagnetic valves 107a to 107c are connected to the electromagnetic valve opening / closing control device 111 by wiring 109, and the opening / closing of the valves is controlled by an electric signal from the electromagnetic valve opening / closing control device 111, respectively. One ends of the pipes 113a to 113c are connected to the outlets of the solenoid valves 107a to 107c. The other ends of the pipes 113a to 113c are connected to the respective inlets of the flow path junction 115. The flow path junction 115 is a member that joins the pipes 113a to 113c and joins the pipe 117, and uses a four-way joint or the like. The outlet of the flow path junction 115 is connected to one end of the pipe 117. The other end of the pipe 117 is connected to the inlet of the mixer 127. The mixer 127 mixes a plurality of solvents therein and causes a mobile phase having a constant composition to flow out from the outlet. The structure of the mixer will be described later.

  The outlet of the mixer 127 and the port 119a of the recycle switching valve 119 are connected via a pipe 121. The port 119b of the recycle switching valve 119 and the inlet (suction side) of the liquid feed pump 123 are connected by a pipe 125, and the outlet (discharge side) of the liquid feed pump 123 and the inlet of the sample introduction device 131 are connected by a pipe 129. The The outlet of the sample introduction device 131 and the inlet of the column 135 are connected by a pipe 133, and the outlet of the column 135 and the inlet of the detector 139 are connected by a pipe 137. The outlet of the detector 139 and the port 119c of the recycle switching valve 119 are connected by a pipe 141. One end of a pipe 143 is connected to the port 119d of the recycle switching valve 119, and the other end is inserted into the collection tank 147.

  The recycle switching valve 119 is configured so that it cannot flow between the ports 119a and 119b, between the ports 119b and 119c, and between the ports 119a and 119d. Further, when the port 119a-119b, the port 119a-119d, and the port 119c-119d can be distributed, the port 119b-119c cannot be distributed.

  Next, the case where HPLC analysis is performed using recycle HPLC having the mobile phase mixing apparatus for HPLC of the present invention will be described.

  The respective solvents 103a to 103c constituting the mobile phase are sucked from the solvent suction pipes 105a to 105c by the liquid feed pump 123 and sent to the electromagnetic valves 107a to 107c. The solenoid valves 107a to 107c are controlled so that when one solenoid valve is open, the other two solenoid valves are closed. When the electromagnetic valve 107a is open, the solvent 103a is sucked from the solvent suction pipe 105a by the liquid feed pump 123 and sent to the flow path junction 115 via the electromagnetic valve 107a and the pipe 113a. The solvent 103a exiting the flow path junction 115 is sent to the mixer 127 via the pipe 117, where it is mixed with another solvent to become a mobile phase. The structure of the mixer will be described later. The mobile phase exiting the mixer 127 reaches the liquid feed pump 123 via the recycle switching valve 119 and the pipe 125. At this time, in the recycle switching valve 119, the flow path between the ports 119a and 119b can flow. Even when the electromagnetic valve 107b or 107c is open, the solvents 103b and 103c are sent to the mixer 127 and mixed with other solvents as described above, and reach the liquid feed pump 123.

  The mobile phase discharged from the liquid feed pump 123 is sent to the sample introduction device 131 through the pipe 129. The sample (containing a plurality of components) introduced from the sample introduction device 131 is sent to the column 135 through the pipe 133 together with the mobile phase.

  Each component in the sample is eluted from the column 135 at different rates due to the difference in partition coefficient between the mobile phase and the stationary phase of the packing material packed in the column 135. The mobile phase containing each component eluted according to the distribution coefficient exits from the column 135 and is sent to the detector 139 via the pipe 137, where each component is detected. The mobile phase containing each component detected by the detector 139 is collected or recycled through the pipe 141.

  When the mobile phase containing each component is recovered, the recycle switching valve 119 is switched to enable the flow between the pipe 141 and the pipe 143. On the other hand, the flow between the pipe 141 and the pipe 125 is blocked. Thereby, the mobile phase containing each component is sent from the pipe 141 to the pipe 143, and the mobile phase containing each component is sent to the recovery tank 147, where the recovered liquid 145 is recovered. The recovered liquid 145 is usually a waste liquid, or the eluted components are collected for each holding time by using a fraction collector (not shown).

  If the mobile phase containing each component is not sufficiently separated, the mobile phase containing each component is recycled.

  When the mobile phase containing each component is recycled, the recycle switching valve 119 is switched to allow the piping 141 and the piping 125 to flow between the flow paths. On the other hand, the flow between the pipe 141 and the pipe 143 is blocked. As a result, a recycle flow path including the recycle switching valve 119, the pipe 125, the liquid feed pump 123, the pipe 129, the sample introduction device 131, the pipe 133, the column 135, the pipe 137, the detector 139, and the pipe 141 is configured.

  The mobile phase containing each component circulates in this recycling channel. Since the mixer 127 is not interposed in the recycle channel, the sample component does not diffuse due to the mixer even if the recycle analysis is performed.

  The mixer used for the mobile phase mixing apparatus for HPLC of the present invention is inserted in the HPLC mobile phase flow path upstream (suction port side) of the liquid feed pump, so long as a plurality of solvents can be mixed uniformly. A simple mixer may be used.

  An example of the structure of the mixer used for the mobile phase mixing apparatus of the present invention will be described.

  Fig.2 (a) is a perspective view which shows an example of the structure of the mixer used for the mobile phase mixing apparatus for HPLC of this invention, FIG.2 (b) is an exploded view of the mixer. FIG. 3 is a cross-sectional view taken along line aa in FIG.

  2 and 3, reference numeral 127 denotes a mixer, which is provided with lids 203 and 207 at both ends of the cylindrical main body 201, respectively, and closes both end openings of the cylindrical main body 201. The lid 203 is provided with a solvent inlet 205. The lid 207 is provided with a mobile phase outlet 209. Columnar spacers 211 a to 211 i are accommodated in the cylindrical main body 201. The outer diameters of the spacers 211a to 211i are slightly smaller than the inner diameter of the cylindrical main body 201.

  4a, 4b, and 4c are top views showing the shapes of the spacers 211a, 211b, and 211c, respectively. 5a, 5b, and 5c are perspective views showing the shapes of the spacers 211a, 211b, and 211c, respectively. 6a, 6b, and 6c are cross-sectional views of the spacers 211a, 211b, and 211c along the lines aa, bb, and cc in FIGS. 5a, 5b, and 5c, respectively.

  Both end surfaces in the axial direction of the columnar spacer 211a are provided with recesses 212a in a cylindrical shape leaving their peripheral edges, and through holes are formed at substantially equal intervals along the peripheral edge of the recesses 212a. A plurality of paths 213a are formed (eight positions in the drawing).

  One end surface in the axial direction of the cylindrical spacer 211b is provided with a cylindrical recess 212b, leaving a peripheral edge thereof, and a through hole is formed at the center of the recess 212b. Is formed.

  One end surface in the axial direction of the columnar spacer 211c is provided with a cylindrical recess 212c leaving the periphery thereof, and through holes are formed at substantially equal intervals along the periphery of the recess 212c. A plurality of passages 213c (eight places in the drawing) are formed.

  The spacer 211b has the same shape as the spacers 211d, 211f, and 211h, and the spacer 211c has the same shape as the spacers 211e, 211g, and 211i. These spacers 211a to 211i respectively form partition walls in the cylinder of the cylindrical main body 201.

  In the mixer 127, spacers 211a to 211i are sequentially arranged from the solvent inlet side toward the mobile phase outlet side. As a result, a structure is formed in which spacers in which one or eight flow paths are formed are alternately stacked. Therefore, after the solvent flowing in from the solvent inflow port stays in the concave portion provided in the spacer, it stays in the next concave portion through the eight flow paths, and then passes through one flow path to the next concave portion. Stay. By repeating this, a plurality of solvents are mixed uniformly and flow out from the mobile phase outlet.

  The mixer 127 usually has an actual capacity of several mL (capacity obtained by adding the capacity of the recess (solvent retention part) provided in the spacer and the capacity of the flow path). In addition, what is necessary is just to adjust the actual capacity | capacitance of a mixer suitably in consideration of the piping diameter used for HPLC. In the case of ordinary analytical HPLC, the actual volume of the mixer is preferably 6 mL or less. Since this mixer is excellent in mixing performance and has a small pressure load, it can be interposed upstream of the liquid feed pump. In addition, the number of the flow paths provided in the spacers 211a and 211c is not particularly limited, but is preferably 4 to 10, and more preferably 6 to 8. Instead of the cylindrical main body 201, both end faces or outer circumferences of the spacers 211a to 211i may be fixed with an adhesive or the like, and the cylindrical main body may be omitted.

  Next, a method for controlling the opening and closing of the solenoid valve performed in the HPLC mobile phase mixing apparatus of the present invention will be described.

  In the mobile phase mixing apparatus for HPLC of the present invention, the electromagnetic valve opening / closing control device 111 controls the opening and closing of the electromagnetic valves 107a to 107c to control the supply amount and supply cycle of the solvent to the mixer 127. By the suction of the liquid feed pump 123, the respective solvents 103a to 103c are sucked from the respective solvent storage tanks 101a to 101c. Each solenoid valve is controlled such that when any one solenoid valve is open, the other two solenoid valves are closed. As a result, each of the solvents 103a to 103c is sucked up from the solvent storage tank and sent to the mixer 127 while the electromagnetic valve belonging to the flow path is open. That is, since the solvent composition of the mobile phase is proportional to the number of unit hours that each solenoid valve opens, the solvent composition of the mobile phase can be controlled by controlling the unit time that each solenoid valve opens. Since mixing of each solvent is performed by a mixer, the number of unit hours that each electromagnetic valve opens is set in consideration of the capacity of the mixer and mixing performance. That is, these three solvents must be mixed uniformly when flowing out from the outlet of the mixer 127. For this reason, the time for which the solenoid valve is opened by one opening / closing operation is reduced to some extent. Each of the solenoid valves 107a to 107c is repeated once for a predetermined period of time (hereinafter also referred to as a solenoid valve opening / closing cycle) to complete mixing in the mixer 127. For example, when the flow rate of the liquid feed pump is 1 (mL / min.), The time required for one cycle is preferably set to 10 to 60 seconds.

  In the plunger type pump generally used for HPLC, the suction of the solvent from the pump inlet side and the discharge of the solvent to the pump outlet side are alternately repeated (hereinafter also referred to as a pump suction-discharge cycle). Therefore, even if the electromagnetic valve is open, the solvent is not sucked from the solvent storage tank when the liquid feed pump is discharging. When the flow rate of the pump is increased, the pump suction-discharge cycle is shortened.

  The control method of the mobile phase mixing apparatus of the present invention makes the open / close cycle of the solenoid valve proportional to the suction-discharge cycle of the pump. That is, when the pump suction-discharge cycle is shortened (the flow rate of the liquid feed pump is increased), the time required for the solenoid valve to open and close in one cycle is reduced in proportion (in inverse proportion to the flow rate of the liquid feed pump). Control to be. Accordingly, the suction amount of each solvent per cycle is constant regardless of the flow rate of the liquid feed pump. As a result, the error in the suction amount of each solvent caused by the suction-discharge cycle of the pump becomes constant regardless of the flow rate (that is, the pulsating flow generated by the liquid feed pump while each solenoid valve is open). The pulse rate is constant even if the flow rate is changed). Therefore, the solvent composition of the mobile phase is constant regardless of the flow rate of the liquid feed pump.

  This point will be further described. In the open / close cycle of each solenoid valve, only the solvent 103a is continuously sent to the mixer 127 while the solenoid valve 107a is open. Next, when the electromagnetic valve 107 a is closed and the electromagnetic valve 107 b is opened, only the solvent 103 b is continuously sent to the mixer 127. Similarly, next, the solvent 103 c is continuously sent to the mixer 127. Therefore, the mixer 127 is required to have a performance capable of uniformly mixing these three types of solvents sent continuously and periodically. Here, when increasing the flow rate of the liquid feeding pump, if the time for opening each electromagnetic valve is kept the same, the amount of liquid delivered to each solvent while the electromagnetic valve is opened once also increases. In this case, the mixing ability of the mixer is exceeded, and uniform mixing cannot be performed. However, if the number of open / close cycles of each solenoid valve is increased in proportion to the flow rate of the liquid feed pump, the amount of liquid delivered in one cycle is the same. As a result, the mixing state in the mixer is not related to the pumping amount and is kept good.

  Hereinafter, the opening / closing control method of the solenoid valve according to the present invention will be described by way of examples.

  In the feeding of each solvent, the volume ratio of the solvent constituting the mobile phase is set according to the desired solvent composition of the mobile phase. The solvent suction time ratio from each solvent storage tank is set in proportion to the volume ratio of the solvent constituting the mobile phase. The time ratio is corrected as appropriate in consideration of the characteristics of the solvent (viscosity and volume expansion coefficient). A cycle in which each solenoid valve is opened and closed once and all kinds of solvents constituting the mobile phase are sucked once is defined as one cycle.

  FIGS. 7A to 7C are explanatory views conceptually showing the presence state of the solvent in the pipe 117 when each solvent is sent to the mixer by the electromagnetic valve opening / closing control method of the present invention. In FIG. 7, a mixer is interposed in the direction of the arrow (m).

  When the solvent composition of the mobile phase is solvent 103a / solvent 103b / solvent 103c = 7/2/1 and the flow rate of the liquid feed pump is 2 (mL / min.), First, from the solenoid valve opening / closing control device 111 In response to the electrical signal, the electromagnetic valve 107a is opened for 7 unit time, and the solvent 103a is sucked from the solvent storage tank 101a for 7 unit time. Next, the electromagnetic valve 107a is closed by the electrical signal from the electromagnetic valve opening / closing control device 111, and the electromagnetic valve 107b is opened for two unit hours substantially simultaneously. As a result, the suction of the solvent 103a is blocked, while the solvent 103b is sucked from the solvent storage tank 101b for 2 unit hours. Next, the electromagnetic valve 107b is closed by the electric signal from the electromagnetic valve opening / closing control device 111, and the electromagnetic valve 107c is opened for one unit time substantially simultaneously. Thereby, the suction of the solvent 103b is cut off, while the solvent 103c is sucked from the solvent storage tank 101c for one unit time. Thus, each solvent is sucked once, and this cycle is repeated (FIG. 7A). The unit time is calculated by the amount of liquid feeding (mL / min.) / The amount of liquid feeding by one stroke (mL) of the liquid feeding pump.

  In the above case, when the flow rate of the liquid feed pump is 1 (mL / min.), The suction times of the solvents 103a, b, and c are controlled to be 14 unit hours, 4 unit hours, and 2 unit hours, respectively. (FIG. 7B). Similarly, when the flow rate of the liquid feed pump is 4 (mL / min.), The suction times of the solvents 103a, b, and c are 3.5 unit time, 0.5 unit time, and 0.25 unit time, respectively. (FIG. 7C).

  Therefore, the amount of each solvent sucked per cycle is constant regardless of the flow rate of the liquid feed pump. That is, the number of suction-discharge cycles of the liquid feeding pump per cycle is also constant ((A) to (C) in FIG. 7).

  It is preferable that the opening and closing of a certain solenoid valve and the opening and closing of another solenoid valve be performed at the same time, but not to the extent that HPLC is damaged and does not cause a substantial deviation in the solvent composition of the mobile phase to be produced. If there is, there may be a delay in opening and closing each solenoid valve (substantially simultaneously).

  In the above description, the case of adjusting the mobile phase by mixing three kinds of solvents has been described. However, the present invention is not limited to this, and a mobile phase can be produced by mixing any number of solvents in the same manner.

100: Recycled HPLC incorporating the mobile phase mixer for HPLC of the present invention
101a-c ... Solvent storage tank 103a-c ... Solvent 105a-c ... Solvent suction pipe 107a-c ... Solenoid valve 109 ... Solenoid valve opening / closing control device wiring 111 ... Solenoid valve opening / closing control Device 115 ... flow path confluence 119 ... recycle switching valve 123 ... liquid feed pump 127 ... mixer 131 ... sample introduction device 135 ... column 139 ... detector 145 ... Recovery liquid 147 ... Recovery tank 113a-c, 117, 121, 125, 129, 133, 137, 141, 143 ... Piping

201 ... cylindrical main body 203,207 ... lid 205 ... solvent inlet 209 ... mobile phase outlet 211a-i ... spacer 212a-c ... concave 213a-i ... flow path

800 ... HPLC incorporating a conventional mobile phase mixer for HPLC
801a-c ... Solvent storage tanks 803a-c ... Solvent 805a-c ... Solvent suction pipes 807a-c ... Solenoid valve 809 ... Solenoid valve opening / closing control device wiring 811 ... Solenoid valve opening / closing control Device 815 ... flow path confluence 823 ... liquid feed pump 827 ... mixer 831 ... sample introduction device 835 ... column 839 ... detector 845 ... recovery liquid 847 ... recovery Tank 813a-c, 817, 825, 829, 833, 837, 841 ... piping

900: Recycled HPLC incorporating the mobile phase mixer for HPLC of the present invention
901a-c ... Solvent storage tanks 903a-c ... Solvent 905a-c ... Solvent suction pipes 907a-c ... Solenoid valve 909 ... Solenoid valve opening / closing control device wiring 911 ... Solenoid valve opening / closing control Device 915 ... flow path confluence 919 ... recycle switching valve 923 ... liquid feed pump 927 ... mixer 931 ... sample introduction device 935 ... column 939 ... detector 945 ... Recovery liquid 947 ... Recovery tanks 913a-c, 917, 921, 925, 929, 933, 937, 941, 943 ... piping

Claims (3)

An HPLC mobile phase mixing device connected to an HPLC liquid feed pump and supplying a mobile phase having a predetermined composition to the liquid feed pump,
(A) a mixer having a mobile phase outlet connected to a mobile phase inlet of an HPLC liquid feed pump;
(B) a plurality of solvent suction tubes that suck solvent from one end and supply solvent from the other end to the mixer inlet;
(C) an electromagnetic valve that is interposed in each of the solvent suction tubes and opens and closes by an electrical signal;
(D) a solenoid valve opening / closing control device that controls opening and closing of the plurality of solenoid valves;
Consists of
By connecting the mobile phase outlet of the mobile phase mixer for HPLC to the mobile phase inlet of the HPLC liquid pump and operating the HPLC liquid pump, the solvent sucked from the plurality of solvent suction pipes is mixed with a mixer. A mobile phase mixing device for HPLC, which mixes to produce a mobile phase of a predetermined composition and supplies it to a liquid feed pump,
The electromagnetic valve opening and closing control in the electromagnetic valve opening and closing control device,
Set the open / close time ratio of each solenoid valve according to the solvent composition of the mobile phase,
By repeating a cycle in which all the solenoid valves installed for each solvent constituting the mobile phase are opened and closed once, a certain amount of each solvent is repeatedly supplied to the mixer,
A mobile phase mixing apparatus for HPLC, comprising a solenoid valve control device having means for controlling the number of cycles per unit time to be proportional to the flow rate of the mobile phase. The mixer
(A) A cylindrical main body having both ends closed and an inlet portion into which each solvent is introduced and an outlet portion that flows out after the introduced solvent is mixed;
(B) a plurality of partition walls formed at predetermined intervals perpendicular to the axial direction along the axial direction of the cylindrical main body,
2. The mixer according to claim 1, wherein the plurality of partition walls have a through hole formed at one position in the center of the partition wall or at a plurality of positions on the periphery of the partition wall, and the partition walls are alternately arranged in the cylindrical main body. The HPLC mobile phase mixing apparatus described. A method for controlling a mobile phase mixer for HPLC, which prepares a mobile phase of a predetermined composition by sequentially sucking a solvent from a plurality of solvent storage tanks by a liquid feed pump and mixing the mixture by sending it to a mixer,
The solvent composition of the mobile phase is controlled by the suction time of each solvent sucked from each solvent storage tank,
While repeating the cycle in which all the solvents constituting the mobile phase are sucked once each time,
A method for controlling a mobile phase mixing apparatus for HPLC, wherein the number of cycles per unit time is proportional to the flow rate of the liquid feeding pump.

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