JP2012037478A - Analysis apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To monitor a specimen is surely discharged to a measuring cell.SOLUTION: An analysis apparatus includes: a specimen discharge means for discharging a blood 24 that is a specimen into a measuring cell 41; an examination sample production means for producing an examination sample by discharging a hemolyzing agent into the measuring cell 41; a detection means for detecting absorbance information of a liquid in the measuring cell 41; a creation means 14 for creating monitor target information on the basis of the absorbance information prior to hemolyzing agent discharge and the absorbance information after hemolyzing agent discharge, time-sequentially detected by the detection means; and a determination means 15 for determining whether the quantity of discharged specimen is suitable while using the created monitor target information and a predetermined threshold value.

Description

  The present invention relates to an analyzer capable of monitoring a discharge amount, and more particularly to an analyzer that measures an immune reaction and a blood cell count from whole blood.

  Conventionally, as a method for detecting whether or not a specimen is properly discharged into a measurement cell, one using a pressure change (see Patent Document 1) or one using bubble detection (see Patent Document 2) is known. Yes.

  Further, in the apparatus having a control unit for discharging the remaining specimen to the sub reaction container, the sub reaction container is provided with a photometry unit for measuring the absorbance by irradiating the measurement light, and the absorbance measured by the photometry unit is less than a predetermined value. There is known an apparatus that determines that a prescribed amount of specimen has not been discharged into the main reaction container if there is any (Patent Document 3).

  In addition, the intensity of light transmitted through the dye solution dispensed into the reaction container is measured, the evaluation absorbance is obtained for each set dispensing amount, and the ratio of the evaluated absorbance to the reference absorbance measured in advance is set to the set dispensing amount. There is also known an apparatus that calculates the deviation from the difference between the maximum ratio and the minimum ratio and the average ratio and determines whether the dispensing accuracy is within an allowable range (Patent Document 4).

  However, those using the above pressure change or those using bubble detection require a dedicated sensor such as a pressure detection sensor or bubble detection sensor, which increases the configuration and leads to high costs. It was.

  The technique described in Patent Document 3 for detecting whether or not the specimen is properly discharged into the main reaction container by measuring the absorbance in the sub-reaction container from which the remaining specimen has been discharged is an estimation technique. Just because the remaining considerable amount of specimen is ejected does not necessarily mean that the specimen has been properly ejected into the main reaction container, but it is a detection technique that has difficulty in certainty.

  Further, the method described in Patent Document 4 for obtaining the ratio of the evaluation absorbance to the reference absorbance measured in advance for each set dispensing degree requires measurement and calculation for each set dispensing degree. There is a problem that it takes a lot.

Japanese Patent No. 4275608 Japanese Patent No. 3043510 JP 2009-168738 A JP 2009-281914 A

  The present invention has been made in view of the current state of the analyzer as described above, and its purpose is to reliably monitor that the specimen has been discharged into the measurement cell, and to save a lot of man-hours and time for measurement. It is to provide an analysis device that does not need to be provided.

  The analyzer according to the present invention includes a sample discharge means for discharging blood as a sample into a measurement cell, a test sample preparation means for preparing a test sample by discharging a hemolytic agent into the measurement cell, and the inside of the measurement cell. Detecting means for detecting the absorbance information of the liquid, and creating means for creating monitoring target information based on the absorbance information before discharge of the hemolytic agent and the absorbance information after discharge of the hemolytic agent detected in time series by the detection means And determination means for determining the suitability of the ejection amount of the specimen using the created monitoring target information and a predetermined threshold value.

  The analyzer according to the present invention is further characterized by further comprising correction means for correcting at least one of the monitoring target information or the predetermined threshold value based on a hemoglobin concentration or a hematocrit value.

  In the analyzer according to the present invention, the detection means detects the absorbance information in a sampling period in consideration of the characteristics of the specimen.

  In the analyzer according to the present invention, the detection means detects absorbance information using light having a light wavelength of 650 nm or more.

  The analyzer according to the present invention comprises a temperature sensor, and temperature alarm control means for outputting an alarm according to the allowable temperature of the reagent contained in the measurement cell and the temperature obtained by the temperature sensor.

  The analyzer according to the present invention includes a temperature control mechanism that controls the apparatus temperature in accordance with the allowable temperature of the reagent contained in the measurement cell.

  The analyzer according to the present invention detects the absorbance information of the liquid in the measurement cell, and monitors the monitoring target information based on the absorbance information before the hemolytic agent discharge detected in time series and the absorbance information after the hemolytic agent discharge. Since the prepared monitoring target information and the predetermined threshold value are used to determine the appropriateness of the discharge amount of the specimen, the discharge to the measurement cell can be reliably monitored, and until a predetermined time after the hemolytic agent discharge Therefore, there is an advantage that a lot of man-hours and time are not required for the measurement.

  The apparatus according to the present invention further includes a correction unit that corrects at least one of the monitoring target information or the predetermined threshold based on the hemoglobin concentration or the hematocrit value, so that the discharge amount can be appropriately monitored. is there.

  According to the analyzer of the present invention, since the detection means detects the absorbance information during the sampling period in consideration of the characteristics of the specimen, it is possible to monitor the discharge amount appropriately without waste.

  According to the analyzer of the present invention, since the detection means detects the absorbance information using light having a light wavelength of 650 nm or more, it is possible to appropriately monitor the discharge amount in accordance with the blood as the sample. .

  According to the analyzer of the present invention, the temperature sensor, the alarm output control means for outputting an alarm according to the allowable temperature of the reagent contained in the measurement cell and the temperature obtained by the temperature sensor, are provided. It can be notified that the monitoring state is inappropriate.

  The analyzer according to the present invention includes a temperature control mechanism that controls the apparatus temperature in accordance with the allowable temperature of the reagent contained in the measurement cell, so that the discharge amount can be monitored in an appropriate state at the allowable temperature of the reagent. is there.

The block diagram of embodiment of the analyzer which concerns on this invention. The flowchart for demonstrating operation | movement of embodiment of the analyzer which concerns on this invention. The flowchart for demonstrating operation | movement of embodiment of the analyzer which concerns on this invention. The figure which shows the absorbance change curve by the monitoring result by embodiment of the analyzer which concerns on this invention. The figure which shows the light-absorbency change curve after the sample discharge and hemolytic agent discharge by an individual difference. The figure explaining the change in a measurement cell when a sample is discharged appropriately. The figure explaining the change in a measurement cell when a sample is not discharged appropriately.

  Hereinafter, embodiments of an analyzer according to the present invention will be described with reference to the accompanying drawings. In each figure, the same components are denoted by the same reference numerals, and redundant description is omitted. FIG. 1 is a block diagram of an analyzer according to the embodiment. This analyzer can measure, for example, CRP (C-Reactive Protein).

  The measuring device includes a specimen suction / discharge section 20 that sucks and discharges blood (whole blood) as a specimen, a hemolysis agent suction / discharge section 30 that sucks and discharges a hemolyzing agent, a measurement cell 41, and a measurement cell 41. An arithmetic processing unit 10 including a measurement cell holding mechanism 40 and a CPU that stirs a liquid is a main component.

  The sample aspirating / discharging unit 20 operates under the control of the arithmetic processing unit 10. The sample aspirating / discharging unit 20 includes a motor or the like as an actuator for aspirating / discharging, and is coupled with a nozzle 21 for aspirating blood, and the nozzle 21 extends to the outside of the housing of the measuring instrument. Further, the sample aspirating / discharging unit 20 is coupled with a nozzle 22 for discharging the sample to the measurement cell 41 held at the holding position S of the measurement cell holding mechanism 40. The sample aspirating / discharging unit 20 is provided with driving means for moving the nozzle 22 up and down. The nozzle 22 is inserted into and removed from the measurement cell 41 by this driving means. The nozzle 21 may be driven without being provided with the nozzle 22 and may be inserted into and removed from the measurement cell 41.

  The hemolytic agent suction / discharge unit 30 operates under the control of the arithmetic processing unit 10. A hemolytic agent tank 31 is attached to the hemolytic agent suction / discharge unit 30, and a nozzle 32 extends into the hemolytic agent tank 31. The hemolytic agent suction / discharge unit 30 includes a nozzle 33 for discharging the specimen to the measurement cell 41 held at the holding position S of the measurement cell holding mechanism 40. The hemolytic agent suction / discharge part 30 is provided with a driving means for moving the nozzle 33 up and down. With this driving means, the nozzle 33 is inserted into and removed from the measurement cell 41. In addition, the nozzle 32 may be driven without being provided with the nozzle 33 and may be inserted into and removed from the measurement cell 41.

  The measurement cell holding mechanism 40 rotates the gripping part 42 that detachably grips the measurement cell 41 in which a measurement reagent (here, a reagent for CRP measurement) is preliminarily sealed, and the gripping part 42 of the arithmetic processing unit 10. And a stirring mechanism 43 that stirs by a motion such as toppling. The operator can set the measurement cell 41 in which the reagent is sealed to the gripping portion 42 of the measurement cell holding mechanism 40 to be gripped, and can remove and discard it after the measurement.

  An operation unit 51, a display unit 52, a temperature sensor 53, a light emitting element 54 and a light receiving element 55 are connected to the arithmetic processing unit 10. The operation unit 51 includes a start switch, a mode selection key, and the like, and can give a start instruction and a mode selection instruction to the arithmetic processing unit 10.

  The display unit 52 is configured by an LED or LCD that displays information, and is configured to display measurement results, alarms, and the like. The arithmetic processing unit 10 may be configured such that a measurement result or the like can be printed out by connecting a printer built in or external to the measuring instrument.

  The temperature sensor 53 is provided at a position for detecting the temperature of the area in the measuring instrument, particularly in the area close to the holding position S of the measurement cell holding mechanism 40. The temperature data measured by the temperature sensor 53 is taken into the arithmetic processing unit 10 and digitized.

  The light emitting element 54 and the light receiving element 55 are arranged at positions facing each other across the measurement cell 41 held at the holding position S of the measurement cell holding mechanism 40. The measurement cell 41 is a transparent or translucent resin container and transmits light emitted from the light emitting element 54. The transmitted light is received by the light receiving element 55, photoelectrically converted, and sent to the arithmetic processing unit 10 as a voltage. Here, the wavelength of the light emitted from the light emitting element 54 is required to be out of the wavelength of the blood as the specimen (red region), and a suitable result is obtained when light having a light wavelength of 650 nm or more is used. Obtainable. As shown in FIGS. 6 and 7, the light emitting element 54 is composed of two LEDs 54A and 54B, and the light receiving element 55 is also composed of two photodiodes 55A and 55B, which are used for original CRP measurement. However, a pair of an LED 54B and a photodiode 55B provided on the lower side is used in the analyzer. Therefore, there is an advantage that it is not necessary to provide a new sensor for monitoring the discharge amount. The arithmetic processing unit 10 uses the voltage output from the photodiode 55B after A / D conversion and sampling.

  The arithmetic processing unit 10 includes a sample control unit 11, a test sample preparation unit 12, a detection processing unit 13, a preparation unit 14, a determination unit 15, a notification output control unit 16, a temperature alarm control unit 17, and a measurement processing unit 18. ing. The sample control means 11 controls the sample aspirating / discharging unit 20 to aspirate and hold the blood 24, which is the sample contained in the test tube (or capillary) 23, and then discharges it to the measurement cell 41. It is.

  The test sample preparation means 12 controls the hemolytic agent suction / discharge unit 30 to discharge the hemolytic agent into the measurement cell 41 to prepare a test sample. The detection processing means 13 controls the light emitting element 54 to emit light, obtains absorbance information from the light receiving element 55, and detects the absorbance information of the liquid in the measurement cell 41. The creating unit 14 creates monitoring target information based on the absorbance information before the hemolytic agent discharge detected by the detection processing unit 13 in time series and the absorbance information after the hemolytic agent discharge. The determination unit 15 determines the suitability of the ejection amount of the sample using the created monitoring target information and a predetermined threshold value. The notification output control unit 16 displays the determination result by the determination unit 15 on the display unit 52.

  Further, the temperature alarm control means 17 obtains temperature information from the temperature sensor 53 and responds to the allowable temperature of the reagent (here, CRP measurement reagent) contained in the measurement cell 41 and the temperature information obtained by the temperature sensor 53. For example, an alarm is output to the display means 52. The alarm may be output by voice by providing a speaker, or may be output by light such as an LED.

  The measurement processing means 18 performs the measurement by implementing the original function of this measuring instrument on the test sample prepared in the measurement cell 41 by the test sample preparation means 12. Here, the CRP measurement is performed. Is what you do. The measurement processing means 18 performs measurement processing using two LEDs 54A and 54B as the light emitting element 54 and two photodiodes 55A and 55B as the light receiving element 55.

  In the measuring instrument configured as described above, each means is realized by the arithmetic processing unit 10 executing a program corresponding to the flowcharts shown in FIGS. 2 and 3. The operation of the measuring device will be described below based on this flowchart. The operation is started by holding the measurement cell 41 at the holding position S of the measurement cell holding mechanism 40 and operating the start switch. When the operator holds a test tube (or capillary) 23 containing blood 24 as a sample directly under the nozzle 22, the sample suction / discharge unit 20 is operated under the control of the sample control means 11, and the nozzle 21 is lowered. The tip is immersed in the blood 24, and a predetermined amount of sample is aspirated (S11). When the suction of the predetermined amount of sample is completed, the sample suction / discharge unit 20 returns the nozzle 21 to the home position.

  Next, the test sample preparation means 12 controls the hemolytic agent suction / discharge unit 30 to suck a predetermined amount of hemolytic agent from the hemolytic agent tank 31 by the nozzle 32 (S12). When the suction of the predetermined amount of the hemolytic agent is completed, the detection processing unit 13 turns on the LED 54B which is the light emitting unit 54 (S13). Further, the detection processing means 13 obtains the output of the photodiode 55B as the light receiving means 55 and starts sampling the absorbance (light receiving voltage) (S14).

  The test sample preparation means 12 monitors the elapse of the predetermined time t1 seconds from the lighting of the LED 54B (S15). When the predetermined time t1 seconds elapses, the test sample preparation means 12 controls the sample suction / discharge unit 20 to transfer the sample from the nozzle 22 to the measurement cell 41. Further, the hemolytic agent suction / discharge unit 30 is controlled to discharge the hemolytic agent from the nozzle 33 into the measurement cell 41 (S17). The predetermined time t1 seconds can be set to the time from when the LED 54B is lit until it is stabilized.

  Next, the detection processing means 13 detects whether or not the absorbance information for a predetermined number of times has been collected based on the sampling result (S18). Here, the meaning of collecting absorbance information for a predetermined number of times is as follows. The change in absorbance (light reception voltage) obtained from the output of the photodiode 55B, which is the light receiving means 55, is as shown in FIG. 4, for example, and when the hemolytic agent is discharged at time T1 following the sample discharge, Since the color of blood is diluted with the hemolytic agent, the absorbance of the solution in the measurement cell 41 gradually decreases after reaching the maximum value (convex peak downward). The light reception voltage draws an absorbance change curve Lg that is convex downward.

  When this absorbance change curve Lg is obtained from a plurality of subjects, it depends on the hemoglobin concentration and hematocrit value (%) in the blood of the individual, and as shown in FIG. It can be seen that the width W and the depth D in FIG. Here, FIG. 5A shows, for example, anemia data in which both the width W and the depth D are small, and FIG. 5B shows data in which the hemoglobin concentration is high, and both the width W and the depth D. large. As can be seen from FIG. 5A, when sampling is performed for a long time, sampling is performed even if the pulse-shaped portion protruding downward is exceeded, and meaningless sampling is performed. Further, according to FIGS. 5A and 5B, a certain period from the time T1 of discharging the hemolytic agent is considered to be an effective period for sampling. Therefore, the detection means constituted by the detection processing means 13, the light emitting element 54, and the light receiving element 55 detects the absorbance information in a predetermined sampling period in consideration of the characteristics of the specimen. In this embodiment, four samplings are performed with a sampling period of 100 msec. When sampling is performed in a range of approximately 300 msec to 500 msec, the voltage is reduced by more than ½ from the initial voltage at which the LED 54B is lit regardless of the characteristics of the specimen, and necessary and sufficient data can be obtained. During this time, the number of samplings can be changed according to the sampling period. It is also possible to separately measure the hemoglobin concentration and hematocrit value (%) of the subject and automatically correct the sampling period and the number of samplings based on the measured values.

  When it is detected that the predetermined number of data has been obtained in step S18 as described above, the detection processing means 13 creates monitoring target information by using the absorbance before the sample discharge and the absorbance after the sample discharge ( S18).

  A specific example of step S18 will be described. In FIG. 4, the sampling points are indicated by black dots. The time T0 in FIG. 4 is the lighting time of the LED 54B. From this time, the sampling point values VS0, VS1, and VS2 are obtained three times, and the average value Vave is calculated. A value (= 1) obtained by dividing the average value Vave by the average value Vave is defined as V1.

  Sampling values VS6, VS7, VS8, and VS9 of 0.6 s, 0.7 s, 0.8 s, and 0.9 s are obtained from time T0, and values V2, V3, V4, and V5 obtained by dividing the sampling values by the average value Vave are obtained. This value (V1, V2, V3, V4, V5) is used as monitoring target information, and the propriety of the discharge amount is determined using this monitoring target information (S20). At this time, absorbance sampling is terminated (S21). Sampling may be performed, but necessary and sufficient data has already been obtained.

  In this embodiment, the values V2, V3, V4, and V5 are subtracted from V1, respectively, and (V1-V2), (V1-V3), (V1-V4), and (V1-V5) are calculated, and the sum of these values is calculated. The value SUM = {(V1−V2) + (V1−V3) + (V1−V4) + (V1−V5)}} is obtained, and compared with the threshold value TH, if SUM ≧ TH, the discharge amount is appropriate. Suppose there is.

  Furthermore, an average of (V1-V2), (V1-V3), (V1-V4), and (V1-V5) may be obtained and compared with a threshold different from the above.

  In this embodiment, the difference from V1 is used, but it may be divided by V1. A value obtained by processing (adding / subtracting / dividing / dividing) V1 with an appropriate coefficient may be used. A determination may be made by obtaining the sum or average value of the values as described above and comparing with a threshold different from the above. Alternatively, the hemoglobin concentration and hematocrit value (%) of the subject may be measured separately, and the threshold value may be corrected manually or automatically based on the measured value.

  After determining whether or not the discharge amount is appropriate in step S20 as described above, the process proceeds from step S21 to step S22 to detect whether or not the discharge amount is appropriate (S22). The test sample preparation means 12 further prepares a test sample by discharging a hemolytic agent or stirring by the stirring mechanism 43, and when the sample is completed in the measurement cell 41, the measurement processing means 18 performs measurement (here, CRP measurement). Is executed (S23), and the inspection result is output to the display means 52 or the like (S24).

  On the other hand, if the discharge amount is determined to be inappropriate in step S22, a message indicating that the discharge amount is inappropriate is output to the display means 52, etc., and a message suggesting that the sample (measurement cell 41) being produced is discarded Is output to the display means 52 and the notification output control means 16 executes the process and waits for operator intervention.

  FIG. 4 shows an absorbance change curve Lg when the specimen is properly ejected and an absorbance change curve Ln when the specimen is not properly ejected. In the absorbance change curve Lg, the blood 24 is discharged from the nozzle 22 to the CRP measurement reagent 60 as shown in FIG. 6A, so the hemolyzed specimen 63 from which the hemolytic agent has been discharged is shown in FIG. 6B. As shown in FIG. 4, the hemoglobin dye exhibits a pink color and the absorbance increases (voltage decreases) as shown in FIG.

  On the other hand, in the absorbance change curve Ln, as shown in FIG. 7A, the blood 24 is not discharged from the nozzle 22 to the CRP measurement reagent 60 as indicated by the broken line, so that the hemolytic agent is discharged. Then, there is no specimen in the measurement cell 41, and the color is almost transparent as shown in FIG. 7B, and the absorbance is lowered as shown in FIG.

  Whether it changes as in the absorbance change curve Lg or in the change in absorbance change curve Ln, the monitoring target information is obtained as described above and compared with a predetermined threshold value. Can be accurately determined.

  During the above analysis and also during the measurement processing by the measurement processing means 18, the temperature alarm control means 17 obtains temperature information from the temperature sensor 53 and uses the allowable temperature of the reagent contained in the measurement cell 41 and the temperature sensor 53. An alarm is output from the display means 52 or the like according to the obtained temperature information. For example, when the allowable range is 30 ° C. to 15 ° C., an alarm is output when the temperature exceeds 35 ° C. or when the temperature falls below 10 ° C.

  The temperature alarm control means 17 may not be provided, and a temperature control mechanism for controlling the apparatus temperature according to the allowable temperature of the reagent may be provided. For example, a temperature control mechanism using a Peltier element may be provided, and the temperature control may be performed so that the temperature is within the allowable range according to the output of the temperature sensor 53.

DESCRIPTION OF SYMBOLS 10 Arithmetic processing part 11 Specimen control means 12 Test sample preparation means 13 Detection processing means 14 Preparation means 15 Determination means 16 Notification output control means 17 Temperature alarm control means 18 Measurement processing means 20 Specimen aspiration / discharge part 30 Agent tank 40 Measurement cell holding mechanism 41 Measurement cell

Claims (6)

A sample discharge means for discharging blood as a sample into the measurement cell;
A test sample preparation means for preparing a test sample by discharging a hemolytic agent into the measurement cell;
Detection means for detecting absorbance information of the liquid in the measurement cell;
Creating means for creating monitoring target information based on the absorbance information before the hemolytic agent discharge detected in time series by the detection means and the absorbance information after the hemolytic agent discharge;
An analysis apparatus comprising: determination means for determining appropriateness of the ejection amount of the specimen using the created monitoring target information and a predetermined threshold value.   The analyzer according to claim 1, further comprising a correction unit that corrects at least one of the monitoring target information or the predetermined threshold based on a hemoglobin concentration or a hematocrit value.   The analyzer according to claim 2, wherein the detection unit detects the absorbance information in a sampling period in consideration of the characteristics of the specimen.   The analyzer according to claim 1 or 3, wherein the detection means detects absorbance information using light having a light wavelength of 650 nm or more. A temperature sensor;
The temperature alarm control means which outputs an alarm according to the allowable temperature of the reagent contained in the measurement cell and the temperature information obtained by the temperature sensor is provided. Analysis equipment.   The analyzer according to any one of claims 1 to 4, further comprising a temperature control mechanism that controls the apparatus temperature in accordance with an allowable temperature of a reagent included in the measurement cell.