JP2011158258A - Analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an analyzer equipped with a means for measuring a pressure loss accompanied by an abnormality of a flow channel without installing a pressure sensor to evaluate a flow channel state. <P>SOLUTION: In a flow cell type detector equipped with a flow cell 202 for detecting a target component, a solution introducing flow channel 205 and a solution discharging flow channel 209, a mechanism for measuring the time required in the passage of air bubbles introduced into the flow channel is provided at the flow cell or the flow channel connected to the flow cell, and the presence of the abnormality of the flow channel is determined from comparison with the air bubble passing time in the case that the flow channel is normal. <P>COPYRIGHT: (C)2011,JPO&amp;INPIT

Description

  The present invention relates to an analyzer including a mechanism capable of flowing a fluid containing a measurement target sample in a container (flow cell) having a constant internal volume, and a mechanism for measuring the measurement target sample in the flow cell.

  There is an analyzer including a mechanism that allows a fluid containing a measurement target sample to flow in a container (flow cell) having a constant internal volume, and a mechanism that measures the measurement target sample in the flow cell. As the measurement mechanism of the analyzer, 1) a sample is wrapped in a liquid called a sheath flow, and the particulate matter contained in the sample is optically measured (the image is taken and analyzed) 2) There is an electrolyte measurement that measures an electromotive force according to the concentration of a component to be measured by bringing the functional membrane into contact with the measurement object in a flow cell. Such a flow cell type detector is characterized in that one measurement means can be reused and can be repeatedly measured as compared with a batch type detector. Such an analyzer includes, for example, a chemical analyzer described in Patent Document 2. In the chemical analyzer described in Patent Document 2, a specimen such as blood or urine is sucked into an ion detector by a specimen suction nozzle, and the electrolyte is quantified by the ion detector.

JP-A-10-332590 Japanese Patent Laid-Open No. 10-300651

  In the flow cell system, a flow path for transporting and discharging the solution to be measured to the measurement unit is necessary. In order to perform analysis with high reproducibility, the solution needs to be transported to the flow cell detection unit with high reproducibility. The shape of the flow cell flow channel and the flow channel connected to the flow cell may change from the design time due to adhesion of components in the solution, bending of the flow channel material, deformation of the flow channel material, and the like. When the flow cell or the shape of the flow path connected to the flow cell changes due to clogging, bending, or adhesion of solution components, the amount and timing of the reaction solution that reaches the detection unit without the solution flowing at the designed flow rate changes, It causes a decrease in analytical performance such as a decrease in reproducibility. Monitoring the flow path state and keeping it normal is a common problem for flow cell type detectors.

  Here, the pressure loss that is an index reflecting the state of the flow path will be described. Since the pressure loss, which is the pressure difference between two points in the flow path, increases when the flow path has a bent portion or a narrowed portion, it is used to evaluate whether such a change has occurred in the flow path. It is possible.

  As a method of measuring the pressure loss and evaluating the channel performance, there is a method as described in Patent Document 1, for example. In the method described in Patent Document 1, pressure loss is evaluated by a pressure sensor. The pressure sensor is directly connected to the flow path whose pressure is to be measured, and measures the pressure of the fluid at that point. The pressure sensor generally has a complicated flow path structure such as a narrow portion. If this is installed in a flow cell or a flow path connected to the flow cell, the pressure sensor itself causes a pressure loss, and the target pressure cannot be measured correctly. Also, the solution enters the flow path inside the pressure sensor, and this solution component remains in the pressure sensor, causing the analysis value to carry over (the analysis value cannot be obtained correctly due to the influence of the residue of the previous measurement). It can be. In addition, the pressure sensor for measuring the pressure loss in the flow path is an unnecessary part for the original analysis purpose, and has a demerit of an increase in cost and an increase in failure risk due to an increase in the number of parts.

  The objective of this invention is providing the analyzer which can measure the pressure loss of a flow path, without installing a pressure sensor.

  The configuration of the present invention for achieving the above object is as follows.

  The main feature of the present invention is that a mechanism for measuring the passage time of bubbles in a flow cell or in a flow channel connected to the flow cell is provided.

  Since the flow cell type detector of the present invention can measure pressure loss without adding a pressure sensor, the flow path configuration necessary for the original analysis purpose can be changed without changing the flow path state. There is an advantage that the flow path state can be evaluated without adding.

The conceptual diagram explaining the relationship between pressure loss and flow path abnormality. The schematic of the analyzer provided with the passage time measuring means by the current measurement among the pressure loss measuring mechanisms of the present invention. The experiment result of flow path abnormality detection by Example 1. FIG.

  According to general textbooks related to fluid dynamics such as “Hydrodynamics (Yoshihiro Miyai, Teruhiko Kida, Hitoshi Nakatani, Morikita Publishing)”, the pressure loss in the flow path is due to pipe friction and due to shape. The laminar flow in the circular pipe is expressed by Hagen-Poiseuille's law of Equation 1.

ハーゲン・ポアズイユの式

Hagen Poiseuille's formula

  In Equation 1, ΔP is the pressure loss, μ is the viscosity of the solution, l is the channel length, Q is the flow rate, and d is the tube diameter. From Equation 1, when the flow rate is constant, the pressure loss is proportional to the length of the flow path. On the other hand, the loss head corresponding to the pressure loss due to the shape is generally expressed by Equation 2.

形状損失の式

Form loss formula

In Expression 2, h is a loss head, and when pressure is applied to the density and gravity acceleration of the solution, pressure loss is obtained. ζ is a loss factor, and V is a flow velocity. If the flow cell or a part of the flow path connected to the flow cell has a narrow part, a closed part, a bent part, etc. that are not designed, a factor of pressure loss is added to the normal flow path. FIG. 1 schematically shows this. FIG. 1 (A) shows the relationship between the distance from the channel inlet when the channel is normal and the pressure, and FIG. 1 (B) shows the distance and pressure from the channel inlet when the channel has a closed portion. Represents the relationship. Reference numerals 101 and 103 denote flow paths, reference numeral 102 denotes a detection unit, and reference numeral 104 denotes a closed part of the flow path. In the case of (A), the pressure at the flow path inlet is P _0, and a pressure loss 105 occurs in the straight pipe portion, so the pressure at the detection portion is P ₁ (108). On the other hand, in the case of (B), the pressure at the inlet is also P _0, and in addition to the pressure loss at the straight pipe portion, the pressure loss 106 at the closing portion 104 is added, and the pressure at the detection portion is lower than P _{1. 2} (109). As exemplified above, the state of the flow path can be evaluated by measuring the pressure loss of the flow path. From the gas equation of state, the pressure at the detector and the volume of the bubble are proportional. If a certain amount of bubbles is introduced, the pressure loss can be calculated from the volume of the gas. Since the bubble volume can be calculated from the passage time and flow rate of the bubbles, the pressure loss of the flow path can be estimated by measuring the passage time of the bubbles. An analysis apparatus targeted by the present invention includes a mechanism that allows a fluid containing a measurement target sample to flow through a container (flow cell) having a constant internal volume, and a mechanism that measures the measurement target sample in the flow cell. is there. The measurement mechanism is as follows: 1) A sample is wrapped in a liquid called a sheath flow, and the particulate matter contained in the sample is optically measured (images taken and analyzed, For example, urine sediment analyzer, etc.) 2) A chemical reaction is caused in the flow cell, and the reaction is measured by an electric method or an optical method (antigen, antibody reaction to sample) There are immunoanalyzers that measure the amount of light emitted by chemical reaction, electrochemical reaction, etc. by illuminating the label provided on the bound reagent. It can be applied to anything.

  FIG. 2 is a block diagram of an embodiment of the apparatus of the present invention in which the bubble passage time is detected by measuring the current flowing through the fluid. Reference numeral 201 denotes a flow cell that performs current measurement, and includes at least two electrodes 202 and 203. The flow cell that measures current is used to measure the main target component, for example, the ion detection electrode for electrolyte measurement, the electrode for electrochemical measurement for electrochemical measurement, etc. A dedicated one may be installed. A flow path 205 for feeding the solution 204 to the flow cell and a nozzle 207 for sucking these solutions from the container 206 are connected to the flow cell by a connecting portion 208. In addition, means for sending fluid such as a flow path 209 and a syringe pump 210 for discharging the solution are installed. Furthermore, an applied voltage control means 211 such as a potentiostat for controlling the voltage applied to the electrode, a means 212 for analyzing the current flowing in the electrode section, and an arithmetic unit 213 for processing the obtained result are provided.

  The solution is sucked by a syringe pump, and the nozzle is raised from the container into the air at a certain timing. At this time, the syringe pump continues to suck at a constant speed, and air is sucked. Further, the nozzle is lowered again into the solution after a predetermined time has elapsed. By the above operation, a gas-liquid two-phase flow in which fluid flows in the order of solution, air (bubbles), and solution is formed in the flow path. A DC voltage of 1.2 V is applied between the electrode pair at the timing when the boundary between the gas and the liquid reaches the detection unit. The solution contains an electrolyte, and an electric current flows between the electrodes when the solution passes through the electrode pair. On the other hand, since no current flows through the air, the current value becomes almost zero when the air passes through the electrode pair. If the electrode pair is passed in the order of solution, bubble, and solution, the time difference from the point when the current is switched from air to zero when the solution is switched to air and the point when the current flows again when switching from the air to the solution and the suction of the syringe The bubble volume can be determined from the velocity. The volume of air introduced into the flow path in the atmospheric pressure can be calculated from the suction speed of the syringe and the time during which the nozzle has been raised in the air.

  When the flow path state is normal, the passage time of bubbles is measured in advance and recorded as a reference value. When the passage time of bubbles is measured by the above method at the time of maintenance, etc., and this passage time fluctuates more than a predetermined ratio with respect to the reference value, there may be a pressure loss factor due to the change in the flow path The alarm that prompts cleaning and replacement of the flow path is displayed. It is possible to display a clear evaluation value for the flow path performance of the apparatus that has been estimated by the user from the analysis result, and the efficiency of apparatus maintenance can be improved.

  FIG. 3 is an example of an experiment for detecting a flow path abnormality according to the present invention. In FIG. 3, the horizontal axis represents the elapsed time, and the vertical axis represents the current flowing between the electrodes. 301 in FIG. 3 is a measurement result in a state where the flow path is normal, and 302 is a measurement result in a case where a folded portion is formed in a part of the flow path on the inlet side to the flow cell and the state where the flow path is closed is reproduced. It is. The suction speed of the syringe is constant at 42.5 μL / s, and the nozzle is lifted into the air for 2.35 seconds to introduce 100 μL of air bubbles. In FIG. 3, voltage application is started at 303. In this region 304, a current flows because a solution containing an electrolyte flows between the electrodes. When bubbles reach between the electrodes, the current value of air decreases because the electrical conductivity of the air is extremely small. When the space between the electrodes is completely replaced with air, the current becomes zero. Thereafter, when the solution reaches again between the electrodes, a current flows again (307). Reference numeral 308 denotes a point in time when the voltage application is finished. Reference numerals 305 and 306 denote the time during which bubbles in each case have passed between the electrodes. When the flow path is normal (A), the bubble passage time is about 2.2 seconds, whereas when the flow path has a blockage (B), the bubble passage time is about 2.5 seconds and zero. Increased by about 3 seconds. This increase in passage time is due to the pressure loss factor upstream of the flow cell, resulting in a decrease in the pressure of the bubbles when passing through the electrode section, and an increase in volume. From this experimental result, an example of detecting an abnormality of the flow path by the method of the present invention was shown.

  In this embodiment, the bubbles are introduced by raising and lowering the nozzle, but the introduction of air can also be performed by switching the three-way solenoid valve. In this embodiment, a DC voltage is applied, but the voltage may be an AC voltage or a pulsed voltage.

  In addition to the current measurement, the bubble passage time can be measured by the following methods.

  In the method using an optical sensor, the passage time of bubbles is measured by using the difference in absorbance or reflectance between air and solution and determining which fluid is passing through the sensor portion. In the method based on image analysis, the passage time of bubbles is measured by taking an image in the flow path and determining whether the fluid passing through the image analysis is bubbles or solutions. In any method, the state of the flow path is evaluated from the passage time of the bubbles as in the example. As a means for measuring the bubble passage time, it is desirable to use the method used in the intended analysis of the apparatus. For example, in an immunoassay apparatus using detection means using electrodes such as an electrolyte and electrochemical, it is desirable to measure the passage time of bubbles by a current measurement method. This is because an additional measurement mechanism is not required, so that the flow path configuration is not complicated and the cost is not increased.

101, 103 Flow path 102 Detection section 104 Blocking section 105 generated in the flow path Pressure loss 106 in the straight pipe section Pressure loss 106 in the blocking section Pressure 108 at the flow path inlet In the detection section when the flow path is normal Pressure 109 Pressure at detection section when flow path is closed 201 Current measurement flow cell 202, 203 Electrode 204 Solution 205 Introduction flow path 206 Solution container 207 Nozzle 208 Flow path connection section 209 Discharge flow path 210 Syringe pump 211 Voltage control means 212 Current analysis means 213 Arithmetic unit 301 Relationship between time elapsed from bubble introduction and current when flow path is normal 302 Relationship between current elapsed time from bubble introduction and current when flow path is abnormal 303 Voltage application start time 304 Area where the solution flows between the electrodes 305 Bubble passage time when the flow path is normal 306 When the flow path is abnormal Region 308 voltage application end of the inter-cell passage time 307 electrode solution is flowing

Claims (7)

In an analyzer comprising: a container having a constant internal volume; and a flow path through which at least a fluid containing a sample to be measured flows in and out of the container.
An analyzer comprising bubble velocity measuring means for measuring the velocity of bubbles passing through the flow path or the container. The analyzer according to claim 1,
Comparing with the bubble speed measuring means and means for recording the measurement result, the comparison means for comparing the measured bubble speed with a predetermined normal value, and the bubble speed measured by the comparison means is not at the normal value. When it is judged, it is provided with the alerting | reporting mechanism which alert | reports that, The analyzer characterized by the above-mentioned. The analyzer according to claim 1,
The bubble velocity measuring means applies a voltage between at least two electrodes installed in the flow path, and measures based on a change in current when the bubble passes between the electrodes. Analysis equipment. The analyzer according to claim 1,
The said bubble speed measurement means measures based on the change of the reflectance or the light absorbency of light when a bubble passes by the optical sensor installed in the said flow path, The analyzer characterized by the above-mentioned. The analyzer according to claim 1,
The said bubble velocity measurement means image | photographs the image in the said flow path, and measures based on the analysis of the image | photographed image, The analyzer characterized by the above-mentioned. The analyzer according to any one of claims 1 to 5,
An analyzer characterized by measuring a bubble velocity using a signal of a measuring means used for measuring a sample. The analyzer according to any one of claims 1 to 6,
It is characterized by evaluating the time during the measurement process and the presence or absence of bubbles, and outputting information related to whether or not each measurement process was normally performed in association with the measurement result by comparing with predetermined information. Analysis equipment.

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