JP2009276214A - Immuno-analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an immuno-analyzer with the reproducibility of measurement results enhanced. <P>SOLUTION: This immuno-analyzer comprises a reaction vessel 1 allowing a sample to react therein with a reagent, a measurement cell 6 for measuring a measuring object substance in a reactant solution formed through a reaction in the reaction vessel, and a pipe P2 for transporting the solution from the reaction vessel to a detection part. The pipe P2 for transporting the solution from the reaction vessel to the detection part is formed out of a single flexible tube. One end part of the flexible tube is connected to an inlet of the detection part by means of a connector. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an immunoassay apparatus for performing an immunoassay utilizing an antigen-antibody reaction, and more particularly to an immunoassay apparatus including a pipe for transporting a reaction solution in which a sample and a reagent react.

  The path for transporting the reaction solution from the reaction container to the detection unit is generally composed of a plurality of parts. For example, it is known that a sipper probe that sucks a reaction solution in a reaction vessel is connected to a detection unit via a conduit (see, for example, Patent Document 1).

JP 7-248330 A

  When the transport path for the reaction solution is composed of a plurality of parts, a connection part between the parts is necessary. Steps and gaps are created in the connection parts of the components. Due to the steps and gaps, there is a problem that the solution remains, and the solution cannot be delivered at the flow rate and timing as intended, resulting in a decrease in the reproducibility of the measurement results.

  An object of the present invention is to provide an immunoassay device with improved reproducibility of measurement results.

(1) In order to achieve the above-described object, the present invention provides a reaction container for reacting a sample and a reagent, a detection unit for measuring a measurement target substance in a reaction solution reacted in the reaction container, An immunoanalyzer having a pipe for transporting from a reaction container to the detection unit, wherein the pipe for transporting a solution from the reaction container to the detection unit is constituted by a single flexible tube, and the flexible tube Is connected to the introduction port of the detection unit by a connector.
With this configuration, the reproducibility of the measurement result can be improved.

  (2) In the above (1), preferably, a rigid member for holding the other end of the flexible tube is provided.

(3) In the above (2), preferably, the rigid member is a metal pipe, and the flexible tube is inserted into the pipe, and the end surface of the flexible tube and the pipe Are arranged so that their end faces coincide. (4) In the above (1), preferably, the flexible container is provided with a heat block that is disposed between the reaction vessel and the detection unit and that heats the reaction solution transported through the pipe note to a predetermined temperature. The tube has a meandering shape and is in contact with the heat block.

  According to the present invention, the reproducibility of measurement results can be improved.

The configuration of the immune analyzer according to one embodiment of the present invention will be described below with reference to FIGS. 1 and 2.
First, the overall configuration of the immune analyzer according to the present embodiment will be described with reference to FIG.
FIG. 1 is a system configuration diagram showing the overall configuration of an immune analyzer according to an embodiment of the present invention.

  The biochemical component analyzer of the present embodiment includes a sample bottle 31 containing a sample, a bead bottle 32 containing a beads solution containing magnetic particles, and a first that binds magnetic particles to a specific component in the sample. A first reagent bottle 33 containing a reagent; a second reagent bottle 34 containing a second reagent that labels a labeling substance that emits light by an electrochemical reaction and binds to a specific component in the sample; Buffer bottle 3 containing a buffer containing a substance that induces chemical chemiluminescence, washing liquid bottle 4 containing a washing liquid, vessel 1 for obtaining a suspension containing a reaction product, and sample in vessel 1 , Sampling probe 30 for dispensing beads, first reagent, second reagent, and buffer, sipper probe 2 for feeding the suspension of vessel 1, and washing tank for washing the tip of sipper probe 2 A measuring cell 6 into which the suspension sent from the sipper probe 2 is introduced, a syringe 11 for sucking and discharging the suspension, washing liquid and buffer, a waste liquid bottle 13 for storing the waste liquid, and distillation A distilled water bottle 14 that contains water and a pump 12 that feeds distilled water from the distilled water bottle 14 to the washing tank 5 are provided.

  The sampling probe 30 is connected to a syringe (not shown) via a conduit P1. The sipper probe 2 is connected to the measurement cell 6 via a conduit P2. The measurement cell 6 is connected to the syringe 11 via the conduit P3, the first pinch valve 7, and the conduit P4. The conduit P4 is connected to the waste liquid bottle 13 via the conduit P5, the second pinch valve 8, and the conduit P6.

  On the other hand, the distilled water bottle 14 is connected to the cleaning tank 5 via the conduit P9, the pump 12, and the conduit P10, and the cleaning tank 5 is connected to the waste liquid bottle 13 via the conduit P11. A conduit P8 branches off from the middle of the conduit P10, and this conduit P8 is connected to the syringe 11 via the third pinch valve 9 and the conduit P7.

  The sample inside the sample bottle 31 is a sample derived from a biological fluid such as serum or urine.

  The bead solution inside the bead bottle 32 is obtained by dispersing beads (Beads: magnetic particles) in which a particulate magnetic substance is embedded in a matrix made of polystyrene or the like in a buffer solution.

  Next, the operation of the immune analyzer of the present embodiment configured as described above will be described.

  A sample derived from a biological fluid inside the sample bottle 31, a bead solution in which magnetic particles inside the bead bottle 32 are dispersed in a buffer solution, a first reagent inside the first reagent bottle 33, and a second reagent bottle The second reagent inside 34 and the buffer inside the buffer bottle 3 are dispensed into the vessel 1 in order by the sampling probe 30 according to a predetermined order.

  In this embodiment, the analysis is performed by the sandwich method, and the beads solution, the first reagent, the sample, and the second reagent are dispensed in this order. In the case of the competitive method, the bead solution, the sample, the second reagent, and the first reagent may be dispensed in this order.

  In addition, during the dispensing operation, the inside of the vessel 1 is kept at a constant temperature (for example, 37 ° C.) while being stirred by a vibration device (not shown) to proceed the reaction, and after the dispensing operation for a certain time (for example, 15 minutes) Continue to keep warm and stir. As a result, a suspension containing a reaction product in which the magnetic particles, the first reagent, the sample, and the second reagent are combined is generated inside the vessel 1. The tip of the sampling probe 30 is cleaned with the cleaning liquid in the cleaning liquid bottle 4 in the same manner as the cleaning of the tip of the sipper probe 2 after each dispensing operation.

  Next, a method for introducing the suspension inside the vessel 1 into the flow chamber inside the measurement cell 6 will be described. At this time, the magnet is moved in the vicinity of the flow chamber. Next, the first pinch valve 7 is opened, and the second pinch valve 8 and the third pinch valve 9 are closed. In this state, first, the sipper probe 2 is moved horizontally above the vessel 1 by a driving device (not shown) and then moved downward, and the tip thereof is inserted into the suspension inside the vessel 1.

  Next, after a certain amount of the suspension containing the reaction product inside the vessel 1 is sucked into the sipper probe 2 by the syringe 11, the sipper probe 2 is moved upward to move the tip of the suspension outside the suspension. Then, the suspension inside the sipper probe 2 is sucked again by the syringe 11. By this suction, a certain amount of suspension is introduced into the measuring cell 6 through the conduit P2 and flows in the flow chamber. At this time, the operation of the syringe 11 is controlled so that the suspension flows through the flow chamber from the flow path inlet 35 at a constant linear velocity. When the suspension reaches the working electrode inside the measuring cell 6, only the reaction product and unreacted magnetic particles are captured on the working electrode by the magnetic field locally formed by the magnet, and other unreacted particles. The first reagent and the second reagent pass through the flow chamber and are sucked into the syringe 11. In this way, all reaction products contained in a certain amount of suspension are collected in the flow chamber and B / F separation is performed.

  Next, the sipper probe 2 is moved horizontally above the washing tank 5 and then moved downward. The tip of the sipper probe 2 is positioned inside the washing tank 5. In this state, the pump 12 is driven and the distilled water bottle 14 is moved. Distilled water inside is discharged into the cleaning layer 5 through the conduit P9, the pump 12, and the conduit P10, and the outside of the tip of the inserted sipper probe 2 is cleaned. The used distilled water discharged into the cleaning tank 5 is sent as a waste liquid from the bottom of the cleaning tank 5 to the waste liquid bottle 13 through the conduit P11.

  Next, the sipper probe 2 is moved upward to bring the tip out of the washing tank 5 and then horizontally moved above the buffer solution bottle 3 to further move the sipper probe 2 downward to buffer the tip. Insert into the buffer inside the liquid bottle 3. Next, the syringe 11 is inserted into the buffer solution inside the buffer solution bottle 3. Next, the buffer solution inside the buffer solution bottle 3 is sucked by the syringe 11, and a certain amount of buffer solution is introduced into the measurement cell 6. By introducing this buffer solution, the unreacted second reagent remaining in the flow chamber of the measurement cell 6 is washed away, and the B / F separation is completed. At this time, the buffer solution used for washing and the unreacted reagent are absorbed into the syringe 11 from the flow chamber 17 through the conduit P3, the first pinch valve 7, and the conduit P4.

  By the above operation, the reaction product and the unreacted first reagent (magnetic particles) are captured on the working electrode in the flow chamber, and the surroundings, that is, the entire flow chamber invites excitation of the labeling substance. Will be filled with the buffer used.

  On the other hand, the buffer solution sucked into the syringe 11 and the unreacted reagent are discharged into the waste liquid bottle 13 by the syringe 11 after the first pinch valve 7 is closed and the second pinch valve 8 is opened.

  After completion of the above process, a voltage based on a sequence determined between the working electrode and the counter electrodes arranged on both sides of the same plane is applied, and the labeling substance in the reaction product emits light. The light generated by this reaction is measured by the light detector through a transparent light receiving window provided on the flow chamber, and the concentration is calculated.

  After completion of the luminescence reaction, the inside of the flow chamber 17 is cleaned. First, the first pinch valve 7 is opened, the second pinch valve 8 and the third pinch valve 9 are closed, and the sipper probe 2 whose tip has been washed with distilled water in the same manner as described above is used as a washing water bottle. After moving horizontally above 4, it moves downward, and its tip is inserted into the cleaning liquid inside the cleaning liquid bottle 4. In this state, suction of the cleaning liquid inside the cleaning liquid bottle 4 is started with the syringe 11. . At this time, in order to increase the cleaning efficiency, it is preferable that the sipper probe 2 is moved up and down while the cleaning liquid is sucked by the syringe 11 to alternately suck the cleaning liquid and air by a certain amount. The washing liquid sucked in this way is guided into the flow chamber 17 inside the measurement cell 6 through the conduit P2, and the buffer solution, reaction product, and unreacted first solution remaining in the flow chamber 17 are left. Wash off the reagent (magnetic particles). Thereafter, the waste liquid and the cleaning liquid sucked into the syringe 11 are discharged into the waste liquid bottle 13 by closing the first pinch pinch valve 7, opening the second pinch valve 8, and pushing out the syringe 11.

  After the above process is completed, the second pinch valve 8 is closed again, the first pinch valve 7 is opened, and the buffer solution is drawn from the buffer solution bottle 3 using the syringe 11 by the sipper probe 2 whose tip has been washed in advance with distilled water. Then, a predetermined amount is sucked to wash away the cleaning solution remaining in the conduit P2 and the flow chamber 17 of the measuring cell 6, and then the conduit P2 and the flow chamber 17 are replaced with a buffer solution. This operation completes the measurement for one sample.

  Furthermore, you may perform the washing | cleaning operation as a maintenance of the syringe 11 as follows.

  First, the first pinch valve 7 is closed, the second pinch valve 8 and the third pinch valve 9 are opened, and the pump 12 is driven to supply distilled water from the distilled water bottle 14 to the conduit P9, the pump 12, the conduit P10, The liquid is sent to the syringe 11 through the conduit P8, the third pinch valve 9, and the conduit P7, and further sent from the syringe 11 to the waste liquid bottle 13 through the conduit P4, the conduit P5, the second pinch valve 8, and the conduit P6. . Next, the third pinch valve 9 is closed, and the distilled water remaining in the syringe 11 is sent by the syringe 11 to the waste liquid bottle 13 through the conduit P4, the conduit P5, the second pinch valve 8, and the conduit P6.

Next, the configuration of the solution introduction pipe from the sample shipper to the measurement cell in the immune analyzer according to the present embodiment will be described with reference to FIG.
FIG. 2 is a front view showing a configuration of a solution introduction pipe in the immune analyzer according to the embodiment of the present invention. The same reference numerals as those in FIG. 1 denote the same parts.

  The measurement cell 6 includes a flow chamber 6A, a magnet 6B disposed in the vicinity of the flow chamber 6A, and a photodetector 6C disposed outside the transparent window portion of the flow chamber 6A. As the photodetector 6C, for example, a photomultiplier tube or the like is used. The flow chamber 6A is provided with a working electrode and a counter electrode, which are not shown.

  The solution introduction pipe P2 is connected to the introduction port of the flow chamber 6A by a connector 6D. The pipe P3 is connected to the outlet of the flow chamber 6A by a connector 6E.

  In the present embodiment, a single flexible tube (sipper tube) is used as the solution introduction pipe P2 for transporting the reaction solution from the reaction container to the detection unit. The sipper tube has, for example, an outer diameter of 1.4 mm, an inner diameter of 0.8 mm, and an overall length of 80 cm. For example, the sipper tube is made of a PTFE tube.

  One end of the solution introduction pipe P2 is connected to the introduction port of the flow chamber 6A by a connector 6D, while the other end is inserted into the pipe 2A to connect the sipper probe 2 It is composed.

  In addition to the reaction solution from the vessel 1, a buffer solution from the buffer solution bottle 3 and a cleaning solution from the cleaning solution bottle 4 need to be introduced into the measurement cell 6. These three types of solutions are fed by a common sipper tube. However, these solutions are stored in separate containers. Therefore, the sipper tube needs to be movable vertically and horizontally in order to move between these containers. However, when the solution is sucked with the flexible tube, the tube is bent and the solution cannot be sucked correctly.

  Therefore, in the present embodiment, the tube end portion is given rigidity by being fixed through the sipper tube in the metal pipe 2A. In addition, the position of the end face of the sipper tube used as the solution introduction pipe P2 is matched with the end face of the pipe 2A. This is because if there is a step between the two, the solution adheres to the step, causing problems of contamination and dilution of the solution. Further, since there is a slight gap between the inner periphery of the pipe 2A and the end of the sipper tube, the two are fixed with an adhesive so that no solution or the like enters the gap.

  The pipe 2A can be moved up and down by a vertical movement mechanism 2C. The pipe 2A is configured to be movable in the horizontal direction by the horizontal movement mechanism 2E.

  The heat block 2H is in contact with the sipper tube at a position close to the flow chamber 6A of the sipper tube. The heat block 2H is heated to a constant temperature (for example, 28 ° C.). Therefore, the reaction solution flowing inside the sipper tube is heated to a constant temperature by the heat block 2H and then introduced into the flow chamber 6A. The reaction solution is heated to a constant temperature (for example, 37 ° C.) as described above. However, when the reaction solution is transferred through the sipper tube and reaches the inside of the flow chamber 6A, the temperature decreases. In addition, if the rate of temperature decrease varies depending on the ambient temperature or the like, a measurement error occurs. Therefore, it is necessary to keep the temperature of the reaction solution introduced into the flow chamber 6A constant.

  Since the sipper tube is made of resin as described above, the sipper tube has a lower thermal conductivity than metal. Therefore, the flexible sipper tube is meandered as shown in the figure, and the contact length with the heat block 2H is increased so that the reaction solution in the tube can be easily heated to a constant temperature. However, since the thickness of the tube is as thin as 0.3 mm as described above, it is relatively easy to conduct heat, so that the length of the sipper tube contacting the heat block 2H is about 40 to 50 cm.

  The connector 6D has a configuration like a female screw. A hole through which the sipper tube passes is formed in the center, and a female screw is formed on the inner peripheral side of the hole. After the end of the sipper tube is inserted into the hole, the outer diameter of the end of the sipper tube is increased by heating the end of the sipper tube. Inside the connector 6D, a countersink hole that can accommodate the end of the sipper tube having an increased outer diameter is formed. In this state, the end of the sipper tube can be fixed to the introduction port of the flow chamber 6A by fastening the connector 6D to the male screw portion provided at the introduction port of the flow chamber 6A.

  The sipper tube is routed to the vicinity of the reaction vessel 1, the buffer solution vessel 3 and the washing solution vessel 4 while avoiding interference with other components inside the apparatus and their movable parts. Since the reaction vessel and the detector are installed at remote locations, piping for transporting the reaction solution is required. Since each part is arranged in the analyzer, it is necessary to arrange the piping while avoiding interference between these parts and the movable part. In this embodiment, since a flexible tube is used for the piping, it is possible to easily install the piping while avoiding interference with other components in the apparatus.

  The path from the conventional sipper probe to the inlet of the flow chamber 6A is generally composed of the following four members. That is, the first is a metal sipper probe. The second is a first resin tube connected to the sipper probe. The third is a metal pipe connected to the first resin tube. The metal pipe is in contact with the heat block, and the reaction solution flowing in the metal pipe is heated to a predetermined temperature. The fourth is a second resin tube connected to a metal pipe. A second resin tube is connected to the flow chamber 6A.

  Thus, when connecting using 4 members, the connection location in a path | route from a sipper probe to the inlet of flow chamber 6A will be four places. In such a connection portion, a gap or a step is generated. When the liquid flows through these gaps and steps, a vortex is generated in the gaps and steps, and the solution remains in these portions. For this reason, particularly in a low-concentration sample, the analysis result changes due to the solution remaining, and the reproducibility is lowered.

  Conventionally, there are four connection locations, but the secular location in the present embodiment can be only one location between the solution introduction pipe P2 using the connector 6D and the flow chamber 6A. Therefore, it is possible to reduce a decrease in reproducibility of the analysis result due to a gap or a step in the connection portion.

  In addition to the method of inserting the tube into the metal pipe as described above, the end of the tube may be fixed to the metal rod as a method for giving the sipper tube rigidity. It ’s good.

As described above, according to the present embodiment, the pipe for transporting the solution from the reaction vessel to the detection unit is configured by a single flexible tube, and one end of the flexible tube is detected. By being connected to the introduction port of the part with a connector, the connection place can be made one place, and the step part and the gap can be reduced, so that the reproducibility of the measurement result can be improved.

1 is a system configuration diagram showing the overall configuration of an immune analyzer according to an embodiment of the present invention. It is a front view which shows the structure of the piping for solution introduction in the immunoassay apparatus by one Embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Reaction container 3 ... Buffer bottle 4 ... Washing solution bottle 6 ... Measurement cell 11 ... Syringe 32 ... Reagent bottle P2 ... Pipe for introduction (sipper tube)
P3 ... Exhaust piping

Claims (4)

An immunoassay having a reaction container for reacting a sample and a reagent, a detection unit for measuring a measurement target substance in a reaction solution reacted in the reaction container, and a pipe for transporting the solution from the reaction container to the detection unit A device,
The piping for transporting the solution from the reaction container to the detection unit is constituted by a single flexible tube,
One end part of the said flexible tube is connected to the inlet of the said detection part with the connector, The immune analyzer characterized by the above-mentioned. The immunoassay device according to claim 1,
An immunoassay apparatus comprising a rigid member that holds the other end of the flexible tube. The immunoassay apparatus according to claim 2,
The rigid member is a metal pipe, the flexible tube is inserted into the pipe, and an end surface of the flexible tube and an end surface of the pipe are coincident with each other. apparatus. The immunoassay device according to claim 1,
A heat block is disposed between the reaction vessel and the detection unit, and heats the reaction solution transported through the pipe note to a predetermined temperature.
The immune analyzer according to claim 1, wherein the flexible tube has a meandering shape and is in contact with the heat block.

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