JP2010048594A - Blood sample detecting method, blood sample dispensing method, blood sample analyzing method dispenser and kind detecting method of blood sample - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method and apparatus capable of simply and accurately dispensing a plasma sample and a blood corpuscle sample. <P>SOLUTION: In a blood sample dispensing method, 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. The specimen dispenser 20 equipped with a pressure detecting means is equipped with a detection part 18b for detecting a pressure change at a plurality of the places different in height in the blood sample housed in the specimen container 9a using a dispensing probe 20b, an arithmetic part 18c for detecting the boundary surface of the plasma layer and the blood corpuscle layer on the basis of the pressure change to calculate the height data of the blood corpuscle layer, and a control part 15 for controlling the suction of the blood corpuscle sample on the basis of the height data of the blood corpuscle layer. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a blood sample detection method, a blood sample dispensing method, a blood sample analysis method, a dispensing apparatus, and a blood sample type detection method.

  Conventionally, blood sugar 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 separated from the plasma sample. HbA1c is analyzed from a blood cell sample. Various dispensing methods have been proposed for dispensing plasma and blood cell samples (see, for example, Patent Documents 1 to 3).

  In Patent Literature 1, an interface between a plasma layer and a blood cell layer is estimated based on a liquid surface position detected by a liquid surface detection means and a hematocrit value set or measured in advance, and a 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.

JP-A-10-246727 JP-A-5-306950 JP-A-9-89902

  By the way, in the method of Patent Document 1, in order to estimate the boundary surface of blood cells, it is necessary to measure a hematocrit value in advance or input a predicted value of hematocrit when not measuring. Therefore, it is good if the hematocrit value is measured in the same sample, but if it is not measured, it will add cost and time due to the addition of test items. 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. 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.

  The present invention has been made in view of the above, and it is possible to easily and accurately determine a blood cell sample by detecting the concentration distribution of the blood sample, the type of the blood sample, and calculating the height of the blood cell layer with a simple configuration. An object of the present invention is to provide a blood sample detection method, blood sample dispensing method, blood sample analysis method, dispensing device, and blood sample type detection method that can be dispensed into the blood.

  To achieve the above object, the blood sample detection method of the present invention uses a means for detecting the pressure in the probe to detect a pressure change at a plurality of different heights in the blood sample contained in the specimen container. And a determination step of determining a concentration distribution of the blood sample based on the pressure change.

  The blood sample detection method of the present invention is characterized in that, in the above invention, the determination step determines a boundary surface of the blood sample.

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

  The blood sample detection method of the present invention is characterized in that, in the above-mentioned invention, the detection step detects a pressure change during ascending or descending suction in the blood sample by the dispensing probe.

  The blood sample dispensing method of the present invention is a method for dispensing a blood sample separated into a plasma layer and a blood cell layer housed in a specimen container, and is a method for dispensing a blood sample comprising a pressure detection means. Using a probe, a detection step that detects pressure changes at multiple locations in the blood sample contained in the specimen container, and a boundary surface between the plasma layer and blood cell layer is detected based on the pressure change. And a calculating step for calculating the height of the blood cell layer and a dispensing step for sucking and collecting a blood cell sample based on the height information of the blood cell layer.

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

  Moreover, the blood sample dispensing method of the present invention is characterized in that, in the above invention, the detecting 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 dispensing method of the present invention, in the above invention, the dispensing step calculates the height of the blood cell layer in the computing step, and then places a dispensing probe in the blood sample in a predetermined amount of blood cell layer. The blood cell sample is lowered and collected by aspiration.

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

  In the blood sample dispensing 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 based on the detection result of the plasma liquid level. A plasma sample is dispensed, and then the blood cell sample is dispensed.

  The blood sample dispensing 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.

  Moreover, the blood sample analysis method of the present invention includes an analysis step of performing optical analysis after the reaction between the blood sample dispensed by the blood sample dispensing method described above and a reagent, To do.

  The dispensing apparatus of the present invention is a dispensing apparatus for dispensing a blood sample separated into a plasma layer and a blood cell layer contained in a specimen container, and means for detecting the pressure in the probe. And detecting means for detecting a pressure change at a plurality of locations having different heights in the blood sample contained in the specimen container, detecting a boundary surface between the plasma layer and the blood cell layer by the pressure change, and detecting the height of the blood cell layer. And a control means for controlling the suction of the blood cell sample based on the height of the blood cell layer.

  In the dispensing device according to the present invention, the detection means detects a change in pressure when the dispensing probe is raised or lowered in the blood sample.

  In the dispensing device according to the present invention, the detection means detects a pressure change at the time of ascending or descending suction of the blood sample by the dispensing probe.

  The blood sample type detection method of the present invention includes a detection step of detecting a pressure change at the time of sample suction or discharge of a dispensing probe having a pressure detection means in the blood sample, and a blood sample by the pressure change. And a determination step for determining the type of the method.

  In the present invention, a blood sample separated into a blood plasma layer and a blood cell layer contained in the specimen container is used to measure the height of the blood sample contained in the specimen container using a dispensing probe equipped with a pressure detection means. Pressure changes are detected at different locations, the boundary between the plasma layer and the blood cell layer is detected based on the pressure change, the height of the blood cell layer is calculated, and a blood cell sample is aspirated based on the height of the blood cell layer Since it can be collected, the blood cell sample can be dispensed easily and accurately.

(Embodiment 1)
A preferred embodiment 1 of a blood sample dispensing method of the present invention will be described 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. 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 specimen 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 second reagent reagent containers 3a arranged in the circumferential direction, and is rotated by a 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 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 2a and 3a and outputs it to the control unit 15 is installed. Yes.

  As shown in FIG. 1, the reaction table 4 has a plurality of reaction vessels 5 arranged in the circumferential direction, and is rotated in a direction indicated by an arrow by a driving means different from the driving means for driving the reagent tables 2 and 3. Then, the reaction vessel 5 is moved 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 the 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 the horizontal plane and dispense reagents to the arms 6a and 7a that are vertically moved up and down. Cleaning means (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 stored in the specimen container 9a in advance, 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 stirrer 13 and the second stirrer 14 stir the dispensed specimen and reagent with the stirrers 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 whole blood sample or other sample other than blood. And the control part 15 is connected with the boundary surface detection part 18 provided with 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 information of the blood cell layer is calculated. The blood cell layer height information is output to the control unit 15, and the control unit 15 drives and controls the probe driving unit 21 based on the blood cell layer height information to stop at the plasma-blood cell interface in the specimen 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 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. 4 is a flowchart showing the dispensing operation of the dispensing probe, and FIG. 5 is a flowchart (special dispensing mode) showing the dispensing operation of the blood sample dispensing method according to the first embodiment. FIG. 7 is a pressure change diagram when a 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). Note 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). If the specimen is a plasma sample or a blood cell sample 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, the control unit 15 confirms whether or not dispensing is a plasma sample (step S200). When the sample is a plasma sample (step S200: Yes), the dispensing probe 20b is moved above the opening of the sample container 9a at the sample aspirating position, and the dispensing probe 20b is lowered into the sample container 9a to obtain a liquid. The plasma liquid level is detected by the surface detection unit 31 (step S201). After detecting the plasma level, the dispensing probe 20b is lowered to dispense a plasma sample (step S202), the plasma sample is aspirated (step S203), and the aspirated plasma sample is discharged into the reaction vessel 5 (step S202). Step S204). Thereafter, the control unit 15 confirms whether or not to dispense a blood cell sample (step S205). Even in the case where the plasma sample is not dispensed in step S200 (step S200: No), it is confirmed whether or not the blood cell sample is dispensed in the same manner.

  When dispensing a blood cell sample (step S205: Yes), the sample is sucked by the dispensing pump 23 while lowering the dispensing probe 20b into the specimen container 9a again, and the pressure at the time of suction is measured by the pressure sensor 25 and the processing unit. It is detected by 18a and the detection unit 18b (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 descent and suction of the dispensing probe 20b are stopped. In 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 plasma fluid is detected by detecting the pressure change. It is also possible to detect the surface.

  The detection unit 18b detects the plasma-blood cell interface based on the detected pressure change, and calculates the blood cell layer height information by the calculation unit 18c together with the size information of the sample container (step S207). After calculating the height of the blood cell layer, a predetermined amount of dispensing probe is lowered (step S208), and a blood cell sample is aspirated (step S209). The sucked blood cell sample is discharged into another reaction container 5 (step S210). Dispensing probe 20b that has been dispensed is washed in a dispensing probe washing tank (step S211), and the dispensed plasma sample and blood cell sample are analyzed. Even in the case where it is determined in step S205 that the blood cell sample is not dispensed (step S205: No), washing is similarly performed to dispense the next specimen.

  Next, it demonstrates further using the operation | movement figure (special dispensing mode) of Embodiment 1 of this invention of FIG. In FIG. 7A, the dispensing probe 20b is lowered into the specimen container 9a containing the blood sample separated into a plasma layer and a blood cell layer, 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 pressure change when the sample is sucked by the dispensing pump 23 while the dispensing probe 20b is lowered may be detected, and the liquid level may be detected by the pressure change at the air-plasma layer interface. Although the descent of the dispensing probe 20b is stopped after the plasma liquid level is detected by any of the above-described methods, as shown in FIG. The plasma sample is aspirated by dropping a predetermined amount. 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 the plasma sample and the second reagent, stirring is performed by the first or second stirring device 13, 14, and then the analysis of the crystal sample in the reaction vessel 5 is performed by the analysis optical system 11.

  On the other hand, in order to dispense the blood cell sample from the specimen container 9a containing the blood sample separated into a plasma layer and a blood cell layer, as shown in FIG. 7D, the dispensing probe 20b is lowered in the specimen container 9a. While detecting a change in pressure when the sample is aspirated by the dispensing pump 23, the plasma-blood cell interface is detected, and the height of the blood cell layer is calculated together with the size information of the specimen container. While 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 predetermined amount as shown in FIG. 7 (e) in order to dispense a desired blood cell sample. The For example, HbA1c, which is a diagnostic marker for diabetes, is analyzed from the blood cell sample. The blood cells in the blood cell layer have different specific gravity depending on their age. It will be different. Therefore, the aspiration position of the blood cell sample is very important and is usually set to be collected from 20 to 80% of the blood cell layer height, preferably 50% which is the median value, but changes depending on the blood sample It is also possible to do. After the dispensing probe 20b is lowered by a set amount and the blood cell sample is sucked, the dispensing probe 20b is transported to discharge the sample into the reaction container 5 held in the reaction table 4, and as shown in FIG. 7 (f). The sample is discharged into a reaction container 5 different from the reaction container 5 into which the plasma sample has been dispensed. 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 dispensing method according to Embodiment 1 of the present invention, after the plasma-blood cell interface is detected by descending suction in the blood sample of the dispensing probe 20b, the blood is sucked into the dispensing probe 20b for detecting the boundary surface. The blood cell sample is continuously aspirated without discharging the sample. In the dispensing probe 20b, the plasma and blood cells of the aspirated blood sample are separated into layers, so that a predetermined amount of blood cell sample can be put into the reaction vessel 5 without sucking the plasma by aspirating the extra blood cell sample. 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.

  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. Further, as a modified example of the first embodiment, the plasma-blood cell interface is detected by lowering and sucking the dispensing probe 20b using the pressure sensor 25 provided for sample dispensing in the sample dispensing apparatus 20. The method of detecting a pressure change by raising or lowering a dispensing probe 20b equipped with a simple pressure sensor in a blood sample to detect a pressure change at a plasma-blood cell interface or an air-plasma interface is modified. Illustrated as an example.

(Embodiment 2)
Next, Embodiment 2 in which the sample sucked into the dispensing probe 20b after the detection of the plasma-blood cell interface is discarded and the dispensing probe 20b is washed will be described. In the second embodiment, the aspirated sample in the dispensing probe 20b is discarded before the blood cell sample is dispensed, and the dispensing probe 20b is washed, so that it is possible to completely prevent plasma from being mixed into the blood cell sample. In addition, since it is not necessary to suck an excessive amount of sample, it is possible to deal with a very small amount of sample.

  FIG. 8 is a flowchart (special dispensing mode) illustrating the dispensing operation of the blood sample dispensing method according to the second embodiment, and FIG. 9 is an operation diagram of the blood sample dispensing method according to the second embodiment. .

  As shown in FIG. 8, the special dispensing mode of the second embodiment is performed in steps S300 to S304, which is a plasma sample dispensing process, and steps S305 to 307, which are a plasma-blood cell interface detection process. This is the same as steps S200 to S207 in the first embodiment. In Embodiment 2, after calculating the height of the blood cell layer, the dispensing probe 20b is once pulled up from the blood sample (step S308), and the sample aspirated into the dispensing probe 20b is discarded. Is transported to a dispensing probe cleaning tank (not shown) disposed at an intermediate position between the specimen container transfer mechanism 8 and the reaction table 4. The sample in the dispensing probe 20b is discarded in the dispensing probe washing tank, and the dispensing probe 20b is washed (step S309). Thereafter, the dispensing probe 20b is conveyed again to the specimen dispensing position for blood cell sample dispensing, and descends from the height of the blood cell layer to the blood cell sample suction position (step S310). Steps S311 to S313, which are subsequent steps of sucking and discharging the blood cell sample and cleaning the dispensing probe 20b, are the same as steps S209 to 211 in the first embodiment.

  Next, the operation of the blood sample dispensing method of Embodiment 2 in FIG. 9 will be further described. In FIG. 9A, the dispensing probe 20b is lowered into the specimen container 9a containing a blood sample separated into a plasma layer and a blood cell layer, 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 liquid level may be detected by lowering the suction of the dispensing probe 20b and changing the pressure at the air-plasma layer interface. After detecting the plasma level, the descent of the dispensing probe 20b is stopped, but as shown in FIG. 9B, a predetermined amount of the dispensing probe 20b is lowered to remove the plasma sample in order to aspirate the sample reliably. 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.

  On the other hand, in order to dispense the blood cell sample from the specimen container 9a containing the blood sample separated into the plasma layer and the blood cell layer, the dispensing probe 20b is lowered in the specimen container 9a as shown in FIG. 9 (d). The blood pressure is detected and the plasma-blood cell interface is detected by detecting the pressure change, and the height information of the blood cell layer is obtained together with the size information of the specimen container. The suction drop of the dispensing probe 20b is stopped after the detection of the plasma-blood cell interface, but in the second embodiment, as shown in FIG. 9 (e), the dispensing probe 20b is once pulled up from the sample container 9a, The sample is transported to a dispensing probe cleaning tank disposed at an intermediate position between the sample container transfer mechanism 8 and the reaction table 4. Thereafter, as shown in FIG. 9 (f), the dispensing probe 20b discards the sample in the dispensing probe 20b in the dispensing probe washing tank, and the dispensing probe 20b is washed. After the washing, as shown in FIG. 9 (g), the dispensing probe 20b is lowered from the height of the blood cell layer to the blood cell sample suction position, and the blood cell sample is sucked. After the blood cell sample is aspirated, the dispensing probe 20b is transported to discharge the sample to the reaction container 5 held in the reaction table 4, and as shown in FIG. 9 (h), the reaction container into which the plasma sample has been dispensed Discharges the sample into another reaction vessel 5. 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.

(Embodiment 3)
In the above, the blood sample dispensing method has been described. However, by detecting the pressure in the dispensing probe used in the present invention, the pressure change during the blood sample suction or discharge of the dispensing probe is detected. Thus, the type and concentration distribution of the blood sample can also be detected.

  FIG. 10 is a diagram illustrating changes in pressure during the suction and discharge of a plasma sample by the dispensing probe 20b, and FIG. 11 is a diagram illustrating changes in pressure during the suction and discharge of a blood cell sample by the same dispensing probe 20b. . 10 and 11, the sample is sucked from t1 to t2, and the sample sucked from t3 to t4 is discharged. Even when driven under the same driving conditions, the pressure change during the blood plasma sample suction is Δv1, whereas it is as large as Δv3 during the blood cell sample suction. Although not shown here, the pressure change when the whole blood sample is aspirated is a numerical value between Δv1 and Δv3. Therefore, it is possible to detect whether a blood sample is whole blood, plasma, or blood cell by setting a threshold value including a numerical value of each pressure change. In addition, since the same difference in pressure change is recognized between the blood samples even when the samples are discharged, it is possible to detect the type of the blood sample based on the pressure value when discharging the aspirated sample. Further, in the above, the type of the blood sample is determined by the pressure change at the time of suction or discharge of the blood sample, but the blood sample is also determined from the pressure change when the probe equipped with the pressure sensor is moved in the blood sample. It is possible to discriminate between different types.

  Furthermore, the blood sample is sedimented over time when the blood sample is left after being collected from the subject. FIG. 12 shows a state in which blood cell components of the specimen S (blood sample) collected in the specimen container 9a are sedimented. Since the specific gravity of the blood cell component is larger than that of the plasma component in the sample S, as shown in FIG. 12, even when the blood cell component is evenly distributed in the plasma at the time of collection, the blood cell component settles with time. However, the upper layer part of the sample S has a thin blood cell component, and the lower layer part of the sample S becomes thicker.

  FIG. 13 is a schematic diagram showing the change over time of the reference concentration R1 of the blood cell component resulting from such sedimentation of the blood cell component in the specimen container 9a. In the specimen S (whole blood sample), as shown in FIG. 12, blood cell components are precipitated with time. For this reason, in the blood cell component, a region having a concentration R0 lower than the reference concentration R1 expands from the upper layer to the lower layer with time, and a region having a concentration R2 higher than the reference concentration R1 expands from the lower layer to the upper layer. It is possible to detect the concentration distribution of the blood sample by inserting the dispensing probe 20b into the blood sample having such a concentration distribution and detecting the pressure change at the time of ascending or descending. FIG. 14 is a diagram illustrating a pressure change when the blood sample having a concentration distribution by the dispensing probe is drawn down. t1 to t2 are when the sample in the region of the reference density R0 shown in FIG. 13 is sucked, t2 to t3 are when the sample of the region of the reference density R1 is sucked, and t3 to t4 are the samples of the sample of the region of the reference density R2. At the time of suction. Since each region has different suction pressure values, it is possible to detect the concentration distribution of the blood sample. Therefore, for example, when it is desired to suck and collect a whole blood sample having the reference concentration R1, a change in pressure is detected when the dispensing probe is inserted into the specimen, and ascending or descending suction is performed, and the reference concentration R1 is detected based on the pressure change. Is determined, and the whole blood sample having the reference concentration R1 can be dispensed by setting to dispense from the region. Alternatively, it is also possible to determine the concentration distribution of the blood sample by detecting the pressure change when the probe provided with the pressure sensor is raised or lowered in the sample having the concentration change.

  In the description of the embodiment of the present invention, the automatic analyzer 1 has been described with respect to the case where two reagent dispensing devices are provided. However, the number of reagent dispensing devices may be one. Moreover, the automatic analyzer using the dispensing method 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. It is a figure showing the pressure change at the time of aspiration and discharge of a plasma sample. It is a figure showing the pressure change at the time of aspiration and discharge of a blood cell sample. It is a schematic diagram which shows a mode that the blood cell component contained in the sample (blood) extract | collected in the sample container precipitates. It is a schematic diagram which shows the time change of the reference | standard density | concentration resulting from sedimentation of the blood cell component contained in a test substance (blood). It is a figure showing the pressure change at the time of aspiration of the blood sample which has concentration distribution.

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)

A detecting step for detecting pressure changes at a plurality of different heights in the blood sample contained in the specimen container using a means for detecting the pressure in the probe;
A determination step of determining a concentration distribution of the blood sample based on the pressure change;
A blood sample detection method comprising:   The blood sample detection method according to claim 1, wherein the determining step determines a boundary surface of the blood sample.   The blood sample detection method according to claim 1 or 2, wherein the detection step detects a pressure change when the probe is raised or lowered in the blood sample.   The blood sample detection method according to any one of claims 1 to 3, wherein the detecting step detects a pressure change during ascending or descending suction in the blood sample by the dispensing probe. . A method for dispensing a blood sample separated into a plasma layer and a blood cell layer contained in a specimen container,
A detection step for detecting a pressure change at a plurality of different heights in a blood sample contained in a specimen container using a dispensing probe of a dispensing apparatus having a pressure detecting means;
An operation step of detecting a boundary surface between a blood plasma layer and a blood cell layer based on the pressure change, and calculating a height of the blood cell layer;
A dispensing step of aspirating and collecting a blood cell sample based on the blood cell layer height information;
A blood sample dispensing method comprising:   6. The blood sample dispensing method according to claim 5, wherein the detecting step detects a change in pressure when the probe is raised or lowered in the blood sample.   The blood sample dispensing method according to claim 5 or 6, 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. Item 8. A blood sample dispensing method according to any one of Items 5 to 7.   9. The blood sample dispensing method according to claim 7, wherein the dispensing step is performed after the dispensing probe is pulled up from the blood sample and the suction sample is discharged and washed. The detecting step detects a plasma liquid level by the dispensing probe,
The dispensing step includes dispensing a plasma sample based on the detection result of the plasma liquid level, and then dispensing the blood cell sample. The blood sample dispensing method described.   The blood sample dispensing method according to claim 10, wherein the detecting step detects a liquid level by a capacitance change by a capacitance type liquid level detection mechanism.   A blood sample analysis method comprising an analysis step of performing optical analysis after the reaction between the blood sample dispensed by the blood sample dispensing method according to any one of claims 5 to 11 and a reagent. . A dispensing device for dispensing a blood sample separated into a plasma layer and a blood cell layer contained in a specimen container,
Detecting means for detecting a pressure change at a plurality of positions having different heights in the blood sample contained in the specimen container, using means for detecting the pressure in the probe;
Calculating means for detecting a boundary surface between a blood plasma layer and a blood cell layer based on the pressure change, and calculating a height of the blood cell layer;
Control means for controlling aspiration of a blood cell sample based on the height of the blood cell layer;
A dispensing device characterized by comprising:   14. The dispensing device according to claim 13, wherein the detecting means detects a pressure change when the dispensing probe is raised or lowered in the blood sample.   15. The dispensing device according to claim 13 or 14, wherein the detecting means detects a pressure change at the time of ascending or descending suction of the blood sample by the dispensing probe. A blood sample type detection method comprising:
A detection step of detecting a pressure change at the time of sample suction or discharge of a dispensing probe provided with a pressure detection means in the blood sample;
A determination step of determining the type of blood sample from the pressure change;
A blood sample type detection method comprising:

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