JP5935696B2 - Portable liquid chromatograph and liquid chromatography - Google Patents

Description

  The present invention relates to a liquid chromatograph and a liquid chromatography.

  Conventionally, as a liquid chromatograph (LC apparatus), a liquid chromatograph (LC apparatus) including a pump that transports a mobile phase solvent containing a target substance to be measured is known (for example, see Patent Document 1). The LC device described in Patent Document 1 is connected to the pump for feeding the liquid, the injection part for mixing the analysis sample (sample liquid) into the mobile phase solvent connected to the outlet side of the pump, and the target substance in the sample liquid is connected to the injection part. A separation column including a filler for detecting the target substance and a detector for detecting a target substance. The mobile phase solvent sent out by the pump is supplied to the separation column as a sample liquid containing the target substance via the injection section, and the characteristics relating to the target substance are detected by the detector.

  An electroosmotic pump (EO pump) is known as a pump for feeding liquid (see, for example, Patent Documents 2 and 3). The EO pumps described in Patent Documents 2 and 3 include a reservoir that stores a liquid to be transported, an electroosmotic material that is attached to an outlet side of the reservoir, and is permeable to the liquid. When a voltage is applied to the electroosmotic material, the electroosmotic material is negatively charged and the liquid that has penetrated the electroosmotic material is locally positively charged. The liquid inside is carried out of the reservoir. This EO pump is preferably employed to supply liquid into the microfluidic chip. The EO pumps described in Patent Documents 2 and 3 are driven at a low voltage.

JP 2006-275640 A JP 2008-074677 A JP 2006-022807 A

  From the viewpoint of life safety or environmental protection, there is a growing social need for on-site analysis that can promptly feed back the obtained information to the site. That is, there is a demand for a small and lightweight mobile analysis device intended for on-site analysis rather than a large analysis device intended for use in a laboratory or laboratory. Applications of small analytical instruments are diverse such as environmental monitoring, food management, clinical testing, plant management, and the ideal form of mobile analytical instruments is versatile and general purpose. Examples of such a versatile general-purpose analytical instrument include an LC apparatus or a high-performance liquid chromatograph (HPLC apparatus) described in Patent Document 1.

  Here, it is conceivable to reduce the size by adopting an EO pump in the LC device described in Patent Document 1. However, since the conventional EO pump has a high driving voltage, it has to be driven by obtaining power from a household power source or the like, and in order to realize the mobility of the analytical instrument, it can be operated with a battery. It is necessary to suppress the power consumption of the EO pump. Even if the EO pump driven at a low voltage described in Patent Documents 2 and 3 is employed, there is room for improvement in terms of power consumption in order to drive it appropriately using a battery.

  In this technical field, a liquid chromatograph and a liquid chromatography capable of suppressing the power consumption of the EO pump are desired.

  As a result of extensive research, the present inventors have been able to remove the mobile phase solvent when it is introduced into the reservoir or the flow path downstream of the EO pump that is arranged downstream of the EO pump and stores the mobile phase solvent. The present invention has been completed by finding that an extra pump drive is required to increase the pressure of the mobile phase solvent to the pressure required for the measurement due to the presence of no air bubbles or loose internal structures .

  That is, the liquid chromatograph according to one aspect of the present invention is a liquid chromatograph for analyzing a sample solution containing an inorganic ion or a soluble organic compound as a target substance. The liquid chromatograph includes an electroosmotic flow pump for transporting a mobile phase solvent, a separation column disposed downstream of the electroosmotic flow pump and holding a filler therein, and a downstream of the separation column. A detector configured to analyze a target substance output from the separation column; and the movement stored in a reservoir provided downstream of the electroosmotic flow pump and stored downstream of the electroosmotic flow pump A pressure adjusting mechanism for adjusting a fluid pressure of the phase solvent or a fluid pressure of the mobile phase solvent stored in the flow path.

  In this liquid chromatograph, it is stored in the fluid pressure or flow path of the mobile phase solvent stored in the reservoir provided on the downstream side of the electroosmotic flow pump by a pressure adjusting mechanism disposed on the downstream side of the electroosmotic flow pump. The fluid pressure of the mobile phase solvent is adjusted. Thus, the mobile phase solvent on the downstream side of the electroosmotic flow pump is provided in order to avoid driving the electroosmotic flow pump for purposes other than liquid feeding by providing a pressure adjustment mechanism independent of the electroosmotic flow pump. The fluid pressure can be adjusted. For this reason, since it becomes possible to avoid giving an extra load to an electroosmotic flow pump, the power consumption of an electroosmotic flow pump can be suppressed.

  In one embodiment, the pressure adjustment mechanism may adjust to increase the fluid pressure. Further, in one embodiment, the pressure adjusting mechanism may adjust the fluid pressure before starting the electroosmotic pump or during starting the electroosmotic pump until a rated flow rate is reached. With this configuration, it is possible to reduce the influence of air bubbles that are difficult to remove or loosening of the internal structure in the flow path on the downstream side of the reservoir or the electroosmotic flow pump.

  In one embodiment, the pressure adjusting mechanism may pressurize by reducing the internal volume of the reservoir or the internal volume of the flow path. With this configuration, it is possible to adjust the pressure with a simple configuration.

  In one embodiment, the pressure adjustment mechanism includes a screw hole provided in the reservoir or the flow path and penetrating to the inside, and a screw inserted into the screw hole and protruding into the reservoir or the flow path. , May be configured. By configuring in this way, it is possible to adjust the pressure with a simpler configuration.

  In one embodiment, the electroosmotic pump, the reservoir, and the pressure adjusting mechanism may be integrated as a pump module. By comprising in this way, since only a pump module is exchangeable, it is excellent in versatility.

  In one embodiment, a battery serving as a power source for the electroosmotic pump may be provided. With this configuration, analysis can be performed regardless of the location of the power source.

  Furthermore, in one embodiment, a flow cell for circulating the target substance output from the separation column is provided, and the flow cell and the detector may be detachably attached to a substrate in which the separation column is formed. Good. By configuring in this way, different detectors can be employed using the same separation column, so that it is excellent in versatility and allows selective and multifaceted analysis.

  In addition, liquid chromatography according to another aspect of the present invention is liquid chromatography in which a sample liquid containing a target substance to be measured is transferred to a separation column by an electroosmotic flow pump and analyzed. The liquid chromatography is disposed downstream of the electroosmotic flow pump before starting the electroosmotic flow pump or during activation of the electroosmotic flow pump until the rated flow rate is reached, and downstream of the electroosmotic flow pump. A pressure adjusting step of adjusting the fluid pressure of the mobile phase solvent stored in the reservoir provided in the reservoir or the fluid pressure of the mobile phase solvent stored in the flow path.

  In this liquid chromatography, the pressure adjustment step is performed before the electroosmotic pump is activated. Therefore, the fluid pressure of the mobile phase solvent on the downstream side of the electroosmotic flow pump can be adjusted in order to reduce the power consumption until the electroosmotic flow pump quickly reaches a constant flow rate and stably delivers liquid. .

  In one embodiment, the pressure adjusting step may be pressurized by reducing the internal volume of the reservoir or the internal volume of the flow path. With this configuration, it is possible to adjust the pressure with a simple configuration.

  According to various aspects and embodiments of the present invention, the power consumption of an EO pump employed in a liquid chromatograph can be suppressed.

It is a composition outline figure showing the liquid chromatograph concerning a 1st embodiment. It is a schematic diagram which shows the liquid feeding system structure of the liquid chromatograph shown in FIG. It is a top view of the separation column of FIG. FIG. 4 is a cross-sectional view of the separation column shown in FIG. 3 taken along line IV-IV. It is a partial cross section figure of the liquid chromatograph shown in FIG. It is sectional drawing of the EO pump module of FIG. (A) shows a state before driving liquid, and (b) shows a state where driving liquid is driven. It is a schematic diagram explaining the effect of the conventional EO pump module. (A) shows a state before driving liquid, (b) shows a state where driving liquid is driven, and (c) shows a state where driving liquid is further driven. It is a schematic diagram explaining the effect of the EO pump module of FIG. (A) is a state before driving the driving liquid, (b) is a state where the insertion member is inserted before driving the driving liquid, and (c) is a state where the driving liquid is driven with the insertion member inserted. Indicates the state. It is a graph which shows the flow volume of FIG. 1 and the conventional EO pump module in a time series. It is a partial cross section figure of the liquid chromatograph which concerns on 2nd Embodiment. It is a graph which shows the flow rate of the EO pump module which concerns on an Example in time series. (A) is a detection amount by a flow sensor built in the pump, and (b) is a detection amount by a flow sensor arranged between the EO pump module and the injector. It is a graph which shows the analysis result of the liquid chromatograph which concerns on an Example. (A) is a detection result of catechins, (b) is a detection result of phenols, (c) is a detection result of catecholamine, and (d) is a detection result of amino acids. It is a graph which shows the flow volume of the pump module of the liquid chromatograph which concerns on an Example and a comparative example in a time series. (A) shows the time dependence of the flow velocity of Comparative Example 1, and (b) shows the time dependence of the flow velocity of Example 3.

  Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In addition, in each figure, the same code | symbol is attached | subjected to the same or an equivalent part, and the overlapping description is abbreviate | omitted.

(First embodiment)
First, the configuration of the present embodiment will be described. FIG. 1 is a configuration diagram of a liquid chromatograph (LC device) according to the first embodiment. The LC apparatus according to the present embodiment is suitably employed for, for example, chemical analysis in general, process management, environmental monitoring, medical diagnosis, drug discovery screening, or cooperation with a microreactor, and particularly in field analysis. Is used as a portable (portable) LC device.

  As shown in FIG. 1, the LC device 1 of the present embodiment includes an electroosmotic pump module (EO pump module) 2 capable of feeding liquid. The EO pump module 2 is connected to the control unit 11 and configured to be driven by a signal from the control unit 11. The control unit 11 is connected to a battery 12 and is configured to be able to be driven using the battery 12 as a power source. The control unit 11 is connected to, for example, an input interface, and is configured to be able to manually drive, stop, and control the EO pump 21.

  The EO pump module 2 includes a first reservoir 20, an electroosmotic flow pump (EO pump) 21, a second reservoir 22, and a pressure adjustment mechanism 80. The first reservoir 20 is connected to the inlet side of the EO pump 21 and has a function of storing the driving liquid driven by the EO pump 21. The EO pump 21 is a pump that feeds liquid by an electric field. For example, the EO pump 21 includes an electroosmotic material made of a dielectric porous material whose surface is charged when contacted with a liquid, and an electrode that can be applied in the liquid feeding direction. I have. The second reservoir 22 is connected to the outlet side of the EO pump 21 and has a function of storing the mobile phase solvent. The mobile phase solvent is a liquid on the downstream side of the EO pump 21. The pressure adjustment mechanism 80 is provided in the second reservoir 22 and has a function of adjusting the fluid pressure of the mobile phase solvent stored in the second reservoir 22. Details of the pressure adjustment mechanism 80 will be described later.

  The EO pump module 2 is connected to the LC chip 4 via the injector 3. The injector 3 has a function of supplying the mobile phase solvent supplied from the EO pump module 2 to the chip 4. The liquid containing the target substance supplied from the injector 3 to the chip 4 is hereinafter referred to as “sample liquid”. That is, the sample liquid means a liquid containing a target substance immediately before being supplied to the chip 4. The target substance is here an inorganic ion or a soluble organic compound.

  The chip 4 is a microfluidic chip device, and includes a separation column 5 containing a filler for separating a target substance in a sample solution, a flow cell 6 for analyzing the target substance, and a detector 7. The separation column 5 is connected to the injector 3, and is configured such that the sample liquid can be injected by the injector 3. Further, the separation column 5 has a function of separating and flowing the target substance with a filler when flowing the mobile phase solvent containing the target substance therein. The flow cell 6 is connected to the outlet side of the separation column 5. Further, the flow cell 6 defines a flow path through which the target substance processed by the separation column 5 flows. The detector 7 has a function of detecting a substance contained in the sample liquid on the basis of characteristics obtained by applying a voltage to a target substance flowing through the flow path defined by the flow cell 6. ing. The mobile phase solvent containing the target substance after analysis is released as a waste liquid.

  Next, details of each component of the LC device 1 will be described. FIG. 2 is a schematic diagram showing a liquid delivery system configuration of the LC device 1. FIG. 2 is a schematic diagram showing a liquid delivery system configuration between the EO pump module 2 and the injector 3. In addition, since the LC apparatus 1 according to the present embodiment may include a plurality of EO pump modules 2, a case where two EO pump modules 2 illustrated in FIG. 1 are provided will be described here.

  As shown in FIG. 2, the liquid feeding system of the LC device 1 includes EO pump modules 2 a and 2 b, two-way valves 9 a and 9 b, and a four-way valve 10. The EO pump module 2a is connected to the injector 3 via a two-way valve 9a and a four-way valve 10. Similarly, the EO pump module 2b is connected to the injector 3 via a two-way valve 9b and a four-way valve 10. That is, the EO pump modules 2a and 2b are connected to the injector 3 in parallel.

  Flow rate sensors 8a and 8b are disposed between the EO pump modules 2a and 2b and the two-way valves 9a and 9b. The control unit 11 is connected to the flow rate sensors 8a and 8b, and is configured to be able to acquire the flow rate detected by the flow rate sensors 8a and 8b. The control unit 11 is connected to the battery 12 and the EO pump modules 2a and 2b, and has a function of applying a voltage to the EO pump modules 2a and 2b using the battery 12 as a power source. That is, the control unit 11 is configured to be able to perform PID control and feedback control based on the flow rate detected by the flow rate sensors 8a and 8b. The control unit 11 may be configured to be able to control the opening and closing of the two-way valves 9a and 9b and the four-way valve 10. With the above configuration, the mobile phase solvent is selectively supplied from one of the pump modules 2a and 2b to the injector 3, or the mobile phase solvent is supplied from both the pump modules 2a and 2b to the injector 3.

  Next, details of the separation column 5 will be described with reference to FIGS. 3 and 4 are a plan view and a cross-sectional view illustrating the separation column 5. As shown in FIGS. 3 and 4, a circular hollow separation column 5 extending from one end of the substrate 40 in a direction orthogonal to the thickness direction is formed inside the rectangular plate-shaped substrate 40. An inlet 5 a connected to the injector 3 is formed on the distal end side of the separation column 5 (that is, one end portion side of the substrate 40). On the other hand, a frit extending in the thickness direction and communicating with the outlet 41 on one main surface side of the substrate 40 is provided on the end side of the separation column 5. The diameter of the frit is made smaller than the diameter of the separation column 5. The mobile phase solvent supplied from the inlet 5a by the injector 3 passes through the separation column 5, and is output from the outlet 41 through the frit. In addition, the board | substrate 40 is a rectangle whose main surface is 60 mm x 50 mm, for example, and the thickness is 1.7 mm. The separation column 5 is, for example, a circular section with a diameter of 0.8 mm and a length of 30 mm. For example, the outlet 41 has a cross section of 0.1 to 0.2 mm.

  FIG. 5 is a schematic diagram illustrating in detail the configuration downstream of the injector 3. The EO pump module 2 is connected to the injector 3 by a tube 50. The injector 3 is connected to the separation column 5 of the substrate 40 by a tube 51. For example, PEEK (Poly Ether Ether Ketone) is used as the material of the tube 51.

  A filler 70 is held in the separation column 5. The filler 70 is not limited to the type, and can be used alone or in combination as long as the filler is used for reverse phase chromatography, ion chromatography, gel chromatography, and affinity chromatography. Further, in order to hold the filler 70 in the separation column, the glass wool 52 is disposed on the end side of the separation column 5 and in a portion communicating with the frit. The frit portion may be a porous filter.

  The flow cell 6 is detachably attached to the substrate 40, and defines a flow path through which a mobile phase solvent containing a target substance can flow between the main surface of the substrate 40. An electrode 53 connected to the detector 7 of FIG. 1 is disposed on the main surface of the substrate 40 that defines the flow path. The target substance is supplied to the flow path from the outlet 41 of the separation column 5, is electrochemically detected via the electrode 53, and is discarded from the tube 54 as a waste liquid after analysis.

  Next, details of the EO pump module 2 will be described. 6A and 6B are schematic diagrams for explaining the EO pump module 2. FIG. 6A shows the EO pump module 2 before driving, and FIG. 6B shows the EO pump module 2 during driving.

  As shown in FIG. 6 (a), the EO pump module 2 includes a housing whose interior is separated into two spaces 20 and 22 by a fixed plate 23, so-called indirect drive type EO pump. It is supposed to be a module. The first reservoir 20 stores a driving liquid, and the second reservoir 22 stores a mobile phase solvent. The fixed plate 23 is provided with an EO pump 21 so that the driving liquid in the first reservoir 20 can be conveyed to the second reservoir 22 side. A flexible variable membrane 24 is provided on the second reservoir 22 side of the fixed plate 23 to transmit the pressure of the driving liquid to the mobile phase solvent and function so that the driving liquid does not enter the mobile phase solvent. It has been. Further, a through hole 22 a communicating with the inside is formed in the side wall of the second reservoir 22, and an insertion member 26 for adjusting the fluid pressure of the mobile phase solvent is attached. That is, the through hole 22 a and the insertion member 26 function as the pressure adjustment mechanism 80. For example, a screw hole is adopted as the through hole 22a, and a screw screwed into the screw hole is adopted as the insertion member 26. The insertion member 26 is inserted into the second reservoir 22 after the mobile phase solvent is stored in the second reservoir 22 and before the EO pump 21 is driven. As a result, the internal volume of the second reservoir 22 is reduced and the mobile phase solvent is pressurized. As described above, the pressure adjusting mechanism 80 has a function of adjusting the fluid pressure to increase. When the EO pump 21 is driven with the pressure adjusted by the pressure adjusting mechanism 80 as shown in FIG. 6B, the driving fluid is supplied from the first reservoir 20 into the second reservoir 22 and is variable. The membrane 24 is pressurized and deforms. Then, the pressurized mobile phase solvent is released from the output nozzle 25.

  Next, the operation of the LC device 1 according to this embodiment will be briefly described. It is assumed that the driving liquid and the mobile phase solvent are respectively injected into the first reservoir 20 and the second reservoir 22 of the EO pump module 2. Before starting the EO pump 21, the pressure adjustment mechanism 80 adjusts the fluid pressure of the mobile phase solvent stored in the second reservoir 22 provided on the downstream side of the EO pump 21 (pressure adjustment step). For example, when the insertion member 26 protrudes into the second reservoir 22, the internal volume of the second reservoir 22 is reduced to increase the pressure. Thereafter, the EO pump 21 is activated to perform liquid feeding. Note that this series of operations may be performed manually, or may be performed automatically using the activation of the EO pump 21 as a trigger.

  Next, the function and effect of the LC device 1 according to this embodiment will be described. First, a conventional EO pump module will be outlined in order to compare with the operational effects of the LC device 1 according to the present embodiment. Since the conventional EO pump module does not have the pressure adjustment mechanism shown in the present embodiment, the power consumption of the EO pump 21 tends to be large. FIG. 7 is a schematic diagram for explaining the operation and effect of the conventional EO pump module. As shown in FIG. 7A, when the mobile phase solvent is injected into the second reservoir 22, it is difficult to completely fill the inside of the second reservoir 22 with the mobile phase solvent. May remain. As shown in FIG. 7B, such an air bubble A is gradually crushed as the internal pressure of the second reservoir 22 increases when the EO pump 21 is driven. Then, as shown in FIG. 7C, when the air bubble A becomes small to some extent, the mobile phase solvent is released from the output nozzle 25. As described above, since the air bubble A exists on the downstream side of the EO pump 21, the EO pump 21 needs to be driven to crush the air bubble A. As a result, power consumption increases.

  On the other hand, the EO pump module 2 of the LC device 1 according to the present embodiment includes a pressure adjustment mechanism on the downstream side of the EO pump 21 as shown in FIG. Therefore, as shown in FIG. 8A, even when the air bubble A remains in the second reservoir 22, the insertion member 26 is moved to the second reservoir 22 as shown in FIG. The air bubble A can be crushed by inserting it into the reservoir 22 and pressurizing the mobile phase solvent. Then, as shown in FIG. 8C, when the EO pump 21 is driven in this state, the mobile phase solvent is released from the output nozzle 25. As described above, the EO pump 21 can perform liquid feeding without extra driving for crushing the air bubbles A. As a result, power consumption can be suppressed.

  FIG. 9 is a graph showing the flow rates of the EO pump module 2 and the conventional EO pump module of the LC device 1 according to this embodiment in time series. As indicated by G2 in FIG. 9, in the case of a conventional EO pump module, time t2 is required until the target flow rate (rated flow rate) can be stably supplied from startup. This is because the EO pump 21 needs to be driven to apply pressure due to the above-described air bubble A or loosening of the internal structure. For example, it is assumed that the second reservoir 22 needs to be pressurized to 10 atm in order to obtain a predetermined flow rate. At this time, assuming that 1 mL of air bubbles A remain, in order to flow the driving liquid with the EO pump 21 and pressurize to 10 atmospheres, it is necessary to flow the driving liquid at least until the bubbles contract to 1/10. Therefore, it is necessary to flow 900 μL of driving liquid. Assuming that the flow rate of the EO pump 21 is 50 μL / min at the maximum, it takes at least 18 minutes just to increase the pressure. Since the EO pump 21 consumes a lot of electric power by such initial driving, battery driving is difficult and a household power source or the like is used. For this reason, when a conventional EO pump module is employed in an LC device, it is difficult to realize portability.

  On the other hand, according to the EO pump module 2 of the LC device 1 according to the present embodiment, the target flow rate can be stably supplied from the start-up at a time t1 shorter than the time t2, as indicated by G1 in FIG. For example, the activation time can be about 5 minutes. That is, by pressurizing by the pressure adjusting mechanism 80 before starting, it is possible to start driving at a high flow rate from the beginning as shown in P1 and P2 without performing pressurization for canceling air bubbles A and looseness of the equipment. it can. In this way, it is possible to reduce the influence of air bubbles A that are difficult to remove or the looseness of the internal structure. Note that the slope indicated by P2 is the same as the slope of G2.

  As described above, in the LC device 1 and the LC according to the first embodiment, the pressure is stored in the second reservoir 22 provided on the downstream side of the EO pump 21 by the pressure adjusting mechanism 80 disposed on the downstream side of the EO pump 21. The fluid pressure of the mobile phase solvent is adjusted. As described above, by providing the pressure adjusting mechanism 80 independently of the EO pump 21, the fluid of the mobile phase solvent on the downstream side of the EO pump 21 in order to avoid the EO pump 21 being driven for purposes other than liquid feeding. The pressure can be adjusted. For this reason, since it becomes possible to avoid giving an extra load to EO pump 21, the power consumption of EO pump 21 can be controlled. Moreover, since it becomes possible to drive the LC apparatus 1 by a battery by suppressing the power consumption of the EO pump 21, it can provide portability as a result.

  In the LC device 1 and LC according to the first embodiment, the EO pump 21, the second reservoir 22, and the pressure adjustment mechanism 80 are integrated as the EO pump module 2, so that only the pump module can be replaced. Therefore, it is excellent in versatility.

(Second Embodiment)
The LC device 1 according to the second embodiment is configured in substantially the same manner as the LC device 1 according to the first embodiment, and only the configuration of the chip 4 is installed. For this reason, in 2nd Embodiment, it demonstrates centering around difference with 1st Embodiment, and the overlapping description is abbreviate | omitted.

  The chip 4 of this embodiment is different in that it includes a flow cell 6 and a detector 7 for ultraviolet light detection or visible light detection instead of the flow cell 6 and the detector 7 described in the first embodiment. In the case of detecting ultraviolet rays, the flow cell 6 is made of quartz, and in the case of detecting only visible light, the flow cell 6 is made of borosilicate glass such as Pyrex (registered trademark) or silicone elastomer such as polydimethylsiloxane. FIG. 10 is a cross-sectional view illustrating the configuration of the chip 4. As shown in FIG. 10, a flow cell 6 having an optical path 61 formed therein is detachably attached to the exit side of the separation column 5 of the substrate 40. The flow cell 6 is attached to the main surface of the substrate 40 by an adhesive layer 58 in a state where the target substance contained in the mobile phase solvent output from the outlet 41 of the separation column 5 passes through the optical path 61. Yes. A plate-like member 59 is disposed on the other main surface of the substrate 40. Further, a set of pressing plates 55 are arranged to face each other with the flow cell 6, the substrate 40, and the plate-like member 59 interposed therebetween, and are screwed in a state of being pressed in the overlapping direction of the members by bolts 56 and nuts 57. A pair of optical fibers 62 are arranged opposite to each other with the optical path 61 interposed therebetween, and are attached by fitting so that the optical axis O and the optical path 61 coincide. Other configurations are the same as those of the LC device 1 according to the first embodiment.

  The target substance supplied from the injector 3 is separated by the separation column 5 and supplied to the optical path 61 inside the flow cell 6. At this time, ultraviolet rays are emitted from one optical fiber 62 and irradiated onto the target substance in the optical path 61. Then, transmitted light is acquired by the other optical fiber 62. The substance contained in the sample can be detected by measuring the amount of ultraviolet absorption.

  As described above, the LC device 1 and the LC according to the second embodiment have the same effects as the LC device 1 and the LC according to the first embodiment. Moreover, since the flow cell 6 is configured to be detachable from the substrate 40 as in the first embodiment, a different detector 7 can be employed using the same separation column 5, so that it is excellent in versatility and selected. And multifaceted analysis is possible.

  Each embodiment mentioned above shows an example of LC device and LC concerning the present invention. The LC device and the LC according to the present invention are not limited to the LC device 1 and the LC according to each embodiment, and the LC device and the LC according to each embodiment are within a range not changing the gist described in each claim. It may be modified or applied to others.

  For example, in the LC device 1 according to the above embodiment, the example in which the pressure adjustment mechanism 80 is provided in the second reservoir 22 has been described, but the pressure adjustment mechanism 80 may be provided in another location. For example, the pressure adjustment mechanism 80 may be provided in a flow path on the downstream side of the EO pump 21. The flow path is not particularly limited as long as it is downstream of the EO pump 21, but is preferably a portion to which pressure is directly applied from the EO pump 21 when the EO pump 21 is started. For example, the EO pump 21 and the separation column 5 In the case where a valve or the like is disposed in the flow path between the two, the upstream side of the valve is preferable.

  Further, in the LC device 1 according to the above embodiment, the example in which the indirect drive type EO pump 21 is employed has been described, but the present invention is not limited to this, and the downstream side of the EO pump 21 is filled with liquid. Any LC device that is driven from the state in which it is operated can be employed.

  In the LC device 1 according to the above embodiment, the pressure adjustment timing of the pressure adjustment mechanism 80 has been described as before the EO pump 21 is started. However, even after the EO pump 21 is started, the pressure adjustment timing is set to the predetermined time shown in FIG. If it is before a certain time t2, the effect of the present invention can be achieved. That is, the fluid pressure may be adjusted during the activation of the electroosmotic pump until the rated flow rate is reached.

  Moreover, although it demonstrated as the LC apparatus 1 or LC in the said embodiment, this invention may be a high performance liquid chromatograph (HPLC apparatus) or a high performance liquid chromatography.

  In the above embodiment, the injector 3 has been described as a component outside the chip 4. However, the injector 3 may be included in the chip 4.

  In the above-described embodiment, an example in which a screw is employed as the insertion member 26 has been described. However, pressurization may be performed using a syringe-like member, a film-like member, or the like. Further, when the insertion member 26 is deformed or inserted, a medium such as gas or liquid may be used as power transmission. Further, a series of operations of the insertion member 26 may be performed manually, or may be performed automatically using the activation of the EO pump 2 as a trigger.

  A case where a syringe is used will be described. For example, an adjustment line including a syringe and a valve is attached to the second reservoir 22, and the second reservoir 22 filled with liquid is set. Thereafter, the EO pump 2 is started and the pressure is increased with a syringe while monitoring the flow rate. When the prescribed flow rate is approached, the syringe is isolated by a valve and switched to automatic control. In addition, you may perform this operation automatically not with a manual but with a pump. For example, a system that employs an adjustment line equipped with a syringe pump and increases the pressure by the operation of the syringe pump is also possible. Compared to the screw method described in the above embodiment, it is expected that the remaining pressure adjustment is large and the operability is improved as compared with the screw method. Note that this method may be applied to the first reservoir 20.

  A case where a film-like member is used will be described. In the pneumatic method, the apparatus is separately provided with a small compressed air container and a pressure regulator. When pressurizing the solvent in the second reservoir 22, a film-like material that deforms by pressurization is provided in the second reservoir 22, and the solvent is pressurized by deforming this. When pressurizing the driving liquid inside the first reservoir 20, the reservoir (driving liquid) pressure is increased by liquid air. In this case, it is also possible to increase the flow rate of the base by this pressurization and perform fine adjustment with the EO pump 2. Furthermore, a system in which both the driving liquid and the solvent are pressurized simultaneously is possible. In this case, the start-up time can be shortened without degrading the performance of the EO pump 2.

Hereinafter, examples carried out by the present inventor will be described in order to explain the above effects.
Example 1
It was verified whether the LC device according to the present invention can be used for a long time by battery driving. The apparatus configuration is the same as that of the LC apparatus 1 according to the first embodiment shown in FIGS. Moreover, as shown in FIG. 2, it was set as the structure which employ | adopts two EO pump modules 2a and 2b, and used only the EO pump module of one side among them. The battery 12 employs eight AA alkaline batteries in series. The measurement conditions were PID control and the flow rate was 5.00 μL / min. The driving liquid was purified water (deionized water) twice, and the liquid sending solvent (mobile phase solvent) was methanol (100%). Under the above conditions, the detection amount by the flow sensor built in the pump and the detection amount by the flow sensor arranged between the EO pump module 2 and the injector 3 were measured. The results are shown in FIG.

  FIG. 11A shows the amount detected by the flow sensor built in the pump, and FIG. 11B shows the amount detected by the flow sensor arranged between the EO pump module 2 and the injector 3. As shown in FIG. 11, the power was turned off after 26 hours. The voltage before the start of the dry battery was 12.98V, and the voltage after the end was 9.84V. The sharp peak seen between 13h and 20h is noise and is essentially irrelevant. For this reason, even when a dry cell is adopted as the battery 12, it was proved that it can be used for at least about 24 hours. In addition, if there are 24 hours, sufficient time can be left for analysis even if the separation column 5 is washed, pre-prepared, and the like.

(Example 2)
It was verified whether or not chromatography was possible using an EO pump. It was verified whether or not four types of phenols, catechins, catecholamines and amino acids were detectable. Amino acids are reacted with Succinimidyl (2R) -6- (Tetrahydro-2H-pyran-2-yloxy) -2,5,7,8-tetramethylchroman-2-carboxylate before being introduced from injector 3 to produce an electroactive substance. Derivatized. The apparatus configuration was the same as in Example 1. The measurement conditions were PID control and the flow rate was 5.00 μL / min. The driving liquid was purified water (deionized water) twice, and the liquid sending solvent (mobile phase solvent) was changed according to the component to be detected. In the case of catechins, water, methanol and 0.5 M phosphoric acid were used in a ratio of 7: 2: 1. In the case of phenols, 0.05M NaClO ₄ aqueous solution and methanol were used in a ratio of 5: 5. In the case of catecholamine, when A is 50 mM phosphoric acid, 50 mM citric acid, 100 mg / L octanesulfonic acid and 40 mg / L EDTA-2Na aqueous solution (pH 3.0), and B is methanol, A: B The ratio was set to 95: 5. In the case of amino acids, water, methanol and 0.5 M sodium perchlorate were used in a ratio of 5: 4: 1. For catechins, phenols, and catecholamines, the detection potential was 0.6 V, and for amino acids, the detection potential was 0.4 V. The experimental results are shown in FIG.

  FIG. 12A shows the detection result of catechins, FIG. 12B shows the detection result of phenols, FIG. 12C shows the detection result of catecholamine, and FIG. 12D shows the detection result of amino acids. As shown in FIG. 12 (a), catechin represented by CA, epigallocatechin gallate represented by EGCg, epicatechin represented by EC, and epicatechin gallate represented by ECg were well detected. Moreover, as shown in FIG.12 (b), the peak of the phenol shown by P, 2-methylphenol shown by 2-MP, 2-ethylphenol shown by 2-EP, and 2-propylphenol shown by 2-PP is shown. Good detection. Moreover, as shown in FIG.12 (c), the peak of noradrenaline shown by NA, the adrenaline shown by AD, and the dopamine shown by DA was detected favorably. Furthermore, as shown in FIG. 12 (d), the peaks of glycine indicated by Gly, tyrosine indicated by Tyr, and valine indicated by Val were detected well. As described above, it was demonstrated that chromatography is possible using an EO pump.

Next, the effect of the pressure adjustment mechanism 80 was verified.
(Example 3)
The apparatus configuration is the same as that of the LC apparatus 1 according to the first embodiment shown in FIGS. As the EO pump module 2 connected to the LC device 1, a pump module having a capacity of about 100 mL was adopted. Further, the pressure of the second reservoir 22 was adjusted by the pressure adjusting mechanism 80 before the EO pump 21 was started. The voltage (applied voltage) to the electroosmotic material was set to 48 V by a booster circuit.
(Comparative Example 1)
The configuration was the same as that of Example 3 except that the pressure adjustment mechanism 80 was not provided. The applied voltage was 60V.

  About said comparative example 1 and Example 3, the flow rate was set to 2.00 microliters / min by PID control, and the flow rate was measured in time series. The results are shown in FIG. FIG. 13A shows the time dependency of the flow rate of Comparative Example 1, and FIG. 13B shows the time dependency of the flow rate of Example 3. As shown in FIG. 13A, in Comparative Example 1 that does not include the pressure adjustment mechanism 80, the time required to reach the set flow rate of 2.00 μL / min was about 2 hours. On the other hand, as shown in FIG. 13B, in Example 3 including the pressure adjustment mechanism 80, the time required to reach the set flow rate of 2.00 μL / min was about 0.4 hours. As described above, by providing the pressure adjustment mechanism 80, even when the applied voltage is lower than when pressure is not adjusted, the time required to reach the set flow velocity is reduced to about 1/5. The effect of the present invention was proved.

  DESCRIPTION OF SYMBOLS 1 ... LC apparatus (liquid chromatograph), 2 ... EO pump module (electroosmotic flow pump module), 5 ... Separation column, 7 ... Detector, 12 ... Battery, 21 ... EO pump (electroosmotic flow pump), 22 ... Second reservoir, pressure adjustment mechanism 80.

Claims (9)

A liquid chromatograph for analyzing a sample solution containing an inorganic ion or a soluble organic compound as a target substance,
An electroosmotic pump for conveying the mobile phase solvent;
A separation column disposed downstream of the electroosmotic flow pump and holding a filler therein;
A detector that is disposed downstream of the separation column and that analyzes a target substance output from the separation column;
Fluid pressure of the mobile phase solvent stored in a reservoir or a fluid pressure stored in a flow path, which is disposed downstream of the electroosmotic pump and stored in a reservoir provided downstream of the electroosmotic pump A pressure adjusting mechanism for adjusting
With
The pressure adjusting mechanism is a liquid chromatograph that adjusts a fluid pressure before starting the electroosmotic flow pump or during starting the electroosmotic flow pump until the rated flow rate is reached. A liquid chromatograph for analyzing a sample solution containing an inorganic ion or a soluble organic compound as a target substance,
An electroosmotic pump for conveying the mobile phase solvent;
A separation column disposed downstream of the electroosmotic flow pump and holding a filler therein;
A detector that is disposed downstream of the separation column and that analyzes a target substance output from the separation column;
Fluid pressure of the mobile phase solvent stored in a reservoir or a fluid pressure stored in a flow path, which is disposed downstream of the electroosmotic pump and stored in a reservoir provided downstream of the electroosmotic pump A pressure adjusting mechanism for adjusting
With
The pressure adjusting mechanism is a liquid chromatograph that pressurizes by reducing the internal volume of the reservoir or the internal volume of the flow path. A liquid chromatograph for analyzing a sample solution containing an inorganic ion or a soluble organic compound as a target substance,
An electroosmotic pump for conveying the mobile phase solvent;
A separation column disposed downstream of the electroosmotic flow pump and holding a filler therein;
A detector that is disposed downstream of the separation column and that analyzes a target substance output from the separation column;
Fluid pressure of the mobile phase solvent stored in a reservoir or a fluid pressure stored in a flow path, which is disposed downstream of the electroosmotic pump and stored in a reservoir provided downstream of the electroosmotic pump A pressure adjusting mechanism for adjusting
With
The pressure adjustment mechanism is
A screw hole provided in the reservoir or the flow path and penetrating to the inside;
A screw inserted into the screw hole and protruding into the reservoir or the flow path;
A liquid chromatograph comprising: A liquid chromatograph for analyzing a sample solution containing an inorganic ion or a soluble organic compound as a target substance,
An electroosmotic pump for conveying the mobile phase solvent;
A separation column disposed downstream of the electroosmotic flow pump and holding a filler therein;
A detector that is disposed downstream of the separation column and that analyzes a target substance output from the separation column;
Fluid pressure of the mobile phase solvent stored in a reservoir or a fluid pressure stored in a flow path, which is disposed downstream of the electroosmotic pump and stored in a reservoir provided downstream of the electroosmotic pump A pressure adjusting mechanism for adjusting
With
A liquid chromatograph in which the electroosmotic flow pump, the reservoir, and the pressure adjusting mechanism are integrated as a pump module. The liquid chromatograph according to any one of claims 1 to 4 , wherein the pressure adjustment mechanism adjusts the fluid pressure to increase. The liquid chromatograph as described in any one of Claims 1-5 provided with the battery used as the power supply of the said electroosmotic flow pump. A flow cell for circulating the target substance output from the separation column;
The liquid chromatograph according to any one of claims 1 to 6 , wherein the flow cell and the detector are detachably attached to a substrate in which the separation column is formed. A liquid chromatography for analyzing a sample liquid containing an inorganic ion or a soluble organic compound as a target substance by an electroosmotic flow pump to a separation column,
The electroosmotic pump is disposed downstream of the electroosmotic flow pump before starting the electroosmotic flow pump or during activation of the electroosmotic flow pump until the rated flow rate is reached, and a reservoir provided downstream of the electroosmotic flow pump A liquid chromatography comprising a pressure adjustment step of adjusting a fluid pressure of a stored mobile phase solvent or a fluid pressure of the mobile phase solvent stored in a flow path. The liquid chromatography according to claim 8 , wherein in the pressure adjusting step, pressurization is performed by decreasing an internal volume of the reservoir or an internal volume of the flow path.

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