Automatic analysis device and analysis method thereof

Abstract

The purpose of the present invention is to provide an automatic analysis device capable of detecting abnormalities at the time of aspiration with high accuracy even when the amount of analyte to be used for analysis is small. To this end, this automatic analysis device is provided with: a dispensing unit that sucks a specimen from a specimen container that accommodates the specimen; and a control unit that controls the dispensing unit such that, after suctioning a third predetermined amount of the sample that is larger than a first predetermined amount, which is the amount of the sample used for analysis, the dispensing unit discharges a second predetermined amount of the sample to a predetermined site different from the sample container, and thereafter dispenses the sample to the sample container. Discharging the first predetermined amount of the sample to a reaction vessel used for analysis; a detection unit that detects a pressure waveform in the dispensing unit; and a determination unit that determines, on the basis of a first waveform, which is the pressure waveform when the dispensing unit sucks the specimen, an empty suction, which is a state in which the dispensing unit sucks the specimen insufficiently, and / or a clogging, which is a state in which the specimen clogs the dispensing unit.

Description

Technical Field

[0001] The present invention relates to an automatic analyzing device. Background Art

[0002] In automatic analysis devices such as biochemical analyzers and immunoassay analyzers, a technology has been disclosed for detecting abnormalities in the dispensing of samples (specimens) or reagents by comparing the difference between the pressure sensor output immediately before the start of the suction operation and the pressure sensor output during the suction operation with a threshold value (see Patent Document 1).

[0003] Prior art literature

[0004] Patent Literature

[0005] Patent Document 1: Japanese Patent Application Laid-Open No. 2007-315984 Summary of the Invention

[0006] Problems to be solved by the invention

[0007] However, the difference between the pressure sensor output immediately before and during the suction operation varies depending on the amount of liquid being sucked. Therefore, the technique described in Patent Document 1 requires changing the threshold value based on the amount of liquid being sucked. In particular, when the amount of liquid being sucked is small, the difference between the pressure sensor output immediately before and during the suction operation is small, making false detection more likely.

[0008] Therefore, an object of the present invention is to provide an automatic analyzer capable of detecting abnormalities during aspiration with high accuracy even when the amount of a sample used in analysis is small.

[0009] Means for solving problems

[0010] In order to solve the above-mentioned problems, the automatic analysis device of the present invention comprises: a dispensing unit, which sucks the specimen from a specimen container containing the specimen; a control unit, which controls the dispensing unit so that after sucking a third predetermined amount of the specimen that is more than the amount of the specimen used in the analysis, i.e., the first predetermined amount, the second predetermined amount of the specimen is discharged to a predetermined position different from the specimen container, and then the first predetermined amount of the specimen is discharged to a reaction container used in the analysis; a detection unit, which detects a pressure waveform in the dispensing unit; and a judgment unit, which judges, based on the pressure waveform, i.e., the first waveform, when the dispensing unit sucks the specimen, that the dispensing unit is in an insufficient state of sucking the specimen, i.e., empty suction, and / or that the specimen is blocking the dispensing unit, i.e., blockage.

[0011] Effects of the Invention

[0012] According to the present invention, it is possible to provide an automatic analyzer capable of detecting an abnormality during aspiration with high accuracy even when the amount of a sample used in analysis is small. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 This is a schematic diagram showing the overall structure of an automatic analyzer.

[0014] Figure 2 This is a schematic diagram showing the configuration of a portion of the automatic analyzer (particularly, a portion related to sample dispensing).

[0015] Figure 3A This is a flowchart showing the first half of the abnormality determination method during dispensing.

[0016] Figure 3B This is a flowchart showing the second half of the abnormality determination method during dispensing.

[0017] Figure 4 This is a flowchart showing a method for determining dry suction.

[0018] Figure 5A This is a diagram showing examples of the first waveform during normal aspiration and the first waveform during empty aspiration, for a specimen whose amount is a second predetermined amount greater than the first predetermined amount.

[0019] Figure 5B 1 is a diagram showing an example of a second waveform for determining empty suction.

[0020] Figure 6A 1 is a diagram showing an example of a case where the first threshold value (threshold value for dry suction determination) can be set.

[0021] Figure 6B This is a diagram showing an example of a case where the first threshold value (threshold value for dry air suction determination) cannot be set.

[0022] Figure 7 1 and 2 are diagrams showing examples of the first waveform when a specimen having a second predetermined amount larger than a first predetermined amount is normally aspirated and the first waveform when a specimen having the first predetermined amount is normally aspirated.

[0023] Figure 8 1 is a diagram showing an example of a setting margin for the first threshold value (threshold value for dry suction determination).

[0024] Figure 9 This is a flowchart showing a method for determining congestion.

[0025] Figure 10 This is a diagram showing examples of pressure waveforms (a first waveform and a second waveform for clogging determination) during normal suction and during clogging.

[0026] Figure 11A1 is a diagram showing an example of a case where the second threshold value (threshold value for congestion determination) can be set.

[0027] Figure 11B This is a diagram showing an example of a case where the second threshold value (threshold value for congestion determination) cannot be set.

[0028] Figure 12 1 and 2 are diagrams showing examples of pressure waveforms during occlusion aspiration of a specimen of a second predetermined amount larger than a first predetermined amount and pressure waveforms during occlusion aspiration of a specimen of a first predetermined amount.

[0029] Figure 13 1 is a diagram showing an example of a setting margin for the second threshold value (threshold value for traffic jam determination). DETAILED DESCRIPTION

[0030] Embodiments of the present invention will be described with reference to the accompanying drawings.

[0031] (Overall structure of automatic analyzer)

[0032] Figure 1 This is a schematic diagram showing the overall structure of the automatic analysis device. Figure 1 As shown, the automatic analysis device is composed of a reaction container tray 20, a dispensing tip / reaction container transport mechanism 17, a reaction disk 1, a reagent / specimen common storage section 3, a first dispensing mechanism 8, a second dispensing mechanism 9, a dispensing tip tray 19, a spectrophotometer 15, a detection mechanism 16, a dispensing tip / reaction container waste box 21, water supply pumps 10, 11, cleaning tanks 12, 13, a control unit 28, etc.

[0033] The reaction container tray 20 stores the reaction containers 2. The pipette tip / reaction container transport mechanism 17 supplies the reaction containers 2 from the reaction container tray 20 to the reaction disk 1. The reaction disk 1 carries a plurality of reaction containers 2 in the circumferential direction and is driven to rotate in order to move the reaction containers 2 to a predetermined position. The reagent / sample common storage section 3 carries a plurality of reagent containers and sample containers. Figure 1 In the figure, the reagent container 4 is located on the inner circumference side of the specimen container 5, but the specimen container 5 may be located on the inner circumference side of the reagent container 4, and the reagent container 4 and the specimen container 5 may be arranged separately in the circumferential direction instead of in the radial direction.

[0034] The first dispensing mechanism 8 and the second dispensing mechanism 9 are arranged between the reaction disk 1 and the reagent / specimen common storage section 3, and suck the specimen from the specimen container 5 and discharge it to the reaction container 2, or suck the reagent from the reagent container 4 and discharge it to the reaction container 2. The first dispensing mechanism 8 and the second dispensing mechanism 9 are used separately in the inspection of different analysis processes. For example, if the first dispensing mechanism 8 is set for biochemistry and the second dispensing mechanism 9 is set for immunity, the specimen and reagent for biochemical examination are dispensed in the first dispensing mechanism 8, and the specimen and reagent for immunological examination are dispensed in the second dispensing mechanism 9. In addition, for specimens used in both biochemical examination and immunological examination, they are accessed and dispensed by the first dispensing mechanism 8 during biochemical examination and by the second dispensing mechanism 9 during immunological examination. In addition, in the second dispensing mechanism 9 for immunity, it is highly necessary to prevent contamination between specimens, so when dispensing, the dispensing probe 102 (refer to Figure 2 ) Install the dispensing tip 18.

[0035] The dispensing tip tray 19 stores the dispensing tip 18 . The dispensing tip / reaction container transport mechanism 17 supplies the dispensing tip 18 to the dispensing tip mounting position 22 , and mounts the dispensing tip 18 on the dispensing probe 102 at the dispensing tip mounting position 22 .

[0036] The dispensing probe 102 is capable of rotational and vertical movement. The rotational trajectory of the dispensing probe 102 includes the reagent suction position 6 and the specimen suction position 7 on the reagent / sample common storage section 3, the first dispensing position and the second dispensing position on the reaction disk 1, and a cleaning tank 12 (13) for cleaning the dispensing probe 102. In the second dispensing mechanism 9, since a dispensing tip 18 is used, the rotational trajectory of the dispensing probe 102 also includes a dispensing tip installation position 22 and a dispensing tip disposal position 23.

[0037] During biochemical tests, the specimen and reagent are aspirated by the dispensing probe 102, and during immunological tests, the specimen and reagent are aspirated by the dispensing tip 18 installed on the dispensing probe 102. The specimen and reagent are stirred and mixed by the aspiration and discharge action of the dispensing probe 102 or the dispensing tip 18 in the reaction container 2.

[0038] In this embodiment, the specimen and reagent are stirred by the pipetting action of the dispensing probe 102 or the dispensing tip 18. However, a stirring mechanism for stirring the specimen and reagent may also be provided. The reaction container 2 containing the reaction solution containing the specimen and reagent is controlled at a predetermined temperature by the reaction disk 1 to promote the reaction within a predetermined time.

[0039] The spectrophotometer 15 for biochemical testing is installed around the reaction disk 1 and includes a light source and a detector (not shown). It measures the absorbance of the reaction solution by irradiating the reaction solution containing a mixture of a specimen and a reagent with a light source, spectroscopically detecting the light transmitted therethrough.

[0040] The detection mechanism 16 for immunoassay uses a photomultiplier tube as a detector and measures the amount of luminescence from a luminescence reaction of a labeling substance contained in a reaction solution that has reacted for a predetermined time on the reaction disk 1 .

[0041] In biochemical tests, reaction vessels 2 whose absorbance has been measured on the reaction disk 1 are discarded by the dispensing tip / reaction vessel transport mechanism 17 into the dispensing tip / reaction vessel disposal box 21. In immunoassays, the dispensing tip / reaction vessel transport mechanism 17 moves reaction vessels 2 containing reaction solution that has reacted on the reaction disk 1 for a predetermined time to the detection mechanism 16, and moves reaction vessels 2 after measurement by the detection mechanism 16 to the dispensing tip / reaction vessel disposal box 21.

[0042] Water supply pumps 10 and 11 are connected to the first dispensing mechanism 8 and the second dispensing mechanism 9, respectively, supplying water for cleaning the interior of the dispensing probe 102 (internal cleaning) and the exterior of the dispensing tip 18 (external cleaning). The cleaning tank 12 performs internal or external cleaning of the first dispensing mechanism 8, while the cleaning tank 13 performs internal or external cleaning of the second dispensing mechanism 9.

[0043] The control unit 28 is connected to each mechanism of the automatic analyzer, and controls, for example, the rotation drive of the reaction disk 1, the rotation drive and the vertical drive of the dispensing probe 102, the suction and discharge of the specimen and reagent, etc. Figure 1 In order to simplify the diagram, the connection between each mechanism constituting the automatic analyzer and the control unit 28 is omitted. In addition, the control unit 28 performs calculations on predetermined analysis items based on the measured values ​​of the spectrophotometer 15 or the detection mechanism 16, and displays the results on the display unit 126 (see Figure 2 ).

[0044] (Structure of the dispensing mechanism)

[0045] Then, according to Figure 2 The structure of the dispensing mechanism (dispensing portion) will be specifically described. Hereinafter, the second dispensing mechanism 9 using the dispensing tip 18 will be described as an example, but the same structure can also be applied to the first dispensing mechanism 8 .

[0046] Figure 2 This is a schematic diagram showing the structure of a part of the automatic analyzer (especially the part related to sample dispensing). Figure 2As shown, the dispensing mechanism (second dispensing mechanism 9) is mainly composed of a dispensing probe 102, a flow path 103, a syringe 104, a syringe driver 106, a probe driver 107, a dispensing control unit 108, a detection unit 117, a branch block 118, a determination unit 121, etc.

[0047] The dispensing probe 102 is connected to a syringe 104 via a flow path 103, and both are filled with cleaning water 105. The syringe 104 includes a cylinder 104a and a plunger 104b, with the plunger 104b connected to a syringe driver 106. The syringe driver 106 drives the plunger 104b vertically relative to the cylinder 104a, thereby sucking and discharging the fluid (liquid and gas) in the dispensing tip 18 connected to the dispensing probe 102.

[0048] The syringe 104 has a flow path connected to the water supply tank 110, and an internal wash solenoid valve 111 and a water supply pump 11 are provided on this flow path. The water supply tank 110 contains wash water 105, and the wash water 105 is discharged from the dispensing probe 102 by driving the water supply pump 11, thereby cleaning the inside of the dispensing probe 102. In addition, the external wash nozzle 123 also has a flow path connected to the water supply tank 110, and an external wash solenoid valve 125 and a water supply pump 11 are provided on this flow path. Therefore, by driving the water supply pump 11, the wash water 105 is discharged from the external wash nozzle 123 toward the dispensing tip 18, thereby cleaning the outside of the dispensing tip 18. In addition, the dispensing probe 102 is cleaned in the cleaning tank 13, for example, before dispensing the reagent 113 and the specimen 115, and the dispensing tip 18 is cleaned in the cleaning tank 13, for example, after dispensing the reagent 113 and the specimen 115.

[0049] The dispensing control unit 108 controls the operation of the syringe driver 106, the probe driver 107, the water supply pump 11, the internal wash solenoid valve 111, and the external wash solenoid valve 125. The dispensing control unit 108 may also be configured to control not only the various components of the dispensing mechanism but also the entire operation of the automatic analyzer. In this case, the functions of the dispensing control unit 108 are performed by the control unit 28.

[0050] The detection unit 117 is, for example, a pressure sensor, is connected to a branch block 118 provided in the middle of the flow path 103 , and measures the pressure in the flow path 103 .

[0051] The determination unit 121 is a circuit for determining whether there are any abnormalities during the dispensing operation of the dispensing mechanism. It includes a storage unit 119 that stores data such as pressure values, and a calculation unit 120 that performs processing related to the data stored in the storage unit 119. Furthermore, the determination unit 121 is configured to communicate with the dispensing control unit 108. If the calculation unit 120 determines that the operation needs to be stopped based on the results of the data processing, the determination unit 121 transmits the details of the operation to the dispensing control unit 108. Alternatively, the determination unit 121 can be incorporated into the dispensing control unit 108.

[0052] The display unit 126 is connected to the dispensing control unit 108 and the determination unit 121 , and displays the presence or absence of abnormality as a result of data processing in the determination unit 121 .

[0053] (Abnormality determination method during dispensing)

[0054] Then, based on Figure 3A and Figure 3B The abnormality determination method during dispensing will be described specifically.

[0055] Figure 3A as well as Figure 3B This is a flowchart showing the abnormality determination method during dispensing. Figure 3A The follow-up is Figure 3B In fact, through Figure 2 The dispensing control unit 108 shown controls the operation of the various components of the dispensing mechanism (syringe drive unit 106, probe drive unit 107, water supply pump 11, internal wash solenoid valve 111 and external wash solenoid valve 125, etc.), but the various components of the dispensing mechanism are sometimes described as the main body of the operation.

[0056] In step S301 , the probe driving unit 107 moves the dispensing probe 102 with the dispensing tip 18 attached thereto to above the specimen container 5 .

[0057] In step S302, syringe driver 106 drives syringe 104 to aspirate air. At this point, detector 117 detects the pressure waveform within flow path 103 within a predetermined time range, including the air aspiration operation by syringe 104. This detection result is stored in storage 119 as a second waveform for determining air aspiration. In this specification, "pressure waveform" refers to data consisting of pressure values ​​arranged in a time series.

[0058] In step S303 , the probe driving unit 107 lowers the dispensing probe 102 until the distal end of the dispensing tip 18 is immersed in the specimen 115 .

[0059] In step S304, the detection unit 117 detects the pressure waveform within the flow path 103 within a predetermined time range while the syringe 104 is stopped before the specimen 115 is aspirated. The detection result is stored in the storage unit 119 as a second waveform for determining clogging. Subsequently, the syringe driver 106 drives the syringe 104 to aspirate a third predetermined amount of the specimen 115, which is a second predetermined amount greater than the first predetermined amount, the specimen amount used for analysis, into the dispensing tip 18. At this time, the detection unit 117 detects the pressure waveform within the flow path 103 within a predetermined time range during the aspiration of the specimen 115, and stores the result as a first waveform in the storage unit 119.

[0060] In step S305 , the probe driving unit 107 moves the dispensing probe 102 upward to separate the distal end of the dispensing tip 18 from the liquid surface of the specimen 115 .

[0061] In step S306 , the syringe driving unit 106 drives the syringe 104 to suck air.

[0062] In step S307 , the probe driving unit 107 moves the dispensing probe 102 to above the cleaning tank 13 .

[0063] In step S308 , the probe driving unit 107 lowers the dispensing probe 102 to a position where the tip of the dispensing head 18 hits the cleaning water.

[0064] In step S309, the syringe driver 106 drives the syringe 104 to discharge the second predetermined amount of sample 115, along with air, into the cleaning tank 13. The second predetermined amount of sample 115 can be discharged from a liquid container, a waste liquid container, or the reaction vessel 2. However, it is more efficient to discharge the second predetermined amount of sample 115 from the cleaning tank 13 where the dispensing probe 102 is parked for external washing. Furthermore, the timing for discharging the second predetermined amount of sample 115 is not limited to step S309; ​​it can be discharged at any time between steps S308 and S310.

[0065] In step S310, the dispensing control unit 108 opens the external wash solenoid valve 125, drives the water supply pump 11, and discharges the wash water 105 from the external wash nozzle 123, thereby washing the exterior of the dispensing tip 18 attached to the dispensing probe 102. At this time, the probe drive unit 107 raises the dispensing probe 102.

[0066] In step 311 , the probe driving unit 107 moves the dispensing probe 102 to above the reaction container 2 .

[0067] In step S312 , the probe driving unit 107 lowers the dispensing probe 102 to a discharge position for discharging the liquid into the reaction container 2 .

[0068] In step S313, the syringe driver 106 drives the syringe 104 to discharge the first predetermined amount of sample 115 and reagent 113 held within the dispensing tip 18. In this embodiment, the amount of sample 115 aspirated in step S304, i.e., the third predetermined amount, is assumed to be the sum of the first and second predetermined amounts. However, it may also be the sum of these amounts plus a fourth predetermined amount. In this case, the fourth predetermined amount remains within the dispensing tip 18 or dispensing probe 102 even after step S213 and is discharged from the cleaning tank 13 or the like.

[0069] In step S314 , the probe driving unit 107 moves the dispensing probe 102 to the dispensing tip discarding position 23 , removes the dispensing tip 18 from the dispensing probe 102 , and discards it into the dispensing tip / reaction vessel discarding box 21 .

[0070] In step S315, the calculation unit 120 of the determination unit 121 determines whether there is an abnormality such as insufficient suction of the specimen by the dispensing mechanism, i.e., empty suction, or a blockage of the specimen in the dispensing mechanism, based on the pressure waveform during specimen suction stored in the storage unit 119. In addition, the pressure waveform in the case of abnormalities such as empty suction or blockage during specimen suction is very different from the pressure waveform in the case of normal suction. Therefore, by referring to the pressure waveform, it is possible to determine whether there is an abnormality. The method for determining whether there is an abnormality using the pressure waveform will be described later. In step S315, the determination unit 121 sends the determination result of whether there is an abnormality to the display unit 126 and the dispensing control unit 108, and the display unit 126 displays the received determination result.

[0071] If it is determined to be normal (no abnormality) in step S315 (No), the process proceeds to step S316. In step S316, the dispensing control unit 108 determines that the dispensing has been completed normally based on the determination result received from the determination unit 121, and ends the dispensing operation.

[0072] On the other hand, if it is determined in step S315 that an abnormality exists (Yes), the process proceeds to step S317. In step S317, the aliquot control unit 108 determines that an abnormality exists during aspiration of the specimen 115 based on the determination result received from the determination unit 121, and the process proceeds to step S318.

[0073] In step S318 , the dispensing control unit 108 causes the display unit 126 to display an alarm, and then the process proceeds to step S319 .

[0074] In step S319, the aliquoting control unit 108 terminates the aliquoting operation for the sample 115 determined to have an abnormality during aliquoting in step S317, and then aborts the aliquoting plan for the sample 115 from the sample container 5. By aborting the aliquoting plan for the abnormal sample 115, the consumption of reagents used in subsequent analyses can be reduced.

[0075] In step S320 , the aliquot control unit 108 displays on the display unit 126 that the aliquot plan for the sample 115 has been suspended.

[0076] If the next analysis request arrives, steps S301 through S320 are repeated. Furthermore, the abnormality determination process of steps S315 through S320 can be performed before or in parallel with steps S305 through S314. In these cases, if an abnormality is determined, the dispensing control unit 108 terminates the dispensing operation after executing steps S305 and S306 without moving to step S307. This prevents the discharge of abnormal specimens 115 into the reaction vessel 2, thereby reducing the consumption of the reaction vessel 2 and the effort required to clean it.

[0077] The following, Figure 3A The details of abnormality determination in step S315 are described below. The two main abnormalities to be determined during specimen aspiration are empty aspiration and blockage, which are described using Examples 1 and 2, respectively. In either case, the calculation unit 120 of the determination unit 121 calculates a determination index based on the pressure waveform during specimen aspiration, and determines whether an abnormality exists during specimen aspiration based on the determination index.

[0078] Here, in this specification, "determination indicators" include, for example, the average pressure value during the suction operation of the specimen 115, the sum or average of the pressure values ​​before and after the suction operation of the specimen 115, the maximum or minimum pressure value, the pulsation period or amplitude of the pressure waveform, and the statistical distance (such as the Euclidean distance) between a pre-set reference pressure waveform and the pressure waveform obtained in this step. Furthermore, in this specification, the "reference pressure waveform" is, for example, a waveform set using a large number of previously acquired pressure values. The pressure value used when the specimen was determined to be suctioned normally can be used, or the pressure value used when an abnormality was determined during specimen suction. The degree of similarity or dissimilarity with the reference pressure waveform can also be used as a determination indicator. Furthermore, an indicator obtained by combining multiple such determination indicators can also be used as a determination indicator.

[0079] Example 1

[0080] Figure 4 Yes Figure 3AFlowchart of the method for determining dry suction in the abnormality determination in step S315.

[0081] In step S401 , the calculation unit 120 reads the first waveform and the second waveform for empty suction determination stored in the storage unit 119 .

[0082] In step S402, the calculation unit 120 calculates a first determination index for determining the presence or absence of air intake based on the first waveform and the second waveform for air intake determination. In this embodiment, the first determination index is the difference between the average value of the first waveform within a predetermined interval detected in step S304 and the average value of the second waveform for air intake determination detected in step S302 (the value obtained by subtracting the average value of the second waveform from the average value of the first waveform). Alternatively, the first determination index may be calculated using other methods.

[0083] In step S403, the calculation unit 120 determines whether or not there has been any unsuccessful aspiration during the aspiration of the specimen 115 based on the first determination index. Examples of methods for determining the presence or absence of unsuccessful aspiration include comparing the first determination index with a predetermined threshold value and determining an abnormality when a combination of multiple first determination indexes meets a certain condition. In this embodiment, the former method, comparing the first determination index with a predetermined threshold value, is used to determine the presence or absence of an unsuccessful aspiration abnormality.

[0084] Figure 5A This figure shows examples of the first waveform during normal aspiration and the first waveform during empty aspiration, for a specimen with a second predetermined amount greater than the first predetermined amount. Compared to the first waveform 501 during normal aspiration, the first waveform 502 during empty aspiration is shifted toward the positive direction of the pressure axis. Therefore, the first judgment index during normal aspiration is smaller than the first judgment index during empty aspiration.

[0085] Figure 5B 1 is a diagram showing an example of the second waveform for determining empty suction. Since the second waveform 503 for determining empty suction is obtained in step S302, it can be said that it is not affected by empty suction or normal suction.

[0086] Next, use Figure 6A as well as Figure 6B , the setting method of the threshold value for empty suction judgment is explained. Hereinafter, the first judgment index during empty suction is set as A, the first judgment index during normal suction is set as B, and the average of the first judgment index A is set as A - , set the average of the first judgment index B to B -The threshold for dry suction determination (first threshold) is set to a constant k1. Furthermore, the lower limit of the values ​​assumed for the first determination indicator A is set to the assumed dry suction lower limit C. Furthermore, the assumed dry suction lower limit C can be set to the lower limit of the distribution of previously acquired dry suction data, or, if tolerance is acceptable, a lower limit value that includes a certain value or more of the dry suction data. Furthermore, the upper limit of the values ​​assumed for the first determination indicator B is set to the assumed normal suction upper limit D. Furthermore, the assumed normal suction upper limit D can be set to the upper limit of the distribution of previously acquired normal suction data, or, if tolerance is acceptable, a lower limit value that includes a certain value or more of the normal suction data. Alternatively, the first threshold may be a function such as y = f(x). For example, the variable x can be the xth dispensing operation when the dispensing amount, temperature, or dispensing action is continuous, or it can be a correction value calculated for each device to eliminate differences between devices. Furthermore, the variable x is not limited to one and can be multiple.

[0087] Figure 6A : is a diagram showing an example of a case where the first threshold value (threshold value for air suction determination) can be set. Figure 6A As shown in A - >B - When C>D, a constant k1 can be set between C and D as the first threshold, thereby enabling high-precision determination of idle suction and normal suction. Specifically, when the first determination index is greater than the first threshold, idle suction can be determined, and when the first determination index is less than the first threshold, normal suction can be determined.

[0088] In addition, when the calculation method of the first judgment index is different, the setting method of the first threshold value and the judgment method of empty suction are also different. For example, when using the first judgment index with a larger value during normal suction than during empty suction, if the upper limit value assumed during empty suction is set to C' and the lower limit value assumed during normal suction is set to D', then in A - <B - When C'<D', the first threshold value can be set between C' and D'. In this case, if the first determination index is less than the first threshold value, it can be determined as empty suction, and if the first determination index is greater than the first threshold value, it can be determined as normal suction.

[0089] Figure 6B This is a diagram showing an example of a case where the first threshold value (threshold value for dry air suction determination) cannot be set.

[0090] like Figure 6B As shown in A - >B -When C<D, the first threshold value cannot be set between C and D, so it is difficult to judge between empty suction and normal suction. In addition, when the first judgment index with a larger value in normal suction than in empty suction is used, in A - <B - Furthermore, when C'>D', it is impossible to set the first threshold between C' and D', and it is difficult to determine whether suction is empty or normal.

[0091] Figure 7 701. It is a diagram showing an example of a first waveform when a specimen having a second predetermined amount more than a first predetermined amount is normally sucked, and a first waveform when a specimen having a first predetermined amount is normally sucked. When the suction speed of the specimen 115 is the same, the first waveform 702 when the first predetermined amount is sucked ends suction earlier than the first waveform 701 when the amount having a second predetermined amount more than the first predetermined amount is sucked. Therefore, in addition to the pressure waveform reflecting the characteristics during the suction action, the pressure waveform reflecting the characteristics after the suction is completed is also included in the calculation interval of the pressure value. Therefore, the pressure value calculated based on the first waveform 702 becomes a value greater than the pressure value calculated based on the first waveform 701. In addition, since the deviation of the pressure waveform after the suction is completed is large, when the pressure waveform after the suction is completed is included, the deviation of the first judgment index becomes larger, thereby reducing the judgment accuracy.

[0092] Here, shortening the calculation interval to exclude the pressure waveform after the end of suction is considered. However, shortening the calculation interval in accordance with the suction amount shortens the pressure waveform reflecting the characteristics of the suction operation, thereby reducing the determination accuracy.

[0093] Alternatively, the time required to acquire the pressure waveform during suction can be extended by reducing the suction speed. However, in this case, according to the following (Equation 1), frictional pressure loss is reduced, and the difference in pressure between dry suction and normal suction is reduced. In (Equation 1), ΔP represents frictional pressure loss, λ represents the tube friction coefficient, L represents the pipe length, d represents the pipe diameter, ρ represents the fluid density, and u represents the average flow velocity.

[0094] [Formula 1]

[0095] On the other hand, when the dispensing tip 18 is made thinner, that is, when the pipe diameter d is reduced, according to (Equation 1), the frictional pressure loss increases, the difference in pressure value between dry suction and normal suction increases, and the determination accuracy improves.

[0096] Figure 8 1 is a diagram showing an example of a setting margin for the first threshold value (threshold value for dry suction determination).

[0097] When the sample 115 in an amount obtained by adding the first predetermined amount and the second predetermined amount is sucked into the dispensing tip 18, the amount A- >B - and C > D, moreover, the difference between C and D, that is, the setting margin m1 of the first threshold is greater than a predetermined value. Therefore, the index region during air aspiration and the index region during normal aspiration can be reliably divided, and the determination accuracy is improved. In addition, in the case of using the first determination index with a value larger during normal aspiration than during air aspiration, it also becomes A - <B - and C’ < D’, and the difference between C’ and D’ is larger than the predetermined value, so the determination accuracy is similarly improved.

[0098] On the other hand, when the first predetermined amount of the specimen 115 is aspirated into the dispensing pipette 18, it becomes one of the following two states. As Figure 8 shown, the first state is A - >B - and C < D, and the state where the setting margin m1 itself does not exist, and a part of the index region during air aspiration overlaps with the index region during normal aspiration. The second state is not shown, but the second state is A - >B - and C > D, and there is a setting margin m1, but this setting margin m1 is in a state where it is small compared to the predetermined value, and the index region during air aspiration and the index region during normal aspiration are close, and there is a possibility of misjudgment due to the deviation of the first determination index. Therefore, when aspirating the first predetermined amount of the specimen 115, compared with the case of aspirating the specimen 115 with the amount obtained by adding the first predetermined amount and the second predetermined amount, the determination accuracy is reduced. In addition, in the case of using the first determination index with a value larger during normal aspiration than during air aspiration, it also becomes A - <B - and the state where C’ > D’, A - <B - and either the state where C’ < D’ but the difference between C’ and D’ is smaller than the predetermined value, the determination accuracy is similarly reduced.

[0099] Therefore, in the present embodiment, a specimen with a second predetermined amount more than the first predetermined amount, which is the amount of the specimen used in the analysis, is aspirated, and it is determined whether it is air aspiration or normal aspiration. Thus, even when the first predetermined amount is small, it is possible to perform high-precision determination without changing the device such as using a highly sensitive pressure sensor or making the pipette thinner. In addition, according to the present embodiment, there is no need to set a calculation interval for each first predetermined amount, or change the threshold for each first predetermined amount. That is, according to the present embodiment, there is an advantage that the calculation method and threshold of the first determination index can be made common regardless of the amount of the specimen used in the analysis.

[0100] Embodiment 2

[0101] Figure 9 It represents Figure 3A Flowchart of the method for determining a blockage in the abnormality determination in step S315.

[0102] In step S901 , the calculation unit 120 reads the first waveform and the second waveform for congestion determination stored in the storage unit 119 .

[0103] In step S902, the calculation unit 120 calculates a second determination index for determining the presence or absence of congestion based on the first waveform and the second congestion determination waveform. In this embodiment, the second determination index is the difference between the cumulative value of the first waveform detected in step S304 within a predetermined interval and the value obtained by multiplying the average value of the second congestion determination waveform detected in step S304 by the number of data points in the cumulative range of the first waveform (the value obtained by subtracting the former from the latter). Alternatively, the second determination index may be calculated using other methods.

[0104] In step S903, the calculation unit 120 determines whether or not there is blockage during aspiration of the specimen 115 based on the second determination index. Examples of methods for determining blockage include comparing the second determination index with a predetermined threshold value and determining an abnormality when a combination of multiple second determination indexes meets a certain condition. In this embodiment, the former method, comparing the second determination index with a predetermined threshold value, is used to determine the presence or absence of a blockage abnormality.

[0105] Figure 10 This figure shows examples of pressure waveforms (a first waveform and a second waveform for determining obstruction) during normal suction and during obstruction. In pressure waveform 1002 during obstruction, the first waveform shifts toward the negative direction of the pressure axis compared to pressure waveform 1001 during normal suction. Therefore, the second determination index during normal suction is smaller than the second determination index during obstruction. Furthermore, the second waveform for determining obstruction is acquired before suction of specimen 115, so it is not affected by either obstruction or normal suction.

[0106] Next, use Figure 11A and Figure 11BThe method for setting the threshold value for congestion determination will be described. Below, let the second determination index for congestion be E, the second determination index for normal suction be F, the average of the second determination index E be E-, the average of the second determination index F be F-, and the congestion determination threshold (second threshold) be a constant k2. Furthermore, the lower limit of the values ​​assumed for the second determination index E is set as the assumed lower limit value G for congestion. The assumed lower limit value G for congestion can be set as the lower limit of the distribution of previously acquired congestion data, or if tolerance is acceptable, a lower limit value that includes a certain value or more in the congestion data can be set. Furthermore, the upper limit of the values ​​assumed for the second determination index F is set as the assumed upper limit value H for normal suction. The assumed upper limit value H for normal suction can be set as the upper limit of the distribution of previously acquired normal suction data, or if tolerance is acceptable, a lower limit value that includes a certain value or more in the normal suction data can be set.

[0107] Alternatively, the second threshold value can be a function such as y = f(x). The variable x can be, for example, the xth dispensing operation, for example, if the dispensing volume, temperature, or dispensing operation is continuous, or it can be a correction value calculated for each device to eliminate inter-device variations. Furthermore, the variable x is not limited to a single value and can be multiple.

[0108] Figure 11A 1 is a diagram showing an example of a case where the second threshold value (threshold value for congestion determination) can be set.

[0109] like Figure 11A As shown, when E->F- and G>H, a constant k2 can be set between G and H as the second threshold, thereby enabling high-precision determination of blockage and normal suction. Specifically, if the second determination index is greater than the second threshold, blockage can be determined, and if the second determination index is less than the second threshold, normal suction can be determined.

[0110] Furthermore, different calculation methods for the second determination index also require different methods for setting the second threshold and determining whether a blockage has occurred. For example, if a second determination index with a larger value for normal suction than for blockage is used, and the upper limit assumed for blockage is G' and the lower limit assumed for normal suction is H', then when E<F and G'<H', the second threshold can be set between G' and H'. In this case, a blockage can be determined when the second determination index is less than the second threshold, and normal suction can be determined when the second determination index is greater than the second threshold.

[0111] Figure 11B : is a diagram showing an example of a case where the second threshold value (threshold value for congestion determination) cannot be set. Figure 11BAs shown, when E->F- and G<H, the second threshold value cannot be set between G and H, so it is difficult to determine whether it is a blockage or a normal suction. In addition, when a second determination indicator with a larger value than that of a blockage is used during normal suction, when E-<F- and G'>H', the first threshold value cannot be set between G' and H', so it is difficult to determine whether it is a blockage or a normal suction.

[0112] Figure 12 This figure shows examples of pressure waveforms when aspirating a sample with a second predetermined amount greater than the first predetermined amount, and pressure waveforms when aspirating a sample with the first predetermined amount. If the pipeline is clogged with fiber contained in blood, the tubing diameter decreases, and frictional pressure loss increases. A large suction volume prolongs the suction time after the pipeline is clogged. Therefore, the waveform indicating a clogged pipeline, i.e., a waveform shifting negatively on the pressure axis, can be obtained over a longer period. On the other hand, a small suction volume shortens the suction time, shortening the waveform indicating a clogged pipeline.

[0113] Figure 13 1 is a diagram showing an example of a setting margin for the second threshold value (threshold value for traffic jam determination).

[0114] When the sample 115, the sum of the first and second predetermined amounts, is aspirated into the dispensing tip 18, E->F- and G>H. Furthermore, the difference between G and H, i.e., the setting margin m2 for the second threshold, is greater than the predetermined value. This allows reliable distinction between the indicator region during clogging and the indicator region during normal aspiration, improving judgment accuracy. Furthermore, when using a second judgment indicator whose value during normal aspiration is greater than that during clogging, E->F- and G'<H' are also achieved, and the difference between G' and H' is greater than the predetermined value, similarly improving judgment accuracy.

[0115] On the other hand, when the first predetermined amount of the sample 115 is sucked into the dispensing tip 18, one of the following two states is achieved. Figure 13As shown, the state is E->F- and G<H, and the setting margin m2 itself does not exist. The index area during blockage partially overlaps with the index area during normal aspiration. Although not shown, the second state is E->F- and G>H. The setting margin m2 exists, but it is smaller than the predetermined value. The index area during blockage and the index area during normal aspiration are close to each other, which may lead to misjudgment due to the deviation of the second judgment index. Therefore, when the first predetermined amount of specimen 115 is aspirated, the judgment accuracy is reduced compared to when the specimen 115 is aspirated in an amount equal to the sum of the first and second predetermined amounts. Furthermore, when using a second judgment index with a larger value during normal aspiration than during blockage, either the state is E->F- and G'>H', or the state is E->F- and G'<H', but the difference between G' and H' is smaller than the predetermined value. Similarly, judgment accuracy is reduced.

[0116] Therefore, in this embodiment, a second predetermined amount of specimen is aspirated, which is greater than the first predetermined amount used in the analysis, to determine whether the aspiration is blocked or normal. This allows for highly accurate determination even when the first predetermined amount is low, without requiring changes such as using a high-sensitivity pressure sensor or reducing the tip size. Furthermore, this embodiment eliminates the need to set a calculation interval for each first predetermined amount or to change the threshold for each first predetermined amount. This provides the advantage of standardizing the calculation method and threshold for the second determination indicator, regardless of the amount of specimen used in the analysis.

[0117] The above description uses Embodiment 1 and Embodiment 2 as examples, but a portion of the structure of one embodiment may be replaced with the structure of another embodiment, or the structure of another embodiment may be added to the structure of one embodiment. In addition, the present invention is not limited to the embodiments and includes various modifications.

[0118] For example, in each embodiment, to further improve determination accuracy, the determination index is calculated based on the difference between the second waveform and the first waveform. However, even if the determination index is calculated based solely on the first waveform, a certain degree of determination accuracy can be achieved. Furthermore, if the requested analysis items include a first analysis item whose first predetermined amount is less than a second threshold value and a second analysis item whose first predetermined amount is greater than the second threshold value, the dispensing unit may be controlled for the first analysis item as in each embodiment, while being controlled for the second analysis item so that only the first predetermined amount of specimen is aspirated and discharged.

[0119] Explanation of symbols

[0120] 1 reaction plate

[0121] 2 reaction vessels

[0122] 3Reagent / sample common storage area

[0123] 4 reagent containers

[0124] 5 specimen containers

[0125] 6 reagent aspiration position

[0126] 7. Specimen suction position

[0127] 8First dispensing mechanism

[0128] 9 Second injection mechanism

[0129] 10, 11 water supply pump

[0130] 12, 13 cleaning tank

[0131] 15 Spectrophotometer

[0132] 16 testing agencies

[0133] 17-dispensing pipette tip / reaction vessel transport mechanism

[0134] 18 minute injection tip

[0135] 19-point pipette tip tray

[0136] 20 reaction vessel tray

[0137] 21-point pipette tip / reaction vessel waste box

[0138] 22-point injection tip installation position

[0139] 23-minute pipette tip disposal location

[0140] 28 Control Department

[0141] 102 injection probe

[0142] 103 flow path

[0143] 104 syringe

[0144] 104a cylinder

[0145] 104b plunger

[0146] 105 cleaning water

[0147] 106 syringe drive unit

[0148] 107 probe drive unit

[0149] 108 points control department

[0150] 110 water supply tank

[0151] 111 internal washing solenoid valve

[0152] 113 reagent

[0153] 115 specimens

[0154] 117 Inspection Department

[0155] 118 branch blocks

[0156] 119 Storage Department

[0157] 120 Computing Department

[0158] 121 Judgment Department

[0159] 123 external washing nozzle

[0160] 125 external wash solenoid valve

[0161] 126 display unit.

Claims

1. An automatic analysis device, characterized in that have: a dispensing unit that sucks the specimen from a specimen container containing the specimen; a control unit configured to control the dispensing unit so that, after aspirating a third predetermined amount of the specimen, which is greater than the first predetermined amount of the specimen used in the analysis, the second predetermined amount of the specimen is discharged to a predetermined location different from the specimen container, and thereafter the first predetermined amount of the specimen is discharged to a reaction container used in the analysis; a detection unit configured to detect a pressure waveform in the dispensing unit; as well as The determination unit determines whether the dispensing unit is insufficiently sucking the specimen, that is, empty suction, and / or is clogged by the specimen, that is, based on the first waveform, that is, the pressure waveform when the dispensing unit sucks the specimen.

2. The automatic analysis device according to claim 1, characterized in that The determination unit calculates a difference between a second waveform, which is a pressure waveform before the dispensing unit aspirates the specimen, and the first waveform, and determines the empty aspiration and / or the clogging based on the difference.

3. The automatic analysis device according to claim 1, characterized in that The determination unit calculates a determination index based on the first waveform, and determines that the waveform is empty suction and / or clogging when the determination index is greater than a first threshold value. The first threshold is preset to a value larger than an assumed upper limit value of the determination index when the aspiration of the specimen by the dispensing unit is normal and smaller than an assumed lower limit value of the determination index during the empty aspiration and / or clogging.

4. The automatic analysis device according to claim 3, characterized in that When the first predetermined amount of the specimen is aspirated, The assumed lower limit value during the dry suction and / or clogging is smaller than the assumed upper limit value during the normal state, or The assumed lower limit value in the case of dry suction and / or clogging is larger than the assumed upper limit value in the normal state, and the difference is smaller than a predetermined value. When the third predetermined amount of the specimen is aspirated, The assumed lower limit value during the dry suction and / or clogging is larger than the assumed upper limit value during the normal state, and the difference therebetween is larger than the predetermined value.

5. The automatic analysis device according to claim 1, characterized in that The determination unit calculates a determination index based on the first waveform, and determines that the waveform is empty suction and / or clogging when the determination index is smaller than a first threshold value. The first threshold is preset to a value smaller than a presumed lower limit value of the determination index when the aspiration of the specimen by the dispensing unit is normal and larger than a presumed upper limit value of the determination index during the empty aspiration and / or clogging.

6. The automatic analysis device according to claim 5, characterized in that When the first predetermined amount of the specimen is aspirated, The assumed upper limit value during the dry suction and / or clogging is greater than the assumed lower limit value during the normal state, or The assumed upper limit value in the case of dry suction and / or clogging is smaller than the assumed lower limit value in the normal state, and the difference is smaller than a predetermined value. When the third predetermined amount of the specimen is aspirated, The assumed upper limit value during the dry suction and / or clogging is smaller than the assumed lower limit value during the normal state, and the difference therebetween is larger than the predetermined value.

7. The automatic analysis device according to claim 1, characterized in that The automatic analyzer further comprises a cleaning tank for cleaning the dispensing portion. The control unit discharges the second predetermined amount of the specimen into the cleaning tank.

8. The automatic analysis device according to claim 1, characterized in that The analysis request items include a first analysis item where the first predetermined amount is less than a second threshold value and a second analysis item where the first predetermined amount is greater than the second threshold value. When the analysis request item is the first analysis item, the control unit controls the dispensing unit so that after aspirating the third predetermined amount of the specimen, the second predetermined amount of the specimen is discharged to a predetermined location different from the specimen container, and then the first predetermined amount of the specimen is discharged to the reaction container. When the analysis request item is the second analysis item, the control unit controls the dispensing unit so as to discharge the first predetermined amount of the sample into the reaction container after aspirating the first predetermined amount of the sample.

9. An analysis method for an automatic analysis device, the automatic analysis device comprising: a dispensing unit that draws a specimen from a specimen container containing the specimen; a control unit that controls the dispensing unit so as to discharge the specimen into a reaction container for analysis; a detection unit that detects a pressure waveform in the dispensing unit; and a determination unit that determines whether the dispensing unit has insufficiently drawn the specimen, i.e., empty suction, and / or whether the specimen has blocked the dispensing unit, i.e., blockage, wherein: The control unit controls the dispensing unit so that after aspirating a third predetermined amount of the specimen, which is larger than the first predetermined amount of the specimen used in the analysis, the second predetermined amount of the specimen is discharged to a predetermined location different from the specimen container, and then the first predetermined amount of the specimen is discharged to the reaction container. The determination unit determines the empty suction and / or the clogging based on the first waveform, which is the pressure waveform when the dispensing unit aspirates the specimen.

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