JP2014062827A - Deaeration liquid feeding device and analyzer - Google Patents

Abstract

Disclosed is a degassing / liquid feeding device and an analyzer using the same, in which the amount of liquid discarded due to degassing from the liquid (drain work) can be made as close to zero as possible, and the running cost can be greatly reduced. .
From upstream to downstream, at least a deaeration mechanism for removing a gas in the liquid, a liquid feeding mechanism for feeding the liquid, and a branching portion divided into a plurality of flow paths are provided in this order. And one of the plurality of flow paths divided by the branching section has a merging section that merges upstream of the deaeration mechanism, and has an opening / closing mechanism in the flow path from the branching section to the merging section. An analyzer comprising: a deaeration liquid feeding device that automatically operates an opening / closing mechanism based on a signal from a pressure sensor or the like arranged; and a liquid chromatograph downstream thereof.
[Selection] Figure 7

Description

  The present invention relates to a degassing / feeding apparatus that efficiently removes bubbles and the like mixed in a flow path in liquid chromatography and the like, and an analyzer using the same.

  In “flow analysis equipment” that performs analysis by introducing a sample into a liquid flow such as liquid chromatography or flow injection, the dissolved gas concentration in the liquid to be fed must be kept below a certain level in order to maintain analysis accuracy. It is considered important. In addition, since analyzers using microchips, which have been remarkably developed in recent years, have fine channels, the generation of bubbles in the channels is a cause of hindering analysis more than in the case of the liquid chromatography described above. . Even in a microreactor that performs reaction / synthesis in a fine channel, the generation of bubbles in the reaction channel leads to a decrease in reaction efficiency, so it is desirable to reduce the gas concentration in the solution as much as possible.

  Among flow analysis devices, for example, liquid chromatography performs separation by feeding an eluent to a column that is a separation medium and injecting a sample into the flow. The separated components are measured for concentration and the like by a detector according to the purpose.

  A general liquid feed pump has a check valve that controls the flow in a certain direction before and after the plunger, and generates a constant flow by the operation of the plunger and the opening and closing of the check valve. For this reason, if bubbles or the like are present in the eluent, the operation of the check valve becomes unstable and the flow rate of the liquid is lowered or the liquid cannot be completely fed. As a solution to this problem, generally, a bubble removing mechanism called a deaeration device is generally introduced upstream of a pump, and bubbles are continuously removed for use.

  In addition, bubbles and gas dissolved in the eluent may affect the output of the detector. The concentration of the gas dissolved in the eluent varies depending on the temperature or the like, and the change may cause the detector output to drift, or bubbles may be generated in the detector cell and appear as large noise. Therefore, by reducing the concentration of the dissolved gas and keeping it at a constant value, the output of the detector can be stabilized and the analysis can be performed with high accuracy.

  In the case of high-pressure liquid chromatography in which the pressure of the column used is several MPa, if a large amount of air is mixed in the eluent, the pump will cause poor delivery and the eluent containing air will be introduced to the downstream column. Never be. However, when using a low-pressure column with a column pressure of several hundred kPa, the pump will cause poor fluid delivery, but the eluent containing air will be led to the downstream column, etc., which will damage the column. May give.

  Therefore, it is desirable to remove bubbles and gas components in the eluent to some extent and use them in the analysis from the viewpoints of liquid feeding stability, detection accuracy, and analysis column protection.

  Various methods have been proposed and put to practical use as a degassing device, such as a heat degassing method, a helium degassing method, and a diaphragm vacuum degassing method. The helium deaeration type deaeration device is a system in which an inert gas typified by helium is bubbled in an eluent to drive out dissolved gas in the eluent (Patent Document 1). Although this method has a stable degassing efficiency, it has recently been used less frequently due to the complexity of facilities such as the use of high-pressure gas. The heated degassing method is a method in which the dissolved gas concentration in the eluent is lowered by continuously stirring the eluent at a temperature higher than room temperature. Although this method has stable deaeration efficiency, it has been rarely used in recent years because of risk factors such as ignition of the eluent and emptying of the eluent tank.

  For these reasons, diaphragm vacuum deaerators have been mainly used in recent years (see FIG. 1). As the diaphragm, a single or multiple tube type or flat membrane type is used. In the case of a tube type, a gas permeable tube (19) made of a material that allows gas components to permeate but does not permeate liquid components is disposed in a sealed container (a deaerator (17)), and the inside of the container is a vacuum pump (18) Depressurize by etc. Thereby, the gas component in a liquid is removed by flowing a liquid in a tube (refer FIG. 1 a) (for example, patent documents 2, 3, and 4). In the case of a flat membrane type, two spaces partitioned by a gas permeable membrane (23) made of a material having the above characteristics are formed, one space is decompressed by a vacuum pump (18), etc., and a liquid is poured into the other space. By flowing, the gas component in the liquid is removed (see FIG. 1b) (for example, Patent Documents 5, 6, and 7).

  In the deaeration device, the removal is possible when bubbles or gases are present in the eluent in the upstream flow path (IN side). However, it cannot be removed if bubbles or gases are present in the eluent in the downstream flow path (OUT side) of the deaerator. Therefore, when bubbles are generated in the flow path (OUT side) on the downstream side of the deaeration device, the drain valve (6) arranged downstream of the pump is opened and the gas-containing solution is discharged out of the system. In many cases, a drain operation is performed to cope with this (see FIG. 2).

  The actual pump unit (16) is composed of a pulsation removing mechanism (4) and a pressure sensor (5) for removing pulsation in addition to a plunger / check valve mechanism for feeding the eluent. The internal capacity is considerably larger than the capacity of the plunger mechanism that controls liquid feeding. Therefore, in order to discharge the solution containing bubbles and gas out of the system, the gas cannot be completely removed unless the amount of several to several tens of the volume is discharged.

  In the case of using a general-purpose column that delivers an eluent of about 1 milliliter per minute, there is no particular problem even if the drain operation requires about several tens of mL. However, when using a microcolumn that delivers an eluent of several tens of microliters per minute, if the drain operation requires about several tens of mL, the ratio of the waste amount to the eluent amount used for analysis is extremely high. Therefore, the effect of reducing the running cost due to the microfabrication of the column is impaired.

  For example, assuming that the measurement of one sample is 20 minutes, the drain operation is performed once every 50 samples, and 20 mL of the eluent is discarded, the drain operation is performed for a column that delivers 1 milliliter per minute. The amount of eluent discarded due to is only 2% of the eluent consumption. However, as the amount of liquid sent decreases, the percentage of waste increases, and the amount of liquid delivered to the column is 9% at 0.2 milliliters per minute, 17% at 0.1 milliliters per minute, and 0.05 milliliters per minute. In 29% and 0.02 milliliters per minute, half of the total eluent consumption is discarded without being used for analysis (see Table 1, FIG. 3).

JP 2003-107063 A JP 2003-047883 A JP 2004-230373 A International Publication No. 2007/094242 Pamphlet JP-A-11-137907 JP 2003-126609 A JP 2010-184239 A

  The present invention provides a degassing liquid feeding device and an analysis device using the same, which can reduce the amount of liquid discarded by degassing work (drain work) from liquid as close to zero as possible and greatly reducing running costs. It is intended to do.

As a result of intensive studies on the above problems, the present inventor has reached the present invention. That is, the present invention is as follows.
(1) From upstream to downstream, at least a deaeration mechanism for removing gas in the liquid, a liquid feeding mechanism for feeding the liquid, and a branching portion divided into a plurality of flow paths in this order, and A degassing / liquid feeding device characterized in that one of a plurality of flow paths divided by a branching portion has a merging portion that merges upstream of a degassing mechanism.
(2) The deaeration liquid feeding device according to (1) above, wherein the branching unit has a flow path switching mechanism.
(3) In the deaeration liquid feeding device described in (2) above, a mechanism for monitoring the flow state is disposed in the flow path, and the operation of the flow path switching mechanism is automatically performed based on the signal from the mechanism. A device to perform in.
(4) The deaeration liquid feeding device according to the above (1), wherein the device has an opening / closing mechanism in a flow path from the branching portion to the merging portion.
(5) In the deaeration liquid feeding device described in (4) above, a mechanism for monitoring the flow state is disposed in the flow path, and the operation of the opening / closing mechanism is automatically performed based on a signal from the mechanism. apparatus.
(6) An analyzer comprising the degassing / feeding device according to any one of (1) to (5) above and a flow analysis device downstream thereof.
(7) The analyzer according to (6), wherein the flow analysis device is a liquid chromatograph.

  Hereinafter, the present invention will be described in more detail. First, the deaeration liquid feeding device of the present invention will be described. The deaeration liquid feeding device of the present invention is as described in the above (1), and has, for example, the configuration of FIG. At the time of normal liquid feeding, as shown in FIG. 4a, the liquid (27) passes through the joining part (13), the degassing mechanism (28), the liquid feeding mechanism (29), and the branching part (12) in this order. Then, it is led out of the deaeration liquid feeding device of the present invention. On the other hand, when a large amount of bubbles or gas is mixed in the flow path, as shown in FIG. 4b, the liquid (27) is combined with the joining portion (13), the deaeration mechanism (28), and the liquid feeding mechanism (29). After passing through the branch part (12) in this order, it is returned to the joining part (13) upstream of the deaeration mechanism (28) via the circulation channel (14), and then the deaeration mechanism (28). Circulation liquid feeding that deaeration is performed again is performed. At this time, the liquid (27) is supplied by the volume reduced by the deaeration operation. By performing such circulating liquid feeding, the liquid in the flow path containing bubbles and gas is degassed, and the bubbles and gas are removed. Thereafter, the liquid may be led out of the deaeration liquid feeding device by returning to the normal liquid feeding state (FIG. 4a). In addition, there is no limitation in particular as a deaeration mechanism (28), A normal deaeration apparatus etc. are used. Further, the liquid feeding mechanism (29) is not particularly limited, and for example, a pump or a pump unit including a pump can be used.

  Preferred examples of the deaeration / feeding device of the present invention include the following first and second embodiments.

  In the first embodiment, as described in (2) above, a flow path switching mechanism is provided at the branch portion. Since this flow path switching mechanism is divided into a plurality of flow paths at the branch portion, this flow path switching is performed. For example, when the configuration shown in FIG. 4 is adopted, the flow path is divided into two from the branch portion (12), and therefore, for example, a two-position switching valve can be used as the flow path switching mechanism. At the first switching position of the two-position switching valve, the liquid from the liquid feeding mechanism (29) flows in the direction led out of the deaeration liquid feeding apparatus of the present invention. Moreover, in the 2nd switching position, the liquid from a liquid feeding mechanism (29) flows in the direction returned to a junction part (13) via a circulation flow path (14). During normal liquid feeding, this valve takes the first switching position. On the other hand, when a large amount of bubbles or gas is mixed in the flow path, the valve is switched to the second position to perform further deaeration as described above. After the required deaeration is performed, the normal liquid feeding state can be restored by returning the valve to the first switching position.

  As described in the above (4), the second form has an opening / closing mechanism in the flow path from the branching portion to the merging portion. This opening / closing mechanism controls opening and closing of the flow path from the branching section to the merging section, that is, the circulation flow path (14). For example, an opening / closing valve (ON / OFF valve) can be used. For example, when the configuration shown in FIG. 4 is adopted, the circulation channel (14) is closed when the opening / closing mechanism is closed, so that the liquid from the liquid feeding mechanism (29) is discharged to the outside of the deaeration liquid feeding device of the present invention. And flow in the derived direction. On the other hand, when the open / close mechanism is in the open state, the flow path leads to both the direction leading out of the deaeration liquid feeding device and the circulation flow path (14). However, when the load on the flow path in the direction led out of the deaeration liquid feeding device is relatively large, for example, when another device with a large load is connected, the liquid substantially flows there. Instead, it flows in the direction returning to the junction (13) via the circulation channel (14). During normal liquid feeding, the opening / closing mechanism is closed. On the other hand, when a large amount of bubbles or gas is mixed in the flow path, the degassing is further performed as described above by switching the open / close mechanism to the open state.

  The operation of the flow path switching mechanism and the opening / closing mechanism may be performed manually by the operator judging the status of the device, and a mechanism for monitoring the flow state is arranged in the flow path, and the signal from there It may be performed automatically based on this. The mechanism for monitoring the flow state is not particularly limited. For example, a pressure sensor, a flow meter, a bubble detection mechanism, and the like are preferable, and a pressure sensor is more preferable. As an example of automation, as shown in FIG. 5, it is effective to measure the system pressure in real time, determine a rapid decrease in pressure, and use it as the starting point of the circulation deaeration operation. It is effective to calculate the end point of the circulation deaeration in consideration of the set flow rate of the liquid feeding mechanism, the internal capacity of the circulation channel, the deaeration capability of the deaeration mechanism, and the like. Note that the above-described automation method is merely an example, and the present invention is not limited to this.

  Next, the analyzer of the present invention will be described. The analyzer of the present invention is as described in the above (6), and has the deaeration liquid feeding device of the present invention and a flow analysis device downstream thereof. For example, the configuration shown in FIGS. Can take. 6 and 7 correspond to cases where the deaeration liquid feeding device of the present invention has the first form and the second form, respectively. As described above, the flow analyzer is a device that performs analysis by introducing a sample into a liquid flow, and is not particularly limited, and examples thereof include a liquid chromatograph, a flow injection, a microreactor, and a microchip. In particular, a liquid chromatograph is preferable.

  Hereinafter, an analytical instrument having a liquid chromatograph downstream of the deaeration liquid feeding device of the present invention will be described as an example.

  First, the case where a flow path switching mechanism is provided at the branching portion will be described with reference to FIGS. A circulation valve (11) is provided between the pump unit (16) and the sample injection valve (7) so that the eluent from the pump can be returned to the upstream side (IN side) of the degassing device (2) again. . The circulation valve (11) is a two-position switching valve. In the first switching position, the eluent from the pump flows to the analysis column (9) side, and in the second switching position, the eluent from the pump circulates. The structure which flows to the deaeration apparatus (2) side via a path (14) and a confluence | merging part (13) is taken. In the normal liquid feeding state, the circulation valve takes the first switching position (FIGS. 8a and 9a). When a large amount of air bubbles is mixed into the flow path, the circulation valve is switched to the second position (FIGS. 8b and 9b → FIG. 9c). As a result, the eluent containing bubbles is returned to the deaerator (2) again after passing through the pump, and deaeration is performed. At this time, the eluent (1) is supplied by the volume reduced by the deaeration operation. By performing such circulating liquid feeding for a certain period of time, the eluent in the flow path containing bubbles and gas advances, and bubbles and gases are removed to a level that does not hinder analysis (FIG. 9c). → Fig. 9d). Thereafter, by returning the circulation valve to the first switching position, the eluent with less bubbles and gas is sent to the analysis column (9) side.

  Next, a case where an opening / closing mechanism is provided in the flow path from the branching portion to the merging portion will be described with reference to FIGS. A branch section (12) is provided between the pump unit (16) and the sample injection valve (7), and the end of the flow path branched by the branch section is connected to the upstream side (IN side) of the deaerator (2). Arrangement is made to connect as a junction (13). A circulation valve (15) is disposed in the branched flow path. The circulation valve (15) is an open / close valve (ON / OFF valve). When the circulation valve (15) is closed, the circulation channel (14) is closed, so that the eluent from the pump flows only to the analysis column (9) side. . In the open state, the eluent from the pump is connected to both the analysis column (9) side flow path and the circulation flow path (14), but the load on the analysis column (9) side flow path is relatively large. It flows only to the deaerator (2) side via the circulation channel (14) and the junction (13).

  In the normal liquid feeding state, the circulation valve (15) is closed (FIGS. 10a and 11a). When a large amount of bubbles is mixed into the flow path, the circulation valve is switched to the open state (FIGS. 10b and 11b → FIG. 11c). As a result, the eluent containing bubbles is returned to the deaeration device after passing through the pump and deaerated. At this time, the eluent is supplied by the volume reduced by the deaeration operation. By circulating the liquid for a certain period of time in this state, the eluent in the circulating flow path containing bubbles advances, and bubbles and gases are removed to a level that does not hinder analysis (FIG. 11c). → FIG. 11 d). Thereafter, by returning the circulation valve (15) to the closed state, the eluent with less bubbles and gas is sent to the analysis column (9) side.

  According to the present invention, in the degassing operation (drain operation) from the liquid, the amount of discarded liquid can be made as close to zero as possible, and the running cost can be greatly reduced.

It is a schematic diagram which shows the principle of the conventional diaphragm vacuum deaeration apparatus. It is a figure which shows the flow-path system of the conventional liquid chromatograph apparatus. It is a figure which shows the use flow rate of an eluent, and the ratio of the discard amount by drain operation which occupies for a use flow rate. It is a figure which shows an example of a structure of the deaeration liquid feeding apparatus of this invention. It is a figure which shows an example of the automatic control of the deaeration liquid feeding apparatus of this invention. It is an example of a flow path diagram and a system configuration diagram of the present invention. It is an example of a flow path diagram and a system configuration diagram of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS It is a flow-path figure and system block diagram of the 1st form of this invention. It is the figure which showed typically the deaeration operation | movement of the 1st form of this invention. It is a flow-path figure and system block diagram of the 2nd form of this invention. It is the figure which showed typically the deaeration operation | movement of the 2nd form of this invention. It is a flow chart of a system used in an example and a comparative example. It is the figure which showed the operation | movement of the system in Example 1. FIG. It is the figure which showed the fluctuation | variation of the pressure in Example 1, and the fluctuation | variation of a detector signal. It is the figure which showed the pressure fluctuation and the fluctuation of a detector signal in the comparative example 1.

  In order to verify the effect of the present invention, a large amount of air was intentionally introduced to confirm the deaeration effect. FIG. 12 shows a flow chart of the liquid chromatograph used. The basic flow path configuration is based on the second embodiment having an opening / closing mechanism. A bifurcated portion (12) is provided between the pump unit (16) and the analysis column (9), and is divided into an analysis flow path and a circulation flow path. 20) was inserted and used as an opening / closing mechanism. The outlet of the circulation channel was connected to the upstream (IN side) of the deaeration device (17) as a merging portion (13). The pump (3) used a metering pump FMM20 manufactured by KNF, at a flow rate of 250 microliters per minute, and the detector (10) used a UV-visible detector UV-8020 manufactured by Tosoh at a wavelength of 415 nm. The deaerator (17) used OMUNIFIT's Bubble Trap (006BT-HT), and the vacuum pump (18) used a small diaphragm pump (DSA-1-24) manufactured by Denso Sangyo Co., Ltd. The analytical column (9) used was TSKgel BORATE-5PW (manufactured by Tosoh Corporation) having an inner diameter of 1.5 mm and a length of 15 mm, and pure water was used as the eluent (1). The pumping liquid pressure is measured by the pressure sensor (5), the value is monitored in real time by the pressure determination unit (24), and the mixing of bubbles into the pump is determined based on the value, and the two-way solenoid valve (20) The opening / closing instruction can be executed. In this embodiment, it is determined that the pressure has dropped sharply, the two-way solenoid valve (20) is opened, and the two-way solenoid valve (20) is closed after 5 minutes.

  For verification purposes, a three-way solenoid valve (21) is arranged upstream of the junction (13) so that air can be quantitatively introduced into the flow path, and the eluent (1) and the air (22). The switchable configuration was adopted.

[Example 1]
As a first step, the two-way solenoid valve (20) was closed, the three-way solenoid valve (21) was the eluent (1) side, and the eluent was sent to the analysis column (9) side. Here, the eluent passes through the deaeration chamber of the deaerator (17) to remove the gas, and then is sent to the analysis column (9) (FIG. 13a). As a second step, the three-way solenoid valve (21) was switched to the air side for 5 minutes and then returned to the eluent side. As a result, air is sucked in along with the pump operation. A certain amount of air is removed by the deaeration device, but when it exceeds a certain amount, the air is sucked into the pump. In the state where the eluent is being sent, the system pressure is maintained at a constant value, but when air is sucked into the pump, the pressure drops (FIG. 13b). As a third step, the two-way solenoid valve (20) is opened in response to the pressure drop detected in the second step. Thereby, the eluent containing a large amount of air (22) does not flow to the analysis column (9) side, but is returned to the junction (13) on the upstream side (IN side) of the degassing device (17). The eluent containing a large amount of air is degassed (17) → pump unit (16) → branch (12) → two-way solenoid valve (20) → merge (13) → degasser (17). It will circulate. The eluent containing air is deaerated again by the deaerator, so that the amount of air decreases with circulation (FIG. 13c). Since the circulating volume decreases due to the deaeration effect, the eluent is newly supplied by the volume. Finally, deaeration progresses to a level that does not hinder analysis (FIG. 13d, fourth step). As a fifth step, the two-way solenoid valve (20) was closed and the eluent was switched to the analysis column (9) side (FIG. 13e).

  In this example, taking into consideration the flow rate, void capacity, and capacity of the deaeration device, the circulation and deaeration time was set to 5 minutes in advance, and the opening / closing control of the two-way solenoid valve (20) was performed.

  FIG. 14a shows the fluctuation of the system pressure during the series of operations, and FIG. 14b shows the fluctuation of the detector signal during the series of operations. 14a and 14b show that the pressure after completion of the circulation deaeration is within a certain range, and stable liquid feeding is performed without the influence of the bubbles of the eluent. In addition, the detector signal at this time is not greatly disturbed, indicating that the influence of dissolved gas is small. Therefore, by taking these steps, the air can be removed without discarding the eluent containing air outside the system, and it can be used as it is as the eluent for analysis. .

[Comparative Example 1]
Using the same system as in Example 1, a large amount of air was sucked by a pump, and circulation deaeration was not performed. Specifically, the eluent was first sent under the above conditions, and then the three-way solenoid valve (21) was turned on to suck air for about 5 minutes. The results are shown in FIG.

  FIG. 15A is a graph showing fluctuations in the pressure of the liquid feed pump, and FIG. 15B is a diagram showing fluctuations in the detector signal at that time. Bubbles reach the pump approximately 25 minutes after the start of liquid feeding, causing liquid feeding failure and a large drop in pressure, but not completely zero. According to FIG. 15a, the column used here was fed at about 100 kPa before being affected by bubbles, and the liquid feed became unstable due to air mixing, but continued to the column side. It is shown that. Further, according to FIG. 15b, after 40 minutes from the start of liquid feeding, the signal of the detector starts maximizing or spike-like noise starts to occur. This is because the bubble sent by the pump reaches the detector cell, or the bubble is generated from the eluent containing a large amount of gas components, and the absorbance changes greatly.

1. 1. Eluent 2. Deaeration device Pump 4. 4. Pulsation removal mechanism Pressure sensor 6. 6. Drain valve Sample injection valve 8. Sample loop9. Analytical column 10. Detector 11. Circulation valve (2-position switching valve)
12 Bifurcation 13. Merge section 14. Circulation channel 15. Circulation valve (open / close valve)
16. Pump unit 17. Deaerator 18. Vacuum pump 19. Gas permeation tube 20.2 way solenoid valve 21.3 way solenoid valve 22. Air 23. Gas permeable membrane 24. Pressure determination unit 26. Flow analysis instrument 27. Liquid 28. Deaeration mechanism 29. Liquid feeding mechanism

Claims (7)

From upstream to downstream, it has at least a deaeration mechanism for removing gas in the liquid, a liquid feeding mechanism for feeding liquid, and a branching part that is divided into a plurality of flow paths in this order, and A degassing / liquid feeding device characterized in that one of a plurality of divided flow paths has a merging portion that merges upstream of the degassing mechanism. The deaeration liquid feeding apparatus according to claim 1, wherein the apparatus has a flow path switching mechanism at a branch portion. The deaeration liquid feeding device according to claim 2, wherein a mechanism for monitoring a flow state is disposed in the flow path, and the flow path switching mechanism is automatically operated based on a signal from the mechanism. The deaeration liquid feeding device according to claim 1, wherein the device has an opening / closing mechanism in a flow path from the branching portion to the merging portion. The deaeration liquid feeding device according to claim 4, wherein a mechanism for monitoring a flow state is disposed in the flow path, and the operation of the opening / closing mechanism is automatically performed based on a signal from the mechanism. An analyzer comprising the deaeration liquid feeding device according to claim 1 and a flow analysis device downstream thereof. 7. The analyzer according to claim 6, wherein the flow analysis device is a liquid chromatograph.

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