Analysis apparatus and analysis method

Abstract

To improve the quantitativity of analysis for a detection target of a microbial substance including endotoxin in an analysis apparatus and analysis method using the FIA method.SOLUTION: An analysis apparatus includes: a membrane filtration device provided with a microfiltration membrane or an ultrafiltration membrane; a flow injection system that analyzes sample water based on the reaction between a detection target contained in the sample water and a reagent contained in carrier water and reacting 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 as sample water to the flow injection system; and a pump that pressurizes the sample water in the first pipe.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present disclosure relates to an analytical apparatus and an analytical method.

Background Art

[0002] Patent Document 1 describes a flow injection analysis (FIA) method in which a liquid-liquid mixture composed of an organic phase and an aqueous phase is introduced into the inner tube of a double tube composed of an inner tube made of a porous polymer membrane and an outer tube containing this inner tube or into a region surrounded by the inner tube and the outer tube, only the organic phase is permeated through the inner tube wall surface made of the porous polymer membrane to separate the organic phase and the aqueous phase, and the obtained organic phase is introduced into a detection unit to analyze a test element.

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

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

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] In an online analyzer and an analysis method using a flow injection analysis (hereinafter abbreviated as "FIA") method, when analyzing a bacterium-derived substance containing endotoxin, it is difficult to perform quantitative analysis even when the concentration of the bacterium-derived substance is low.

[0007] An object of the present disclosure is to enhance the quantification of analysis in an online analyzer and an analysis method using the FIA method.

Means for Solving the Problem

[0008] The analyzer according to the first aspect includes a membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane, a detection target contained in sample water, and a reagent contained in carrier water that reacts with the detection target, and a flow injection system for analyzing the sample water from the reaction between them, a first pipe through which concentrated water in which the detection target has been concentrated by the membrane filtration device flows as the sample water to the flow injection system, and a pump for pressurizing the sample water in the first pipe.

[0009] In this analyzer, 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 has been concentrated can be obtained. The concentrated water flows as sample water, is pressurized by a pump in the first pipe, and flows into the flow injection system. In the flow injection system, the sample water is analyzed from the reaction with the reagent contained in the carrier water. In this way, since the concentrated water in which the detection target has been concentrated by the membrane filtration device is sent as sample water to the flow injection system, the quantification of the analysis of the sample water for the detection target of the bacterium-derived substance containing endotoxin can be enhanced.

[0010] The analyzer according to the second aspect is the same as the first aspect, except that the inner diameter of the outlet pipe in the flow injection system is smaller than the inner diameter of the first pipe.

[0011] As a result, in the first pipe, the water pressure of the sample water on the downstream side of the pump can be maintained higher than the water pressure on the upstream side of the pump. Since the flow rate of the sample water discharged from the pump can be stabilized, the concentration magnification of the detection target in the sample water can be increased.

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

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

[0014] In the analyzer according to the fourth aspect, in the third aspect, the membrane filtration device has a second pipe through which at least a part of the permeated water of the membrane filtration device flows as the carrier water into the flow injection system.

[0015] An apparatus for obtaining carrier water is not required, and the configuration of the analyzer can be simplified.

[0016] In the analyzer according to the fifth aspect, 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 permeated water of the membrane filtration device can be sent to the second pipe as carrier water without being exposed to the outside air, and the entry of foreign substances into the carrier water can be suppressed.

[0018] In the analyzer according to the sixth aspect, in any one of the first to fourth aspects, the pressure on the inlet side of the membrane filtration device is smaller than the pressure at the outlet 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 way, the quantification of the analysis of the sample water can be enhanced.

[0020] The analysis method of the seventh aspect generates sample water in which the detection target is concentrated by a membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane, pressurizes the sample water with a pump, and sends it to a flow injection system. In the flow injection system, the sample water is analyzed based on the reaction between the reagent contained in the carrier water and reacting with the detection target and the detection target.

[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 can be obtained. The concentrated water is pressurized by a pump and sent as sample water to a flow injection system. In the flow injection system, the detection target is analyzed based on the reaction with the reagent contained in the carrier water. In this way, since the concentrated water in which the detection target is concentrated by the membrane filtration device is sent as sample water to the flow injection system, the quantification of the analysis for the detection target of bacteria-derived substances containing endotoxin can be enhanced.

[0022] In the analysis method of the eighth aspect, in the seventh aspect, the water pressure on the downstream side of the pump is higher than the water pressure on the upstream side of the pump.

[0023] Thereby, the flow rate of the sample water discharged from the pump can be stabilized, so that the concentration magnification of the detection target in the sample water can be increased.

[0024] In the analysis method of the ninth aspect, in the seventh or eighth aspect, in the membrane filtration device, the permeated water that has permeated through the ultrafiltration membrane is discharged outside the membrane filtration device in a non-pressurized state.

[0025] By discharging most of the permeated water that has permeated through the ultrafiltration membrane of the membrane filtration device from the discharge part in a non-pressurized state, 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 the analysis method of the tenth aspect, in the ninth aspect, at least a part of the permeated water of the membrane filtration device is sent as the carrier water to the flow injection system.

[0027] The process for obtaining carrier water is unnecessary, and the configuration of the procedure of the analysis method can be simplified.

[0028] In the analysis method of the eleventh aspect, in any one of the seventh to tenth aspects, the pressure on the inlet side of the membrane filtration device is made smaller than the pressure at the outlet of the pump and is 0.05 MPa or more.

[0029] By setting the pressure on the inlet side of the membrane filtration device in this way, the quantification of the analysis of the sample water can be enhanced.

Advantages of the Invention

[0030] In the technology of the present disclosure, in an analyzer and an analysis method using the FIA method, it is possible to enhance the quantification of the analysis.

Brief Description of the Drawings

[0031]

Figure 1

Figure 2

Figure 3

Modes for Carrying Out the Invention

[0032] Hereinafter, the analyzer 12 according to the first embodiment will be described with reference to the drawings. As shown in FIG. 1, this analyzer 12 analyzes water obtained from a water treatment system (not shown) or water during treatment. In the present embodiment, the analyzer 12 analyzes endotoxin contained in the analysis target. Endotoxin is an example of a bacterium-derived substance and is also an example of a detection target in the disclosed technology. That is, in the analyzer 12 and the analysis method of the disclosed technology, bacterium-derived substances containing endotoxin are the detection targets. The detection targets are not limited to endotoxin, that is, lipopolysaccharide as a constituent use of the cell wall of Gram-negative bacteria, and may be, for example, various fungi (the fungi themselves).

[0033] Examples of the water obtained by the water treatment system include, but are not limited to, water for injection, pharmaceutical water, etc. Specifically, the water treatment system may include, for example, pharmaceutical water production facilities such as purified water and water for injection (WFI).

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

[0035] In the illustrated example, the preconcentration unit 12A has a preconcentration pump 14 and a membrane filtration device 16. The analysis target water is sent from the water treatment system to the preconcentration pump 14. The preconcentration pump 14 pressurizes the analysis target water and sends it to the subsequent membrane filtration device 16 through the pipe 18. For example, when the analyzer 12 is directly attached to the sampling line of a purified water production device or an ultrapure water production device for online measurement, if the pressure of the sampling line is appropriate, the preconcentration pump 14 is unnecessary. Also, when the pressure of the sampling line is too high compared to the appropriate pressure, a pressure reducing means such as a pressure reducing valve may be installed instead of the preconcentration pump 14.

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

[0037] Inside the outer cylinder 20, a plurality of hollow fiber ultrafiltration membranes 30 are arranged. The sample water flowing into the outer cylinder 20 from the inlet portion 22 is filtered by the ultrafiltration membrane 30. Specifically, since endotoxin does not permeate through the ultrafiltration membrane 30, concentrated water in which endotoxin is concentrated is generated and reaches the outlet portion 24. The pore size of the ultrafiltration membrane 30 is generally 0.01 to 0.001 μm. When detecting a bacterium-derived substance containing endotoxin as in the technology of the present disclosure, it can be said that it is preferable to use the 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 bacterium-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 substance of 90% or more is more preferable, and a membrane with a removal rate of 95% or more is even more preferable.

[0038] In the present embodiment, as the material of the ultrafiltration membrane 30, it is possible to use cellulose acetate, polyacrylonitrile, polysulfone, polyethersulfone, modified polyethersulfone, polyvinylidene fluoride, etc. In particular, modified polyethersulfone is preferable as the material of the ultrafiltration membrane 30 because it is difficult to adsorb endotoxin.

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

[0040] The permeated water that has passed through the ultrafiltration membrane 30 does not contain endotoxin or contains only a very small amount. That is, this permeated water 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. By the membrane filtration device 16, the sample water is concentrated 10 to 100,000 times. 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. Substantially, the permeated water is discharged from the discharge section 26 in an unpressurized state. This unpressurized state means that atmospheric pressure acts on the permeated water discharged from the discharge section 26, but no pressure exceeding this atmospheric pressure acts.

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

[0043] In the present embodiment, the water supply section 24 and the pump 42 are directly attached. That is, since no storage section is provided between the water supply section 24 and the pump 42, there is no risk of contamination of the sample water in the storage section or evaporation of the sample water. Further, in order to reduce the influence of contamination and evaporation in the storage section, it is necessary to take measures such as increasing the flow rate to the storage section and discharging a part of the sample water in the storage section. In that case, however, the concentration ratio decreases and the measurement accuracy may decrease. In the present 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 endotoxin has 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, the plunger reciprocates within the pump housing to pressurize the fluid and send it from the upstream side to the downstream side. In particular, in the example shown in FIG. 1, as the pump 42, a double plunger pump having two parallel - arranged plungers is used, and it is commonly provided in the first pipe 32 and the second pipe 34. Thereby, the pump 42 can pressurize the sample water and the carrier water synchronously and send them to the downstream side. Note that the pump 42 can also use a peristaltic pump, a syringe pump, or a solenoid pump. The plunger pump is more preferable.

[0046] In the second pipe 34, a reagent injection part 44 is provided on the downstream side of the pump 42. In the reagent injection part 44, a reagent that reacts with endotoxin is injected into the carrier water to obtain the carrier water.

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

[0048] As the reagent in this application, it is possible to use the fluorescent reagent described in Japanese Patent Application Laid - Open No. 2022 - 011525, in which the fluorescent part and the recognition part are connected by a spacer, but it is not particularly limited thereto.

[0049] In the merged pipe 46, the sample water flowing through the first pipe 32 and the carrier water flowing through the second pipe 34 are merged to become the merged water. In the merged 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 confluence pipe 46. The analyzer 48 analyzes the concentration of endotoxin from the reaction between the endotoxin and the reagent. In the present embodiment, inside the analyzer 48, a pipe (not shown) and a quartz cell connected to the pipe are disposed. The analyzer 48 irradiates light onto the confluent water flowing through the quartz cell, and detects the concentration of endotoxin from the obtained fluorescence signal intensity.

[0051] The analyzer 48 has an outlet pipe 50 for discharging the analyzed confluent water. The inner diameter of the outlet pipe 50 is made smaller than the inner diameter of the first pipe 32. Thereby, a state is realized in which the pressure P2 on the downstream side of the pump 42, for example, the outlet part 24, is higher than the pressure P1 on the inlet side of the pump 42, for example, the upstream side of the membrane filtration device 16.

[0052] In the analyzer 48, for example, excitation light having a wavelength of 340 to 360 nm is irradiated, and the generated fluorescence of 440 to 520 nm is observed to perform quantification. In the analyzer 48, the flow rate of the sample water is 0.01 to 4.00 mL / min, and by setting the flow rate within this range, the measurement accuracy is improved.

[0053] The materials of the first pipe 32, the second pipe 34, and the confluence pipe 46 are not limited as long as they can each flow the sample water, the carrier water, and the confluent water. Similarly, the pipe of the analyzer 48 is not particularly limited, but for example, when a fused silica tube is used, the reaction between the confluent water flowing inside and the pipe using this fused silica tube can be suppressed, and more accurate analysis becomes possible.

[0054] In the present embodiment, a so-called online analyzer and an online analysis method are realized in which the concentration of endotoxin is analyzed by the analyzer 48 while continuously flowing the water to be analyzed.

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

[0056] The water to be analyzed sent from a water treatment system (not shown) is pressurized by a pre-concentration 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, and concentrated water with endotoxin concentrated and permeated water (endotoxin-free water) without endotoxin are obtained.

[0057] The permeated water is discharged outside the membrane filtration device 16 from a discharge part 26 and an outlet part 24. In the analyzer 12 of this embodiment, the discharge port of the discharge part 26 is open, and the permeated water is discharged from the discharge part 26 in an unpressurized state. That is, most of the permeated water that has passed through the ultrafiltration membrane 30 is discharged from the discharge part 26. Therefore, compared with a configuration in which a pressure exceeding atmospheric pressure acts on the permeated water discharged from the discharge part 26, the flow rate that can be discharged increases. Per unit time, more endotoxin can be concentrated from the water to be treated, and the concentration of the concentrated water can be increased. <3, 9>

[0058] Here, it is preferable that the inner diameter of the discharge part 26 is 2 mm or more and 30 mm or less, or the linear velocity of the permeated water flowing through the discharge part 26 is 0.1 m / sec or more and 2.0 m / sec or less. Also, the pipe length of the discharge part 26 (the length from the outer cylinder 20 to the discharge port of the discharge part 26) is preferably 30 m or less. By setting the shape of the discharge part 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. Also, since the inlet pressure of the pump 42 on the downstream side of the water supply part 28 is maintained within an appropriate range and the addition amount of the reagent in the reagent injection part 44 can be appropriately maintained, the measured value in the analyzer 48 becomes more stable. Note that the inner diameter of the discharge part 26 refers to the inner diameter of the narrowest part of the cross-sectional area of the flow path of the discharge part 26, and the above linear flow velocity is the linear velocity at this part.

[0059] Alternatively, as shown in FIG. 2 as a first modification example, the discharge section 26 may be provided in a branched form between the water supply section 28 and the pump 42. In that case, the pipe diameter of the pipe from the water supply section 28 to the discharge section 26 is set within the above range, and the inner diameter of the second pipe 34 between the discharge section 26 and the pump 42 is preferably, for example, 0.5 mm or more and 2.0 mm or less.

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

[0061] When the membrane filtration device 16 is of the internal pressure type, either of the methods shown in FIGS. 1 and 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 section 26, and the permeated water is not exposed to the outside air. Thereby, it is possible to suppress the contamination of foreign substances in the permeated water (carrier water) as endotoxin-free water. <5>

[0063] The carrier water is pressurized by the pump 42 and sent to the downstream side. On the downstream side of the pump 42, a reagent is injected by the reagent injection section 44.

[0064] The concentrated water obtained by the membrane filtration device 16 is sent as sample water from the outlet section 24 to the reagent injection section 44 of the flow injection system 40 through the first pipe 32. Then, it is pressurized by the pump 42 and sent to the downstream side. In the analyzer 12 of the present embodiment, in this way, using the concentrated water in which endotoxin is concentrated at a high concentration by the membrane filtration device 16 as sample water, the concentration of endotoxin can be analyzed by the flow injection system 40. It is possible to enhance the quantification of endotoxin analysis as compared with the case of using sample water with a low endotoxin concentration without using the membrane filtration device 16. <1, 7>

[0065] The first pipe 32 is connected to the outlet portion 24, and the concentrated water is not exposed to the outside air. Thereby, it is possible to suppress foreign matter from mixing into the concentrated water (sample water).

[0066] The sample water in the first pipe 32 and the carrier water in the second pipe 34 merge in the merging pipe 46 to become merged water. Then, a reaction occurs between the endotoxin contained in the sample water and the reagent contained in the carrier water. Further, the merged water is sent to the analyzer 48. In the analyzer 48, the concentration of endotoxin is obtained from the reaction between the endotoxin and the reagent, and the sample water is analyzed.

[0067] In the analyzer 12 of the present embodiment, the inner diameter of the outlet pipe 50 of the analyzer 48 is smaller than the inner diameter of the first pipe 32. Thereby, a state is realized in which the pressure P2 at the outlet portion 24 on the downstream side of the pump 42 is higher than the pressure P1 on the upstream side of the membrane filtration device 16 on the upstream side of the pump 42. Since the discharge pressure on the outlet side of the pump 42 is higher than the water pressure on the inlet side of the pump 42, it becomes difficult to be affected by the water pressure on the inlet side when driving the pump 42. In other words, regarding the influence on the flow rate of the sample water discharged from the pump 42, the water pressure on the outlet side becomes dominant. Since the discharge flow rate of the sample water from the pump 42 is not affected by the pressure fluctuation on the inlet side, the flow rate on the outlet side can be stabilized and maintained within a certain range. Thereby, the concentration magnification of endotoxin in the sample water becomes higher than in the case where the discharge pressure on the outlet side of the pump 42 is lower than the water pressure on the inlet side of the pump 42. And as the concentration magnification of endotoxin increases, the signal intensity in the analyzer 48 also increases. That is, in the flow injection system 40, it is possible to enhance the quantification of the analysis of endotoxin. <2, 8>

Example

[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, using the analyzer 12 of the first embodiment, the endotoxin concentration of the sample water in which endotoxin was injected into carrier water so as to have an endotoxin concentration of 10 nM was analyzed. Specifically, the measurement value 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 an excitation wavelength of 350 nm, a detection fluorescence wavelength of 500 nm, a fluorescent reagent Zn-dpa-C2OPy (see the following chemical formula (1)), and a fluorescent reagent concentration of 10 μM in the reagent injection section.

[0071]

Chemical formula

[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 on the inlet side of the membrane filtration device 16, the pressure P2 at the outlet of the pump 42, and the measurement value range in the analyzer 48 for each of the examples and comparative examples. This measurement value range is the range of values actually measured as the endotoxin concentration in the analyzer 48. Specifically, five measurements were performed, and the maximum value and the minimum value obtained are shown.

[0074] The pressure P1 on 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 analyzer 12 and the preconcentration pump 14.

[0075] Examples 1 to 7 and Comparative Examples 1 to 3 shown in Table 1 are those in which, in the analyzer 12 shown in FIG. 1, the values of the pressure P1 and the pressure P2 were changed and the measurement value range was verified.

[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 in 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 can be obtained and the measured numerical values can 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 previous stage of the tank 54 on the subsequent stage of the tank 54.

[0081] In particular, as the value of the pressure P1, it is preferable that the condition of P1 < P2 described above 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, and 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, if 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 or the concentration is unstable in the confluence pipe 46. 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 pipe 34 Second pipe 40 Flow injection system 42 Pump 44 Reagent injection part 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 the sample water from the reaction between the detection target contained in the sample water and the reagent contained in the carrier water and reacting with the detection target, A first pipe through which the 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 pump for pressurizing the sample water in the first pipe, An analyzer having the above.

2. The analyzer according to claim 1, wherein the inner diameter of the outlet pipe in the flow injection system is smaller than the inner diameter of the first pipe.

3. The membrane filtration device, The analyzer according to claim 1 or claim 2, which has a discharge part that is open to the outside and discharges the permeated water that has permeated through the ultrafiltration membrane.

4. The analyzer according to claim 3, further comprising a second pipe through which at least a part of the permeated water of the membrane filtration device flows into the flow injection system as the carrier water.

5. The analyzer according to claim 4, wherein the membrane filtration device has a connection port to which the second pipe is connected.

6. The analyzer according to claim 1, wherein the pressure on the inlet side of the membrane filtration device is smaller than the pressure at the outlet of the pump and is 0.05 MPa or more.

7. Generating sample water in which the detection target is concentrated by a membrane filtration device equipped with a microfiltration membrane or an ultrafiltration membrane, Pressurizing the sample water with a pump and sending it to a flow injection system, In the flow injection system, analyzing the sample water from the reaction between the reagent contained in the carrier water and reacting with the detection target and the detection target, An analysis method.

8. The analysis method according to claim 7, wherein the water pressure on the downstream side of the pump is higher than the water pressure on the upstream side of the pump.

9. The analysis method according to claim 7 or claim 8, wherein in the membrane filtration device, the permeated water that has permeated through the ultrafiltration membrane is discharged to the outside of the membrane filtration device in a non-pressurized state.

10. The analysis method according to claim 9, wherein at least a part of the permeated water of the membrane filtration device is sent to the flow injection system as the carrier water.

11. The analysis method according to claim 7, wherein the pressure on the inlet side of the membrane filtration device is made smaller than the pressure at the outlet of the pump and is 0.05 MPa or more.

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