JP2010048593A - Autoanalyzer and blood sample analyzing method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an autoanalyzer capable of obtaining the stable analyzed result of HbA1c. <P>SOLUTION: In the autoanalyzer 1 constituted so that a predetermined amount of the blood sample, which is housed in a specimen container 9a and separated into a plasma layer and a blood corpuscle layer, is dispensed by a specimen dispenser 20 and reacted with a reagent to be analyzed, a pressure change is detected at a plurality of the places different in height in the blood sample, which is housed in the specimen container 9a, using the dispensing probe 20b of the specimen dispenser 20 equipped with a pressure detecting means, by a detection part 18b, the boundary surface of the plasma layer and the blood corpuscle layer is detected on the basis of the pressure change by an arithmetic part 18c to calculate the height of the blood corpuscle layer, a blood corpuscle sample is sucked and collected on the basis of the height of the blood corpuscle layer by the specimen dispenser 20 and the analysis of the item affected by the specific gravity of the blood corpuscle sample is performed with respect to the collected blood corpuscle sample by an analyzing optical system 11. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an automatic analyzer for analyzing a blood sample and a blood sample analyzing method.

  Conventionally, blood glucose and hemoglobin A1c (HbA1c) have been used as a diagnostic marker for diabetes. In an automatic analyzer, a blood sample collected from a subject is separated into plasma and blood cells by centrifugation, and blood glucose is collected from the supernatant plasma sample. HbA1c is analyzed from a blood cell sample precipitated at the bottom. Generally, in order to dispense a plasma sample, the blood level of the plasma is detected and aspirated by a liquid level detection mechanism provided in the dispensing probe for blood glucose analysis, and the blood cell sample enters the dispensing probe to the bottom of the sample container. The HbA1c is analyzed.

  However, the lower blood cell layer that has been centrifuged has a specific gravity difference in the blood cell itself, a low specific gravity blood cell (young blood cell) in the upper blood cell layer, and a higher specific gravity blood cell (senescent blood cell) in the lower blood cell layer. Existing. This difference in specific gravity of blood cells changes due to an excess of the binding ratio of glucose to hemoglobin, and it is known that as senescent blood cells bind glucose to hemoglobin, the specific gravity increases and the value of HbA1c also increases. ing. Accordingly, when a blood cell sample is aspirated and collected from the bottom of the specimen container, senescent blood cells with a high HbA1c concentration are collected, and therefore, development of a sampling technique that is not affected by the concentration gradient generated in the blood cell layer has been desired (for example, Patent Document 1).

  In response to this, various dispensing methods have been proposed (see, for example, Patent Documents 1 to 4). In Patent Document 1, the interface between the plasma layer and the blood cell layer is estimated based on the liquid level position detected by the liquid level detection means and the hematocrit value set or measured in advance, and the blood cell is determined based on the interface position. A method of dispensing a layer of analyte is disclosed.

  In Patent Document 2, an electrode combined plasma suction nozzle that sucks blood plasma and an electrode combined blood cell suction nozzle that sucks blood cells are detected, and the impedance between the two nozzles is detected, and the interface position between the plasma layer and the blood cell layer is detected. An apparatus for detecting the above is disclosed.

  In Patent Document 3, the identification code is read based on the amount of light reflected from the surface of the identification label affixed to the sample container, and the amount of reflected light from the sample obtained through a gap formed between both ends in the circumferential direction of the identification label. An analyzer that detects a plasma surface and a blood spherical surface of a blood sample in a sample container based on the difference is disclosed.

  Patent Document 4 discloses an analyzer that performs analysis by aspirating a sample in a whole blood state by providing a stirring unit between a plasma analysis unit and a whole blood analysis unit.

JP-A-10-246727 JP-A-5-306950 JP-A-9-89902 JP-A-9-89907 JJCLA Journal of Japanese Society for Clinical Laboratory Automation 2004, VOL. 29, P181-189

  By the way, in the method of Patent Document 1, in order to estimate the plasma-blood cell interface, it is necessary to measure the hematocrit value in advance or to input the predicted value of the hematocrit value when not measuring. Therefore, it is good if the hematocrit value is measured in the same specimen, but if it is not measured, additional test items will result in increased costs and time. There is a problem that it is difficult to detect.

  Further, in the apparatus of Patent Document 2, since it is necessary to use two metal sample probes for detecting the interface between plasma and blood cells, not only the structure of the automatic analyzer becomes complicated, but also depending on the type of sample container. Has a problem that it is difficult to insert two probes.

  Furthermore, in the apparatus of Patent Document 3, a mechanism for holding, raising and lowering and rotating the specimen container is provided for reading the identification label, so that not only the structure becomes complicated, but the identification is performed without paying attention to the application of the identification label. There is a possibility that gaps formed at both ends in the circumferential direction of the label are not made and detection becomes impossible.

  Further, the apparatus of Patent Document 4 has a problem that a process such as pretreatment is required to analyze HbA1c from a whole blood sample, and an additional stirring unit is required, which complicates the apparatus. .

  The present invention has been made in view of the above, and provides an automatic analyzer that can accurately set a blood cell sample aspiration collection position in a blood cell layer with a simple configuration and obtain a stable analysis result. With the goal.

  In order to achieve the above object, the automatic analyzer of the present invention dispenses a predetermined amount of a blood sample separated into a plasma layer and a blood cell layer accommodated in a specimen container, and reacts with a reagent. In the automatic analyzer for analyzing, detection using a dispensing probe of the dispensing apparatus having pressure detecting means to detect a pressure change at a plurality of different heights in the blood sample accommodated in the specimen container Means for calculating the height of the blood cell layer by detecting a boundary surface between the plasma layer and the blood cell layer based on the pressure change, and for collecting the blood cell sample by suction based on the height of the blood cell layer It is characterized by comprising injection means and analysis means for analyzing a blood cell sample collected by the dispensing means.

  In the automatic analyzer according to the present invention, the analysis item by the analysis means is an item affected by the specific gravity of the blood cell sample.

  In the automatic analyzer according to the present invention as set forth in the invention described above, the analysis item by the analyzing means is HbA1c.

  In the automatic analyzer according to the present invention as set forth in the invention described above, the detecting means detects a pressure change when the dispensing probe is raised or lowered in the blood sample.

  In the automatic analyzer according to the present invention as set forth in the invention described above, the detecting means detects a pressure change at the time of ascending or descending suction of the blood sample by the dispensing probe.

  In addition, the automatic analyzer of the present invention, in the above invention, issues a warning that the sample is abnormal when the blood cell layer height calculated by the calculating means is out of an allowable range, and the blood sample is separated. Control means for controlling to stop the ordering and analysis is provided.

  Moreover, the automatic analyzer according to the present invention is characterized in that, in the above invention, the dispensing means can arbitrarily set a blood cell sample aspirating and collecting position in the blood cell layer.

  The automatic analyzer according to the present invention is characterized in that, in the above invention, the dispensing means detects a plasma liquid level with the dispensing probe and dispenses a plasma sample.

  The automatic analyzer according to the present invention is characterized in that, in the above-mentioned invention, HbA1c is analyzed from the blood cell sample, and blood glucose is analyzed from the plasma sample.

  Further, the blood sample analysis method of the present invention dispenses a predetermined amount of a blood sample separated into a plasma layer and a blood cell layer contained in a specimen container by a dispensing device, and reacts with a reagent to optically analyze the blood sample. A blood sample analyzing method for detecting a pressure change at a plurality of different heights in the blood sample accommodated in a specimen container using a dispensing probe of the dispensing apparatus having a pressure detecting means. Based on the detection step, a calculation step for detecting a boundary surface between the blood plasma layer and the blood cell layer based on the pressure change detected by the detection step, and calculating the height of the blood cell layer, based on the height of the blood cell layer It includes a dispensing step for sucking and collecting a blood cell sample, and an analysis step for analyzing HbA1c of the blood cell sample collected by the dispensing step.

  The blood sample analysis method of the present invention is characterized in that, in the above invention, the detection step detects a pressure change when the dispensing probe is raised or lowered in the blood sample.

  The blood sample analysis method according to the present invention is characterized in that, in the above invention, the detection step detects a pressure change at the time of ascending or descending suction of the blood sample by the dispensing probe.

  In the blood sample analysis method of the present invention, in the above invention, the dispensing step calculates the blood cell layer height in the computing step, and then drops the dispensing probe in the blood sample into the blood cell layer by a predetermined amount. Then, a blood cell sample is collected by suction.

  The blood sample analysis method of the present invention is characterized in that, in the above invention, the dispensing step is performed after the dispensing probe is pulled up from the blood sample and the suction sample is discharged and washed.

  In the blood sample analysis method of the present invention, in the above invention, the detecting step detects a plasma liquid level with the dispensing probe, and the dispensing step is performed based on the detection result of the plasma liquid level. A sample is dispensed, and then the blood cell sample is dispensed, and the analyzing step analyzes blood glucose of the plasma sample.

  The blood sample analysis method of the present invention is characterized in that, in the above invention, the detection step detects the liquid level by a change in capacitance by a capacitance type liquid level detection mechanism.

  In the present invention, a change in pressure is detected at a plurality of locations in the blood sample at different heights using a dispensing probe of a dispensing device equipped with a pressure detection means, and the computing means detects the plasma layer and blood cell bath based on the pressure change. , The blood cell layer height is calculated, the blood cell sample aspiration collection position in the blood cell layer can be accurately set based on the height of the blood cell layer, and stable HbA1c etc. with a simple configuration It is effective in that the analysis result of can be obtained.

(Embodiment 1)
Exemplary embodiments of an automatic analyzer according to the present invention will be explained below in detail with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of an automatic analyzer according to the first embodiment of the present invention. FIG. 2 is a block diagram showing a schematic configuration of a sample dispensing apparatus used in the automatic analyzer of FIG.

  The automatic analyzer 1 is an apparatus that automatically analyzes a sample such as blood or urine containing blood cell components. As shown in FIG. 1, the first and second reagent tables 2 and 3, the reaction table 4, the first and first 2 reagent dispensing devices 6 and 7, sample container transfer mechanism 8, rack 9, analysis optical system 11, cleaning mechanism 12, first and second stirring devices 13 and 14, control unit 15, input unit 16, display unit 17, A storage unit 19 and a sample dispensing device 20 are provided.

  As shown in FIG. 1, each of the first and second reagent tables 2 and 3 includes a plurality of first reagent reagent containers 2a and a plurality of second reagent reagent containers 3a arranged in the circumferential direction and rotated by driving means. The containers 2a and 3a are transported in the circumferential direction. Each of the plurality of reagent containers 2a and 3a is filled with a reagent corresponding to the inspection item, and an information recording medium (not shown) on which information such as the type, lot, and expiration date of the stored reagent is recorded is added to the outer surface. ing. Here, on the outer periphery of the first and second reagent tables 2 and 3, a reading device (not shown) that reads the reagent information recorded on the information recording medium added to the reagent containers 2 a and 3 a and outputs it to the control unit 15. ) Is installed.

  As shown in FIG. 1, the reaction table 4 includes a plurality of reaction vessels 5 arranged in the circumferential direction. The reaction table 4 is arrowed by a driving means different from the driving means for driving the first and second reagent tables 2 and 3. To move the reaction vessel 5 in the circumferential direction. The reaction table 4 is disposed between the light source 11a and the spectroscopic unit 11b, and has a holding unit 4a that holds the reaction vessel 5 and an optical path 4b that includes a circular opening that guides the light beam emitted from the light source 11a to the spectroscopic unit 11b. is doing. The holding part 4a is arranged on the outer periphery of the reaction table 4 at a predetermined interval along the circumferential direction, and an optical path 4b extending in the radial direction is formed on the inner peripheral side of the holding part 4a.

  The reaction vessel 5 is an optically transparent material that transmits 80% or more of the light contained in the analysis light (340 to 800 nm) emitted from the analysis optical system 11, such as glass containing heat-resistant glass, cyclic olefin, or polystyrene. It is a container called a cuvette formed into a square cylinder shape by the like. In the reaction container 5, reagents are dispensed from the reagent containers 2 a and 3 a of the first and second reagent tables 2 and 3 by first and second reagent dispensing devices 6 and 7 provided in the vicinity. Here, the first and second reagent dispensing devices 6 and 7 are respectively provided with nozzles 6b and 7b that rotate in a horizontal plane and dispense reagents to arms 6a and 7a that are moved up and down in the vertical direction. A cleaning tank (not shown) for cleaning the nozzles 6b and 7b with cleaning water is provided.

  As shown in FIG. 1, the specimen container transfer mechanism 8 transfers the plurality of arranged racks 9 while stepping one by one along the arrow direction. The rack 9 holds a plurality of sample containers 9a that store samples. Here, the sample container 9a is affixed with a bar code or the like on which information on the stored sample is affixed, and every time the advance of the rack 9 transported by the sample container transport mechanism 8 stops, Is dispensed into each reaction vessel 5. A blood sample whose analysis item is blood glucose or hemoglobin A1c is centrifuged in a state where it is previously stored in the sample container 9a, and the plasma sample and the blood cell sample are analyzed items from the blood sample separated into the plasma layer and the blood cell layer. It will be dispensed individually. Here, on the outer periphery of the rack, a reading device (reading device) that reads the sample information and the container information of the sample container 9a recorded on an information recording medium (not shown) attached to the sample container 9a and outputs the information to the control unit 15. (Not shown) is installed.

  The analysis optical system 11 is an optical system for analyzing by transmitting the analysis light (340 to 800 nm) through the liquid sample in the reaction container 5 in which the reagent and the sample have reacted, and includes a light source 11a, a spectroscopic unit 11b, and a light receiving unit. 11c. The analysis light emitted from the light source 11a passes through the liquid sample in the reaction vessel 5 and is received by the light receiving unit 11c provided at a position facing the spectroscopic unit 11b. The light receiving unit 11 c is connected to the control unit 15.

  The cleaning mechanism 12 sucks and discharges the liquid sample in the reaction vessel 5 by the nozzle 12a, and then repeatedly injects and sucks a cleaning liquid such as detergent and cleaning water by the nozzle 12a, thereby performing analysis by the analysis optical system 11. The reaction vessel 5 that has been completed is washed.

  The first and second stirring devices 13 and 14 stir the dispensed specimen and reagent with the stirring rods 13a and 14a to promote the reaction.

  The control unit 15 includes the first and second reagent tables 2 and 3, the first and second reagent dispensing devices 6 and 7, the sample container transfer mechanism 8, the analysis optical system 11, the cleaning mechanism 12, and the first and second stirring. The devices 13 and 14, the input unit 16, the display unit 17, the storage unit 19, and the sample dispensing device 20 are connected. In order to control the operation of these units, a microcomputer or the like is used as the control unit 15. The control unit 15 obtains the absorbance for each wavelength of the liquid sample in each reaction vessel 5 based on the light amount signal for each wavelength input from the light receiving unit 11c, and analyzes the component concentration and the like of the specimen. In addition, the control unit 15, based on the information read from the information recording medium added to the reagent containers 2 a, 3 a, the automatic analyzer 1 so as to stop the analysis work when the reagent lot is different or when the expiration date is out of date. Or alert the operator.

  Furthermore, the control unit 15 has mode switching means 15a. The mode switching means 15a is for switching the dispensing mode of the sample dispensing device 20. As the dispensing mode, there are a special dispensing mode and a normal dispensing mode. The special dispensing mode is a mode for dispensing a plasma and blood cells by the specimen. The normal dispensing mode is a mode in which the specimen dispenses a sample other than blood such as a whole blood sample or urine. And the control part 15 is connected with the boundary surface detection part 18 which consists of the process part 18a, the detection part 18b, and the calculating part 18c, as shown in FIG.

  FIG. 2 is a block diagram showing a schematic configuration of the sample dispensing apparatus. As shown in FIG. 2, the sample dispensing apparatus 20 includes a dispensing probe 20b, a dispensing pump 23, a pump driving unit 24, a pressure sensor 25 as pressure detecting means, a washing water pump 27, an amplification circuit 28, and a liquid level detection. Unit 31, control unit 15, and boundary surface detection unit 18.

  As shown in FIG. 1, the specimen dispensing apparatus 20 is provided with a dispensing probe 20b that rotates in a horizontal plane and dispenses a specimen to an arm 20a that is moved up and down in the vertical direction. A cleaning tank (not shown) for cleaning the probe 20b is provided. As shown in FIG. 2, the dispensing probe 20 b is connected to a dispensing pump 23, a pressure sensor 25, and a washing water pump 27 by a pipe 22. The dispensing probe 20b is moved by the probe driving unit 21 in the horizontal direction indicated by the arrow X in the drawing and the vertical direction indicated by Z in the drawing, and aspirates the sample from the sample container 9a sequentially conveyed to the lower part of the dispensing probe 20b. The specimen is dispensed by discharging the specimen into the reaction container 5 on the reaction table 4.

  The dispensing pump 23 is a syringe pump that aspirates the sample in the sample container 9 a to the dispensing probe 20 b and then discharges the sample sucked into the reaction container 5 conveyed by the reaction table 4. The piston 23a is reciprocated.

  The pressure sensor 25 detects the pressure in the pipe 22 and outputs the pressure signal (analog) to the amplifier circuit 28.

  The cleaning water pump 27 sucks up the degassed cleaning water 30 stored in the tank 29 and pumps it into the pipe 22 via an electromagnetic valve 26 provided between the pressure sensor 25. At this time, the electromagnetic valve 26 is switched to “open” in response to a control signal from the control unit 15 when the sucked washing water 30 is pumped into the pipe 22, and the dispensing probe 23 causes the dispensing probe 20 b to be liquid. When the sample is sucked and discharged, it is switched to “closed”.

  The amplification circuit 28 amplifies the pressure signal (analog) output from the pressure sensor 25, and the amplified pressure signal is output to the boundary surface detection unit 18 via the control unit 15.

  The boundary surface detection unit 18 includes a processing unit 18a, a detection unit 18b, and a calculation unit 18c, detects the boundary surface between the plasma layer and the blood cell layer based on the pressure change detected by the pressure sensor 25, and increases the height of the blood cell layer. However, the interface between air and plasma can be detected in the same manner. For example, a computer device is used as the boundary surface detection unit 18.

  The processing unit 18a is a part that converts the pressure signal (analog) input from the amplifier circuit 28 into a digital signal, and uses, for example, an A / D converter. The detection unit 18b detects the pressure in the pipe 22 from the pressure signal converted into a digital signal by the processing unit 18a. The calculation unit 18c detects the boundary surface between the plasma layer and the blood cell layer from the pressure change detected by the detection unit 18b, acquires the size of the sample container from the information of the sample container read by the reading unit (not shown), and Based on the above, the height of the blood cell layer is calculated. The height of the blood cell layer is output to the control unit 15, and the control unit 15 drives and controls the probe driving unit 21 based on the height of the blood cell layer to stop at the plasma-blood cell interface in the sample container 9a. The dispensing probe 20b is lowered by a set amount, and the pump drive unit 24 is driven to suck and collect a blood cell sample.

  The liquid level detection unit 31 detects the interface between air and the plasma layer, that is, the plasma liquid level, and includes an oscillation circuit 101, a differentiation circuit 102, and a voltage detection circuit 103 as shown in FIG.

  FIG. 3 is a block diagram illustrating a schematic configuration of the electrostatic capacity type liquid level detection unit 31. The oscillation circuit 101 oscillates an AC signal and inputs it to the differentiation circuit 102. As shown in FIG. 3, the differentiating circuit 102 includes resistors 102a and 102b, capacitors 102c and 102d, and an operational amplifier 102e, and is adjusted so that the input sensitivity is increased according to the frequency of the AC signal oscillated by the oscillation circuit 101. . The + side input end of the differentiating circuit 102 is connected to the dispensing probe 20b via the lead wire 10a. The voltage detection circuit 103 is connected to the output terminal of the differentiating circuit 102 to detect the output voltage Vout of the differentiating circuit 102, and the lower end of the dispensing probe 20b is in contact with the liquid level of the liquid in the sample container 9a according to this value. Detect whether or not. The output voltage signal detected by the voltage detection circuit 103 is output to the control unit 15, and the plasma liquid level (air-plasma interface) in the sample container 9a is detected.

  The differentiation circuit 102 in which the dispensing probe 20b is adjusted so that the input sensitivity is increased at the frequency of the oscillation circuit 101 by the capacitance value in a non-contact state with the liquid surface of the liquid has a sensitivity in the capacitance value in the contact state. descend. Therefore, the voltage detection circuit 103 detects the liquid level based on the change in the output voltage Vout.

  When the liquid level detection unit 31 or the boundary surface detection unit 18 detects the liquid level in the sample container 9a (air-plasma interface), the control unit 15 dispenses a predetermined amount for plasma sample dispensing. After descending the probe 20b, a plasma sample is aspirated.

  Next, the dispensing operation by the dispensing probe 20b will be described. FIG. 4 is a flowchart showing the dispensing operation of the dispensing probe 20b, and FIG. 5 is a flowchart (special dispensing mode) showing the dispensing operation of the blood sample dispensing method according to the first embodiment. 6 is a pressure change diagram when the blood sample separated into plasma-blood cells is aspirated by a dispensing probe, and FIG. 7 is an operation diagram of the blood sample dispensing method according to the first embodiment (special Dispensing mode).

  As shown in FIG. 4, the control unit 15 acquires analysis information 15b such as the type of sample and analysis items from the storage unit 19 (step S100). The control unit 15 switches the dispensing mode by the mode switching unit 15a based on the analysis information 15b (step S101). When the analysis items are blood glucose and HbA1c in step S101, the mode is switched to the special dispensing mode (step S101: Yes). The control unit 15 executes the special dispensing mode as the blood sample dispensing method according to the first embodiment, and ends this control (step S102). On the other hand, when switching to the normal dispensing mode in step S101 (step S101: No), the control unit 15 executes the normal dispensing mode and ends this control (step S103).

  As shown in FIG. 5, in the special dispensing mode (step S102), first, a position for sucking and collecting a blood cell sample from the blood cell layer is input (step S200). When HbA1c analysis is performed by aspirating a blood cell sample from the blood cell layer of the blood sample separated into plasma and blood cells, the value of HbA1c changes depending on the position of the aspiration. Set. The blood cell sample is preferably aspirated and collected at 20 to 80% of the blood cell layer. Usually, the blood cell sample is aspirated and collected at a position of 50% of the median value, but may be changed according to the blood sample. Next, information on the specimen container 9a containing the blood sample layer-separated into plasma-blood cells is confirmed through a reading unit (not shown) (step S201). The automatic analyzer 1 has information such as the size of the specimen container 9a used in the storage unit 19, acquires the container information before sample dispensing, and the height of the blood cell layer detected and calculated later Based on the above, the descending amount of the dispensing probe 20b is determined. Thereafter, the dispensing probe 20b is moved above the opening of the sample container 9a at the sample aspirating position, the dispensing probe 20b is lowered into the sample container 9a, and the liquid level detection unit 31 detects the plasma liquid level ( Step S202). After detecting the plasma level, the dispensing probe 20b is lowered to dispense a plasma sample (step S203), the plasma sample is aspirated (step S204), and the aspirated plasma sample is discharged into the reaction vessel 5. (Step S205).

  After dispensing the plasma sample, the dispensing probe 20b is lowered again into the specimen container 9a in order to dispense a blood cell sample. While lowering the dispensing probe 20b in the blood sample, the sample is sucked by the dispensing pump 23, and the pressure at the time of suction is detected by the pressure sensor 25 or the like (step S206). FIG. 6 is a pressure change diagram when the blood sample separated into plasma-blood cells is lowered while being sucked by the dispensing probe 20b. When the dispensing probe 20b is lowered and sucked, the suction pressure changes on the plasma liquid level (t1 to t2), and when sucking and dropping in the plasma (t2 to t3), the pressure becomes constant (V1). When the dispensing probe 20b is further sucked down, the pressure changes in the vicinity of the plasma-blood cell interface (t3 to t4), and when completely inserted into the blood cell sample layer (plasma-blood cell interface), the suction pressure is constant again. (V2). Therefore, after recognizing the plasma-blood cell interface (t5), the control unit 15 temporarily stops the descent and suction of the dispensing probe 20b. Further, as apparent from FIG. 6, when the dispensing probe 20b is aspirated and lowered, the suction pressure changes at the time (t1) when the dispensing probe 20b sucks the plasma sample, so that the pressure change is detected. Thus, it is possible to detect the plasma liquid level.

  Based on the pressure change, the detection unit 18b detects the plasma-blood cell interface, and the calculation unit 18c calculates the height of the blood cell layer based on the size information of the specimen container 9a (step S207). When the height of the blood cell layer is within an allowable range (step S208: Yes), the amount of descent of the dispensing probe 20b is determined from the calculated blood cell layer height and the blood cell sample aspiration collection position input in step S200, In order to dispense a desired blood cell sample, the dispensing probe 20b is lowered to the position set and input in step S200 (step S209). Usually, the ratio of plasma to blood cells is 55:45, and the allowable range of the height of the blood cell layer is set in consideration of this ratio.

  Thereafter, the blood cell sample is aspirated by the dispensing probe 20b (step S210), and the aspirated blood cell sample is discharged into another reaction vessel 5 (step S211). Dispensing probe 20b that has been dispensed is washed in the dispensing probe washing tank (step S212), blood sugar is analyzed from the plasma sample dispensed into reaction vessel 5, and HbA1c is analyzed from the blood cell sample. Done. On the other hand, when the height of the blood cell layer is outside the allowable range (step S207: No), the control unit 15 displays the display unit because the plasma layer-blood cell layer boundary surface is lowered or not detected due to hemolysis of red blood cells. The sample abnormality is notified by 17 (step S213), and the control is performed to stop the dispensing of the blood cell sample and the analysis of the plasma sample sucked in step S204 (step S214).

  Next, the special dispensing mode will be further described with reference to the operation diagram of the first embodiment of the present invention shown in FIG. In FIG. 7A, the dispensing probe 20b is lowered into the specimen container 9a containing a blood sample separated into a plasma layer and a blood cell tank, and the tip of the dispensing probe 20b comes into contact with the liquid surface. The liquid level detection unit 31 detects the plasma liquid level based on the voltage. Alternatively, the dispensing probe 20b may be lowered while the sample is sucked by the dispensing pump 23, and the plasma liquid level may be detected by a pressure change at the air-plasma layer interface. After the plasma liquid level is detected, the drop of the dispensing probe 20b is stopped. However, as shown in FIG. 7B, a predetermined amount of the dispensing probe 20b is lowered to reliably collect the sample by suction, as shown in FIG. Suction. After the sample is aspirated, the dispensing probe 20b is transported by the probe driving unit 21 to discharge the sample to the reaction container 5 held in the reaction table 4, and the plasma is put into the reaction container 5 as shown in FIG. Discharge the sample. In the reaction container 5, the first reagent in the reagent container 2a held in the first reagent table 2 is already dispensed by the first reagent dispensing device 6, and after the plasma sample is dispensed, the second reagent is further dispensed. The second reagent in the reagent container 3a held in the second reagent table 3 is dispensed by the device 7. After dispensing of the plasma sample and the second reagent, stirring is performed by the first or second stirring device 13, 14, and then analysis of the plasma sample in the reaction vessel 5 is performed by the analysis optical system 11.

  Further, in order to dispense the blood cell sample from the specimen container 9a that contains the blood sample separated into a plasma layer and a blood cell tank, as shown in FIG. 7 (d), the dispensing probe 20b is dispensed in the specimen container 9a. The sample is aspirated while being lowered by the injection pump 23, the plasma-blood cell interface is detected from the pressure change during the aspiration, and the height of the blood cell layer is calculated. Although the descending suction of the dispensing probe 20b is stopped after the detection of the plasma-blood cell interface, the dispensing probe 20b is lowered by a set amount as shown in FIG. 7 (e) in order to suck the desired blood cell sample. After the blood cell sample is aspirated by the dispensing probe 20b, the dispensing probe 20b is transported to discharge the sample into the reaction container 5 held in the reaction table 4, and dispenses the plasma sample as shown in FIG. 7 (f). The sample is discharged into a reaction vessel 5 different from the reaction vessel 5 that has been obtained. Like the plasma sample, the first reagent in the reagent container 2a held in the first reagent table 2 is already dispensed to the reaction container 5 by the first reagent dispensing device 6, and after dispensing the blood cell sample, Further, the second reagent in the reagent container 3 a held in the second reagent table 3 is dispensed by the second reagent dispensing device 7. After dispensing the blood cell sample and the second reagent, stirring is performed by the first or second stirring device 13, 14, and then analysis of the blood cell sample in the reaction vessel 5 is performed by the analysis optical system 11.

  In the analyzer according to the first embodiment of the present invention, after the detection of the plasma-blood cell interface by descending suction in the blood sample of the dispensing probe 20b, the sample sucked into the dispensing probe 20b for detecting the boundary surface The blood cell sample is continuously aspirated without discharging. In the dispensing probe 20b, the aspirated blood sample is separated into plasma and blood cells, so that a predetermined amount of blood cell sample can be put into the reaction vessel 5 without sucking the plasma by aspirating extra blood cell samples. Can be discharged. Accordingly, it is possible to omit the time required for discharging and washing the sample sucked into the dispensing probe 20b, and to enable rapid dispensing and analysis.

  On the other hand, in step S209, the set dispensing probe 20b is lowered and the blood cell sample is aspirated (step S210), and the aspirated sample in the dispensing probe 20b is discarded in a dispensing probe washing tank (not shown). Thus, the dispensing probe 20b can be washed. By passing through this step, it is possible to completely prevent plasma from being mixed into the blood cell sample, and it is not necessary to suck an excessive amount of sample, so that it is possible to deal with a very small amount of sample.

  In the first embodiment, the pressure at a plurality of locations is measured while continuously moving the dispensing probe upward or downward. However, in addition to measuring the pressure while continuously moving, the dispensing probe is moved upward or downward. It is also possible to move downward, stop once, and measure the pressure at multiple locations. As a modification of the first embodiment, the pressure sensor 25 provided for sample dispensing is used in the sample dispensing apparatus 20 to detect the plasma-blood cell interface by lowering and sucking the dispensing probe 20b. An analyzer for detecting a pressure change at a plasma-blood cell interface or an air-plasma interface by detecting a pressure change by raising or lowering a dispensing probe 20b having a new pressure sensor in the blood sample. Is exemplified as a modification.

(Embodiment 2)
In the first embodiment, the plasma sample is dispensed first, and then the blood cell sample is dispensed. However, in the second embodiment, the blood cell sample is dispensed first, and then the plasma sample is dispensed. This is different from the first embodiment in that analysis is performed. FIG. 8 is a flowchart showing a dispensing operation in the special dispensing mode of the second embodiment for dispensing a blood cell / plasma sample, and FIG. 9 is an operation diagram of the special dispensing mode of the second embodiment. Whether the special dispensing mode or the normal dispensing mode is determined is performed as in the flowchart shown in FIG.

  As shown in FIG. 8, in the special dispensing mode (step S102), first, a position for sucking and collecting a blood cell sample from the blood cell layer is input (step S300). When HbA1c analysis is performed by aspirating a blood cell sample from the blood cell layer of the blood sample separated into plasma and blood cells, the value of HbA1c changes depending on the position of the aspiration. Set. The blood cell sample is preferably aspirated and collected at 20 to 80% of the blood cell layer. Usually, the blood cell sample is aspirated and collected at a position of 50% of the median value, but may be changed according to the blood sample. Next, information on the specimen container 9a containing the blood sample separated into plasma and blood cells is confirmed through a reading unit (not shown) (step S301). The automatic analyzer 1 has information such as the size of the specimen container 9a used in the storage unit 19, acquires the container information before dispensing the sample, and sorts it based on the blood cell layer height information to be performed later. The amount of descent of the probe 20b is determined. Thereafter, the dispensing probe 20b is moved above the opening of the sample container 9a at the sample aspirating position, the dispensing probe 20b is lowered into the sample container 9a, and the liquid level detection unit 31 detects the plasma liquid level ( Step S302).

  After the plasma liquid level is detected, the dispensing probe 20b sucks the sample by the dispensing pump 23 while lowering the blood sample, and the suction pressure is detected by the pressure sensor 25 (step S303). As shown in FIG. 6, when the dispensing probe 20b is aspirated and lowered, the aspiration pressure changes at the plasma liquid level (t1 to t2), and when the plasma is aspirated and lowered (t2 to t3), the pressure is It becomes constant (v1). When the dispensing probe 20b is further lowered by suction, the pressure changes in the vicinity of the plasma-blood cell interface (t3 to t4), and when completely inserted into the blood cell sample layer (plasma-blood cell interface), the suction pressure is constant again. (V2). Therefore, after recognizing the plasma-blood cell interface (t5), the descent and suction of the dispensing probe 20b are stopped. Based on the detected pressure change, the detection unit 18b detects the plasma-blood cell interface, and the calculation unit 18c calculates the height of the blood cell layer based on the size information of the sample container 9a (step S304). If the height of the blood cell layer is within the allowable range (step S305: Yes), the amount of descent of the dispensing probe 20b is determined from the calculated height of the blood cell layer and the suction collection position of the blood cell sample input in step S300, In order to dispense a desired blood cell sample, the predetermined amount dispensing probe 20b is further lowered (step S306).

  Thereafter, the blood cell sample is aspirated by the dispensing probe 20b (step S307), and the aspirated blood cell sample is discharged into the reaction vessel 5 (step S308). Subsequently, in order to clean the dispensing probe 20b, the dispensing probe 20b is transported to the dispensing probe washing tank, and the suction sample in the probe is discarded and washed (step S309). After washing, the dispensing probe 20b is transported to the specimen aspirating position, lowered into the specimen container 9a, and the plasma level is detected again by the liquid level detector 31 (step S310). A predetermined amount of the dispensing probe 20b is lowered to dispense the plasma sample (step S311), the plasma sample is aspirated (step S312), and the aspirated plasma sample is discharged into another reaction container 5 (step S313). .

  After the dispensing of the plasma sample, the dispensing probe 20b is washed again (step S314), blood sugar is analyzed from the dispensed plasma sample, and HbA1c is analyzed from the blood cell sample. On the other hand, when the height of the blood cell tank is out of the allowable range (step S305: No), the control unit 15 displays the display unit because the plasma layer-blood cell layer interface is lowered or not detected due to hemolysis of red blood cells. The sample abnormality is notified by 17 (step S315), and the dispensing / analysis of the plasma / blood cell sample from this specimen is stopped (step S316).

  Next, the special dispensing mode for blood samples separated into plasma-blood cells will be further described with reference to the operation diagram of FIG. In FIG. 9 (a), the dispensing probe 20b is lowered into the specimen container 9a containing a blood sample separated into a plasma layer and a blood cell tank, and the tip of the dispensing probe 20b comes into contact with the liquid surface. The liquid level detection unit 31 detects the plasma liquid level based on the voltage. After the plasma liquid level is detected, as shown in FIG. 9 (b), the dispensing probe 20b is aspirated and collected while the blood sample is lowered by the dispensing pump 23 in the specimen container 9a. The blood cell interface is detected, and the height of the blood cell layer is calculated based on the size information of the specimen container 9a. Although the descending suction of the dispensing probe 20b is stopped after the detection of the plasma-blood cell interface, the dispensing probe 20b is used as shown in FIG. A predetermined amount is lowered. After sucking the blood cell sample with the dispensing probe 20b, the dispensing probe 20b is transported to discharge the sample to the reaction container 5 held in the reaction table 4, and the sample is put into the reaction container 5 as shown in FIG. Is discharged. In the reaction container 5, the first reagent in the reagent container 2a held in the first reagent table 2 is already dispensed by the first reagent dispensing device 6, and after the blood cell sample dispensing, the second reagent dispensing is further performed. The second reagent in the reagent container 3a held in the second reagent table 3 is dispensed by the device 7. After dispensing the blood cell sample and the second reagent, stirring is performed by the first or second stirring device 13, 14, and then analysis of the blood cell sample in the reaction vessel 5 is performed by the analysis optical system 11.

  Next, as shown in FIG. 9 (e), the dispensing probe 20b is transported to a dispensing probe washing tank disposed at an intermediate position between the specimen container transfer mechanism 8 and the reaction table 4, and is dispensed in the dispensing probe washing tank. The sample in the injection probe 20b is discarded, and the dispensing probe 20b is washed. After washing, the dispensing probe 20b is transported to the specimen aspirating position, is lowered into the specimen container 9a as shown in FIG. 9 (f), and the liquid level detector 31 detects the plasma liquid level again. After the detection, as shown in FIG. 9 (g), the plasma sample is aspirated by lowering the predetermined amount of the dispensing probe 20b in order to reliably aspirate and collect the sample. After the sample is aspirated, the dispensing probe 20b is conveyed by the probe driving unit 21 to discharge the sample to the reaction container 5 held in the reaction table 4, and the reaction in which the blood cell sample is discharged as shown in FIG. 9 (h). A plasma sample is discharged into a reaction container 5 different from the container 5. In the reaction container 5, the first reagent in the reagent container 2a held in the first reagent table 2 is already dispensed by the first reagent dispensing device 6, and after the plasma sample is dispensed, the second reagent is further dispensed. The second reagent in the reagent container 3a held in the second reagent table 3 is dispensed by the device 7. After dispensing of the plasma sample and the second reagent, stirring is performed by the first or second stirring device 13, 14, and then analysis of the plasma sample in the reaction vessel 5 is performed by the analysis optical system 11.

  On the other hand, although the automatic analyzer of the present invention has been described with respect to the case where two reagent dispensing devices are provided, the number of reagent dispensing devices may be one. Moreover, the automatic analyzer of the present invention may be configured by combining a plurality of units with the automatic analyzer 1 as one unit.

It is a schematic block diagram of the automatic analyzer which uses the dispensing method of the blood sample concerning Embodiment 1 of this invention. It is a block diagram which shows schematic structure of the sample dispensing apparatus used with the automatic analyzer of FIG. FIG. 2 is a block diagram showing a schematic configuration of a liquid level detection unit used in the automatic analyzer of FIG. It is a flowchart which shows the dispensing operation | movement of a dispensing probe. It is a flowchart which shows the dispensing operation | movement of the dispensing method (special dispensing mode) of the blood sample concerning Embodiment 1 of this invention. It is a pressure change figure when the inside of the blood sample layer-separated into plasma-blood cells is made to descend and suck with a dispensing probe. It is an operation | movement figure of the dispensing method (special dispensing mode) of the blood sample concerning Embodiment 1 of this invention. It is a flowchart which shows the dispensing operation | movement of the dispensing method (special dispensing mode) of the blood sample concerning Embodiment 2 of this invention. It is an operation | movement figure of the dispensing method (special dispensing mode) of the blood sample concerning Embodiment 2 of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Automatic analyzer 2, 3 1st and 2nd reagent table 4 Reaction table 4a Holding part 4b Optical path 4c Metal plate 5 Reaction container 6, 7 1st and 2nd reagent dispensing apparatus 8 Specimen container transfer mechanism 9 Rack 9a Specimen container DESCRIPTION OF SYMBOLS 11 Analysis optical system 12 Washing mechanism 13, 14 1st and 2nd stirring apparatus 15 Control part 15a Mode switching means 16 Input part 17 Display part 18 Boundary surface detection part 18a Processing part 18b Detection part 18c Calculation part 19 Storage part 20 Sample part Injection device 21 Probe drive unit 22 Piping 23 Dispensing pump 24 Pump drive unit 25 Pressure sensor 26 Solenoid valve 27 Washing water pump 28 Amplifying circuit 29 Tank 30 Washing water 31 Liquid level detection unit 101 Oscillation circuit 102 Differentiation circuit 103 Voltage detection circuit

Claims (16)

In an automatic analyzer that dispenses a predetermined amount of a blood sample separated into a blood plasma layer and a blood cell layer contained in a specimen container by a dispensing device and reacts with a reagent for analysis.
Detecting means for detecting pressure changes at a plurality of different locations in the blood sample contained in a specimen container using a dispensing probe of the dispensing apparatus provided with pressure detecting means;
Calculating means for detecting a boundary surface between the plasma layer and the blood cell layer based on the pressure change, and calculating the height of the blood cell layer;
Dispensing means for collecting a blood cell sample by suction based on the height of the blood cell layer;
Analyzing means for analyzing a blood cell sample collected by the dispensing means;
An automatic analyzer characterized by comprising:   The automatic analysis apparatus according to claim 1, wherein the analysis item by the analysis unit is an item affected by the specific gravity of the blood cell sample.   The automatic analysis apparatus according to claim 1 or 2, wherein the analysis item by the analysis means is HbA1c.   The automatic analyzer according to any one of claims 1 to 3, wherein the detection means detects a pressure change when the dispensing probe is raised or lowered in the blood sample.   5. The automatic analyzer according to claim 1, wherein the detection unit detects a pressure change when the blood sample is lifted or lowered by the dispensing probe.   A control means for giving a warning that the sample is abnormal when the height of the blood cell layer calculated by the calculating means is outside an allowable range, and for controlling to stop dispensing and analyzing the blood sample; The automatic analyzer according to any one of claims 1 to 5.   The automatic analyzer according to any one of claims 1 to 6, wherein the dispensing means can arbitrarily set a blood cell sample aspiration collection position in the blood cell layer.   The automatic analyzer according to any one of claims 1 to 7, wherein the dispensing means detects a plasma liquid level with the dispensing probe and dispenses a plasma sample.   9. The automatic analyzer according to claim 8, wherein HbA1c is analyzed from the blood cell sample, and blood glucose is analyzed from the plasma sample. A blood sample analysis method in which a blood sample separated into a plasma layer and a blood cell layer contained in a specimen container is dispensed in a predetermined amount by a dispensing device and optically analyzed by reacting with a reagent,
A detection step of detecting a pressure change at a plurality of different positions in the blood sample contained in a specimen container using a dispensing probe of the dispensing apparatus provided with a pressure detecting means;
Based on the pressure change detected in the detection step, a calculation step for detecting the boundary surface between the plasma layer and the blood cell layer and calculating the height of the blood cell layer;
A dispensing step for aspirating and collecting a blood cell sample based on the height of the blood cell layer;
An analysis step of analyzing HbA1c of the blood cell sample collected by the dispensing step;
A blood sample analysis method comprising the steps of:   The blood sample analysis method according to claim 10, wherein the detection step detects a change in pressure when the dispensing probe is raised or lowered in the blood sample.   The blood sample analysis method according to claim 10 or 11, wherein the detecting step detects a pressure change at the time of ascending or descending suction of the blood sample by the dispensing probe.   The dispensing step is characterized in that, after calculating the height of the blood cell layer in the computing step, the dispensing probe in the blood sample is lowered into the blood cell layer by a predetermined amount and the blood cell sample is aspirated and collected. The blood sample analysis method according to any one of 10 to 12.   The blood sample analysis method according to claim 12 or 13, wherein the dispensing step is performed after the dispensing probe is pulled out of the blood sample and the suction sample is discharged and washed. The detecting step detects a plasma liquid level with the dispensing probe,
The dispensing step dispenses a plasma sample based on the detection result of the plasma liquid level, and then dispenses the blood cell sample,
The blood sample analysis method according to any one of claims 10 to 14, wherein in the analysis step, blood glucose of the plasma sample is analyzed.   The blood sample analysis method according to claim 15, wherein the detecting step detects a liquid level by a capacitance change by a capacitance type liquid level detection mechanism.

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