JP2019002693A - Supercritical fluid separation device - Google Patents

Abstract

To provide a device for bringing a fluid reserved in a cylinder into a supercritical state and thereby separating a component from a sample, which enables easy confirmation of decrease in a residual amount of the fluid in the cylinder.SOLUTION: A supercritical fluid separation device 100 of the present invention which is a device for isolating a component in a sample using a supercritical fluid comprises: a sample container 11 which houses the sample; a flow passage 211 for supplying the supercritical fluid reserved in a cylinder 20 to the sample container 11; a liquid-sending pump provided in the flow passage 211; an opening-closing valve provided in the flow passage nearer to the cylinder than the liquid-sending pump, which opens and closes the flow passage; a pressure sensor provided in the flow passage nearer to the sample container than the liquid-sending pump; a residual amount detection unit which executes detection processing of decrease in a residual amount of the supercritical fluid in the cylinder 20 on the basis that a detection value of the pressure sensor falls below a predetermined pressure threshold value in a state in which the opening-closing valve is opened and the liquid-sending pump is stopped; and a notification unit 43 which, when the decrease in the residual amount of the supercritical fluid in the cylinder 20 is detected by the residual amount detection unit, performs notification of the detection.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an apparatus for separating a target component from a sample using a supercritical fluid, and more particularly to a supercritical fluid chromatograph using a supercritical fluid containing the separated component as a mobile phase.

  A supercritical fluid is a fluid having a temperature and pressure exceeding the critical point (critical temperature, critical pressure), and exhibits an excellent dissolving power for many substances. It is used as a solvent for extracting a drug component from a liquid or as a mobile phase of a supercritical fluid chromatograph (SFC). In addition, there is provided an apparatus that combines an extraction apparatus using a supercritical fluid as an extraction solvent and a supercritical fluid chromatograph (see Patent Documents 1 to 3). In the following description, these devices are collectively referred to as a supercritical fluid separation device, and a portion in which processing for extracting a component from a sample or separating a component in the supercritical fluid separation device is performed will be described as a component separation unit.

JP 2005-172679 A JP 2010-101875 A JP 2014-160055

  In the supercritical fluid separation device, the fluid that is the source of the supercritical fluid is stored in a cylinder, and the fluid in the cylinder is supplied to the component separation unit while being pressurized by a pump. In order to bring the fluid into a supercritical state in the component separation unit, the pump is driven at a discharge pressure such that the pressure in the flow path from the pump to the component separation unit exceeds the critical pressure. However, when the remaining amount of fluid in the cylinder decreases and the pressure in the cylinder falls below a predetermined value, the pressure in the flow path from the pump to the component separation unit decreases, or the amount of fluid supplied to the component separation unit As a result, the performance of separating (or extracting) components from the sample in the component separation unit is degraded. For this reason, in the supercritical fluid separator, it is necessary to know the remaining amount of fluid in the cylinder. Usually, however, such a cylinder is not provided with a pressure gauge or the like. It was inconvenient because it was necessary to check the remaining amount by measuring the weight.

  The problem to be solved by the present invention is that a fluid stored in a cylinder is brought into a supercritical state, thereby enabling easy confirmation of a decrease in the remaining amount of fluid in the cylinder in an apparatus for separating components from a sample. That is.

The present invention made to solve the above problems is a supercritical fluid separation apparatus for separating components from a sample using a supercritical fluid,
a) component separation unit;
b) a flow path for supplying the fluid stored in the cylinder to the component separation unit;
c) a liquid feed pump provided in the flow path for making the inside of the component separation part a pressure exceeding a critical pressure;
d) an on-off valve that opens and closes the flow path on the cylinder side of the liquid feed pump;
e) a pressure sensor provided in the flow path closer to the component separation unit than the liquid feed pump;
f) a remaining amount detecting unit for detecting that the detected value of the pressure sensor is below a predetermined pressure threshold value in a state where the on-off valve is opened and the liquid feed pump is stopped. To do.

  Examples of the supercritical fluid separation device according to the present invention include an extraction device using a supercritical fluid as an extraction solvent, a supercritical fluid chromatograph, and a device combining the extraction device and the supercritical fluid chromatograph. In the case of an extraction device, the extraction container corresponds to a component separation unit, and in the case of a supercritical fluid chromatograph, the separation column corresponds to a component separation unit. Moreover, in the case of the apparatus which combined the extraction apparatus and the supercritical fluid chromatograph, the part from an extraction container to a separation column becomes a component separation part. In such a supercritical fluid separation device, it is necessary to maintain the pressure in the component separation part at a pressure exceeding the critical pressure, and the pressure sensor for confirming this is a flow path on the component separation part side of the liquid feed pump. Is provided. In the present invention, the pressure sensor is used to detect a decrease in the remaining amount of the supercritical fluid in the cylinder. Specifically, the remaining amount detection unit is in a state where the on-off valve is opened. The detected value of the pressure sensor when the liquid feed pump is in a stopped state is compared with a predetermined pressure threshold value, and it is detected that the detected value has fallen below the pressure threshold value.

  The state in which the detection value of the pressure sensor is lower than the predetermined pressure threshold means that the fluid supplied from the liquid feed pump to the component separation unit when the liquid feed pump is driven because the remaining amount of fluid in the cylinder has decreased. This corresponds to a state in which the flow rate of the liquid falls below a predetermined value, or the inside of the component separation unit does not reach the critical pressure. Therefore, the predetermined pressure threshold is determined according to the type of supercritical fluid, the length of the flow path from the cylinder to the pressure sensor, and the like. The predetermined pressure threshold may be set in advance, or the user may set the pressure threshold.

When the remaining amount detection unit detects that the detection value of the pressure sensor falls below a predetermined pressure threshold, the supercritical fluid separation device (the control unit thereof) indicates that the remaining amount of fluid in the cylinder has decreased. It is good to comprise so that it may alert | report by a voice message, a warning sound, etc. Thus, the user can recognize that the cylinder needs to be replaced.
In addition, a connection unit that selectively connects a plurality of cylinders to the flow path, and when the remaining amount detection unit detects that the detection value of the pressure sensor falls below a predetermined pressure threshold, the connection unit You may make it switch automatically the cylinder connected to a flow path.

  In the present invention, it is preferable that the remaining amount detection unit further includes an instruction unit for detecting that the detection value of the pressure sensor has fallen below a predetermined pressure threshold. In addition, it is preferable that the remaining amount detection unit includes a timing setting unit for causing the user to set a timing for detecting that the detection value of the pressure sensor is below a predetermined pressure threshold. In these configurations, the remaining amount detection unit can detect that the detection value of the pressure sensor has fallen below a predetermined pressure threshold only at a necessary time.

  Moreover, it is preferable that the said remaining amount detection part detects that the detection value of the said pressure sensor fell below the predetermined | prescribed pressure threshold value, after predetermined time passed since stopping the said liquid feeding pump. In this configuration, it is possible to detect whether or not the remaining amount of the fluid in the cylinder has decreased while the pressure in the flow path is stable.

  According to the supercritical fluid separation device of the present invention, it is possible to easily detect a decrease in the remaining amount of supercritical fluid in a cylinder using a pressure sensor which is an existing facility.

1 is an overall configuration diagram of a supercritical fluid separation device according to an embodiment of the present invention. The schematic block diagram of a supply apparatus. The flowchart of the operation and process regarding a presetting. The flowchart of the control and process for pressure monitoring.

An embodiment of the present invention will be described with reference to the drawings. FIG. 1 is a schematic configuration diagram of a supercritical fluid separation device (hereinafter referred to as a separation device) according to the present embodiment. The separation device 100 includes a component extraction unit 10, a chromatograph unit 26, and a fraction collector 27. In this separation apparatus 100, the component extraction unit 10, the chromatograph unit 26, and the flow path connecting them correspond to the component separation unit of the present invention.
The component extraction unit 10 includes a container rack 12 that can store four sample containers 11, a needle moving mechanism 16 that is disposed above the container rack 12, moves the outflow needle 15 in the left-right and up-down directions, A rack mounting table 17 on which the rack 12 is mounted, and a heating block 171 disposed in the lower part of the rack mounting table 17 are provided. The sample container 11 includes a cylindrical main body 111 and a lid part 112 fixed to the upper end portion thereof. An inlet and an outlet are formed at the lower end center and upper end center of the sample container 11, respectively. Has been.

  The rack mounting table 17 holds four inflow needles 13 inserted into the inlet of the sample container 11 stored in the container rack 12. These four inflow needles 13 are connected to the four ports of the flow path switching valve 19, respectively. In one port of the flow path switching valve 19, a carbon dioxide cylinder 20, a supply device 21 that pressurizes the carbon dioxide flowing out from the cylinder 20 and supplies the carbon dioxide to the inflow needle 13, and a modifier that supplies a modifier (modifier). A pump 22 is connected. The detailed configuration of the supply device 21 will be described later.

A chromatograph section 26 and a fraction collector 27 are connected to the needle moving mechanism 16 via a flow path switching valve 25. The chromatograph unit 26 includes a separation column 261, a detector 262, and a back pressure adjustment valve 263. The detector 262 is composed of, for example, an ultraviolet-visible spectrophotometer. The detection signal from the detector 262 is stored in the storage unit 40 included in the extraction control unit 39. The fraction collector 27 includes a plurality of sorting containers 271 and an electromagnetic valve 272 that is a flow path switching valve. The electromagnetic valve 272 operates in accordance with a control signal from the extraction control unit 39 and connects the flow path from the chromatograph unit 26 to either the sorting container 271 or the drain (not shown).
An elution solvent container 31 is also connected to the flow path switching valve 25 via an elution pump 29. Furthermore, the other end of the flow path having one end connected to one port of the flow path switching valve 19 is connected to the flow path connecting the flow path switching valve 25 and the chromatograph unit 26.

  The component extraction unit 10 is provided with a needle outer periphery cleaning port 35 and a needle inner surface cleaning port 45. A rinse liquid container 37 is connected to the needle outer periphery cleaning port 35 via a rinse pump 36. The needle inner surface cleaning port 45 is connected to one port of the flow path switching valve 19.

  As shown in FIG. 2, the supply device 21 includes a channel 211 that connects the carbon dioxide cylinder 20 and the channel switching valve 19, a liquid feeding pump 212 provided in the channel 211, and a cylinder 20 side of the liquid feeding pump 212. The on-off valve 213 provided in the channel 211, the cooling device 214 installed in the channel 211 between the liquid feed pump 212 and the on-off valve 213, and the channel 211 on the channel switching valve 19 side from the liquid feed pump 212. Has a pressure sensor 215 provided on the surface. The on-off valve 213 is a normally-closed shut-off valve (sealed valve) that is closed when the power of the separation apparatus 100 is off. The liquid feed pump 212 performs a suction / discharge operation at a predetermined discharge / suction pressure. The predetermined discharge / suction pressure is such that when a predetermined amount of fluid is stored in the carbon dioxide cylinder 20, the pressure in the portion from the liquid feed pump 212 through the sample container 11 to the separation column 261 exceeds the critical pressure. Such a value. Thereby, the liquefied carbon dioxide from the carbon dioxide cylinder 20 is supplied to the sample container 11 without being vaporized along with the suction / discharge operation by the liquid feed pump 212. A detection signal from the pressure sensor 215 is input to the extraction control unit 39.

  The cooling device 214 includes a cooling block 220 through which the flow path 211 passes, a Peltier element 221 and a cross flow fan 222 for cooling the cooling block 220, and a pump head of the cooling block 220 and the liquid feed pump 212. A coolant liquid flow passage 223 provided across the diaphragm and a diaphragm pump 224 for circulating the coolant liquid are included. In the cooling block 220, a portion of the flow path 211 from the on-off valve 213 to the liquid feed pump 212 is embedded. The coolant liquid is made of, for example, a 30% ethanol aqueous solution and is stored in a replaceable container 225. By causing the coolant liquid to flow through the flow passage 223, a part of the flow path 211 and the pump head of the liquid feed pump 212 are cooled, and thus vaporization of liquefied carbon dioxide in the liquid feed pump 212 is prevented.

The operation of each of the component extraction unit 10, the chromatograph unit 26, and the fraction collector 27 is controlled by the extraction control unit 39. In the separation apparatus 100 of the present embodiment, the pressure monitoring unit 41, the remaining unit are used as characteristic function blocks. A quantity determination unit 42 is provided. The extraction control unit 39 is connected to a notification unit 43 that outputs a voice announcement, a buzzer sound, and the like.
The central control unit 50 is connected to an input unit 51 and a display unit 52 including a pointing device such as a keyboard and a mouse, and is responsible for input / output control and basic control of the separation device 100. The extraction control unit 39 and the central control unit 50 are implemented by using a personal computer as a hardware resource and executing dedicated control / processing software installed in the personal computer on the personal computer. be able to. The central control unit 50 is electrically connected to the extraction control unit 39, and the extraction control unit 39 can be operated through the central control unit 50 by operating the input unit 51.

The operation of the separation apparatus 100 according to the present embodiment will be described by taking as an example the case where one or more components contained in the sample are separated by the separation column 261 and collected in each sorting container 271.
First, the sample container 11 containing the sample is stored in the container rack 12, and the container rack 12 is set on the rack mounting table 17. Thereby, the needle 13 is inserted into the inlet of the sample container 11. Further, the moving mechanism 16 is driven to insert the needle 15 into the outlet of the sample container 11. Subsequently, the ports of the first flow path switching valve 19 and the second flow path switching valve 25 are set to the connection state shown in FIG.

  Next, liquefied carbon dioxide (supercritical fluid) is drawn out from the carbon dioxide cylinder 20 while being pressurized by the liquid feed pump 212. Further, a modifier (modifier) that is a polar solvent (methanol, ethanol, etc.) is drawn out from the solvent container by the modifier pump 22. Both of these are sent to the sample container 11 whose temperature is adjusted by the heating block 171 via the first flow path switching valve 19. The pressure from the liquid feed pump 212 to the separation column 261 is set to a pressure exceeding the critical pressure of carbon dioxide (7.4 MPa) by the liquid feed pump 212 and the back pressure regulating valve 263, and the sample container is taken by the heating block 171. When 11 is set to a temperature exceeding the critical temperature (31 ° C.) of carbon dioxide, carbon dioxide (supercritical fluid) is in a supercritical state in the sample container 11. Carbon dioxide in the supercritical state has a dissolving power corresponding to its temperature and pressure, and the sample in the sample container 11 is dissolved in accordance with this dissolving power, and the target component in the sample is extracted.

  The supercritical fluid containing the extract in the sample container 11 reaches the chromatograph section 26 from the needle 15 via the second flow path switching valve 25. In the chromatograph section 26, the separation column 261 is heated to a temperature exceeding the critical temperature by a column oven (not shown), and the supercritical fluid containing the extract from the sample is converted into each component when passing through the separation column 261. After being separated, each component is detected by the detector 262. The detection signal of the detector 262 is output to the extraction control unit 39, temporarily stored in the storage unit 40, and then input to the central control unit 50. Based on this, the central control unit 50 creates a chromatogram and displays it on the display unit 52.

  In addition, the central control unit 50 calculates the change rate of the detection signal from the detector 262. Then, the point in time when the absolute value of the rate of change in the value of the detection signal exceeds a predetermined value is determined as the start of elution of the target component. Then, the electromagnetic valve 272 of the fraction collector 27 is operated at a time after a predetermined delay time from that time, and the target component is collected in the sorting container 271. Here, the predetermined delay time is a value obtained based on the length of the flow path from the detector 262 to the electromagnetic valve 272, the flow velocity of the mobile phase, and the like, and is stored in advance in the central control unit 50. The supercritical fluid that flows through the flow path of the chromatograph unit 26 passes through the back pressure regulating valve 263 and disappears in the supercritical state, and is then collected in the sorting container 271 of the fraction collector 27.

  In addition, the central control unit 50 determines that the time when the absolute value of the rate of change of the value of the output signal becomes smaller than a predetermined value is the end of elution of the target component. Then, at the time point after the above-mentioned delay time from that time point, the electromagnetic valve 272 of the fraction collector 27 is operated to end the collection of the target component.

  When the remaining amount of carbon dioxide in the carbon dioxide cylinder 20 is reduced during the above-described target component separation process, the pressure from the liquid feed pump 212 to the separation column 261 falls below the critical pressure of carbon dioxide, and the sample Carbon dioxide in the container 11 and the separation column 261 does not reach the supercritical state. Then, the expected extraction performance and separation performance cannot be obtained in the sample container 11 and the separation column. Therefore, in this embodiment, it has a function of monitoring the remaining amount of the carbon dioxide cylinder 20. Hereinafter, the function of monitoring the remaining amount of the carbon dioxide cylinder 20 will be described with reference to the flowchart of FIG.

  Prior to the use of the apparatus, the user makes a preset for determining a decrease in the remaining amount of the carbon dioxide cylinder 20. That is, the user selects whether or not to use the remaining amount monitoring function by performing a predetermined operation using the input unit 51 (step S1), and when the setting for using the remaining amount monitoring function is made (in step S2). In the case of Yes), the input unit 51 is further operated to select or input the determination threshold value of the pressure of the carbon dioxide cylinder 20 and the execution timing of the remaining amount monitoring function (steps S3 and S4). Since the remaining amount monitoring function needs to be performed in a state in which the liquid feed pump 212 is stopped, the execution timing of the remaining amount monitoring function is, for example, a flow path switching valve for switching the sample container 11 into which carbon dioxide and a modifier are introduced. When the switching operation of 19 is performed, or when the process of separating the components from the sample of the sample container 11 stored in the container rack 12 is completed and the container rack 12 is replaced. In addition, when the setting which does not use the remaining amount monitoring function is made in step S2 (in the case of No in step S2), since the subsequent setting is unnecessary, the pre-setting process is ended.

  All the setting information in steps S3 and S4 is stored in the storage unit 40 of the extraction control unit 39. When the setting for using the remaining amount monitoring function is made, a series of control and processing as shown in FIG. 4 are executed at the timing set in S4.

  That is, in the extraction control unit 39, the pressure monitoring unit 41 resets the internal timer and starts to elapse (step S11). Subsequently, the pressure threshold value set in step S3 and stored in the storage unit 40 is read (step S12). Next, the extraction control unit 39 opens the on-off valve 213 and stops driving the liquid feed pump 212 (step S13), and the pressure monitoring unit 41 acquires the detection value of the pressure sensor 215 (step S14). Then, the remaining amount determination unit 42 compares the detection value acquired by the pressure monitoring unit 41 with a pressure threshold value (step S15). When the detected value of the pressure sensor 215 is smaller than the pressure threshold value, it is determined that the remaining amount of the carbon dioxide cylinder 20 is insufficient and there is a possibility that a sufficient flow rate cannot be secured (Yes in step S15). If). On the other hand, if the detected value of the pressure sensor 215 exceeds the pressure threshold (No in step S15), there is no problem and the process returns to step S11.

  The pressure monitoring unit 41 may acquire the detection value of the pressure sensor 215 immediately when the on-off valve 213 is opened and the liquid feed pump 212 is stopped. The detection value of the pressure sensor 215 may be acquired when a waiting time has elapsed since the stop 212. Further, the pressure monitoring unit 41 may continue to acquire the detection value of the pressure sensor 215 until the waiting time elapses from the stop, and the average value may be used as the pressure value in the flow path.

  When it is determined that there is a possibility that the remaining amount of the carbon dioxide cylinder 20 is insufficient, the extraction control unit 39 causes the notification unit 43 to perform a warning notification to notify the user (step S16). Thereby, the user can recognize that the remaining amount of the carbon dioxide cylinder 20 is lowered, and can exchange the carbon dioxide cylinder 20. When the replacement of the carbon dioxide cylinder 20 is completed, the user instructs the input unit 51 to return to the state before execution of the remaining amount monitoring function.

It should be noted that the above embodiment is merely an example of the present invention, and it is obvious that modifications, alterations, and additions within the scope of the present invention are included in the scope of the claims of the present application.
In the above-described embodiment, the components in the sample are extracted using the supercritical fluid, and introduced into the separation column for separation. However, the present invention uses the supercritical fluid in the sample. It can also be applied to an apparatus for extracting components and a supercritical fluid chromatograph.

In addition, when it is determined that there is a possibility that the remaining amount of the carbon dioxide cylinder 20 is insufficient, a warning notification is made.
In the above embodiment, the detector is a multi-wavelength detector using a PDA (Photo Diode Attay), an optical rotation detector, a circular dichroism detector, a fluorescence detector, a refractive index detector, and evaporative light scattering detection. An optical detector such as a detector may be used, and a mass spectrometer may be used as the detector.

DESCRIPTION OF SYMBOLS 100 ... Supercritical fluid separation apparatus 10 ... Component extraction part 11 ... Sample container 12 ... Container rack 121 ... Holding part 122 ... Gripping part 124 ... Cylindrical member (sample container holding part)
125 ... Cap 13 ... Inflow needle 15 ... Outflow needle 16 ... Needle moving mechanism 17 ... Rack mounting table 171 ... Heating block 175 ... Heater 176 ... Temperature sensor 19, 25 ... Channel switching valve 21 ... Supply device 211 ... Channel 212 ... Liquid feed pump 213 ... On-off valve 214 ... Cooling device 215 ... Pressure sensor 220 ... Cooling block 221 ... Peltier element 222 Cross flow fan 223 ... Container 224 ... Extraction control unit 40 ... Storage part 41 ... Pressure monitoring part 42 ... Remaining amount determination unit 50 ... central control unit 51 ... input unit 52 ... notification unit 53 ... display unit

Claims (5)

A supercritical fluid separation device for separating components from a sample using a supercritical fluid,
a) component separation unit;
b) a flow path for supplying the fluid stored in the cylinder to the component separation unit;
c) a liquid feed pump provided in the flow path for making the inside of the component separation part a pressure exceeding a critical pressure;
d) an on-off valve that opens and closes the flow path on the cylinder side of the liquid feed pump;
e) a pressure sensor provided in the flow path closer to the component separation unit than the liquid feed pump;
f) a remaining amount detecting unit for detecting that the detected value of the pressure sensor is below a predetermined pressure threshold value in a state where the on-off valve is opened and the liquid feed pump is stopped. Supercritical fluid separator. The supercritical fluid separation device of claim 1, further comprising:
g) A supercritical fluid separation device comprising a notifying unit for notifying when the remaining amount detecting unit detects a decrease in the remaining amount of the supercritical fluid in the cylinder. The supercritical fluid separator according to claim 1 or 2, further comprising:
h) A supercritical fluid separation device comprising: an instruction unit for causing the remaining amount detection unit to detect that a detection value of the pressure sensor has fallen below a predetermined pressure threshold value. The supercritical fluid separator according to claim 1 or 2, further comprising:
A supercritical fluid separation device, comprising: a timing setting unit for allowing a user to set a timing for causing the remaining amount detection unit to detect that a detection value of the pressure sensor falls below a predetermined pressure threshold value. In the supercritical fluid separator according to any one of claims 1 to 4,
The remaining amount detection unit detects a decrease in the remaining amount of supercritical fluid in the cylinder based on a detection value of the pressure sensor after a predetermined time has elapsed since the liquid feeding pump was stopped. Supercritical fluid separator.

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