JP3353487B2 - Liquid sample continuous measurement device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid sample continuous measuring device for rapidly and continuously measuring a liquid sample containing fine solids, proteins, contaminants, etc. It is suitable for online measurement of liquids, fermented liquids and the like.

[0002]

2. Description of the Related Art Conventionally, as a method for measuring and quantifying a substance to be detected in a sample, a fixed amount of the sample is injected into a continuous flow, and a spectrophotometer equipped with a flow cell, an atomic absorption spectrometer, or an electric spectrometer. There are known a flow injection analysis method leading to a chemical detector or the like, and a flow analysis method using a bubble segmentation in which a sample is segmented by bubbles at regular intervals to separate the solution from the preceding and following solutions and sent to the detector.

[0003] These analysis methods require a short analysis time, enable high-precision analysis, and obtain the operations such as mixing, separation, and chemical reaction that have been performed by humans in a continuous flow. There are advantages such as being able to. In particular, the flow injection analysis method requires a small amount of sample,
It does not require a complicated mechanism for inserting and removing bubbles strictly like a bubble segment, and has features such as a simple mechanism and small size of the device itself.

In recent years, analysis has been automated by combining an autosampler as a device for automatically injecting a small amount of a sample into an analytical instrument based on the flow injection analysis method. However, if the sample contains minute solids, proteins, contaminants, etc., such as culture solution and fermentation solution, it will be difficult to promote the automation of analysis because it will cause various troubles in analytical instruments. I have.

[0005] For example, solid matter adheres or contaminates the pipes of the equipment, causing the pipes to be pinched, causing abnormal high pressure and the like. In addition, even before these problems occur, for example, if an autosampler is used, a suction error of a sample, a weighing error, a damage to a working liquid contact member, and the like may be caused. Further, in the case of an analytical instrument, there is a problem that the sensitivity may fluctuate due to the attachment of contaminants to the detection unit.

[0006] Particularly, in the case of an analytical instrument utilizing a bio-related substance such as an enzyme, the enzyme may be deactivated due to adhesion of proteins and microorganisms. Therefore, such a sample needs to be centrifuged or filtered in advance before introducing the sample into the autosampler, which requires a great deal of time and effort.

Further, when the sample exceeds the concentration range that can be quantified by the analytical instrument, an operation for diluting the sample in advance is necessary. Specifically, this is an operation in which a fixed amount of a sample and a diluent are separately collected, mixed, and stirred to obtain a solution having a uniform concentration, but this is also complicated and requires a long-time treatment. In addition, there is a problem that errors and human errors due to instruments and containers used are added. A dilution apparatus in which a series of operations required for the dilution are directly replaced with a mechanical operation is also known, but has a problem in terms of a complicated configuration and a long time required for processing.

In particular, when performing so-called on-line measurement for continuously analyzing the concentration of a specific component in a constantly changing solution such as a culture solution or a fermentation solution, obstruction relating to an analytical instrument such as a minute solid content and a protein contained in a sample is eliminated. Of course, appropriate dilution must be performed promptly and allow for accurate analysis. Using a dialysis membrane, it is possible to separate minute solids and proteins from the sample solution and supply only diffusible low molecular species to the analyzer. For example, a method is known in which after a certain amount of blood is weighed by a syringe and injected into a buffer solution, the protein in the blood is prevented from entering the detector by passing through a dialyzer, and the amount of transmitted glucose is measured. (Japanese Patent Publication No. 61-20279). In this case, the partial permeation of glucose through the dialysis membrane also has a dilution effect.

However, in this method, the dispersion pattern of the low-molecular-weight substance after permeation becomes large due to a subtle change in dialysis conditions such as a change in the speed at which the sample is sent. Is low in the reproducibility of the transmission state, and there is a great difficulty in measuring accuracy. In addition, the reproducibility of the permeation state through the semipermeable membrane is low because a small amount of the sample comes into contact with the dialyzer membrane instantaneously. Since the sample stock solution is supplied to the injector itself, it is difficult to avoid contamination of the injector. This also causes a problem that the weighing changes with the attachment of solids and proteins in the injector, which is the weighing portion of the sample.

[0010]

DISCLOSURE OF THE INVENTION The present invention solves the above-mentioned problems, and enables rapid and high-precision analysis of a sample having minute solids, proteins, contaminants, and the like of the sample. It is an object of the present invention to provide a continuous liquid sample measurement device capable of continuously measuring a plurality of samples efficiently by online measurement of a culture solution, a fermentation solution, and the like.

[0011]

The liquid sample continuous measuring apparatus of the present invention selects a plurality of liquids to be measured including a sample, a filtration cell having a sample liquid passage and a carrier liquid passage which are in contact with each other via a semipermeable membrane. The measurement liquid supply system including the switching means and the measurement liquid supply means for supplying the selected liquid to be measured to the sample liquid passage of the filtration cell at a constant flow rate, in the carrier liquid passage of the filtration cell. A carrier liquid supply system including a carrier liquid supply means for supplying a carrier at a constant flow rate, an injector connected to a carrier liquid passage outlet of a filtration cell and intermittently injecting a carrier into a detector, and both liquid supply means After a certain period of time has elapsed since the start of the liquid sending, at least a part of the sample in the liquid to be measured is stably moved into the carrier through the semipermeable membrane in the filtration cell, and the obtained carrier is detected by the injector. With the function of injecting Before ending the measurement step of the sample in the measurement liquid, the control unit is provided with a function of switching the switching means, selecting the next liquid to be measured, and sending it to the sample passage of the filtration cell. I do.

Further, the control unit switches the switching means before the injection step by the injector for measuring the sample in one liquid to be measured so that the next liquid to be measured passes the sample through the filtration cell. It is better to control so that the liquid is sent to the road. Further, the control unit sends the next liquid to be measured to the sample passage of the filtration cell after the time when the sample of the next liquid to be measured is mixed in the carrier before the end of the injection step. It may be controlled.

[0013]

The liquid to be measured containing the sample is sent to the sample passage of the filtration cell at a constant flow rate by the measuring liquid sending means. Similarly, the carrier is sent to the carrier liquid passage at a constant flow rate by the carrier liquid sending means. In the filtration cell, at least a part of the sample in the liquid to be measured flowing through the sample passage moves to the carrier flowing through the carrier passage through the semipermeable membrane. Since the liquid to be measured and the carrier are respectively sent at a constant flow rate, this movement is sufficiently stable when the liquid is sent to some extent. The controller injects the carrier obtained by performing such a stable movement into the detector at an appropriate time by the injector.

Since the movement of the sample in the filtration cell is performed between the liquid to be measured having a certain concentration and being sent at a constant flow rate and the carrier being sent at a constant flow rate, the liquid sending time can be taken to some extent. Stable movement can be obtained. That is, since a sufficient amount of the sample can be controlled so as to be in contact with the semipermeable membrane as long as necessary until it is constantly stabilized, the reproducibility of the moving state in the semipermeable membrane is improved. Further, since the injector is not connected to the sample liquid supply path side, the injector which is liable to give a measurement error or the like is less likely to be contaminated.

In the above measurement, one of the plurality of liquids to be measured including the sample is switched and selected by the switching means, sent to the sample passage of the filtration cell, and measured at the above timing. One measurement process is completed. In such one step, a time is required until a stable moving state of the sample through the semipermeable membrane is obtained. Attention was paid to this time, and after securing this time for each sample, an attempt was made to start the measurement process for the next sample as soon as possible, regardless of whether the measurement of that sample was completed. In other words, before ending the measurement step of one liquid to be measured, the switching means is switched to control the next liquid to be measured to be sent to the sample passage of the filtration cell, and the apparatus at the preceding stage is used as the apparatus. By starting the next sample measurement step before the measurement step was completed, the measurement efficiency was improved.

After all, when the detection by the detector and the analysis of the detected value are performed, the operation of the valve and the pump for switching the sample is controlled so that the introduction of the next sample into the filtration cell has already been started. Thus, a plurality of samples can be measured continuously and efficiently in a short time. That is, the analysis is usually performed by shortening the time required for transporting the sample to the filtration cell and replacing the sample in the sample passage and the time required for detection and analysis.

In the present invention, after the current sample is switched to the next sample, the next sample passes through the sample passage of the filtration cell, and the replacement of that portion is completed. The time required to reach the steady state and reach the injector sufficiently is hereinafter simply referred to as the filtration time. Similarly, the time from switching the current sample to the next sample, passing through the sample passage of the filtration cell, and arriving at the injector at the next sample and starting to mix with the current sample is simply referred to as the sample arrival time. Called.

Further, the time required for the filtered sample to be injected into the detector by the injector and for the detection and analysis of the output is hereinafter simply referred to as the detection time. The filtration processing time mainly depends on the length of the pipe, the diameter of the pipe, the capacity of the sample liquid passage of the filtration cell, the liquid sending speed, and the like. For example, the sample guided to the filtration cell may be switched to the next sample in synchronization with the injection of the sample into the detector.

Further, if the filtration time is longer than the detection time, the sample before the injector is injected into the detector within a certain time after the sample to be guided to the filtration cell is switched to the next sample. be able to. However, in this case, it is necessary to inject the sample into the detector before the sample arrival time of the next sample is exceeded so that the influence of the next sample does not occur. The semipermeable membrane referred to in the present invention refers to a membrane that allows some components in a solution or dispersion system to pass through but does not allow other components to pass through. For example, among the substances contained in the sample, a regenerated cellulose-based membrane, a polysulfone-based membrane, and a membrane that does not pass through macromolecules such as minute solids and proteins that are inconvenient to the detector and that can transmit a low-molecular component to be measured. Fluororesin films, carbonate films and the like can be mentioned.

A structure having a sample liquid passage and a carrier liquid passage partially in parallel with each other via a semipermeable membrane is a filtration cell. The filtration cell is formed from a pair of two blocks having grooves at mirror symmetric positions, and both ends of the groove of each block are respectively pierced so as to form a flow path toward an entrance to a cell provided outside the block. ing. Then, the two blocks are aligned so that the grooves face each other, and a structure in which a semipermeable membrane is sandwiched between the portions where the grooves face each other. The liquid flowing direction of the sample and the liquid flowing direction of the carrier are the same or opposite, and flow in parallel on both sides of the membrane. By increasing the effective area of the groove of the filtration cell (for example, the product of the length in the flow direction and the width in the direction parallel to the membrane in the direction perpendicular to the flow direction), the integrated amount of the component permeating the carrier increases. In addition, when the effective area is large, a uniform effect of filtration can be obtained to mitigate fluctuation factors caused by pump pulsation and the like.
The time required for replacement increases. Therefore, the size of the effective area is preferably set to a size corresponding to the detection concentration range of the subsequent detector.

In particular, if the width of the groove is excessively large, the surface of the semipermeable membrane will fluctuate. If the width is too narrow, fine solids and the like contained in the sample will be clogged. However, it is preferable to set it in the range of 0.5 to 5 mm. The depth of the groove is also preferably about the same as the width, but the depth on the sample side and the carrier side may be different, and the cross-sectional shape of the groove with the normal to the direction in which the liquid flows is also rectangular. , Semi-circle, semi-ellipse and the like. In addition, the shape of the flow path in the flow direction of the groove can be various shapes such as a linear shape, a spiral shape, and a bent shape, but the liquid flow partially stays or the flow path partially narrows. It is desirable that the shape be such that there is no void.

In the present invention, unlike the case where the segmented sample is instantaneously brought into contact with the semipermeable membrane, the sample permeates the measurement target component in a state where the sample is filled in the sample passage of the filtration cell. In addition, the transmission state to the carrier passage is averaged, and measurement with high reproducibility is enabled. In the present invention, the sample guided to the sample passage includes the actual analyte solution and the standard solution when calibration is required for the detector. Therefore, in order to calibrate the detection device, a valve is arranged as a switching means for sequentially switching a plurality of sample solutions and standard solutions. As this valve, a three-way valve having a three-way switching function is often used. Further, a plurality of three-way valves are arranged and used so that a plurality of standard liquids or the like can be supplied.

In addition to the standard solution used for calibrating the sample and the detector, distilled water or the like can be similarly disposed as a washing solution for washing the filtration cell and the piping before and after it. A plunger pump, a geared pump, a peristaltic pump, and a carrier pump for passing the sample liquid through the sample liquid passage and the carrier through the carrier liquid passage of the filtration cell. Conventionally known various pumps such as a tallic pump can be used.

The sample passing pump is desirably a pump having resistance to minute solids and attached matter, and a peristaltic pump is preferably used. The position of the sample flow pump can be located at the sample supply side or the discharge side of the sample flow path of the filtration cell.However, when the pump is located at the former position, the sample and the diluent are further stirred. This is desirable in that the effect is obtained and that air bubbles are not generated without reducing the pressure in the sample passage of the filtration cell.

The carrier transport pump can also be arranged on the carrier supply side to the filtration cell or on the discharge side of the carrier fluid passage of the filtration cell. In order not to generate air bubbles in the road, it is desirable to arrange the former position. Each pump used in the present invention has a mechanism capable of performing one liquid supply, and is a peristaltic pump capable of simultaneously operating multiple tubes with a single power source and coaxially rotating rollers. Is, of course, equivalent to a single set of multiple pumps.

The passing speed of the carrier in the carrier passage is as follows:
It is possible to change the amount of the carrier to receive the component to be measured per unit time, that is, the magnitude of the dilution in the filtration cell. For example, the dilution rate increases as the flow rate of the carrier increases, and the dilution rate decreases as the flow rate decreases, so that the concentration of the component to be measured in the carrier exiting the filtration cell may be appropriately adjusted according to the passing rate of the carrier. It is adjustable.

In view of these characteristics, it is desirable to use a carrier transport pump having excellent stability and precision in liquid sending in order to maintain a stable dilution rate in the filtration cell. As the carrier in the present invention, for example, distilled water or various buffers can be used, but it is also possible to add a reagent required for detection and the like.

In the present invention, the carrier containing the analyte of the sample discharged from the carrier passage of the filtration cell is sent as a sample to an injector having a detector connected to the subsequent stage, and is detected by the detector. I have to. In addition, the injector weighs a certain amount of sample and injects it into a continuous flow to the detector, and uses a mechanism such as a 6-way switching valve generally used in an autosampler or the like. It is a device.

According to the present invention, before the sample is brought into contact with the semipermeable membrane, the treatment liquid is diluted so that the transmittance of the component to be measured is constant, so that the processing solution is proportional to the concentration of the component to be measured in the original sample. Can be supplied.

[0030]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A continuous liquid sample measuring apparatus will be described in detail below based on embodiments, but the present invention is not limited thereto. In addition, what was simply expressed as% represents% by weight.
FIG. 1 is a system diagram of an embodiment of a liquid sample continuous measuring apparatus according to the present invention, which is for measuring a glucose concentration in a solution.

The control unit (21) controls the sample A (1
0), sample B (11), standard solution (12), washing solution (1
In 3), any one of the liquids to be measured is selected by the three-way electromagnetic valves (7), (8), and (9), connected to the sample transport pump (5), and the sample passage of the filtration cell (1) ( 3)
Supplied to In addition, the carrier (14) is supplied to the carrier passage (4) of the filtration cell (1) by the carrier transport pump (6).

The filtration cell (1) has a sample liquid passage (3) and a carrier liquid passage (4) that are partially in parallel with each other via a semipermeable membrane (2) and are in parallel with each other. A part of the component to be measured permeates through the sample passage (3) to the carrier passage (4), is conveyed to the injector (18), and is injected into the detector (19) at a constant amount. . The transport of the sample from the carrier passage (4) to the injector (18) is performed by the carrier transport pump (6).
Performed by the carrier (14) by the injector (1).
The liquid not injected in 8) is discharged to a waste liquid bottle or the like (not shown).

The transport of the sample from the injector (18) to the detector (19) is performed by a buffer solution (16) for the detector by a buffer solution transport pump (17), and the measured solution is a waste liquid bottle (20). ). Each of the sample transport pump (5) and the carrier transport pump (6) uses a peristaltic pump at 1.0 ml / min, and the buffer transport pump (17) uses a plunger pump. 1.0 ml / min.

In the filtration cell (1), the shape of the groove of each of the two blocks forming the carrier liquid passage (4) and the sample liquid passage (3) on both sides of the semipermeable membrane (2) is 0 depth. 0.5 mm, width 2 mm, rectangular section, length 120 mm
Spectra / Pore CE type (Spectrum Medic) having a molecular weight cut off of 300,000 as a semipermeable membrane.
al Industries, Inc.).

The buffer was 100 mM sodium phosphate buffer (pH 6), and the same carrier (14) was used. Further, distilled water was used as the washing liquid (13).
The detector (19) is configured by arranging a flow cell inside a thermostat kept at 37 ° C. In this flow cell, an immobilized enzyme electrode for detecting glucose, A
A g / AgCl reference electrode is disposed, and a counter electrode formed of a stainless steel connection joint is adjacent to the liquid in the flow cell. It should be noted that the potentiostat on the immobilized enzyme electrode,
A voltage of +0.6 V is applied to the Ag / AgCl reference electrode, a current value output based on the glucose amount of the injected sample is obtained, and the peak height of the waveform of the current value is detected as a response value. I do.

A method for producing an immobilized enzyme electrode for detecting glucose will be described below. A side surface of a platinum wire having a diameter of 2 mm is covered with a heat-shrinkable Teflon, and one end of the wire is sanded and 150 mm thick.
Finish smoothly with No. 0 emery paper. The platinum wire was used as a working electrode, a 1 cm square platinum plate was used as a counter electrode, and a saturated calomel electrode (hereinafter abbreviated as SCE) was used as a reference electrode.
Electrolysis treatment is performed at 2.0 V for 5 minutes. Thereafter, the platinum wire was thoroughly washed with water, dried at 40 ° C. for 10 minutes, immersed in an anhydrous toluene solution of 10% γ-aminopropyltriethoxysilane for 1 hour, and washed. The enzyme was immobilized on the aminosilanized platinum wire as follows.

5 mg of glucose oxidase (manufactured by Sigma, type II) and 5 mg of bovine serum albumin (manufactured by Sigma, Fraction V) were dissolved in 1 ml of 100 mM sodium phosphate buffer (pH 7), and glutaraldehyde was dissolved in 0.2%. Add so that 5 μl of this mixed solution was quickly placed on the previously prepared platinum wire, dried and cured at 40 ° C. for 15 minutes, and then used in a 100 mM sodium phosphate buffer (pH 6).

FIG. 2 is a first example of a time chart expressing the sample processing and measuring steps of the liquid sample continuous measuring apparatus of the present invention. From this time chart, it can be seen that in synchronization with the injection of the sample into the detector, the sample guided to the filtration cell is switched to the next sample, and a series of analyzes is controlled and performed by the control unit. First, at the same time as turning on the carrier transport pump and the sample transport pump, the electromagnetic valve is controlled so that the standard solution is connected to the sample transport pump, and the standard solution is guided to the filtration cell.

In this case, the standard solution is introduced into the filtration cell, the inside of the flow path is sufficiently replaced with the standard solution, and the amount of the standard solution to be filtered to the carrier passage becomes a steady state, which is reflected on the injector. After a sufficient time, the filtered carrier is injected into the detector by the injector. This corresponds to the portion a in the figure. When the injection is completed, the solution connected to the filtration cell is switched from the standard solution to the next sample A by controlling the solenoid valve almost simultaneously with the detection and analysis by the detector. This corresponds to the portion b in the figure.

The switching timing of these samples is as follows.
Immediately before the injection, at the same time as the injection, after the end of the injection operation, or some time after the injection operation, it may be immediately before the injection so as not to impair the effects of the present invention. Of course, the inside of the pipe to the filtration cell may be washed by flowing the washing solution while switching from the standard solution to the sample A.

When switching between the standard solution and the sample at the timing shown in FIG. 2, the sample is switched to the next sample, then the sample reaches the filtration cell, and the sample filtered by the carrier in the filtration cell reaches the injector. You have some time to start. FIG. 3 shows a second example of a time chart expressing the sample processing and the measuring process of the liquid sample continuous measuring apparatus of the present invention for further shortening the entire measuring time using this time.

FIG. 3 shows a state in which after the sample guided to the filtration cell is switched to the next sample, the sample amount before the injector is injected into the detector and analysis is performed before the sample arrival time of the next sample is reached. Is shown. First, at the same time as turning on the carrier transport pump and the sample transport pump, the electromagnetic valve is controlled so that the standard solution is connected to the sample transport pump, and the standard solution is guided to the filtration cell.

Then, the standard solution is guided to the filtration cell, the inside of the flow path is sufficiently replaced with the standard solution, and the amount of the standard solution to be filtered toward the carrier passage becomes a steady state, which is reflected on the injector. The solution connected to the filtration cell is switched from the standard solution to the next sample A by controlling the solenoid valve. This corresponds to the portion c in the figure. After that, before the next sample A reaches the filtration cell and the sample A filtered into the carrier reaches the injector and starts to mix with the standard solution, the carrier portion containing only the standard solution is sent to the detector. inject. This corresponds to the portion d in the figure.

However, during the time from the first flow of the standard solution to the time when the standard solution is injected by the injector, the standard solution is guided to the filtration cell, the inside of the flow path is sufficiently replaced with the standard solution, and the filtration is performed to the carrier passage. It takes time for the volume of the standard solution to reach a steady state and reflect that state in the injector. However, as compared with the case of FIG. 2, after switching the flowing liquid from the standard solution to the sample A, the time required for one sample source is equal to the time until the next sample A starts to reach the pipe of the injector. It is possible to shorten it. The timing in this case can be realized according to the flow velocity or the piping system or by measuring these times in advance.

[0045]

According to the liquid sample continuous measuring apparatus of the present invention, fine solids, protein,
While performing sample pre-treatment steps such as eliminating contamination, etc., at the same time detecting and analyzing the processing solution,
A plurality of samples can be analyzed quickly and efficiently, which is suitable for automation of analysis and on-line measurement of a culture solution, a fermentation solution and the like.

[Brief description of the drawings]

FIG. 1 is a schematic view of an example of an apparatus for carrying out a liquid analysis method of the present invention, for measuring a glucose concentration in a solution.

FIG. 2 is a first example of a time chart expressing a sample processing and a measuring process of the liquid sample continuous measuring apparatus of the present invention.

FIG. 3 is a second example of a time chart expressing a sample processing and a measuring process of the liquid sample continuous measuring apparatus of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Filtration cell 2 Semi-permeable membrane 3 Sample passage 4 Carrier passage 5 Sample transfer pump 6 Carrier transfer pump 12 Standard solution 13 Washing solution 14 Carrier 16 Buffer solution 17 Buffer solution transfer pump 18 Injector 19 Detector 21 Controller

──────────────────────────────────────────────────の Continuation of the front page (51) Int.Cl. ⁷ Identification symbol FI G01N 33/48 G01N 27/46 336A (56) References JP-A-64-49968 (JP, A) JP-A-1-94263 ( JP, A) JP-A-4-212064 (JP, A) JP-A-56-66867 (JP, U) JP-B-61-20279 (JP, B1) (58) Fields investigated (Int. Cl. ⁷ , (DB name) G01N 35/08 G01N 27/327 G01N 27/416 C12M 1/34 G01N 33/48

Claims (3)

(57) [Claims] 1. A filtration cell having a sample passage and a carrier passage which are in contact with each other via a semi-permeable membrane, a switching means for selecting a plurality of liquids to be measured including a sample, and A measuring liquid feeding system provided with a measuring liquid sending means for sending a sample liquid at a constant flow rate, a carrier liquid sending means for sending a carrier at a constant flow rate into a carrier flowing path of a filtration cell. A carrier liquid feeding system equipped with: a carrier liquid passage outlet of the filtration cell is connected, an injector for intermittently injecting the carrier into the detector, and a certain time after starting the liquid feeding of both liquid feeding means, In the filtration cell, a function is provided in which at least a part of the sample in the liquid to be measured is stably moved into the carrier through the semipermeable membrane, and the obtained carrier is injected into the detector by the injector, and one sample to be measured is provided. Before finishing the measurement process of the sample in the liquid,
A liquid sample continuous measurement device comprising a control unit having a function of switching the switching means to select the next liquid to be measured and to feed the same to the sample passage of the filtration cell. 2. The method according to claim 1, wherein the control unit switches the switching unit before the injection step using an injector for measuring a sample in one liquid to be measured so that the next liquid to be measured is sampled in the filtration cell. The liquid sample continuous measurement device according to claim 1, wherein the liquid sample is controlled to be sent to a liquid passage. 3. The method according to claim 1, wherein the controller is configured to:
3. The continuous liquid sample measuring apparatus according to claim 2, wherein control is performed such that the next liquid to be measured is sent to a sample passage of the filtration cell.