JP2000046843A - Automatic chemical analysis device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To securely sample a blood cell constituent and to achieve automation in the measurement of Hb (hemoglobin) A1c using an automatic chemical analysis device. SOLUTION: Measurement items are inputted to an analysis condition setting part 32 and samples start to be collected. The liquid surface of the samples is detected by a liquid surface detection part 34. A nozzle descent distance is calculated based on information regarding the nozzle penetration distance of the analysis condition setting part 32 and the liquid surface position information of the liquid surface detection part 34 by a nozzle descent distance calculation part 30. When the inputted measurement items are Hb measurement or HB A1c measurement, a nozzle descent distance is calculated by the nozzle descent distance calculation part 30, a sample-dispensing mechanism 6 is operated by a sample dispensation mechanism control part 28, and the nozzle is penetrated into the sample. As a result, even if the blood cell constituent of a whole blood sample settles out, the tip of the nozzle reaches the blood cell part to collect the blood cell constituent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic chemical analyzer for measuring the concentration or activity of a target component in a sample containing multiple components such as blood and urine. Such an automatic analyzer is also used for general chemical analysis of other samples.

[0002]

2. Description of the Related Art In an automatic chemical analyzer (reaction cell direct photometric type automatic analyzer) which stores a prepared reaction solution in a reaction container and a photometric cell and quantifies the target component in the sample by an absorbance measurement method, the sample solution is stored in a sample container. When collecting a sample by injecting the nozzle, according to the type of sample container and the amount of use for each item, do not suck air at the time of aspirating the sample, and minimize the penetration depth of the nozzle tip from the liquid surface. So that
The penetration distance of the nozzle from the sample liquid surface is controlled. This is to reduce the adhesion of the sample to the outer wall surface of the nozzle and to reduce the error. As a sample for performing such a sampling method, a sample such as serum or urine which is homogeneous even after a lapse of time has been assumed.

When measuring hemoglobin (hereinafter abbreviated as Hb) and hemoglobin A _1C (hereinafter abbreviated as HbA _1C ) in blood using a whole blood sample as a specimen, it is necessary to collect blood cell components. Measured HbA _1C and Hb, when determining the ratio of HbA _1C to total Hb (%), the HbA _1C
Is an indicator of diabetes. Therefore, if the collected sample contains a blood cell component, there is no problem if the plasma component is mixed to some extent, but HbA _1C cannot be measured in all plasma components.

[0004]

FIG. 1 is a schematic diagram showing the separation of components when a whole blood sample is left in a sample container. For Hb measurement and HbA _1C measurement, it is necessary to sample blood cell components. However, when a large number of sample containers containing a whole blood sample are placed in the storage unit and measurement is started, the blood cell components sediment over time. Then, it is divided into two layers, a plasma part and a blood cell part. Therefore, if a sample is collected with a minimum penetration depth as in the conventional case, a blood cell component cannot be collected from a sample from which components are separated, and only a plasma component is collected. In order to solve such a problem, it is necessary for the operator to invert and mix again just before the sample is collected, which is an obstacle to automation.

[0005] Accordingly, the present invention provides an automatic analyzer for H
It is an object of the present invention to ensure the collection of blood cells and to realize automation in order to enable measurement of blood cell components such as b measurement and HbA _1C measurement.

[0006]

FIG. 2 is a block diagram showing one embodiment of the present invention. The operation of the sample dispensing mechanism 6 for sucking and discharging the sample using the nozzle is controlled by the sample dispensing mechanism control unit 28. The sample dispensing mechanism control unit 28 controls the nozzle based on the nozzle intrusion distance information of the analysis condition setting unit 32 and the liquid level position information of the liquid level detection unit 34 in which the nozzle intrusion distance to the sample is preset according to the measurement item. A nozzle descent distance calculation unit 30 that calculates a descent distance is connected.

Specifically, this embodiment is described below. A reaction vessel for reacting a sample with a reagent, a sample dispensing mechanism for collecting a sample using a nozzle and dispensing the reaction into the reaction vessel, and dispensing a reagent to the reaction vessel. A reagent dispensing mechanism, and an absorptiometer that measures the absorbance in the reaction vessel, wherein at least the measurement items for the blood cell component are applied to the sample more than other measurement items. An analysis condition setting unit in which two or more types of information relating to the nozzle penetration distance are set so as to increase the nozzle penetration distance, a liquid level detection unit that detects the liquid surface of the sample, and a nozzle penetration distance of the analysis condition setting unit A nozzle descending distance calculating section that calculates a nozzle descending distance based on the information and the liquid level position information of the liquid level detecting section, and a sample dispensing mechanism that operates based on the nozzle descending distance calculated by the nozzle descending distance calculating section. And a sample dispensing mechanism control unit.

[0008] The measurement items are input to the analysis condition setting section 32, and sampling of a sample is started. The liquid level detecting section 34 detects the liquid level of the sample. By the nozzle descent distance calculation unit 30,
The nozzle descent distance is calculated based on the information on the nozzle intrusion distance of the analysis condition setting unit 32 and the liquid level position information of the liquid level detection unit 34. If the input measurement item is Hb measurement or Hb
When a blood cell component is required as in the case of A _1C measurement, the nozzle descending distance calculated by the nozzle descending distance calculating unit 30 becomes large. Based on the nozzle descending distance, the sample dispensing mechanism 6 is operated by the sample dispensing mechanism control unit 28 to cause the nozzle to enter the sample. As a result, even if the blood cell component of the whole blood sample is sedimented, the tip of the nozzle reaches the blood cell portion, and the blood cell component can be collected. If the measurement item does not require a blood cell component, the nozzle descent distance calculated by the nozzle descent distance calculation unit 30 is the minimum penetration depth. Based on the nozzle descending distance, the sample dispensing mechanism 6 is operated by the sample dispensing mechanism control unit 28 to cause the nozzle to enter the sample.

[0009]

FIG. 3 is a block diagram showing another embodiment of the present invention. The operation of the sample stirring mechanism 36 for stirring the sample using the stirring blade is controlled by the sample stirring mechanism control unit 38. A liquid level detection unit 40 that detects the liquid level of the sample is connected to the sample stirring mechanism control unit 38.

Specifically, this embodiment is described below. A reaction vessel for reacting a sample with a reagent, a sample dispensing mechanism for collecting a sample using a nozzle and dispensing the reaction into the reaction vessel, and dispensing a reagent to the reaction vessel. A chemical dispensing mechanism, and an absorptiometer for measuring the absorbance in the reaction vessel, wherein the sample is a sample stirring mechanism for stirring the sample using stirring blades, and the liquid level of the sample And a sample stirring mechanism control unit that operates by causing a stirring blade to enter a position at a predetermined distance from the sample liquid level based on the liquid level position information of the liquid level detection unit.

The liquid level of the sample is detected by the liquid level detecting section 40. The liquid level position information of the liquid level detecting unit 40 is sent to the sample stirring mechanism control unit 38, and based on the liquid level position information, the stirring can be reliably performed and the intrusion distance of the stirring blade is minimized. As described above, the sample stirring mechanism control unit 38 operates the sample stirring mechanism 36 to cause the stirring blades to enter the sample and stir the sample.

[0012]

Embodiment 1 FIG. 4 shows an example of an automatic chemical analyzer to which one embodiment of the present invention is applied. Reference numeral 2 denotes a reaction disk, and reaction vessels 4 also serving as cuvettes are arranged in a row along a cuvette roller 3 to form an annular reaction line 5. A sample dispensing mechanism 6 is arranged near the reaction line 5 for injecting a sample into the reaction vessel. In the sample dispensing mechanism 6, sample containers 7 are arranged along the circumference of the sampling table 8, and a sample dispenser 9 is disposed for dispensing a sample from the sample container 7 at the sample suction and sampling position 13. I have. A nozzle 10 is provided at the tip of the sample dispenser 9, and the nozzle 10 moves along a movement path 11 between the reaction container at the sample dispensing position 14 and the sample container at the sample suction and sampling position 13. A cleaning pot 12 is provided on the moving path 11 so that the nozzle 10 can be cleaned.

A reagent injection device 16 is arranged near the reaction line 5 for injecting a reagent into the reaction container. In the reagent injecting device 16, a reagent container 17 is arranged along the circumference of the reagent tray 18, and a reagent dispenser 19 is arranged for dispensing a reagent from the reagent container 17 at the reagent suction and sampling position 23. . A nozzle 20 is provided at the tip of the reagent dispenser 19.
The nozzle 20 moves along the movement path 21 between the reaction container at the reagent dispensing position 24 and the reagent container at the reagent suction and sampling position 23. A cleaning pot 22 is arranged on the moving path 21 so that the nozzle 20 can be cleaned.

A washing and dehydrating device 2 is further provided on the reaction line 5.
6 and an absorptiometer 27 along the reaction line 5. The reaction line 5 rotates intermittently in the direction of arrow 15. Although not shown in the figure, a warm water tank for keeping the reaction solution in the reaction vessel 4 under the reaction line 5 is provided. Further, a control unit (not shown) for controlling the operation of each unit and calculating the concentration or activity value of the sample based on the absorbance from the absorptiometer 27 is also provided.

When the measurement is performed in the two-reagent system, another reagent injection device having the same configuration as the reagent injection device 16 is arranged along the reaction line. A first reagent is dispensed from the one reagent injector to the reaction container 4 and a second reagent is dispensed from the other reagent injector at the respective reagent injection positions.

A plurality of washing nozzles are arranged in the washing and dehydrating unit 26 along the reaction line 5 to suck a reaction solution, supply and discharge a washing solution, supply water for measuring a reaction container blank,
The process of discharging and drying the water is sequentially performed. Pure water or a detergent solution is used as the cleaning liquid. Sample dispensing, reagent dispensing, stirring, and reaction vessel washing during one cycle are performed when the reaction disk is stopped, and optical reading of the reaction solution in the reaction vessel by the absorptiometer 27 is performed when the reaction disk is rotated.

FIG. 5 is a view showing the state of a sample at the time of sampling in the first embodiment.
It is a mimetic diagram showing a chisel, a sample, and a sample container, (A)
At the time of collecting a whole blood sample immediately after inversion mixing, (B)
At the time of collecting the whole blood sample, (C)
(D) is a glucose with sedimented blood cell components
At the time of sampling. Glucose is a common measurement
One, HbA_1CCan be an indicator of diabetes
You. Glucose and HbA _1CBy measuring together
Thus, the accuracy of diabetes diagnosis is improved. (A), (B),
In (C) and (D), a sample container for measuring blood cell components is used.
(A) and (C)
In this case, since the plasma component and the blood cell component are mixed immediately after
However, in (B) and (D), blood cell components sediment and plasma
The part is separated from the blood cell part.

FIG. 6 is a flowchart showing the operation of the first embodiment at the time of sampling. The operation will be described with reference to FIGS. The measurement item is input to the analysis condition setting unit 32. In the analysis condition setting section 32, the nozzle intrusion distance to the sample is preset according to the measurement item. Table 1 shows an example.

[0019]

[Table 1]

Next, the liquid level of the sample is detected. By rotating the sampling table 8, the sample container 7 containing the sample to be measured is moved to the sample suction / collection position 13, and the sample dispenser 9 is also moved to the sample suction / collection position 13. The nozzle 10 is lowered while operating the counter to detect the liquid level of the sample, and the liquid level position information is sent to the nozzle descent distance calculation unit 30. Here, the liquid level is detected using a sample dispensing mechanism, but the liquid level may be detected by another liquid level detection method such as optical reading.

The descending distance of the nozzle 10 is calculated by the nozzle descending distance calculating section 30 from the liquid surface position information indicated by the counter and the nozzle descending distance information from the analysis condition setting section 32. If the measurement item is glucose, a nozzle with a 2 mm nozzle penetration distance added to the liquid surface position so that the air does not suck at the time of aspirating the sample and the penetration depth of the nozzle tip from the liquid surface is minimized. Ten descending distances are calculated. If the measurement item is Hb or HbA _1C , the descending distance of the nozzle 10 is calculated by adding the 10 mm nozzle penetration distance to the liquid surface position so that the tip of the nozzle 10 reaches the blood cell component even if the blood cell component is sedimented. Is done.

The tip of the nozzle 10 is lowered to the calculated lowering distance (see FIG. 5), and a predetermined amount of the sample is sucked. After raising the nozzle 10, the sample dispenser 9 is moved to move the nozzle 10 to the dispensing position 14. The nozzle 10 is lowered, and the sucked sample is dispensed into the reaction container 4.

After the sample has been dispensed into the reaction vessel 4, the reaction disk 2 is rotated by a predetermined angle to move the reaction vessel 4 to the reagent dispensing position 24, and the reagent injection device 16 adjusts the setting according to the set items. The reagent is dispensed, the reaction disk 2 is further rotated by a predetermined angle, and a desired component in the reaction container 4 is measured by the absorptiometer 27. The nozzle 10 in which the sample has been dispensed and the sample has adhered to the outer wall is made to penetrate into the washing crucible 12 for the amount that has penetrated the sample, and is washed.

By the way, the volume percentage (%) of the blood cell portion with respect to the whole blood sample is defined as a hematocrit value (hereinafter referred to as Ht).
That is, about 45% of men and about 40% of women are the median values of healthy people. However, depending on the sample, 25 to 60
%, The blood cell component must be able to be collected after being allowed to stand naturally even at the lowest of about 25%.
On the other hand, the amount of blood collected by the blood collection tube varies depending on the sample, and the height of the liquid level is not constant. For example, even with the specification of a 2 ml blood collection tube, suction of about 2.5 ml may be performed, and the amount of blood to be collected increases. Considering these two,
When the sample has a large blood collection volume and a small Ht, the thickness of the plasma layer is large (see FIG. 7B).

In the first embodiment, the nozzle penetration distance during Hb measurement and HbA _1C measurement is fixed to 10 mm. However, as shown in FIG. When the distance to the bottom dead center is smaller than the set nozzle penetration distance, the sample is sucked at the bottom dead center.

In Example 1, Hb measurement and HbA_1CMeasurement
The nozzle penetration distance is fixed at the time of
It is preferable to have a configuration that can change the nozzle penetration distance
No. FIG. 2 shows an example of a method for calculating the nozzle penetration distance.
To explain, first, the liquid level of the sample is
Detect the surface position. The measurement items are set in the analysis condition setting unit 32.
Set the measurement items for the sample whose liquid level is detected.
This is sent to the slur descent distance calculation unit 30. Nozzle descent distance calculation unit
According to 30, the measurement item is Hb measurement or HbA _1CPlace of measurement
In this case, based on the liquid level position information and the bottom dead center information of the sample container,
The sample volume is calculated by the following method, and Ht is the lowest 25%.
Assuming that the blood cell component sediments, the surface of the blood cell part
Calculate the position and calculate the position from the liquid surface position to the surface position of the blood cell part.
Calculate the nozzle penetration distance that is longer than the distance. Nozzle penetration
The nozzle can be lowered based on the distance and liquid level information.
Thus, the blood cell component can be reliably collected.

Embodiment 2 FIG. 8 shows an example of an automatic chemical analyzer to which another embodiment of the present invention is applied. The description of the same parts as in FIG. 5 is omitted. The sample stirring mechanism 36 is arranged near the sample dispensing mechanism 6. In the sample stirring mechanism 36, a sample stirrer 44 is provided to stir the sample placed in the sample container 7 at the sample stirring position 52. A stirring blade 46 is provided at the tip of the sample stirrer 44.
Numeral 6 moves along the movement path 48 between the reaction vessel at the sample stirring position 52 and the washing pot 50 provided on the movement path 48. In the cleaning pot 50, the stirring blade 46 can be cleaned.

FIGS. 9A to 9D are schematic diagrams showing the operation during sample agitation in the second embodiment. FIGS. 9A to 9D show the normal blood collection amount, and FIGS. 9A to 9D show the blood collection amount. It represents the case where there are many. The operation will be described with reference to FIGS. 3, 8, and 9. First, in the same manner as in Example 1, the sample container 7 and the sample dispenser 9
Is moved to the sample suction and sampling position 13, and the nozzle 10 is lowered while operating the counter to detect the liquid level of the sample (FIGS. 9A and 9A '). Here, the liquid level is detected using a sample dispensing mechanism, but the liquid level may be detected by another liquid level detection method such as optical reading.

The sample table 7 is moved to the sample stirring position 52 by rotating the sampling table 8, and the sample stirrer 44 is also moved to the sample stirring position 52. The sample stirring mechanism control unit 38 lowers the stirring blade 46 so that the stirring can be reliably performed based on the liquid level position information of the liquid level detection unit 40 and the penetration distance of the stirring blade is minimized. (FIGS. 9B and 9B). Next, the sample is stirred by rotating the stirring blade 46. Due to this stirring operation, the sedimented blood cell component soars and becomes a uniform sample (FIG. 9).
(C), (C ')).

After raising the stirring blade 46, the sampling table 8 is rotated to move the sample container 7 to the sample suction / collection position 13, and the sample dispenser 9 to the sample suction / collection position 13. The sample is collected by lowering the nozzle 10 without sucking air at the time of sucking the sample and so as to minimize the penetration depth of the nozzle tip from the liquid surface (FIGS. 9D and 9D). ). After dispensing the sample into the reaction container 4, desired components in the reaction container 4 are measured in the same manner as in Example 1. The nozzle 10 in which the sample has been dispensed and the sample has adhered to the outer wall is made to penetrate into the washing crucible 12 for the amount that has penetrated the sample, and is washed. The stirring blade 46 having the sample agitated and the sample adhered to the outer wall is allowed to penetrate into the washing pot 50 as much as it has entered the sample to be washed. If there is a new sample that needs stirring, the above operation is repeated.

The depth at which the nozzle 10 or the stirring blade 46 penetrates into the sample is constant even if the blood collection amount differs depending on the sample, and regardless of the blood collection amount, the nozzle 10 or the stirring blade 46 is moved by the same washing pot 22 or 50. Washing is possible. Further, the stirring of the sample is performed for 1) all the arranged samples.
2) Performed only for the sample at the designated position, 3) Performed only for the designated sample container, and 4) Performed only for the sample containing the designated item. In any case, the purpose is to make the sample uniform before sampling. Example 2 is not limited to a whole blood sample, but may be applied to a sample whose homogeneity changes, for example, a urine sample in which crystals are precipitated when left for a long time. it can.

Although an embodiment to which the present invention is applied has been described above, the present invention is not limited to this, and an automatic analyzer having a dispensing mechanism for dispensing a sample and an analytical reagent into a reaction vessel. Alternatively, any automatic analyzer that further includes a stirring mechanism can be applied. Further, the present invention is not limited to collection of blood cell components for measuring HbA _1C , but can be applied to collection of other blood cell components.

The present invention can be variously modified within the scope of the present invention described in the claims.
Examples of embodiments of the present invention will be illustrated below. A reaction container for reacting a sample with a reagent, a sample dispensing mechanism for collecting a sample using a nozzle and dispensing the reaction container, a reagent dispensing mechanism for dispensing a reagent to the reaction container, and the reaction container And an absorptiometer that measures the absorbance of the inside, a liquid level detection unit that detects the liquid level of the sample, and the measurement items are hemoglobin measurement or hemoglobin A _1C.
In the case of the measurement, the sample amount is calculated based on the liquid level position information and the bottom dead center information of the sample container, and further, assuming that the hematocrit value is 25%, the blood cell portion when the blood cell component sediments is assumed. A nozzle descending distance calculating unit that calculates a surface position and calculates a nozzle intrusion distance that is equal to or greater than a distance from the liquid level position to the surface position of the blood cell portion, and the nozzle descending distance calculated by the nozzle descending distance calculating unit, An automatic chemical analyzer, comprising: a sample dispensing mechanism control section for operating a sample dispensing mechanism.

[0034]

In the automatic chemical analyzer according to the present invention, the liquid level of the sample is detected by the liquid level detecting section, and the nozzle intrusion distance information of the measuring condition setting section and the liquid level of the liquid level detecting section are detected by the nozzle descending distance calculating section. The nozzle descent distance is calculated based on the surface position information, and when the measurement item is Hb measurement or HbA _1C measurement,
Since the nozzle entry distance from the sample liquid surface is increased to calculate the nozzle descent distance, it is possible to reliably sample the blood cell component even if the blood cell component has settled with the passage of time. Further, since it is not necessary to mix by inversion just before the sampling, it can be automated.

[Brief description of the drawings]

FIG. 1 is a schematic diagram showing separation of components when a whole blood sample is left.

FIG. 2 is a block diagram illustrating one embodiment of the present invention.

FIG. 3 is a block diagram showing another embodiment of the present invention.

FIG. 4 is a schematic perspective view illustrating an example of an automatic chemical analyzer to which one embodiment of the present invention is applied.

FIGS. 5A and 5B are schematic diagrams showing a nozzle, a sample solution, and a sample container at the time of sampling in Example 1. FIG. 5A is a time when a whole blood sample is collected immediately after inversion and mixing, and FIG. FIG. 7C is a diagram illustrating a time of collecting a blood sample, (C) is a time of collecting a glucose sample immediately after mixing by inversion, and (D) is a diagram illustrating a time of collecting a glucose sample in which blood cell components have sedimented.

FIG. 6 is a flowchart showing an operation at the time of sampling in the embodiment.

FIG. 7 is a schematic diagram showing a whole blood sample in which a blood cell component has sedimented, wherein (A) shows a sample with a small amount of collected blood and (B) shows a sample with a large amount of collected blood.

FIG. 8 is a schematic perspective view showing an example of an automatic chemical analyzer to which another embodiment of the present invention is applied.

FIGS. 9A to 9D are schematic diagrams illustrating an operation at the time of sample agitation in Example 2. FIGS.
(A ′) to (D ′) represent cases where the amount of blood collected is large.

[Explanation of symbols]

 6 Sample dispensing mechanism 28 Sample dispensing mechanism control unit 30 Nozzle descent distance calculation unit 32 Analysis condition setting unit 34 Liquid level detection unit

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 2G058 BB02 BB09 BB16 CB04 CD04 CE08 CF02 CF12 CF16 CF22 EA02 EA04 ED03 ED06 ED07 ED22 FA02 FB01 FB02 FB05 FB14 FB25 GA03 GB03 GD00

Claims (2)

[Claims] 1. A reaction vessel for reacting a sample with a reagent,
A sample dispensing mechanism that collects a sample using a nozzle and dispenses the reaction container, a reagent dispensing mechanism that dispenses a reagent to the reaction container, and an absorptiometer that measures absorbance in the reaction container, In an automatic chemical analyzer equipped with at least two types of analysis, information on a nozzle penetration distance is set to two or more types of measurement items for measuring blood cell components so that the nozzle penetration distance to the sample is larger than other measurement items. A condition setting section, a liquid level detection section for detecting the liquid level of the sample, and a nozzle descent distance based on information on the nozzle intrusion distance of the analysis condition setting section and liquid level position information of the liquid level detection section. A nozzle descending distance calculating unit; and a sample dispensing mechanism control unit that operates the sample dispensing mechanism based on the nozzle descending distance calculated by the nozzle descending distance calculating unit. Automatic chemical analyzer. 2. A reaction vessel for reacting a sample with a reagent,
A sample dispensing mechanism that collects a sample using a nozzle and dispenses the reaction container, a reagent dispensing mechanism that dispenses a reagent to the reaction container, and an absorptiometer that measures absorbance in the reaction container, A sample stirring mechanism for stirring a sample using a stirring blade, a liquid level detection unit for detecting a liquid level of the sample, and a liquid level position information of the liquid level detection unit. A sample stirring mechanism control unit for operating the stirring blade by moving the stirring blade into a position at a predetermined distance from the sample liquid level.