JP2016217921A - Automatic analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To reduce influences of circulating and bubbles generated when a reagent and a specimen are mixed.SOLUTION: A device includes: an optical measuring part comprising a reaction container 104, a dispensation nozzle, a light source 115, and a detector 116 of the light source 115; and a control part 120 of the dispensation nozzle. When any of a reagent or a sample are discharged into the reaction container 104 by the dispensation nozzle, a top end point of the dispensation nozzle is controlled to be located inside of the reaction container 104, upper than a liquid surface within the reaction container 104 in the wall surface region of the reaction container 104 and other than the center point of the first plane approximately in parallel with the liquid surface. The optical measuring instrument makes a light-receiving axis of the detector 116 intersect with a straight line including the top end point of the dispensation nozzle and the center point of the first plane, and a second plane including two cross points with the wall surface of the reaction container 104 and an extended line of the top end of the dispensation nozzle within a region closed by the wall surface of the reaction container 104 and the liquid surface within the reaction container 104.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an automatic analyzer for analyzing the amount of components contained in a specimen such as blood or urine.

  As an analyzer for analyzing the amount of components contained in a specimen, a single or a reaction liquid obtained by irradiating light from a light source to a reaction liquid (hereinafter sometimes simply referred to as reaction liquid) that is a mixed liquid of the specimen and a reagent. Automatic analysis that measures the amount of transmitted light or scattered light at multiple wavelengths, and based on the measurement results, determines the concentration of components contained in the sample or items including blood coagulation time as an analysis of the blood coagulation reaction of the sample The device is known.

  As a means for stirring the reaction liquid, a method of rotating it coaxially in the liquid using a spatula-shaped stirring rod, a technique of inserting a nozzle into the liquid and performing suction and discharge operations, vibration of the liquid by ultrasonic waves Or a method of stirring using a pressure at the time of discharging a reagent or a specimen (hereinafter sometimes referred to as discharge stirring). Among these, the discharge agitation can be performed without contact and can be carried out quickly without using a complicated structure. In particular, blood whose reaction starts immediately after mixing of the reagent and the specimen. It is used when analyzing the coagulation reaction.

  Patent Document 1 discloses a sample stirring mechanism in which a nozzle having a driving means for moving a sample in a sample container up and down performs both stirring by suction and discharge of the sample and stirring by rotation of the nozzle itself. A technique is described in which a liquid amount detecting means is provided and stirring is performed only by suction and discharge of a sample when the liquid amount is small, and stirring is not performed by rotation of a nozzle.

  In Patent Document 2, when stirring with the discharge pressure of a reagent or a specimen, either one of the reagent dispensing mechanism and the specimen dispensing mechanism is performed, and a predetermined liquid amount is discharged into a reaction container first, In addition, a method is disclosed in which the other dispensing mechanism discharges a liquid at a relatively lower rate than when the amount of discharged liquid is large, and when the amount of discharged liquid is large, compared to a discharge speed when the amount is small. .

  In Patent Document 3, a reagent dispensing probe having an opening for sucking and discharging a reagent at one end, and a flow path leading to an opening inclined obliquely downward in one end including the one end is moved to flow. A configuration is described in which the path extension line stops at the reagent discharge position where it intersects the inner surface other than the bottom surface in the reaction vessel.

JP-A-11-142414 WO2014 / 097973 JP 2014-41144 A

  As described above, in an automatic analyzer that obtains the concentration of a component, blood coagulation time, and the like based on the amount of light obtained by irradiating the reaction solution with light, it is required to stir and sufficiently mix the sample and the reagent. . This is because if the stirring is insufficient, the reaction in the mixed solution becomes non-uniform and there is a possibility that an accurate measurement result cannot be obtained.

  However, when agitation is further performed in the reaction container in which the reagent or specimen is accommodated by using the moment of discharging the specimen or reagent, the reagent or specimen previously contained in the reaction container and a new The liquid flow generated while the sample or reagent discharged to the vessel is agitated and mixed, or bubbles entrained in the flow may affect the optical measurement result of the reaction solution. However, Patent Document 1 does not consider the stirring itself by the specimen or reagent discharge operation itself except when the amount of liquid is small, and Patent Document 3 tilts obliquely downward as described above. Since a specially-shaped dispensing probe having the above-described flow path is required, the structure becomes complicated. Furthermore, in Patent Document 2, it can be applied when the amount of the sample or reagent previously contained in the reaction container is larger or smaller than the amount of the sample or reagent added later. This condition is not considered. Moreover, in such a method, since it is necessary to change the discharge speed of the sample or reagent added later, control of the operation of the dispensing probe becomes complicated.

  None of the literature recognizes the flow of the reaction liquid, which is a mixed liquid of the specimen and the reagent generated during the discharge stirring, and the influence of the generated bubbles being involved in this flow. It has not been.

  An object of the present invention is to discharge a reagent or sample from a dispensing mechanism to a sample or reagent accommodated in a reaction container, and to stir the reaction liquid using the liquid discharge momentum. The present invention relates to the realization of highly accurate analysis by suppressing the flow of liquid generated in a reaction liquid by discharge and the occurrence of bubbles in the flow.

  As an aspect for solving the above-described problem, a reaction container that contains a mixed solution of a specimen and a reagent, a dispensing nozzle that dispenses the specimen and the reagent, and the mixed liquid are housed in the reaction container. An optical measurement unit comprising a light source for irradiating light to the reaction vessel and a detector for detecting the light emitted from the light source, and a control unit for controlling the operation of the dispensing nozzle, An automatic analyzer that mixes the reaction container holding any of the reagents by discharging either the reagent or the sample through the dispensing nozzle, and the control unit includes the sample or the reagent When either the reagent or the specimen is discharged by the dispensing nozzle to the reaction container holding any of the above, the tip of the dispensing nozzle is inside the reaction container, and the reaction container Of the region partitioned by the wall surface, the center point of the first plane that is above the liquid level of either the sample or the reagent contained in the reaction container and is substantially parallel to the liquid level The dispensing nozzle is controlled so that it is located outside, and the optical measurement unit uses the light receiving axis of the detector as a wall surface of the reaction vessel and either the sample or the reagent contained in the reaction vessel. Of the region closed by the liquid level, two intersections of the straight line including the tip point of the dispensing nozzle and the center point of the first plane and the wall surface of the reaction vessel and the extension of the tip point of the dispensing nozzle It is provided so that it may cross | intersect the 2nd plane containing a line.

  According to the above aspect, when the sample or sample is discharged from the dispensing mechanism to the sample or sample accommodated in the reaction container and the reaction liquid is stirred using the liquid discharge force, Since the detection range does not include the flow of liquid that occurs in the reaction liquid due to the discharge of gas and the occurrence of bubbles in the flow, the noise in the measurement results can be reduced, and high-precision analysis can be performed. Contribute to realization.

It is the schematic which shows the basic composition of the automatic analyzer which concerns on this Embodiment (1st Embodiment). It is the schematic which shows the positional relationship of the dispensing nozzle which concerns on this Embodiment (1st Embodiment), reaction container, and a 1st plane. It is the modification which concerns on this Embodiment (1st Embodiment), Comprising: It is the schematic which shows the positional relationship of the nozzle provided with the bent shape, reaction container, and a 1st plane. It is the schematic which shows arrangement | positioning of the light source and detector of an optical measurement part based on this Embodiment (1st Embodiment). It is the modification which concerns on this Embodiment (1st Embodiment), Comprising: It is the schematic which shows arrangement | positioning of a 2nd plane and an optical measurement part in case the dispensing nozzle is bent. It is the modification which concerns on this Embodiment (1st Embodiment), Comprising: It is the schematic which shows arrangement | positioning of a 2nd plane and an optical measurement part in the case of using a prismatic reaction container. It is the other modification which concerns on this Embodiment (1st Embodiment), Comprising: It is the schematic which shows arrangement | positioning of a 2nd plane and an optical measurement part in the case of using a prismatic reaction container. It is another modification which concerns on this Embodiment (1st Embodiment), Comprising: The nozzle before and after dispensing, reaction container, and 2nd plane in the case of dispensing after dropping a nozzle to liquid level vicinity It is the schematic which shows a positional relationship. It is a figure which shows the simulation result of the movement of the liquid mixture and bubble at the time of mixing of a test substance and a reagent. It is an optical measurement result by this Embodiment (1st Embodiment), and a comparative example. It is the schematic which shows the positional relationship of the nozzle which concerns on this Embodiment (2nd Embodiment), reaction container, a 1st plane, and a 2nd plane. It is the schematic which shows the structure provided with the some measurement port which concerns on this Embodiment (3rd Embodiment). It is the schematic which shows arrangement | positioning of the detector of the optical measurement part which concerns on this Embodiment (4th Embodiment). It is the schematic which shows arrangement | positioning of the detector of the optical measurement part which concerns on the modification of this Embodiment (4th Embodiment). It is the schematic which shows an example of the variation of the reaction container and optical measurement part which concern on this Embodiment (5th Embodiment).

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. Throughout the description, description of the same components in each drawing may be omitted.

First embodiment

<Device configuration>
FIG. 1 is a schematic diagram showing a basic configuration of an automatic analyzer according to the present embodiment. In the present embodiment, a biological sample such as blood or urine (hereinafter sometimes simply referred to as a specimen) is taken as an example of a composite automatic analyzer (hereinafter sometimes simply referred to as an automatic analysis device or apparatus). An apparatus capable of processing analysis items in the biochemical field after mixing reagents and reagents and processing analysis items in the blood coagulation field will be described as an example. Of course, the configuration of the apparatus is not limited to this. That is, the automatic analyzer according to the present embodiment measures the transmitted light amount or scattered light amount of single or plural wavelengths obtained by irradiating light from the light source to the reaction liquid in which the sample and the reagent are mixed. The present invention can be applied to an apparatus that calculates the amount of a component from the relationship between the light amount and the concentration, or an apparatus that obtains items including blood coagulation time as an analysis of the coagulation reaction of blood as a specimen.

  In FIG. 1, an automatic analyzer 100 mainly includes a sample dispensing nozzle (sample dispensing mechanism) 101, a sample rack 102, a reagent dispensing nozzle (reagent dispensing mechanism) 106, a reagent rack 107, a reaction container stock unit 111, It includes an optical measurement unit 124 including a reaction container carry-out and transport mechanism 112, a light source 115 and a detector 116, a measurement port 113, a reaction container discarding unit 117, an operation unit 118, a storage unit 119, and a control unit 120.

  The sample dispensing nozzle 101 is accommodated in a sample (sample) accommodated in a sample container (sample container) 103 arranged in a sample rack 102 that rotates clockwise and counterclockwise, or in a quality control sample container (not shown). The quality control sample is sucked and discharged to the reaction vessel 104. The sample dispensing nozzle 101 is connected to the sample syringe pump 105 and is controlled by a computer that is the control unit 120 to execute the operations of aspirating and discharging the sample.

  The reagent dispensing nozzle 106 sucks the reagent accommodated in the reagent container 108 arranged in the reagent rack 107 and discharges it to the reaction container 104 in which the specimen is accommodated. In the above description, the reagent is dispensed after the sample is dispensed into the reaction container. However, depending on the measurement item, the sample is dispensed into the reaction container into which the reagent has been dispensed first. It can also be configured to be ordered.

  Here, the mixed solution of the sample (including the diluted solution of the sample) and the reagent is referred to as a reaction solution. The reagent dispensing nozzle 106 is connected to the reagent syringe pump 110 and is controlled by a computer that is the control unit 120 to execute the operation of sucking and discharging the reagent.

  Here, when performing analysis in the blood coagulation field, a reagent temperature raising mechanism 109 can be incorporated in the reagent dispensing nozzle 106. The controller 120 controls the reagent temperature raising mechanism 109 to raise the temperature of the reagent sucked by the reagent dispensing nozzle 106 and adjust it to an appropriate temperature (predetermined temperature).

  The reaction container transport mechanism 112 transports and installs the reaction container 104. The reaction container transport mechanism 112 transports and installs the reaction container 104 from the reaction container stock unit 111 to the reaction container installation unit 114 of the measurement port 113 by holding the reaction container 104 and rotating in the horizontal direction.

  In the present embodiment, the measurement port 113 is a measurement having one or more reaction container installation parts 114 for placing the reaction container 104 (in this embodiment, one case is shown as an example). Displayed as port 113. The reaction vessel 104 may be held by the measurement port 113 as in the present embodiment, or a plurality of reaction vessels are fixed to a disk-shaped disk formed to be rotatable, and the disk is rotated during measurement. You may comprise so that the reaction container of a measurement object may pass the optical axis of an optical measurement part (not shown). Here, the light source 115 and the detector 116 may be collectively referred to as an optical measurement unit. The light intensity of the reaction vessel 104 inserted into the reaction vessel installation unit 114 is measured. In the present embodiment, the case where one measurement port 113 is arranged is shown, but the present invention is not limited to this, and a plurality of measurement ports 113 may be provided.

  The light source 115 of the optical measurement unit provided in the measurement port 113 can be selected from a halogen lamp, a xenon lamp, a deuterium lamp, a mercury lamp, a mercury xenon lamp, a laser, and an LED. The light source 115 irradiates the reaction vessel 104 with light. The light emitted from the light source 115 is attenuated and transmitted by the reaction solution accommodated in the reaction vessel 104 or scattered. The detector (photosensor) 116 can be selected from a photodiode, a photomultiplier tube, a photoconductive element, a photovoltaic element, and the like. The detector 116 receives transmitted light attenuated and transmitted by the reaction solution in the reaction vessel 104 or scattered scattered light, and converts the light / current into a photometric signal indicating the received light intensity A. A function of outputting to the / D converter 121 is provided. A measurement signal of transmitted light or scattered light A / D converted by the A / D converter 121 is input to the control unit 120 via the interface 122. The operation of the measurement port 113 is controlled by a computer that is the control unit 120.

  The reaction container transport mechanism 112 holds the reaction container 104 that has been measured, transports it to the reaction container discarding unit 117, and discards it.

  Sample analysis items analyzed by the automatic analyzer 100 are input from the operation unit 118 to the control unit 120 via an operation screen displayed on the keyboard 118b or the display unit 118c as input means. Note that a GUI (Graphical User Interface) for inputting analysis items by operating the analysis items displayed on the display unit 118c with a pointer or the like with the mouse 118a may be used.

  Here, the control unit 120 will be described. The control unit 120 mainly includes an overall control unit 120a, a measurement control unit 120b, and the like.

  The overall control unit 120a controls the operation of the automatic analyzer 100 such as the above-described dispensing of samples and reagents, transfer of the reaction container 104, and disposal of the reaction container 104.

  The measurement control unit 120b calculates the measurement value of the light intensity that changes with time according to the degree of the mixing reaction between the sample and the reagent, and based on the calibration value acquired in advance, the concentration of the analyte or the reaction time (In the blood coagulation field, this refers to the clotting time, etc.). Moreover, based on the comparison result with a predetermined determination threshold value, it is also possible to determine the quality by determining the concentration and reaction time of the analyte contained in the sample. The calculated concentration or reaction time is output to the display unit 118c and stored in the storage unit 119. The concentration or reaction time as the calculation result may be printed out to the printer 123 via the interface 122.

<Configuration of detection unit>
FIG. 2 is a schematic diagram showing the positional relationship between the nozzle, the reaction vessel, and the first plane according to the present embodiment. FIG. 2 shows a top view (200) of the reaction vessel and the like, an XY cross-sectional view (201), and a right side view (202).

  Here, the nozzle 203 indicates the reagent dispensing nozzle 106 or the sample dispensing nozzle 101 in FIG. The nozzle 203 is connected to a nozzle drive mechanism (not shown). The nozzle drive mechanism is connected to the control unit 120 through the interface 122 as shown in FIG. The reagent dispensing nozzle 106 and the sample dispensing nozzle 101 are connected to the sample syringe pump 105 and the reagent syringe pump 110, respectively, thereby sucking and discharging the liquid. The operations of the nozzle drive mechanism and the syringe pump are controlled by the control unit 120.

<Nozzle operation>
Next, the flow of the dispensing operation according to the present embodiment will be described.

  Here, a case will be described in which a sample or reagent is further dispensed in a state where the reagent or sample 205 is dispensed into the reaction container 204 by the nozzle 203 and left still. A nozzle 203 that sucks and holds the specimen or reagent descends inside the reaction vessel 204. The descending amount at this time may be a predetermined value according to the measurement item or the like, or may be determined by measuring or measuring the dispensed liquid amount. The dispensing of the dispensed liquid here may be carried out by providing a weight sensor in the reaction container 204, or from the volume of the already dispensed sample or reagent and the capacity and dimensional information of the reaction container, You may obtain | require by estimating height by calculation.

  Further, the amount by which the nozzle 203 is lowered can also be determined by a method of detecting the liquid level of the dispensed liquid. That is, the liquid level position is detected by an electrical signal between the nozzle 203 and the liquid, or the reaction container 204 and the liquid contained in the liquid container are imaged from the side surface, and the acquired data is subjected to image processing. The liquid level may be detected.

  One of the advantages of detecting the liquid level position when dispensing is that stirring can be reliably performed under non-contact conditions when using the discharge stirring method. In automatic analyzers, reagents and specimens are mixed, the reaction induced is optically measured, and the concentration and function of specific substances contained in the specimen are generally measured. Contacting the nozzle with the liquid 205 in the reaction container may cause contamination between the reagent and the specimen, or between the specimen or the reagents. Therefore, if this can be reliably prevented during discharge stirring, the accuracy of analysis can be improved. This leads to further improvement.

In particular, in blood clotting time measuring devices that measure blood clotting time, fibrin may precipitate in the reaction solution produced by mixing the reagent and sample, and the viscosity of the reaction solution may increase. It is desirable to carry out without contact. Above all,
In an item such as fibrinogen, particularly in a sample containing a high concentration of fibrinogen, this reaction is started several seconds after mixing of the reagent and the specimen. When this reaction is measured optically, time-series data is measured by measuring scattered light intensity and transmitted light intensity, and the blood coagulation time is calculated based on the obtained data. That is, it is required to perform optical measurement immediately after mixing the reagent and the specimen.

  Therefore, while ensuring that the nozzle 203 and the liquid 205 are not in contact with each other, the specimen or reagent is discharged from the nozzle 203 toward the extension line 206 of the nozzle 203, and stirring with the liquid 205 by this momentum It is excellent in that contamination can be prevented and measurement can be performed immediately after mixing.

  Here, when agitation is performed by the ejection force of the reagent or the specimen, the reagent and the specimen are more uniformly mixed as the liquid ejection speed from the nozzle 203 increases. On the other hand, when the discharge speed of the liquid from the nozzle 203 increases, it becomes easy to entrain bubbles in the mixed liquid.

  Therefore, as a relative positional relationship between the nozzle 203 and the reaction vessel 204 when the stirring by the ejection force of the reagent or the specimen is performed, the nozzle tip point 207 is inside the reaction vessel 204, and the reaction vessel 204 Among the areas separated by the wall surface, the information is more than the liquid level of either the specimen or the sample stored in the reaction vessel 204, and other than the center point of the first plane substantially parallel to the liquid level It is desirable to control by a nozzle drive mechanism so that it may be located in. Here, the first plane 210 is preferably parallel to the liquid level 208 in the reaction vessel, but in reality, the liquid 205 in the reaction vessel has a meniscus depending on the material of the reaction vessel, the surface treatment, and the nature of the liquid. As a result, the liquid level 208 is not a plane as schematically shown in FIG. Therefore, the first plane in the present embodiment does not need to be a plane strictly parallel to the liquid surface 208, and may be substantially parallel.

  The reason for controlling the position of the nozzle tip point 207 as described above is that when the nozzle tip point 207 is positioned at the center point 211 of the first plane 210 and a sample or reagent is dispensed, the liquid surface 208 of the liquid 205 is tapped. This is because the sample or reagent is dispensed in this manner, and bubbles are likely to be mixed into the liquid mixture of the liquid 205 and the sample or reagent, and the two liquids are not mixed well.

  Therefore, the nozzle tip point 207 is preferably positioned at a point other than the center point 211. By doing so, the dispensed specimen or reagent causes reflux 212 in the liquid in the reaction container in the reaction container 204, and the two liquids of the dispensed specimen or reagent and the liquid in the reaction container are sufficiently obtained. Mixed.

  More preferably, the nozzle tip point 207 should be close to the reaction vessel inner wall surface 209 so that the sample or reagent to be dispensed can be mixed along the reaction vessel inner wall surface 209. This is because the reagent or sample 205 in the reaction container and the sample or reagent held in the nozzle 203 and the nozzle 203 are not in contact with each other at the time of dispensing. In this state, since the liquid level 208 and the liquid level of the liquid to be discharged are close to each other, bubbles may be generated in the liquid depending on the viscosity of the mixed liquid. This is because the generation of bubbles can be suppressed by mixing along the wall surface 209. As described above, bubbles can be a noise factor that fluctuates data in the optical measurement of the reaction solution, which can be reduced.

  FIG. 3 is a schematic diagram showing a positional relationship among a nozzle having a bent shape, a reaction vessel, and a first plane, which is a modification according to the present embodiment. As shown in this figure, when the nozzle tip point 207 is brought close to the reaction vessel inner wall surface 209, the tip of the nozzle 203 can be bent toward the reaction vessel inner wall surface 209.

  Next, details of the arrangement of the light source and detector of the optical measurement unit in the present embodiment will be described.

  FIG. 4 is a schematic diagram showing the arrangement of the light sources and detectors of the optical measurement unit according to the present embodiment. This figure shows a top view (400) and an XY cross-sectional view (401) of the reaction vessel, respectively. When the specimen or reagent is discharged from the nozzle 203 which is either the specimen dispensing nozzle 101 or the reagent dispensing nozzle 106 into the reaction container 204 containing the reagent or specimen 205, the nozzle tip point 207 is set to the reaction container 204. Of the region separated by the wall surface of the reaction vessel 204 and is more information than the liquid level of either the specimen or the sample accommodated in the reaction vessel 204 and substantially parallel to the liquid level. When the light receiving axis 402 of the detector 409 of the optical measuring unit is controlled to be located at a position other than the center point of the first flat surface 210, the specimen or sample contained in the reaction vessel inner wall surface 209 and the reaction vessel 204 Of the region closed by any liquid level, two intersections and nose of the straight line including the nozzle tip point 207 and the center point 211 of the first plane 210 and the inner wall surface 209 of the reaction vessel It is arranged so as to intersect the second plane 405 including the extension 206 of the tip point 207.

  On the light receiving axis 402, a constant photometric range is formed in a range where the reaction liquid in the reaction vessel 204 intersects. This photometric range can be arbitrarily determined according to the height of the liquid surface 410 of the reaction liquid that combines the reagent or specimen 205 and the discharged specimen or reagent, the size, shape, measurement item, etc. of the reaction vessel 204. . In order to obtain a stable measurement result, generally, the intersection of the light receiving axis 402 and the second plane 405 is a closed plane formed by the second plane 405, the reaction vessel inner wall surface 209, and the reaction liquid level 410. It can be adjusted to be near the center.

  One reason for this is to suppress the influence of bubbles existing near the liquid level 410. In particular, when the sample or reagent is stirred at the moment of discharge, bubbles generated in the reaction solution move along the inner surface 209 of the test tube along the reflux 212 and then escape from the liquid surface. There are cases where the liquid level remains. Such a bubble has a relatively large volume, and if it exists in the photometric range, the optical measurement result may be affected as noise generation. In order to avoid the influence of bubbles remaining on the liquid surface, it can be provided in a state where an appropriate distance is separated from the liquid surface in the above-mentioned photometric range.

  By the way, for the reaction of the reaction solution, two kinds of reactions are mainly used: a color reaction between the substrate and the enzyme and an agglutination reaction between the antigen and the antibody. The former is biochemical analysis, and test items include LDH (lactate dehydrogenase), ALP (alkaline phosphatase), AST (aspartate aminotransferase) and the like. The latter is immunoassay, and test items include CRP (C-reactive protein), IgG (immunoglobulin), RF (rheumatoid factor) and the like.

  Since the measurement substance measured by the latter immunoassay has a low blood concentration, a highly sensitive detection system is required. For example, when the latex particles are aggregated by an antigen-antibody reaction with an antigen contained in a sample using a reagent in which an antibody is sensitized (bound) on the surface of the latex particles, the reaction solution is irradiated with light. And the sensitivity enhancement by the latex agglutination method which measures quantity of the component contained in a sample by measuring the light quantity permeate | transmitted without being scattered by the latex agglomerate has been achieved.

  In addition, there is a technique that does not measure the amount of light transmitted from the sample, but obtains higher sensitivity, or measures the amount of scattered light depending on the measurement item. In measurement in the blood coagulation field, measurement by the amount of scattered light is preferably used. In this case, a light source and one or a plurality of detectors are used as the optical measurement unit. As an example of the arrangement in this embodiment, as shown in the top view (400) and the XY sectional view (401), the light source The detector 407 or the detector 409 can be arranged with respect to 406 or the light source 408. That is, light sources 406 and 408 are provided at positions where light is irradiated upward from the bottom surface of the reaction container, and detectors 407 and 409 having light receiving axes at positions where the reaction container 204 has a photometric range from the side surface. Can be configured. The light reception angle may be set in advance from the viewpoint of sensitivity and reproducibility depending on the device configuration and reagent composition. Alternatively, the light reception angle may be set in advance. You may comprise so that a measurement precision may be improved by complementing and correcting light intensity, or removing an abnormal value.

  The periphery of the reaction vessel is surrounded by a temperature-controlled thermostat, for example, a thermostat (not shown in FIG. 4) for circulating a thermostatic liquid. An optical window for realizing the measurement is provided. The reason why the detector and its light receiving axis are arranged in this way will be described below.

  In the reaction vessel having a cylindrical shape and an inverted conical shape in FIG. 4, the operation of the nozzle 203 is controlled so that the nozzle tip point 207 comes to a position other than the center point 211 of the first plane 210 indicated by the oblique line in the top view (400). In this state, for example, when the reagent or specimen is discharged after the nozzle 203 is brought into contact with the inner wall surface 209 of the reaction container, if the momentum is sufficiently strong, The reflux is formed on the plane surrounded by the intersecting line between the inner wall surface 209 of the reaction vessel and the liquid level 410 of the reaction solution. The flow of the discharged liquid is refluxed 212 on this plane and along the inner wall surface 209 of the reaction vessel. In the present embodiment, the light receiving axis 402 of the optical system detector 409 is disposed so as to intersect the second plane 405.

  As described above, in order to mix the two liquids, it is necessary to discharge the liquid from the nozzle 203 at a sufficient speed. Furthermore, from the viewpoint of preventing contamination, it is desirable that the nozzle 203 and the sample or reagent 205 accommodated in the reaction vessel 204 are reliably in non-contact. If dispensing is performed at a sufficient speed while the nozzle 203 and the specimen or reagent 205 contained in the reaction container are reliably in non-contact, bubbles may be generated in the mixed solution. Then, in the second plane 405, since there is reflux of the mixed liquid for a certain time immediately after dispensing, the bubbles may be involved in the reflux. If the bubbles and the liquid recirculation are present in the light receiving range of the detector, the data acquired at that moment may be affected by noise.

  Particularly in the blood coagulation field, the reagent sample mixture may become viscous, and even when the nozzle tip point 207 is located at a position other than the center point 211 of the first plane 210 and dispensed. In some cases, bubbles may be involved in the reflux of the mixed solution.

  Therefore, in this embodiment, the light receiving axis 402 of the detector 409 intersects the second plane 405 in order to arrange the light receiving range of the detector at a position that is not affected by the reflux of the liquid and the bubbles entrained therein. Arranged. Thereby, the photometric range using the light receiving element of the detector 409 can be set to a position that is not affected by the flow of the liquid generated in the liquid mixture by the discharge of the liquid and bubbles entrained in the flow.

  If the light receiving shaft 402 of the detector 409 is arranged as in the present embodiment, even if bubbles are mixed in the mixed solution and moved in the reaction vessel by reflux, dispensing is not affected by this. Stable measurement can be performed immediately after.

  Note that the light receiving range of the detector 409 is adjusted by appropriately adjusting the slit, lens, distance between the light receiving surface and the reaction vessel, etc., so as to further reduce or eliminate the influence of the optical signal from the reflux unit. Can be provided.

  The detectors 407 and 409 of the optical measurement unit may be arranged so that the light receiving axis 402 intersects the second plane 405, and can be provided in various directions as shown in each example of FIG. This direction can be arbitrarily selected depending on the configuration of the apparatus, measurement items, and the like. At this time, if the light receiving shaft 402 is arranged so as to be orthogonal to the second plane 405, the reflux direction 212 and the light receiving shaft 402 are orthogonal, so that the influence of bubbles entrained in the reflux and reflux is reduced most. As a result, the influence of noise on the optical measurement result can be best avoided.

  Here, in the present embodiment, the nozzle 203 may not be linear. FIG. 5 is a schematic diagram showing a modification of the present embodiment and the arrangement of the second plane and the optical measurement unit when the dispensing nozzle is bent. In this figure, a top view (500), an XY cross-sectional view (501), and a right side view (502) of the reaction vessel are shown.

  The nozzle 203 is bent toward the inner wall surface 209 of the reaction container so that the reagent or the specimen can be easily dispensed along the inner wall surface 209 of the reaction container when dispensing the reagent or the specimen into the reaction container 204. It consists of Also in this modified example, the light receiving axis 503 of the detector 409 of the optical measurement unit has two intersection points 404 of the straight line 403 including the center point 211 of the first plane 210 and the nozzle tip point 207 and the inner wall surface 209 of the reaction vessel and the nozzle. What is necessary is just to be arrange | positioned so that the 2nd plane 405 containing the extension line 206 of the front-end | tip may cross | intersect.

  In addition, the reaction vessel 204 may not have a shape composed of a cylinder and an inverted cone. The same effect can be obtained in a cylinder, a cone, a rectangular parallelepiped, and the like. FIG. 6 is a schematic diagram showing the arrangement of the second plane and the optical measurement unit when a prismatic reaction vessel 604 is used as a modification of the present embodiment. In the drawing, a top view (600), an XY cross-sectional view (601), and a right side view (602) of the reaction vessel are shown. Even in this case, the light receiving shaft 612 of the detector of the optical measurement unit can be configured in the same manner as in the above embodiment. That is, the nozzle tip point 607 is inside the reaction vessel 604 and is above the liquid level 608 of either the specimen or the reagent contained in the reaction vessel 604 in the region partitioned by the wall surface of the reaction vessel 604. The nozzle 603 is controlled so as to be located at a position other than the center point 611 of the first plane 610 that is substantially parallel to the liquid level 608, and the light receiving axis 612 of the detector of the optical measuring unit is the reaction vessel 604. Of the reaction vessel 604 and the straight line including the nozzle tip point 607 and the center point 611 of the first plane 610 and the region of the reaction vessel 604. It arrange | positions so that the 2nd plane 615 containing the two intersections with a wall surface and the extended line of the nozzle tip point 607 may be crossed.

  At this time, a constant photometric range is formed on the light receiving axis 612 in a range intersecting with the reaction liquid in the reaction vessel. The photometric range includes the height of the liquid level 616 of the reaction solution and the size of the reaction vessel 604. It can be arbitrarily determined depending on the shape, measurement item, and the like. In order to obtain a stable measurement result, in general, the intersection of the light receiving axis 612 and the second plane 615 is a plane formed by the intersection of the second plane 615, the reaction vessel inner wall surface 609, and the reaction liquid level 616. It can adjust so that it may become the center part inside.

  By comprising as mentioned above, even if it is a case where the shape of reaction container differs, there can exist an equivalent effect.

  Further, when the prismatic reaction vessel 605 is used, the position of the nozzle tip point 607 can be controlled to a position different from that in FIG. FIG. 7 is a schematic diagram showing the arrangement of the second plane and the optical measurement unit when another prism-shaped reaction vessel is used, which is another modification according to the present embodiment. Here, a case where the position of the nozzle tip point 607 is controlled at a position different from that in FIG. 6 will be described. In this figure, a top view (700), an XY sectional view (701), a right side view (702), and a perspective view (703) of the reaction vessel are shown.

  In the present modification, the second plane 615 is a straight line that is not parallel to each side of the reaction vessel 604 and different from the diagonal line in relation to the reaction vessel 604, as shown in the top view (700) of FIG. The other components can be formed in the same manner as described above. A perspective view (704) of FIG. 7 shows a first plane 610 and a second plane 615 in this modification.

  FIG. 8 shows another modification of the present embodiment, and shows the positional relationship between the nozzle before and after dispensing, the reaction vessel, and the second plane when dispensing after the nozzle is lowered to the vicinity of the liquid level. FIG.

  In this figure, a top view (800) of the reaction container and nozzle 803 when dispensing the reagent or specimen into a reaction container that already contains the specimen or reagent, an XY sectional view (801), and this state Further, a front view (802) of the reaction container and the nozzle after the reagent or specimen has been dispensed is shown. In this modification, the reagent or sample is dispensed while the nozzle 803 is raised in the vertical direction. By controlling the operation of the nozzle 803 at the time of dispensing as in this modified example, dispensing can be performed with the nozzle tip point closer to the liquid level 807. The possibility of mixing can be further reduced. At this time, if the nozzle 803 is configured to contact the inner wall surface of the reaction vessel, the effect is higher. Even in this case, the first plane 804 and the second plane 805 are set as shown in the figure, and the nozzle 803 is placed on the liquid surface by providing the light receiving axis 808 of the detector so as to intersect the second plane 805. Even when it is lowered to the vicinity, the same effect as described above can be obtained. When the reagent or sample is further dispensed from the nozzle 803 to the sample or reagent 806 contained in the reaction container, refluxing 809 occurs in the second plane 805 in the reaction solution. The effect of can be produced.

  FIG. 9 is a diagram showing a simulation result of the movement of the mixed liquid and bubbles when the specimen and the reagent are mixed. This shows the reflux that occurs in the mixed liquid after the reagent 904 is discharged from the reagent dispensing nozzle 902 to the specimen 903 accommodated in the reaction container 901. It is also shown that when bubbles 905 are involved in reflux, the reflux surface moves along the inner wall of the reaction vessel. Here, the example in which the specimen 903 is stored in advance in the reaction container 901 and the reagent is further dispensed from the reagent dispensing nozzle 902 has been described, but the present invention is not limited to this example. The present invention is also applicable to a form in which a reagent is accommodated and a sample is further dispensed.

  FIG. 10 is a diagram showing an optical measurement result (1000) and a comparative example (1001) according to the present embodiment. In FIG. 10, the optical measurement result (1000) and the comparative example (1001) respectively show the optical measurement data of the reaction liquid acquired by the optical measurement unit. In each chart, the horizontal axis represents time (t) and the vertical axis represents optical measurement intensity (I). Here, the optical measurement result (1000) is optical measurement data obtained by the configuration in the above-described embodiment, in which the influence of the mixed liquid circulation and bubbles is reduced. The comparative example (1001) showed optical measurement data affected by the reflux of the mixed liquid and the bubbles without applying the configuration according to the present embodiment. In the comparative example (1001), it can be seen that immediately after the measurement is started, bubbles (1002) such as a deviation of the reaction curve are generated due to the burst of bubbles remaining in the reaction solution. In measurement items that require measurement data from immediately after the reaction, this noise may cause a reduction in the accuracy of the measurement data.

  On the other hand, in the optical measurement result (1000) according to the present embodiment, it is configured to avoid bubbles passing through or remaining in the reaction solution from the photometric range, thereby eliminating the influence of bubbles, or It can be seen that the analysis accuracy can be improved.

  Further, in order to improve the analysis accuracy, it is necessary to make the mixing of the sample and the reagent more uniform. Therefore, it is necessary to increase the discharge speed of the reagent, but according to this configuration, the reflux of the bubbles is increased as the discharge speed is increased. Becomes along the inner wall of the reaction vessel, and can achieve both uniform mixing and accurate optical measurement.

Second embodiment

  FIG. 11 is a schematic diagram showing the positional relationship between the nozzle, the reaction vessel, the first plane, and the second plane according to the present embodiment. More specifically, it is a diagram illustrating a case where the nozzle tip point 1103 is dispensed while being in contact with the inner wall surface 1105 of the reaction vessel. Dispensing while the nozzle tip point 1103 is in contact with the reaction vessel inner wall surface 1105 causes the dispensed sample or reagent liquid to fall along the reaction vessel inner wall surface 1105, so that bubbles are formed in the mixed solution. The possibility of mixing is further reduced. Further, the nozzle is made of a material such as an elastic body, pressed against the inner wall surface 1105 of the reaction container by the nozzle control mechanism, and configured to discharge the specimen or reagent in a state where the nozzle 1104 is pressed against the inner wall surface of the reaction container by the control unit. For example, when dispensing a specimen or a reagent along the inner wall surface 1105 of the reaction container, errors such as the dimensions and installation of each reaction container can be absorbed by the elastic deformation of the nozzle 1104, so that individual position adjustment is strictly performed. Without any simple control, each of the plurality of reaction vessels can be executed at a fixed position.

  According to the above configuration, the possibility that bubbles are generated in the mixed solution is further reduced. However, by providing the light receiving axis of the detector so as to intersect the second plane, the influence of reflux and bubbles is further increased. Reduced optical measurement results can be obtained.

Third embodiment

  In this embodiment, a configuration including a plurality of measurement ports each having an optical measurement unit including a light source and a detector will be described. FIG. 12 is a schematic diagram showing a configuration including a plurality of measurement ports according to the present embodiment. Here, a configuration including six measurement ports is shown as an example, but the configuration is not limited to this. The automatic analyzer according to the present embodiment further includes a plurality of measurement ports 1200 and 1201, the control unit 120 shown in FIG. 1, and a storage unit 119, and each of the plurality of measurement ports has one reaction. The container installation part 114 and the one or some optical measurement part which consists of a light source and a detector are provided. The control unit 120 sets nozzles (not shown) according to the set values of the liquid storage amount in the reaction container, the discharge speed of the sample or reagent, or the discharge amount set according to the analysis item of each measurement port and recorded in the recording unit 119. Control the control mechanism. In addition, the control unit 120 causes the optical measurement unit to determine each angle and the position of the intersection that the reaction container of each measurement port forms with the second plane according to the measurement item of each measurement port, and the adjusted light receiving axis. Having a detector.

  According to the present embodiment, since the parameters and photometry range related to dispensing are optimized for each measurement port, even in an analysis where a plurality of assays are processed, the effect of increasing the processing capability is achieved. In addition, the types of assays that can be handled can be increased.

Fourth embodiment

  In this embodiment, the measurement results obtained from a plurality of detectors are compared, and the configuration of the arrangement of the reaction vessel and the optical measurement unit that can determine the measurement results used to calculate the analysis results will be described with reference to FIGS. explain.

  FIG. 13 is a schematic diagram illustrating a configuration example of the arrangement of a plurality of detectors of the optical measurement unit according to the present embodiment. According to this configuration, a plurality of light receiving angles can be provided for a plurality of incident lights. That is, a light source is provided on the side surface 1302 and the bottom surface 1307, and a detector 1303 provided with a light receiving axis 1304 so as to intersect the second plane 1305 with respect to the incident light 1306 is provided. By configuring in this way, a light receiving angle with high sensitivity and reproducibility can be selected according to the composition of the reagent, measurement items, and the like, so that the measurement system can be improved. In addition, it is possible to improve the measurement accuracy by receiving light at a plurality of light receiving angles and using each data to complement or correct the scattered light intensity, or to remove an abnormal value, for example.

  FIG. 14 is a schematic diagram illustrating a configuration example of the arrangement of a plurality of detectors of the optical measurement unit according to the present embodiment. According to this configuration, a plurality of photometric ranges can be provided. When the total amount of the reaction liquid becomes larger than that in the example of the first embodiment described above, it is effective to expand the photometric range in order to reduce variation due to the degree of mixing of the reaction liquid. The optical measurement unit in the present embodiment includes one or a plurality of light sources 1407 and a plurality of detectors 1403 and 1405 each having a light receiving axis provided so as to intersect the second plane. By configuring in this way, it is possible to expand the photometric range, obtain a sufficient signal intensity, and reduce variations in measurement results due to the degree of reaction liquid mixing. In addition, by changing the direction of each detector 1403 and 1405 and selecting the signal to be used for analysis data, an optimal configuration can be realized for each assay with different reactions, reaction times, reagent sample volumes, etc. Analysis accuracy can be improved.

Fifth embodiment

  In the present embodiment, a single or a plurality of light sources and a plurality of measurement ports having an optical measurement unit including a single or a plurality of detectors are provided, and according to the analysis items set for each measurement port, A technique for selecting the measurement results of one or a plurality of detectors from the measurement results of the plurality of detectors in the measurement port and obtaining the analysis result using the selected measurement results will be described with reference to FIG. FIG. 15 is a schematic diagram illustrating an example of variations of the reaction vessel and the optical measurement unit according to the present embodiment. In this figure, a plurality of measurement port top views (1501) and an XY cross-sectional view (1502) thereof are also shown.

The automatic analyzer 1500 has a disk-shaped reaction disk 1503 that repeatedly rotates and stops, and a plurality of reaction container setting sections 114 that hold the reaction container 104 that stores a reaction liquid (mixed liquid of a specimen and a reagent). Are arranged along. Here, the measurement port 113 refers to a port having an optical measurement unit including a single or a plurality of light sources 116 and a single or a plurality of detectors 115 as described above. In the process of rotating the reaction disk 1503, when the reaction vessel 104 held by the reaction vessel installation unit 114 passes the position of the measurement port 113, the optical measurement unit performs optical measurement.
In the present embodiment, a configuration in which one reaction container 104 is provided in each measurement port 113 is shown, but a plurality of reaction containers 104 may be accommodated. Further, the shape of the reaction vessel 104 may be a prismatic shape other than the Spitz shape shown in the present embodiment, and the shape of the reaction vessel may be different for each measurement port. Each measurement port is provided with a detector 116 so that each light receiving axis intersects the second plane 405. The number of detectors may be the same or different for each measurement port 113. Further, the light receiving angle may be the same for each measurement port 113 or may be different. The light source 115 of each measurement port 113 can also be provided in the direction of the bottom surface in addition to the side surface direction of the reaction vessel 104, and the number thereof may be different for each measurement port 113.

  In the above example, the configuration in which six measurement ports are provided in the same block has been described. However, each measurement port 113 may be provided in a separate block.

  By configuring as described above, the optimal position and number of reaction vessels, light sources, and detectors can be selected for each assay with different reactions, reaction times, reagent sample volumes, etc. Analysis accuracy can be improved by using an integrated optical system, and various inspection items can be collectively processed by a single automatic analyzer.

100 automatic analyzer 101 sample dispensing nozzle 102 sample rack 103 sample container (sample container)
104 Reaction container 105 Sample syringe pump 106 Reagent dispensing nozzle 107 Reagent rack 108 Reagent container 109 Reagent temperature raising mechanism 110 Reagent syringe pump 111 Reaction container stock section 112 Reaction container transport mechanism 113 Measurement port 114 Reaction container installation section 115 Light source 116 Detector 117 Reaction container discarding unit 118 Operation unit 118a Mouse 118b Keyboard 118c Display unit 119 Storage unit 120 Control unit 120a Overall control unit 120b Measurement control unit 121 A / D converter 122 Interface 123 Printer 200 Top view 201 XY sectional view 202 Right side Plane 203 nozzle (specimen dispensing nozzle or reagent dispensing nozzle)
204 Reaction vessel 205 Liquid in reaction vessel 206 Nozzle extension line 207 Nozzle tip point 208 Liquid surface in reaction vessel before dispensing 209 Reaction vessel inner wall surface 210 First plane 211 First plane center point 212 Liquid reflux direction 400 Top view 401 XY sectional view 402 Detector light receiving axis 403 Straight line 404 including the nozzle tip point and the center point of the first plane 404 Intersection point 405 of the straight line including the nozzle tip point and the center point of the first plane and the inner wall surface of the reaction vessel Second plane 406 Light source 407 Detector 408 Light source 409 Detector 410 Reaction liquid level 500 Top view 501 XY sectional view 502 Right side view 503 Detector light receiving axis 600 Top view 601 XY sectional view 602 Right side view 603 Nozzle ( Sample dispensing nozzle or reagent dispensing nozzle)
604 prismatic reaction vessel 605 liquid in reaction vessel 606 nozzle extension line 607 nozzle tip point 608 liquid level in reaction vessel 609 before dispensing reaction vessel inner wall surface 610 first plane 611 first plane center point 612 optical measurement Light receiving axis 613 of the detector of the part 614 A straight line 614 including the nozzle tip point and the center point of the first plane 614 An intersection point 615 of the nozzle tip point and the straight line including the center point of the first plane and the inner wall surface of the reaction vessel Liquid level 700 in the subsequent reaction container Top view 701 XY cross-sectional view 702 Right side view 703 Perspective view 800 Top view 801 Reaction container and dispenser when dispensing a reagent or specimen into a reaction container containing the specimen or reagent XY cross-sectional view 802 of the injection nozzle 802 XY cross-sectional view 803 of the reaction container and the dispensing nozzle after the reagent or sample is dispensed into the reaction container containing the sample or reagent Nozzle or reagent dispensing nozzle)
804 1st plane 805 2nd plane 806 Liquid 807 in reaction container before dispensing 807 Liquid surface 808 Receiving axis 809 of optical receiver of optical measuring unit Reflux direction 901 Reaction container 902 Nozzle (reagent dispensing nozzle)
903 Sample 904 Reagent 905 Bubble 1000 Optical measurement result 1001 according to the present embodiment Optical measurement result 1001 according to the comparative example 1002 Noise 1100 due to the influence of the bubble Top view 1101 XY plan view 1102 Right side view 1103 Nozzle tip point 1104 Nozzle (sample portion) Injection nozzle or reagent dispensing nozzle)
1105 reaction vessel inner wall surface 1200 first measurement port 1201 second measurement port 1300 top view 1301 perspective view 1302 light source 1303 detector 1304 detector light receiving axis 1305 second plane 1306 incident light 1307 light source 1400 top view 1401 perspective view 1402 Detector 1403 Detector 1404 Detector 1405 Detector 1406 Second plane 1407 Light source 1500 Automatic analyzer 1503 Reaction disk

Claims (7)

A reaction container that contains a mixture of the specimen and the reagent;
A dispensing nozzle for dispensing the sample and the reagent into the reaction container;
An optical measurement unit comprising: a light source that irradiates light to the reaction container in which the liquid mixture is contained; and a detector that detects light emitted from the light source;
A control unit for controlling the operation of the dispensing nozzle,
An automatic analyzer that mixes the reaction vessel holding either the sample or the reagent by discharging either the reagent or the sample with the dispensing nozzle,
The controller is
When either the reagent or the sample is discharged by the dispensing nozzle to the reaction container holding either the sample or the reagent, the tip of the dispensing nozzle is set inside the reaction container. In the region partitioned by the wall surface of the reaction container, the surface is higher than the liquid level of either the sample or the reagent contained in the reaction container and is substantially parallel to the liquid level. Controlling the dispensing nozzle so that it is located outside the center point of the first plane;
The optical measurement unit is configured to distribute the light receiving axis of the detector in a region of the wall closed by the wall of the reaction container and the liquid level of either the specimen or the reagent contained in the reaction container. Preparing to intersect with two intersections of a straight line including the tip point of the nozzle and the center point of the first plane and the wall surface of the reaction vessel and a second plane including an extension line of the tip point of the dispensing nozzle. A featured automatic analyzer. The automatic analyzer according to claim 1,
The controller is
When discharging either the reagent or the sample by the dispensing nozzle to a reaction container holding either the sample or the reagent, at least a part of the dispensing nozzle is
An automatic analyzer controlled to contact an inner wall surface of the reaction vessel. The automatic analyzer according to claim 1,
A plurality of measurement ports including the optical measurement unit and a reaction vessel installation unit for holding the reaction vessel,
The controller is
According to each analysis item of the plurality of measurement ports, set the amount of liquid stored in the reaction container, the discharge speed or discharge amount of the specimen or the reagent,
An automatic analyzer characterized in that the dispensing nozzle is controlled based on the set condition. The automatic analyzer according to claim 3,
The light receiving axis of the detector of the optical measurement unit in each of the measurement ports is
An automatic analyzer characterized in that an angle formed with the second plane and a position of an intersection are determined based on each analysis item of the measurement port. The automatic analyzer according to claim 1,
The optical measurement unit includes a plurality of detectors,
The control unit compares detection results obtained from the plurality of detectors, and determines a detector to be used for calculation of an analysis result based on the comparison results. The automatic analyzer according to claim 3,
The optical measurement unit includes a plurality of detectors,
The controller is
Based on the analysis items in each of the plurality of measurement ports, one or more detectors are selected from the plurality of detectors in the optical measurement unit, and analysis is performed based on the detection results of the selected detectors. An automatic analyzer characterized by obtaining a result. The automatic analyzer according to claim 1,
The automatic analyzer according to claim 1, wherein a light receiving axis of the detector is perpendicular to the second plane.

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