Analytical device and analytical method

Abstract

In an analytical device and an analytical method using the FIA ​​method, the quantitativeness of analysis of a detection target of a bacterial-derived substance containing endotoxin is improved. [Solution] The analytical apparatus includes a membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane, a flow injection system that analyzes sample water through a reaction between a detection target contained in the sample water and a reagent contained in carrier water that reacts with the detection target, a first pipe through which concentrated water in which the detection target has been concentrated by the membrane filtration device flows into the flow injection system as sample water, and a pump that pressurizes the sample water in the first pipe.

Description

[Technical field]

[0001] The present disclosure relates to an analysis device and an analysis method. [Background technology]

[0002] Patent Document 1 describes a flow injection analysis (FIA) method in which a liquid-liquid mixture consisting of an organic phase and an aqueous phase is introduced into the inner tube of a double tube consisting of an inner tube made of a porous polymer membrane and an outer tube that encloses the inner tube, or into a region surrounded by the inner tube and the outer tube, and only the organic phase is allowed to permeate through the wall surface of the inner tube made of a porous polymer membrane to separate the organic phase and the aqueous phase, and the resulting organic phase is introduced into a detection section to analyze the target element.

[0003] In general, endotoxin is a pyrogen that must not be contained in pharmaceutical water such as purified water and water for injection (WFI). Therefore, when producing purified water, water for injection (WFI), etc., it is necessary to remove endotoxin as much as possible, and online monitoring is also required. Online measurement is required to be able to quantify endotoxin down to low concentrations, and to measure it accurately and stably.

[0004] The inventors have performed low-concentration analysis of endotoxins and the like by using an FIA analysis method using a fluorescent substance in Patent Document 2 and the like. However, it has been difficult to measure the low concentrations required for online measurement. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 62-280652 [Patent Document 2] Patent Publication No. 2022-011525 Summary of the Invention [Problem to be solved by the invention]

[0006] When analyzing bacterial substances containing endotoxins using an online analytical device and analytical method that uses flow injection analysis (hereinafter abbreviated as "FIA"), it is difficult to perform quantitative analysis even when the concentration of the bacterial substance is low.

[0007] An object of the present disclosure is to improve the quantitativeness of analysis in an online analysis device and analysis method using the FIA ​​method. [Means for solving the problem]

[0008] The analytical apparatus of the first embodiment includes a membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane, a flow injection system that analyzes sample water from a reaction between a detection target contained in the sample water and a reagent contained in carrier water that reacts with the detection target, a first pipe through which concentrated water in which the detection target has been concentrated by the membrane filtration device flows into the flow injection system as the sample water, and a pump that pressurizes the sample water in the first pipe.

[0009] In this analysis device, the membrane filtration device is equipped with a microfiltration membrane or an ultrafiltration membrane. By passing the water to be analyzed through the membrane filtration device, concentrated water in which the detection target is concentrated is obtained. The concentrated water is pressurized by a pump in the first pipe as sample water and flows into the flow injection system. In the flow injection system, the sample water is analyzed from a reaction with a reagent contained in the carrier water. In this way, the concentrated water in which the detection target is concentrated by the membrane filtration device is sent to the flow injection system as sample water, so that the quantitativeness of the analysis of the sample water for the detection target of bacteria-derived substances including endotoxins can be improved.

[0010] The analytical device of the second aspect is the first aspect, wherein an inner diameter of an outlet pipe in the flow injection system is smaller than an inner diameter of the first pipe.

[0011] This allows the water pressure of the sample water downstream of the pump in the first pipe to be maintained higher than the water pressure of the sample water upstream of the pump, and the flow rate of the sample water discharged from the pump can be stabilized, thereby increasing the concentration rate of the detection target in the sample water.

[0012] In a third aspect of the analytical device, in the first or second aspect, the membrane filtration device has a discharge part that is open to the outside and through which permeated water that has permeated the ultrafiltration membrane is discharged.

[0013] By discharging most of the permeated water that has permeated the ultrafiltration membrane of the membrane filtration device from the discharge section, the amount of permeated water discharged per unit time in the membrane filtration device can be increased, and the concentration of the concentrated water can be increased.

[0014] The analytical device of a fourth aspect is the third aspect, further comprising a second pipe through which at least a portion of the permeated water from the membrane filtration device flows as the carrier water into the flow injection system.

[0015] Since no device for obtaining carrier water is required, the configuration of the analysis device can be simplified.

[0016] In a fifth aspect of the analysis device, in the fourth aspect, the membrane filtration device has a connection port to which the second pipe is connected.

[0017] By connecting the second pipe to the connection port of the membrane filtration device, the permeate water from the membrane filtration device can be sent to the second pipe as carrier water without being exposed to the outside air, thereby preventing foreign matter from being mixed into the carrier water.

[0018] The analytical device of a sixth aspect is any one of the first to fourth aspects, wherein the pressure on the inlet side of the membrane filtration device is lower than the pressure at the outlet part of the pump and is 0.05 MPa or more.

[0019] By setting the pressure on the inlet side of the membrane filtration device in this manner, the quantitativeness of the analysis of the sample water can be improved.

[0020] The seventh aspect of the analytical method involves producing sample water in which the target substance is concentrated using a membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane, pressurizing the sample water using a pump and sending it to a flow injection system, and analyzing the sample water in the flow injection system from the reaction between the target substance and a reagent contained in carrier water that reacts with the target substance.

[0021] In this analysis method, the membrane filtration device is equipped with a microfiltration membrane or an ultrafiltration membrane. By passing the water to be analyzed through the membrane filtration device, concentrated water in which the detection target is concentrated is obtained. The concentrated water is pressurized by a pump and sent to a flow injection system as sample water. In the flow injection system, the detection target is analyzed from a reaction with a reagent contained in carrier water. In this way, the concentrated water in which the detection target is concentrated by the membrane filtration device is sent to the flow injection system as sample water, so that the quantitativeness of the analysis of the detection target for bacteria-derived substances containing endotoxins can be improved.

[0022] An eighth aspect of the analysis method is the seventh aspect, wherein the water pressure downstream of the pump is higher than the water pressure upstream of the pump.

[0023] This makes it possible to stabilize the flow rate of the sample water discharged from the pump, thereby increasing the concentration rate of the detection target in the sample water.

[0024] In a ninth aspect of the analysis method according to the seventh or eighth aspect, in the membrane filtration device, permeated water that has permeated the ultrafiltration membrane is discharged outside the membrane filtration device under no pressure.

[0025] By discharging most of the permeated water that has permeated the ultrafiltration membrane of the membrane filtration device from the discharge section under no pressure, the discharge amount per unit time in the membrane filtration device can be increased, and the concentration of the concentrated water can be increased.

[0026] In a tenth aspect of the analysis method according to the ninth aspect, at least a portion of the permeate from the membrane filtration device is sent to the flow injection system as the carrier water.

[0027] Since a step for obtaining carrier water is not required, the procedure of the analysis method can be simplified.

[0028] In an eleventh aspect of the analysis method, in any one of the seventh to tenth aspects, the pressure on the inlet side of the membrane filtration device is set to be lower than the pressure at the outlet part of the pump and to be 0.05 MPa or higher.

[0029] By setting the pressure on the inlet side of the membrane filtration device in this manner, the quantitativeness of the analysis of the sample water can be improved. Effect of the Invention

[0030] The technique disclosed herein makes it possible to improve the quantitativeness of analysis in an analysis device and analysis method using the FIA ​​method. [Brief description of the drawings]

[0031] [Figure 1] FIG. 1 is a configuration diagram showing the analysis device of the first embodiment. [Diagram 2] FIG. 2 is a configuration diagram showing an analysis device according to a modified example of the first embodiment. [Diagram 3] FIG. 3 is a block diagram showing the analysis device of the eighth embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] The analysis device 12 according to the first embodiment will be described below with reference to the drawings. As shown in FIG. 1, the analysis device 12 analyzes water obtained from a water treatment system (not shown) or water in the middle of treatment. In this embodiment, the analysis device 12 analyzes endotoxin contained in the analysis target. Endotoxin is an example of a substance derived from bacteria, and is also an example of a detection target in the disclosed technology. That is, in the analysis device 12 and analysis method of the disclosed technology, a substance derived from bacteria containing endotoxin is detected as a detection target. The detection target is not limited to endotoxin, i.e., lipopolysaccharide used to constitute the cell wall of gram-negative bacteria, but may be, for example, various kinds of fungi (the bacteria themselves).

[0033] Examples of water obtained by the water treatment system include, but are not limited to, water for injection, water for pharmaceutical use, etc. Specific examples of the water treatment system include equipment for producing water for pharmaceutical use such as purified water, water for injection (WFI), etc.

[0034] The analyzer 12 includes a preconcentration section 12A, a reagent mixing section 12B, and a detection section 12C.

[0035] In the illustrated example, the preconcentration section 12A has a preconcentration pump 14 and a membrane filtration device 16. Water to be analyzed is sent to the preconcentration pump 14 from a water treatment system. The preconcentration pump 14 pressurizes the water to be analyzed and sends it to the downstream membrane filtration device 16 through piping 18. Note that, for example, when the analyzer 12 is directly attached to the sampling line of a purified water production system or an ultrapure water production system for online measurement, the preconcentration pump 14 is not necessary if the pressure of the sampling line is appropriate. Also, if the pressure of the sampling line is higher than the appropriate pressure, a pressure reducing means such as a pressure reducing valve can be installed instead of the preconcentration pump 14.

[0036] The membrane filtration device 16 has an outer cylinder 20. An inlet section 22 is provided at one end in the longitudinal direction of the outer cylinder 20, and an outlet section 24 is provided at the other end. Furthermore, a discharge section 26 and a water supply section 28 are provided on the outer periphery of the outer cylinder 20. A pipe 18 extending from the pre-concentration pump 14 is connected to the inlet section 22. A first pipe 32, which will be described later, is connected to the outlet section 24.

[0037] A plurality of hollow fiber-shaped ultrafiltration membranes 30 are arranged inside the outer cylinder 20. The sample water flowing into the outer cylinder 20 from the inlet 22 is filtered by the ultrafiltration membrane 30. Specifically, since endotoxin does not permeate the ultrafiltration membrane 30, concentrated water in which endotoxin is concentrated is generated and reaches the outlet 24. The pore size of the ultrafiltration membrane 30 is approximately 0.01 to 0.001 μm. When a bacterial-derived substance containing endotoxin is to be detected as in the technology disclosed herein, it can be said that it is preferable to use an ultrafiltration membrane 30 having such a pore size in order to concentrate the detection target and obtain concentrated water in relation to the size of the bacterial-derived substance. Note that a microfiltration membrane may be used instead of the ultrafiltration membrane. As the ultrafiltration membrane or the microfiltration membrane, a membrane with a removal rate of the detection target of 90% or more is more preferable, and a membrane with a removal rate of 95% or more is even more preferable.

[0038] In this embodiment, cellulose acetate, polyacrylonitrile, polysulfone, polyethersulfone, modified polyethersulfone, polyvinylidene fluoride, etc. can be used as the material of the ultrafiltration membrane 30. In particular, modified polyethersulfone is preferable as the material of the ultrafiltration membrane 30 because it is difficult for it to adsorb endotoxins.

[0039] As the membrane filtration device to be used, for example, KROSFLO 20CM 5K MPES manufactured by Repligen, etc. can be used without any limitation.

[0040] The permeate that has permeated the ultrafiltration membrane 30 contains no endotoxin or only a very small amount of endotoxin. In other words, this permeate is endotoxin-free water. The endotoxin-free water is discharged from the discharge section 26 and the water supply section 28 to the outside of the membrane filtration device 16. The sample water is concentrated 10 to 100,000 times by the membrane filtration device 16. From the viewpoint of measurement accuracy, a concentration ratio of 1,000 to 100,000 times is more preferable.

[0041] The discharge port of the discharge section 26 is open. The permeate water is substantially discharged in an unpressurized state from the discharge section 26. This unpressurized state means that the permeate water discharged from the discharge section 26 is subjected to atmospheric pressure, but is not subjected to pressure exceeding the atmospheric pressure.

[0042] One end of a first pipe 32 is connected to the outlet 24 of the membrane filtration device 16. Concentrated water in which endotoxin has been concentrated in the membrane filtration device 16 flows through the first pipe 32 as sample water.

[0043] In this embodiment, the water supply unit 24 and the pump 42 are directly attached. That is, since no storage unit is provided between the water supply unit 24 and the pump 42, there is no risk of contamination of the sample water in the storage unit or evaporation of the sample water. In addition, in order to reduce the effects of contamination and evaporation in the storage unit, it is necessary to take measures such as increasing the flow rate to the storage unit and discharging part of the sample water in the storage unit, but in that case, the concentration rate decreases, and there is a risk of a decrease in measurement accuracy. In this embodiment, there is no such risk, and accurate measurement is possible.

[0044] One end of a second pipe 34 is connected to the water supply section 28 of the membrane filtration device 16. Endotoxin-free water, from which endotoxins have been removed in the membrane filtration device 16, flows as carrier water through the second pipe 34. The water supply section 28 is an example of a connection port to which the second pipe 34 is connected.

[0045] The flow injection system 40 has a pump 42. In this embodiment, the pump 42 is a plunger pump. In this plunger pump, a plunger reciprocates in a pump housing to pressurize a fluid and send it from the upstream side to the downstream side. In particular, in the example shown in FIG. 1, a double plunger pump having two plungers arranged in parallel is used as the pump 42, and is provided in common with the first pipe 32 and the second pipe 34. This allows the pump 42 to synchronously pressurize the sample water and the carrier water and send them downstream. Note that the pump 42 may also be a peristaltic pump, a syringe pump, or a solenoid pump. A plunger pump is more preferable.

[0046] A reagent injection section 44 is provided in the second pipe 34 downstream of the pump 42. In the reagent injection section 44, a reagent that reacts with endotoxin is injected into the carrier water, thereby obtaining the carrier water.

[0047] In the reagent mixing section 12B, the first pipe 32 and the second pipe 34 reach the inside of a flow injection system 40. Inside the flow injection system 40, the first pipe 32 and the second pipe 34 are joined to form a junction pipe 46. The junction pipe 46 is included in the detection section 12C.

[0048] As the reagent in the present application, it is possible to use a fluorescent reagent in which a fluorescent moiety and a recognition moiety are linked by a spacer, as described in JP 2022-011525 A, but the reagent is not particularly limited thereto.

[0049] In the junction pipe 46, the sample water flowing through the first pipe 32 and the carrier water flowing through the second pipe 34 are joined together to form the junction water. In the junction water, a reaction occurs between the endotoxin contained in the sample water and the reagent contained in the carrier water.

[0050] An analyzer 48 is disposed in the junction pipe 46. The analyzer 48 analyzes the concentration of endotoxin from the reaction between endotoxin and a reagent. In this embodiment, piping (not shown) and a quartz cell connected to the piping are disposed inside the analyzer 48. The analyzer 48 irradiates light onto the junction water flowing through the quartz cell, and detects the concentration of endotoxin from the signal intensity of the resulting fluorescence.

[0051] The analyzer 48 has an outlet pipe 50 for discharging the combined water after analysis. The inner diameter of the outlet pipe 50 is smaller than the inner diameter of the first pipe 32. This allows the downstream side of the pump 42, e.g. Exit part The pressure P2 on the inlet side of the pump 42, for example, the pressure P1 on the upstream side of the membrane filtration device 16, is set to be higher than the pressure P1.

[0052] In the analyzer 48, for example, quantification is performed by irradiating excitation light with a wavelength of 340 to 360 nm and observing the generated fluorescence of 440 to 520 nm. In the analyzer 48, the flow rate of the sample water is 0.01 to 4.00 mL / min, and by keeping the flow rate in this range, the measurement accuracy is improved.

[0053] There are no limitations on the materials of the first pipe 32, the second pipe 34, and the junction pipe 46, so long as they can carry the sample water, the carrier water, and the junction water, respectively. Similarly, there are no particular limitations on the piping of the analyzer 48, but for example, using a fused silica tube can suppress reactions between the junction water flowing inside and the piping using this fused silica tube, enabling more accurate analysis.

[0054] In this embodiment, a so-called online analysis device and online analysis method are realized in which the endotoxin concentration is analyzed by the analyzer 48 while the analysis target water is continuously flowing.

[0055] Next, the operation of the analysis device 12 and the analysis method of this embodiment will be described.

[0056] The water to be analyzed sent from a water treatment system (not shown) is pressurized by a preconcentration pump 14 and sent to a membrane filtration device 16. In the membrane filtration device 16, the water to be analyzed is filtered by an ultrafiltration membrane 30 to obtain concentrated water in which endotoxins are concentrated and permeate water that does not contain endotoxins (endotoxin-free water).

[0057] The permeated water is discharged from the discharge section 26 and the outlet section 24 to the outside of the membrane filtration device 16. In the analysis device 12 of this embodiment, the discharge port of the discharge section 26 is open, and the permeated water is discharged from the discharge section 26 under no pressure. That is, most of the permeated water that has passed through the ultrafiltration membrane 30 is discharged from the discharge section 26. Therefore, the flow rate that can be discharged is greater than in a configuration in which a pressure exceeding atmospheric pressure acts on the permeated water discharged from the discharge section 26. Endotoxins can be concentrated from a larger amount of water to be treated per unit time, and the concentration of the concentrated water can be increased. <3, 9>

[0058] Here, it is preferable that the inner diameter of the discharge section 26 is 2 mm or more and 30 mm or less, or that the linear velocity of the permeated water flowing through the discharge section 26 is 0.1 m / sec or more and 2.0 m / sec or less. In addition, it is preferable that the length of the piping of the discharge section 26 (the length from the outer tube 20 to the outlet of the discharge section 26) is 30 m or less. By setting the shape of the discharge section 26 or the linear velocity of the permeated water in this way, a sufficient amount of permeated water can be obtained, and endotoxin can be sufficiently concentrated in the membrane filtration device 16. In addition, the inlet pressure of the pump 42 downstream of the water supply section 28 can be kept within an appropriate range, and the amount of reagent added in the reagent injection section 44 can be kept appropriate, so that the measured value in the analyzer 48 becomes more stable. Note that the inner diameter of the discharge section 26 refers to the inner diameter of the part where the cross-sectional area of ​​the flow path of the discharge section 26 is the narrowest, and the above-mentioned linear flow velocity is the linear velocity at this part.

[0059] 2 as a first modified example, the discharge part 26 may be provided by branching off from between the water supply part 28 and the pump 42. In that case, the pipe diameter from the water supply part 28 to the discharge part 26 is set within the above-mentioned range, and the inner diameter of the second pipe 34 between the discharge part 26 and the pump 42 is preferably, for example, 0.5 mm or more and 2.0 mm or less.

[0060] At least a portion of the permeate that has permeated the ultrafiltration membrane 30 is sent as carrier water from the water supply section 28 through the second pipe 34 to the reagent injection section 44 of the flow injection system 40. There is no need to use another device to obtain carrier water, and it is possible to simplify the configuration of the analysis device 12 and the procedure of the analysis method. <4, 10>

[0061] When the membrane filtration device 16 is of the internal pressure type, either the method shown in FIG. 1 or the method shown in FIG. 2 can be applied, but when it is of the external pressure type, the method shown in FIG. 2 can be preferably used.

[0062] Moreover, the second pipe 34 is connected to the discharge part 26, and the permeated water is not exposed to the outside air. This makes it possible to prevent foreign matter from being mixed into the permeated water (carrier water) as endotoxin-free water. <5>

[0063] The carrier water is pressurized and sent downstream by a pump 42. Downstream of the pump 42, a reagent is injected by a reagent injector 44.

[0064] The concentrated water obtained by the membrane filtration device 16 is sent as sample water from the outlet 24 through the first pipe 32 to the reagent injection section 44 of the flow injection system 40. Then, the concentrated water is pressurized by the pump 42 and sent downstream. In the analysis device 12 of this embodiment, the concentrated water in which endotoxin has been concentrated to a high concentration by the membrane filtration device 16 is used as sample water, and the endotoxin concentration can be analyzed by the flow injection system 40. Compared to the case where the membrane filtration device 16 is not used and sample water with a low endotoxin concentration is used, the quantitativeness of endotoxin analysis can be improved. <1, 7>

[0065] The first pipe 32 is connected to the outlet 24, and the concentrated water is not exposed to the outside air. This makes it possible to prevent foreign matter from being mixed into the concentrated water (sample water).

[0066] The sample water in the first pipe 32 and the carrier water in the second pipe 34 are joined at a junction pipe 46 to become joined water. Then, a reaction occurs between the endotoxin contained in the sample water and the reagent contained in the carrier water. The joined water is then sent to an analyzer 48. In the analyzer 48, the endotoxin concentration is obtained from the reaction between the endotoxin and the reagent, and the sample water is analyzed.

[0067] In the analysis device 12 of this embodiment, the inner diameter of the outlet pipe 50 of the analyzer 48 is smaller than the inner diameter of the first pipe 32. Exit part A state is realized in which the pressure P2 at the outlet side of the pump 42 is higher than the pressure P1 at the upstream side of the membrane filtration device 16, which is the upstream side of the pump 42. Since the discharge pressure at the outlet side of the pump 42 is higher than the water pressure at the inlet side of the pump 42, the pump 42 is less affected by the water pressure at the inlet side when it is driven. In other words, the water pressure at the outlet side is dominant in the effect on the flow rate of the sample water discharged from the pump 42. Since the discharge flow rate of the sample water from the pump 42 is not affected by pressure fluctuations at the inlet side, the flow rate at the outlet side can be stabilized and maintained within a certain range. As a result, the concentration rate of endotoxin in the sample water is higher than when the discharge pressure at the outlet side of the pump 42 is lower than the water pressure at the inlet side of the pump 42. And, as the concentration rate of endotoxin increases, the signal intensity in the analyzer 48 also becomes stronger. That is, in the flow injection system 40, it is possible to improve the quantitativeness of the analysis of endotoxin. <2, 8> EXAMPLES

[0068] Next, the technology of the present disclosure will be described in more detail with reference to examples and comparative examples. However, the technology of the present disclosure is not limited to the contents of the examples shown below.

[0069] In the examples and comparative examples, the analyzer 12 of the first embodiment was used to analyze the endotoxin concentration of sample water in which endotoxin was injected into carrier water to give an endotoxin concentration of 10 nM. Specifically, the measurement range of the endotoxin concentration of the sample water by the analyzer 48 was verified.

[0070] In the examples and comparative examples, the measurement conditions were as follows: excitation wavelength 350 nm, detection fluorescence wavelength 500 nm, fluorescent reagent Zn-dpa-C2OPy (see chemical formula (1) below), and fluorescent reagent concentration at the reagent injection part 10 μM.

[0071] [ka]

[0072] In the examples and comparative examples, the measurement conditions were an excitation wavelength of 350 nm and a detection fluorescence wavelength of 500 nm.

[0073] Table 1 shows the pressure P1 at the inlet side of the membrane filtration device 16, the pressure P2 at the outlet of the pump 42, and the measurement value range of the analyzer 48 in each of the examples and comparative examples. This measurement value range is the range of values ​​actually measured as the endotoxin concentration by the analyzer 48, and specifically, the maximum and minimum values ​​obtained by performing five measurements are shown.

[0074] The pressure P1 at the inlet side of the membrane filtration device 16 can be set to a desired pressure value by a water treatment system (not shown) arranged upstream of the analysis device 12 and the preconcentration pump 14.

[0075] In Examples 1 to 7 and Comparative Examples 1 to 3 shown in Table 1, the settings of the pressures P1 and P2 in the analyzer 12 shown in FIG. 1 were changed and the ranges of the measurement values ​​were examined.

[0076] Example 8 shown in Table 1 is an example when the analyzer 52 shown in FIG. 3 is used. In this analyzer 52, a small tank 54 is installed between the outlet 24 and the pump 42 with respect to the analyzer 12 shown in FIG. 1. In this case, the sample water concentrated by the membrane filtration device 16 is once stored in the tank 54, and the stored sample water is sucked by the pump 42. The capacity of the tank 54 is 10 ml.

[0077]

Table 1

[0078] As can be seen from Table 1, in Examples 1 to 7, the relationship of P1 < P2 is satisfied, and measurement values almost equivalent to the concentration of endotoxin in the supply water are obtained as the measurement value range. That is, in Examples 1 to 7, quantitative measurement of the endotoxin concentration is possible for the sample water. This is because, in the case of Examples 1 to 7, the flow rate of the sample water flowing through the first pipe 32 is appropriately controlled, and the flow rate ratio between this sample water and the carrier water flowing through the second pipe 34 is an appropriate value. And since the endotoxin concentration of the concentrated water is high, the analyzer 48 functions properly.

[0079] In the case of Example 8, the pressures of P1 and P2 are set as specified values, and the relationship of P1 < P2 is satisfied. In Example 8, compared with other examples, the numerical values in the measurement value range tend to be larger. This is because when the sample water is received by the tank 54, contamination occurs in the tank 54. Since it is known in advance that the numerical values in the measurement value range in the case of Example 8 are measured larger than the actual values, correspondingly, for example, a predetermined correction coefficient is obtained, and the measured numerical value may be multiplied by the correction coefficient.

[0080] This Example 8 has an advantageous point that the pressure P1 can be freely set because the tank 54 does not affect the pressure in the front stage of the tank 54 on the rear stage of the tank 54.

[0081] In particular, as the value of the pressure P1, it is preferably such that the above condition of P1 < P2 is satisfied and P1 ≥ 0.03 MPa, and more preferably P1 ≥ 0.05 MPa. By setting the lower limit value of the value of the pressure P1 in this way, sufficient concentration can be performed by the ultrafiltration membrane 30, so that the measurement accuracy becomes higher. In each of the examples shown in Table 1, the smallest value of the pressure P1 is 0.03 MPa, and the next smallest value is 0.06 MPa. Substantially, as long as the pressure P1 satisfies P1 ≥ 0.05 MPa, sufficient concentration can be performed by the ultrafiltration membrane 30.

[0082] On the other hand, in Comparative Examples 1 to 3, the relationship of P1 ≥ P2 holds, and the measured value range is a value smaller than the concentration of endotoxin in the supply water. This is because, in the case of Comparative Examples 1 to 3, a large amount of sample water flows through the first pipe 32, and the flow rate ratio between this sample water and the carrier water flowing through the second pipe 34 is not appropriate, so that the reagent concentration becomes low in the confluence pipe 46, or the concentration is not stable. In addition, the amount of sample water flowing through the first pipe 32 is not stable, and the endotoxin concentration cannot be maintained high, so that the measured value does not reach the appropriate measured value range of the analyzer 48.

[0083] In addition, in the analyzer 52 shown in FIG. 3, it is also conceivable to install a pressure regulating valve instead of the tank 54. However, since there is no valve on the market that can adjust the pressure of this level of flow rate, this method cannot be implemented.

Explanation of Signs

[0084] 12 Analyzer 12A Pre-concentration section 12B Reagent mixing section 12C Detection section 14 Pre-concentration pump 16 Membrane filtration device 18 Pipe 20 Outer cylinder 22 Inlet section 24 Outlet section 26 Discharge section 28 Water supply section (an example of a connection port) 30 Ultrafiltration membrane 32 First piping 34 Second piping 40 Flow Injection System 42 Pump 44 Reagent injection section 46 Confluence pipe 48 Analyzer 50 outlet pipe 54 Tank

Claims

1. A membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane; a flow injection system for analyzing sample water based on a reaction between a detection target contained in the sample water and a reagent contained in a carrier water and reacting with the detection target; a first pipe through which concentrated water in which the detection target is concentrated by the membrane filtration device flows as the sample water into the flow injection system; a sample water pump that pressurizes the sample water in the first pipe; having An analytical device, wherein an inner diameter of an outlet pipe in the flow injection system is smaller than an inner diameter of the first pipe.

2. A membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane; a flow injection system for analyzing sample water based on a reaction between a detection target contained in the sample water and a reagent contained in a carrier water and reacting with the detection target; a first pipe through which concentrated water in which the detection target is concentrated by the membrane filtration device flows as the sample water into the flow injection system; A second pipe through which at least a portion of the permeate from the membrane filtration device flows into the flow injection system as the carrier water; a sample water pump that pressurizes the sample water in the first pipe; An analytical device having

3. A membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane; a flow injection system for analyzing sample water based on a reaction between a detection target contained in the sample water and a reagent contained in a carrier water and reacting with the detection target; a first pipe through which concentrated water in which the detection target is concentrated by the membrane filtration device flows as the sample water into the flow injection system; a second line through which the carrier water flows into the flow injection system; a sample water pump that pressurizes the sample water in the first pipe; having The membrane filtration device is an analytical device having a connection port to which the second pipe is connected.

4. A membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane; a flow injection system for analyzing sample water based on a reaction between a detection target contained in the sample water and a reagent contained in a carrier water and reacting with the detection target; a first pipe through which concentrated water in which the detection target is concentrated by the membrane filtration device flows as the sample water into the flow injection system; a sample water pump that pressurizes the sample water in the first pipe; having An analytical apparatus, wherein the pressure on the inlet side of the membrane filtration device is lower than the pressure at the outlet of the sample water pump and is 0.05 MPa or higher.

5. The membrane filtration device comprises: A discharge part is provided which is open to the outside and through which permeated water which has permeated the microfiltration membrane or the ultrafiltration membrane is discharged; 5. The analyzer according to claim 1, wherein the linear velocity of the permeated water discharged from the discharge portion is 0.1 m / sec or more and 2.0 m / sec or less.

6. A membrane filtration device having a microfiltration membrane or an ultrafiltration membrane is used to generate sample water in which the target substance is concentrated; The sample water is pressurized by a sample water pump and sent to a flow injection system; In the flow injection system, the sample water is analyzed based on a reaction between the target substance and a reagent contained in carrier water and reacting with the target substance; An analytical method, wherein the water pressure downstream of the sample water pump is higher than the water pressure upstream of the sample water pump.

7. A membrane filtration device having a microfiltration membrane or an ultrafiltration membrane is used to generate sample water in which the target substance is concentrated; The sample water is pressurized by a sample water pump and sent to a flow injection system; Sending at least a portion of the permeate that has permeated the microfiltration membrane or the ultrafiltration membrane in the membrane filtration device to the flow injection system as carrier water; In the flow injection system, the sample water is analyzed based on a reaction between the target substance and a reagent contained in the carrier water and reacting with the target substance. Analysis method.

8. A membrane filtration device having a microfiltration membrane or an ultrafiltration membrane is used to generate sample water in which the target substance is concentrated; The sample water is pressurized by a sample water pump and sent to a flow injection system; The pressure on the inlet side of the membrane filtration device is set to be lower than the pressure at the outlet of the sample water pump and is set to be 0.05 MPa or more; In the flow injection system, the sample water is analyzed based on a reaction between the target substance and a reagent contained in carrier water and reacting with the target substance. Analysis method.

9. In the membrane filtration device, The permeate that has permeated the microfiltration membrane or the ultrafiltration membrane is discharged from a discharge portion of the membrane filtration device to the outside in an unpressurized state and at a linear velocity of 0.1 m / sec or more and 2.0 m / sec or less. The analytical method according to any one of claims 6 to 8.

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