JP2014092427A - Automatic analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatic analyzer that can reduce errors caused by temperature variation of segmented air and can improve accuracy of the sample dispensation amount.SOLUTION: A tubular probe 27 sucks a predetermined amount of sample. A pipetter for sample sucks the sample into the probe. In a state in which the inside of the tubular probe is filled with liquid 37X as a pressure transmission medium, a predetermined amount of air is sucked from the tip of the probe. Then, the predetermined amount of sample 25X is sucked from the tip of the probe, thereby arranging the predetermined amount of segmented air AR between the sample and the pressure transmission medium. A heater 38 is disposed in the probe so as to heat the position of the segmented air when the total amount of sample is sucked in a state in which the segmented air is caught.

Description

  The present invention relates to an automatic analyzer used for analysis such as a biochemical test and an immune serum test, and more particularly, an automatic analysis suitable for a sample or a reagent having a probe that sucks and discharges a liquid such as water as a pressure medium. Relates to the device.

  Usually, in an automatic analyzer, water as a pressure medium is filled in a probe, and a syringe, a diaphragm, a micropump, and the like are operated to dispense a sample into a reaction vessel and stir the reaction. At this time, for example, segmental air of about 5 microliters is put between the sample in the probe and the water of the pressure medium to prevent the sample from thinning.

  The amount of reagent in the automatic analyzer is 1) Reducing reagent costs in laboratory work, 2) Reducing patient burden by reducing the number of samples, 3) Improving the processing speed of the automatic analyzer, 4) Reducing the amount of waste liquid from the laboratory Reduction is desired for the following four reasons. Since the ratio of the reagent amount to the sample amount is determined in the automatic analyzer, when the reagent amount is reduced, the minimum sample amount to be guaranteed is reduced. At present, the minimum value of the sample amount guaranteed by each automatic analyzer is about 1 microliter.

  Phenomena that have been found by making samples and reagents minute are phenomena in which air expands and contracts when the temperature of the air in the probe differs from the temperature of the environment around the probe. The expansion or contraction phenomenon occurs in several seconds from when the sample is sucked to when the discharge is completed. If the temperature of the probe is higher than the temperature of the air, the air sandwiched between the water and the sample will expand. If the temperature of the probe is lower than the temperature of the air, the air sandwiched between the water and the sample contracts. In the expansion phenomenon, the sample protrudes to the tip of the sample probe. At this time, a large amount of sample is discharged because the amount jumped out to the set amount is added. In the contraction phenomenon, since the air enters the tip of the sample probe, the sample is discharged less than the set amount.

  When the amount of the sample was about 3 microliters or more, there was no effect on the dispensing amount of the expansion / contraction caused by the temperature change of the segmental air. In recent years, when dispensing of samples of 1 microliter or less has come into practical use, the number of probes until the probe that has sucked the sample rises from the sample container and the probe that has been discharged into the reaction container leaves the sample droplet. It was found that the expansion or contraction of segmental air per second caused an error in the sample dispensing amount.

  For this reason, at present, in order to make the temperature of the washing water and air the same as the room temperature, the flow path is extended and heat is exchanged inside the apparatus. However, since the flow path becomes longer, there is a disadvantage that the amount of cleaning water is reduced and the cleaning power is weakened.

  Conventionally, the temperature change of water as a pressure medium has been focused on rather than the temperature change of segmental air, and the temperature difference between the inlet side and the outlet side of water as the pressure medium has been measured, and the volume of water has changed. One that calculates the amount and corrects the dispensing amount is known (see, for example, Patent Document 1).

JP 2008-203909 A

  However, as in Patent Document 1, if the washing water temperature is measured at the inlet side and the outlet side of the apparatus, the amount of change in the water volume is calculated, and the dispensing amount is corrected, the cost of the apparatus increases. . The reason is that a certain amount of temperature sensor inside the apparatus is required. Control is complicated by monitoring with all sensors and feedback to the control system.

  Further, as described above, the one described in Patent Document 1 focuses on the temperature change of water as a pressure medium, and does not focus on the temperature of segmental air. About the error of dispensing amount, it cannot deal with at all.

  The objective of this invention is providing the automatic analyzer which can reduce the error by the temperature change of segment air, and can improve the precision of sample dispensing amount.

In order to achieve the above object, the present invention includes a tubular probe that sucks a predetermined amount of a sample, and a sample pipettor that sucks the sample inside the probe, and transmits pressure inside the tubular probe. While a liquid as a medium is filled, a predetermined amount of air is sucked from the tip of the probe, and then a predetermined amount of sample is sucked from the tip of the probe. An automatic analyzer in which a predetermined amount of segmented air is disposed in the probe, wherein the probe is provided with a heater that heats the position of the segmented air when the entire amount of the sample is sucked across the segmented air It is a thing.
With this configuration, an error due to a temperature change of the segmented air can be reduced, and the accuracy of the sample dispensing amount can be improved.

According to the present invention, errors due to temperature changes of segmented air can be reduced, and the accuracy of sample dispensing can be improved.

1 is a system configuration diagram showing an overall configuration of an automatic analyzer according to an embodiment of the present invention. It is a whole block diagram which shows the structure of the sample probe used for the automatic analyzer by one Embodiment of this invention. It is sectional drawing which shows the structure inside the front-end | tip of the sample probe used for the automatic analyzer by one Embodiment of this invention. It is a flowchart which shows the content of the temperature control process of the sample probe used for the automatic analyzer by one Embodiment of this invention. It is a flowchart which shows the content of the temperature control process of the sample probe used for the automatic analyzer by other embodiment of this invention.

Hereinafter, the configuration of an automatic analyzer according to an embodiment of the present invention will be described with reference to FIGS.
First, the overall configuration of the automatic analyzer according to the present embodiment will be described with reference to FIG.
FIG. 1 is a system configuration diagram showing the overall configuration of an automatic analyzer according to an embodiment of the present invention.

  A large number of sample containers 25 are arranged in the sample disk mechanism 1. A predetermined amount of the sample held in the sample container 25 is extracted by the sample probe 27 of the serum sampling mechanism 2 and injected into the predetermined reaction container 4.

  The reagent disk mechanisms 5A and 5B include a large number of reagent containers 6. A reagent barcode reader 30 for the first reagent and a reagent barcode reader 31 for the second reagent are installed beside the reagent disk mechanisms 5A and 5B. Reagent pipetting mechanisms 7A and 7B are arranged in the reagent disk mechanisms 5A and 5B. Reagents are sucked by a predetermined amount by the reagent probes 28A and 28B of the reagent pipetting mechanisms 7A and 7B. It is injected into the reaction vessel 4.

  Between the photometer 10 and the light source 26, the reaction disk 3 that accommodates the measurement object is disposed. On the outer periphery of the reaction disk 3, for example, 160, a large number of reaction vessels 4 are installed. Further, the entire reaction disk 3 is held at a predetermined temperature by a thermostatic chamber 9. The cleaning mechanism 11 sucks the measured reaction liquid from the reaction container 4 and discards it in the waste container, and discharges the cleaning liquid held in the cleaning liquid container 13 into the reaction container 4 by the detergent injection nozzle 14. The discharged cleaning liquid is sucked and discarded by the detergent injection nozzle 14 to clean the inside of the reaction vessel 4.

  In FIG. 1, 19 is a microcomputer, 23 is an interface, 18 is a Log converter and A / D converter, 17 is a reagent pipetter, 16 is a washing water pump, and 15 is a serum pipettor. Reference numeral 20 denotes a printer, 21 denotes an operation screen, 22 denotes a hard disk as a storage device, and 24 denotes an operation panel.

  The operation of the automatic analyzer having the above configuration will be described. The operator uses the operation panel 24 to input analysis request information. The input analysis request information is stored in a memory in the microcomputer 19. The measurement target sample placed in the sample container 25 and set at a predetermined position on the sample disk 1 is obtained by the serum pipettor 15 and the sample probe 27 of the serum sampling mechanism 2 according to the analysis request information stored in the memory of the microcomputer 19. A predetermined amount is dispensed into the reaction vessel 4. The sample probe 27 is washed with water. A predetermined amount of reagent is dispensed into the reaction container 4 by the reagent probes 28A and 28B of the reagent pipetting mechanism 7A and 7B. After the reagent probes 28A and 28B are washed with water, the reagent for the next reaction container is dispensed. The mixed solution of the sample and the reagent is stirred by the stirring rod 29 of the stirring mechanism 8. After the stirring rod 29 is washed with water, the mixed solution in the next reaction vessel is stirred. The reaction vessel 4 is held at a constant temperature by a thermostatic chamber 9, and a reaction is performed. The reaction process is measured by the photometer 10 at regular intervals, and the absorbance of the mixed solution is measured using two set wavelengths. The measured absorbance is taken into the microcomputer 19 via the Log converter and A / D converter 18 and the interface 23.

  The absorbed absorbance is converted into a concentration value, stored in the hard disk 22, and output to the printer 20. In addition, inspection data can be displayed on the operation screen 21.

  After completion of the measurement, the reaction vessel 4 is washed by the washing mechanism 11. The reaction vessel 4 that has been washed is repeatedly used for the next analysis.

Next, the configuration of the sample probe 27 used in the automatic analyzer according to the present embodiment will be described with reference to FIG.
FIG. 2 is an overall configuration diagram showing the configuration of the sample probe used in the automatic analyzer according to the embodiment of the present invention.

  The sample probe 27 of this embodiment is attached with a heater 38 for heating. In general, since the sample probe 27 is a thin metallic tube, the heater 38 to be attached is preferably a thin film heater made of polyimide. The sample probe 27 descends to the sample container 25 and stops the descending operation when it touches the sample. A liquid level sensor is provided at the tip of the sample probe 27, and it can be detected that the liquid level of the sample is touched by the liquid level sensor.

  After the descent of the sample probe 27 is stopped, the sample pipettor 34 performs a quantitative operation to suck a predetermined amount of sample. Thereafter, the sample probe 27 moves directly above the reaction container 4, the tip of the sample probe 27 is brought into contact with the bottom of the reaction container 4, and the sample is discharged. After the sample is discharged, the electromagnetic valve 35 is released, and the cleaning water accumulated in the cleaning water tank 37 is pressurized by the pump 36 to clean the inside of the sample probe 27.

  The sample probe temperature sensor 40 measures the temperature of the sample probe 27 and the room temperature sensor 43 measures the room temperature. In accordance with the processing of the control circuit 42 that has captured both signals, the apparatus performs processing to reduce the temperature difference between the room temperature and the sample probe. Details thereof will be described later with reference to FIG.

  The cleaning water temperature sensor 39 detects the temperature of the cleaning water, which is used when a second embodiment described later is carried out.

Next, the detailed configuration inside the tip of the sample probe 27 used in the automatic analyzer according to the present embodiment will be described with reference to FIG.
FIG. 3 is a cross-sectional view showing the internal configuration of the tip of the sample probe used in the automatic analyzer according to the embodiment of the present invention.

  The sample probe 27 is a thin metallic tube, and the sample 25X is sucked into the opening side at the tip inside. The base side of the sample probe 27 is filled with the cleaning liquid 37X. Between the sample 25X and the cleaning liquid 37X, segmental air AR for separating the two is located.

  For example, when the sample pipettor 34 performs a quantitative operation in a state where the entire interior of the sample probe 27 is filled with the cleaning liquid 37X and the open end of the sample probe 27 is in contact with air, a predetermined amount is obtained. Air AR is sucked. Thereafter, when the sample probe 27 descends to the sample container 25 and the sample pipettor 34 performs a quantitative operation with the tip of the sample probe 27 touching the sample, the vicinity of the tip of the sample probe 27 is as shown in FIG. Then, a predetermined amount of sample is aspirated.

  Thereafter, the sample probe 27 moves right above the reaction container 4, the tip of the sample probe 27 is brought into contact with the bottom of the reaction container 4, and a predetermined amount of sample is discharged. Thereafter, at the cleaning position, the inside of the sample probe 27 can be cleaned by discharging the cleaning liquid 37X inside the sample probe 27 at the cleaning liquid discarding position.

  A heater 38 is attached to the outer periphery of the sample probe 27 on the tip side.

Here, the cross-sectional area S of the sample probe 27 is, for example, 0.1 mm ² . For example, when dispensing a 1 μL sample, a sample larger than the dispensed amount (here, 1 μL) is sucked into the tip of the sample probe 27. Here, for example, a 10 μL sample is sucked. Therefore, the distance L1 in FIG. 3 is 100 mm.

  If the amount of segmented air AR is, for example, 5 μL, the distance L2 in FIG. 3 is 50 mm. The position of the segmented air AR moves according to the suction / discharge of the sample 25X. Before the sample 25X is aspirated, it is in the vicinity of the opening end of the tip of the sample probe 27. When the sample 25X is moved from the opening end to the inside according to the suction of the sample 25X, the position shown in FIG. In addition, the segmental air AR is located. Thereafter, a predetermined amount (1 μL in this case) of the sample is discharged. At this time, the segmented air AR moves from the position shown in FIG. 3 to the open end of the tip of the sample probe 27 by a distance of 10 mm. The operation up to this time affects the accuracy in quantitative dispensing of the sample. Thereafter, the remaining 9 μL sample inside the sample probe 27 is discarded, but at this time, the dispensing of the sample has already been completed.

  As described above, the movement position of the segment air AR is a position moved from the tip of the sample probe 27 by the amount of the aspirated sample and the amount of segment air. A heater 38 is attached to this position. In particular, the state shown in FIG. 3 is a state in which the sample is sucked with the segment air interposed therebetween, and the attachment position of the heater 38 at this time is determined so that the segment air AR is heated by the heater 38. .

  In this way, the thin film heater 38 such as a polyimide heater is covered so as to cover the range where the segmental air of the probe comes. As shown in FIG. 3, the heater 38 is attached so as to heat the position of the segmented air AR when the entire amount of the sample is sucked with the segmented air interposed therebetween. After the sample is sucked from the sample container to the probe 27 at the position of the sample disk 1 in FIG. 1, the probe 27 is positioned at the position of the sample disk 1 until the sample is discharged into the reaction container held by the reaction disk 3. It takes a predetermined time to move to the position of the reaction disk 3. Although the time is slight, since the probe 27 is made of metal and has good thermal conductivity, the segmented air can be heated to a predetermined temperature in a sufficiently short time. Therefore, the position where the heater is attached is at least the position of the segment air AR when the entire amount of the sample is sucked with the segment air interposed therebetween. However, in this embodiment, as shown in FIG. 3, the heater 38 is further positioned near the tip of the probe 27. This is because heating of the air is started from the time when the air is sucked from the tip of the probe 27, and then the segment air is moved from the position of the tip of the probe 27 to the position shown in FIG. This is because it can be heated all the time. Thus, by providing the heater 38 at a position that covers the range where the segmental air of the probe comes, it becomes easier to maintain the temperature of the segmental air at a predetermined temperature.

  Also, for example, when dispensing a 1 μL sample, a 10 μL sample is aspirated and then a 1 μL sample is ejected more than when a 1 μL sample is aspirated and the entire aspirated amount is ejected. This is because the dispensing accuracy can be increased.

Next, the contents of the temperature control process of the sample probe 27 used in the automatic analyzer according to the present embodiment will be described with reference to FIG.
FIG. 4 is a flowchart showing the contents of the temperature control process of the sample probe used in the automatic analyzer according to the embodiment of the present invention.

  In addition, the temperature control process of this embodiment is performed by the control circuit 42 of FIG.

  In step S10, the automatic analyzer is turned on. In step S <b> 20, the control circuit 42 measures the room temperature by the room temperature sensor 43. In step S30, the temperature of the probe is measured by the sample probe temperature sensor 40.

  In step S40, if the room temperature is higher than the room temperature and there is a difference of 5 ° C. or more in step S40, the probe heater 38 is energized to heat the probe 27 in step S50. In step S60, heating is continued until the temperature difference is within ± 5 ° C. The temperature difference of 5 ° C. here is an allowable temperature calculated from the body expansion coefficient of air and the dispensing volume. When the temperature difference is within ± 5 ° C. in step S70, the heater is turned off. Again, if the probe temperature is lower than room temperature, the heater is energized.

  On the other hand, in step S40, the room temperature is compared with the probe temperature. If the room temperature is lower, or if there is no difference of 5 ° C. or higher, it is determined in step S80 whether to turn off the apparatus. Repeat until cut.

  As described above, in this embodiment, the probe is heated to the same temperature as the room temperature by covering with a thin film heater such as a polyimide heater so as to cover the range where the segmental air of the probe comes. A temperature sensor for measuring the temperature of the probe itself is attached at an intermediate position in a range where segmental air is sucked. Instead of one sensor, a plurality of sensors may be attached and data of a plurality of sensors may be used on average. The room temperature sensor is installed near the probe. In the case of a device that closes the cover, the room temperature sensor is installed in a closed space with the cover closed.

  According to the present embodiment described above, since the expansion / contraction of segmental air caused by the temperature difference between the room temperature and the probe can be suppressed, a very small amount of sample or reagent can be accurately dispensed.

  In the above-described embodiment, the heater 38 as a heating unit is provided near the tip of the sample probe 27 for dispensing the sample. On the other hand, as what provided the heating means in the vicinity of the probe which dispenses a reagent, what was described in Unexamined-Japanese-Patent No. 2001-174465 is known, for example. The reason why a heating means (constant temperature water) is provided in JP-A-2001-174465 is to preliminarily heat the aspirated reagent. That is, the reagent is stored at a low temperature to prevent deterioration. On the other hand, the reaction after mixing the sample and the reagent proceeds in a thermostatic chamber (for example, 37 ° C.). In order to prevent the measurement accuracy from being lowered due to this temperature gap, it is described in Japanese Patent Laid-Open No. 2001-174465, and heating means (constant temperature water) is provided. That is, in the thing of Unexamined-Japanese-Patent No. 2001-174465, there is no idea of heating segmental air.

  Generally, the sample dispensing accuracy is required to be about ± 1%. In order to perform such high-precision dispensing, it is necessary to control the temperature of the segmental air as in the above-described embodiment. On the other hand, what is required as the reagent dispensing accuracy is about ± 2%, which is lower than the sample dispensing accuracy. In addition, when a sample is dispensed in 1 μL, the amount of reagent used for the sample is 50 μL, and the amount of reagent is larger than the amount of sample. Accuracy is required.

  As a result, in the device described in Japanese Patent Application Laid-Open No. 2001-174465, there is no idea of heating the segmental air, and in the device described as an example, the heating means (in the position where the reagent sucked near the tip of the nozzle is heated) If the heating means is provided at the position of segmented air, the idea is not disclosed.

Next, an automatic analyzer according to another embodiment of the present invention will be described with reference to FIG. The overall configuration of the automatic analyzer according to the present embodiment is the same as that shown in FIG. The configuration of the sample probe 27 used in the automatic analyzer according to the present embodiment is the same as that shown in FIG. Further, the detailed configuration inside the tip of the sample probe 27 used in the automatic analyzer according to the present embodiment is the same as that shown in FIG.
FIG. 5 is a flowchart showing the contents of the temperature control process of the sample probe used in the automatic analyzer according to another embodiment of the present invention.

  In this embodiment, the room temperature and the probe temperature are compared, and measures are taken not only when the probe temperature is lower than the room temperature but also when the probe temperature is higher than the room temperature.

  The flow from step S10 to step S70 is the same as that shown in FIG.

  If it is determined in step S40 that "the room temperature is higher than the probe temperature and the room temperature is higher and there is a difference of 5 ° C or more", the answer is "No. The temperature is higher and the temperature difference is 5 ° C. or more ”. In this case, since the washing water is cold water at about room temperature, the washing water is used. The probe is cooled by taking out cold wash water in step S120 using the timing when the specimen becomes empty other than the probe dispensing operation and the probe washing operation. In step S130, the operation of discharging wash water in the idle time is continued until the temperature difference becomes within ± 5 ° C. If the temperature difference is within ± 5 ° C. in step S140, the operation of cooling the probe is stopped. The temperature of the probe can be accurately maintained by combining heating by the probe heater and cooling by flowing cold washing water. The above processing is repeated until the apparatus is turned off in step S80.

  In addition, in order to cool a probe using washing water, the temperature of washing water needs to be low. Therefore, the cleaning water temperature sensor 39 shown in FIG. 2 is provided to detect the temperature of the cleaning water, and when the temperature is not suitable for cooling, the cooling with the cleaning water in step S120 is not performed. .

  A sensor 39 for measuring the temperature of the pressure medium liquid, generally water (washing water), is attached in the vicinity of the connection portion of the probe. In rare cases, when the temperature of the pressure medium water is higher than room temperature, the washing water is not used for cooling, and an alarm is generated to alert the operator.

According to the present embodiment described above, since the expansion / contraction of segmental air caused by the temperature difference between the room temperature and the probe can be suppressed, a very small amount of sample or reagent can be accurately dispensed. At this time, in this embodiment, not only when the temperature of the probe is higher than room temperature, but also when the temperature of the probe is lower than room temperature, expansion / contraction of segmental air can be suppressed.

DESCRIPTION OF SYMBOLS 1 ... Sample disk mechanism 2 ... Serum sampling mechanism 3 ... Reaction disk 4 ... Reaction container 5A, 5B ... Reagent disk mechanism 6 ... Reagent container 7A, 7B ... Reagent pipetting mechanism 8 ... Stirring mechanism 9 ... Constant temperature bath 10 ... Photometer 11 Reaction container cleaning mechanism 12 Suction nozzle 13 Cleaning agent container 14 Detergent injection nozzle 15 Serum pipetter 16 Washing water pump 17 Reagent pipetter 18 Log converter and A / D converter 19 Microcomputer 20 ... Printer 21 ... Operation screen 22 ... Hard disk 23 ... Interface 24 ... Operation panel 25 ... Sample container 26 ... Light source 27 ... Sample probe 28A, 28B ... Reagent probe 29 ... Stirring rod 30 ... First reagent reagent barcode reader 31 ... First Reagent barcode reader 34 for two reagents ... Pipettor 35 for sample ... Solenoid valve 36 ... Pump 7 ... washing water tank 38 ... Heater 39 ... washing water temperature sensor 40 ... sample probe temperature sensor 41 ... Joint 42 ... control circuit board 43 ... Room sensor

Claims (3)

A tubular probe for aspirating a predetermined amount of the sample;
A sample pipettor for sucking the sample inside the probe;
With the inside of the tubular probe filled with a liquid as a pressure transmission medium, a predetermined amount of air is sucked from the tip of the probe, and then a predetermined amount of sample is sucked from the tip of the probe, An automatic analyzer in which a predetermined amount of segmental air is arranged between a sample and the pressure transmission liquid,
An automatic analyzer comprising: a heater for heating a position of segmented air when the entire amount of the sample is sucked with the segmented air interposed in the probe. The automatic analyzer according to claim 1, wherein
The automatic analyzer according to claim 1, wherein the heater is arranged to cover a range where the segmental air of the probe comes. The automatic analyzer according to claim 2,
A room temperature measuring unit for measuring the room temperature around the probe;
A probe temperature measuring unit for measuring the temperature of the probe itself;
A controller that controls heating of the probe by the heater so that a temperature difference between the room temperature measured by the room temperature measuring unit and the probe measured by the probe temperature measuring unit is within a predetermined temperature range; Automatic analyzer characterized by

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