JPH0737993B2 - Continuous chemical analysis method - Google Patents

Description

TECHNICAL FIELD The present invention relates to a continuous chemical analysis method, and particularly to a turntable, a sample dispensing device, and a first reagent capable of intermittent rotation drive and continuous rotation drive. A first sample dispensing device having a tray,
The present invention relates to a continuous chemical analysis method using an automatic chemical analysis device including a second sample dispensing device including a second reagent tray, a washing-dehydration device, and a measuring device.

Further, the present invention includes, for example, body fluids such as blood, plasma, serum, lymph fluid, excrements such as urine, gastric juice, pancreatic juice, bile, saliva, secretory fluid such as sweat, ascites fluid, pleural fluid, puncture fluid such as synovial fluid. The present invention relates to a continuous chemical analysis method for a liquid sample such as a specimen.

(B) Conventional technology For example, in a turntable-type automatic chemical analyzer, a turntable in which reaction vessels such as reaction cuvettes are arranged is arranged in accordance with a preset time program.
For example, by intermittently driving the rotation, when the turntable is stopped, analysis of the sample dispensing region, the first reagent dispensing region, the stirring region, the second reagent dispensing region, the stirring region, the reaction region, the washing-dehydration region, etc. A predetermined amount of sample is dispensed by the sample dispenser from the sample container of the sample rack and a predetermined amount of the first reagent is dispensed by the first reagent dispenser from the first reagent tray to the reaction containers located in the work area. Dispensing, dispensing a predetermined amount of the second reagent from the second reagent tray with the second reagent dispenser, stirring and mixing the reaction solution, reacting, discharging the reaction solution from the measured sample container, and subsequently brushing In addition to performing analysis operations such as washing and dehydration, the absorbance of the analysis item components is measured for the sample located in the measurement area, and then the turntable is intermittently driven to rotate and the reaction container is sent to the next stop position. Analysis work area For reaction container positioned in, respectively As before sample dispensing, the first and second reagent dispensing, stirring,
Analysis operations such as reaction, brushing, washing, and dehydration are performed, and the driving operation of such a turntable and the analysis operation in each analysis work area are continuously repeated to perform analysis.

(C) Problems to be Solved by the Invention In the analysis by such an automatic chemical analyzer, the reagent is dispensed after a certain time after the sample is dispensed, so that when the reagent runs out during dispensing, the reagent Therefore, the reaction container moves along the reaction line with a sample or without the second reagent being dispensed.

On the other hand, the amount of sample per analysis in such an automatic chemical analyzer is extremely small, and if the reaction line is moved without adding a reagent, precipitates are deposited in the reaction container due to evaporation of water during that time. This makes it difficult to remove it by washing, and it remains in the reaction vessel even after washing, and the next step of analysis is performed. Is apt to appear and is a problem.

In particular, it is empirically recognized that the reagent shortage in the analysis of amylase affects the analysis value of cholesterol, and it is a problem.

It is an object of the present invention to solve the problem relating to the influence of the subsequent analysis value due to the running out of the first reagent in the conventional automatic chemical analyzer.

(D) Means for Solving the Problems The present invention aims to provide a continuous analysis method in which subsequent analysis values are not affected by running out of reagents.

That is, the present invention, the reaction container is sent to the sample dispensing position to dispense a predetermined amount of sample, the sample dispensed sample container is sent to the reagent dispensing position to dispense the reagent, After measuring the absorbance of the reaction product, the reaction container is sent to the washing position, the reaction container is washed, the washed reaction container is sent to the sample dispensing position, and a new sample is dispensed. In the continuous analysis method, the amount of reagent in the reagent container is measured for the reagent to be dispensed, the lack of the reagent amount is detected, and the diluent is dispensed into the reaction container in which the reagent is dispensed at the reagent dispensing position. It is a continuous analysis method characterized by dispensing.

In the present invention, when performing the next reagent dispensing to the reaction container in which the sample is dispensed or the reaction container in which the reagent is dispensed in the reagent dispensing step of the preceding stage, the dispensing is performed before the reagent dispensing. The amount of the reagent in the reagent container is measured by a conventional method such as a liquid level detector. By this measurement, when a shortage of the reagent amount is detected for the reagent to be dispensed, a diluent is dispensed into the reaction container in which the reagent is dispensed, instead of the reagent to be dispensed.

In the present invention, as the diluent, tap water, pure water, physiological saline, or a cleaning solution or a diluent for the reagent dispensing nozzle is used.

Dispensing of these diluents can be performed, for example, by operating a valve or the like through a flow path for introducing a cleaning liquid or the like of a reagent dispensing nozzle, but it may also be performed by separately providing a flow path for introducing a diluent. it can.

(E) Action In the present invention, the amount of the reagent in the reagent container is measured for the reagent to be dispensed at the reagent dispensing position, the lack of the reagent amount is detected, and the reagent is sent to the reagent dispensing position to dispense the reagent. Since the diluent is dispensed into the reaction container to be poured, when the reagent volume for the reagent to be dispensed is insufficient, the diluent will be dispensed into the reaction container instead of the reagent. Due to the shortage of the reagent amount, the reaction container does not move on the reaction line while the liquid amount in the reaction container is small.

Therefore, according to the present invention, the diluent is dispensed in place of the reagent even if the reagent is not dispensed in the reaction vessel and the reagent is not dispensed. This does not occur, and the cleaning operation at the cleaning position can easily perform the cleaning, which does not affect the next analysis.

Therefore, according to the present invention, it is possible to avoid the abnormality of the analytical value due to the shortage of the reagent to be dispensed, and accordingly, the accuracy of the analytical value can be improved, and the reliability of the analytical value is increased. be able to.

(F) Example Hereinafter, an example of an embodiment of the present invention will be described with reference to the accompanying drawings, but the present invention is not limited to the following description and examples.

FIG. 1 is an explanatory view showing an outline of a reagent dispensing section in one embodiment of the present invention.

The reagent dispenser 1 of the present example is provided at a position next to a sample dispenser (not shown) in an automatic chemical analyzer, and is a reagent dispenser provided in a so-called first reagent dispenser. The reagent dispensing nozzle 2 and the liquid level sensor 3 are held by a holding unit 4 attached to an arm (not shown).

The reagent dispensing nozzle 2 is movable up and down as shown by an arrow 5 by the operation of the holding portion 4, and is moved downward in FIG. 1 to be located at the first reagent collecting position 6 in the reagent container. It can be inserted into 7 and the reagent can be collected by suction. In addition, the reagent dispensing nozzle 2 causes the arrow 8
It is possible to move in the horizontal direction as shown in FIG. 3, and by this horizontal movement, the reaction cuvette 10 at the reagent dispensing position 9 is moved.
The first reagent can be dispensed by reciprocating between the reagent container 7 and the reagent container 7 at the first reagent collecting position 6. The upper end of the reagent dispensing nozzle 2 is connected to the pipe line 11, and the pipe line 11 is connected to the first connection line 13 of the three-way valve 12. Of the remaining two connecting paths 14 and 15 of the three-way valve 12, one connecting path 14 is connected via a pipe 16.
It communicates with the cleaning liquid reservoir 17 for cleaning the reagent dispensing nozzle 2, and the tip 18 of the conduit 16 is immersed in the cleaning liquid 19 so that the cleaning liquid 19 can be sucked. The other connecting path 15 is
It is connected to the reagent dispensing pump 20. The three-way valve 12 is composed of a stator section 21 and a rotor section 22, and operates a drive section (not shown) of the rotor section 22 to operate the rotor section 22.
By, for example, rotating 180 degrees in the direction of arrow 23, or rotating in the forward or reverse direction to 180 degrees, to switch the connection of the flow path 24 of the rotor portion 22 to the connection path, and the reagent dispensing pump 20.
The channel 25 can be connected to the conduit 11 on the reagent container 7 side or the conduit 16 on the washing liquid reservoir 17 side.

The piston 26 of the reagent dispensing pump 20 is connected to a driving device 27 including a stepping motor and a motion transmitting device, and the piston 26 is moved toward the arrow 28 by the operation of the driving device 27 to move the reagent dispensing pump 20. Perform the suction operation.

In this example, the reagent dispensing nozzle 2 is made of stainless steel,
Along with the liquid level sensor 3, it is connected to a liquid level detection device 29 having a liquid level detection circuit via conducting wires 30 and 31, respectively. The liquid level detection device 29 is connected to a main computer 32 via a lead wire 33, and the main computer 32 is connected to a controller 35 of the first reagent dispenser 1 via a lead wire 34. The control unit 35 of the first reagent dispenser 1 controls the three-way valve 12 via the lead wire 36.
Drive and drive 37 (not shown)
It is connected to the stepping motor of the drive device 27 of the piston 26 via.

The main computer 32 includes, in addition to the control unit 35 of the first reagent dispenser, a reaction disk, a cuvette rotor, a sample table, a sample dispenser, a second reagent dispenser, a cleaning device, an absorbance measuring device, and the like. It is connected to a sub-computer (not shown) of the control unit of each drive unit, and the drive of each unit is controlled by this connection.

Since this example is configured as described above, a plurality of reaction cuvettes 10 are arranged on the cuvette rotor 38 to form a reaction line. The reaction cuvette 10 is intermittently driven by the cuvette rotor 38 intermittently at a constant pitch in the direction of the arrow 39 for one pitch, a sample dispensing region, a first reagent dispensing region, a second reagent dispensing region, a reaction region, While being sent in the order of the washing region, while being positioned in the measurement region, the absorbance is measured and analyzed, for example, a plurality of times.

First, at the sample dispensing position, the sample dispenser dispenses a sample from the sample cup located at the sample collecting position while the cuvette rotor 38 is stopped. The reaction cuvette 10 into which this sample has been dispensed intermittently moves in the direction of the arrow 39 along the reaction line, is sent to the first reagent dispensing position 9, and is moved to the first reagent dispenser 1 by the first reagent dispenser 1. The first reagent is dispensed from the first reagent container 7 located at the first reagent collection position 6 of the one reagent tray 40 into the reaction cuvette 10.

For dispensing the first reagent, the arm is operated to move the reagent dispensing nozzle 2 to the first reagent sampling position 6, and then the holding unit 4 is moved downward to move the reagent dispensing nozzle 2 and the liquid surface. The sensor 3 is inserted into the first reagent 41 of the first reagent container 7. When the reagent dispensing nozzle 2 and the liquid level sensor 3 are both immersed in the first reagent 41, electrical continuity is detected. When this electrical continuity is detected, the liquid level detection device 29 is A signal is sent to the computer 32 indicating that the liquid level has been detected. On the other hand, the main computer 32 receives this signal and informs each control unit that there is no abnormality. Each control unit records this signal, but the control unit 35 receives the signal from the main computer 32 and operates the arm, the holding unit 4, the three-way valve 12, and the reagent dispensing pump 20 according to a normal program. Control. First, the rotor 22 of the three-way valve 12 is set to the position shown in FIG. 1 and the piston of the reagent dispensing pump 20 is set.
26 is moved downward by a predetermined stroke, and reagent dispensing nozzle 2
The first reagent 41 is sucked and collected therein.

When the first reagent 41 is sucked and collected in the reagent dispensing nozzle 2, the holding unit 4 is raised, and then the arm is operated to move the reagent dispensing nozzle 2 to the first reagent dispensing position 9. Next, the holder 4 is lowered, the piston 26 of the reagent dispensing pump 20 is moved in the direction opposite to the arrow 28, and the first reagent 41 sucked and collected in the reaction cuvette 10 is dispensed.

Unlike this case, when the holding part 4 is lowered and electrical connection is not obtained between the reagent dispensing nozzle 2 and the liquid level detection sensor 3, the liquid level detection device 29 is not electrically connected. It sends a signal to the main computer 32 that it is not available. Upon receiving this signal, the main computer 32 sends an abnormal signal to each control unit together with the sample number. Each control unit records this signal, but the control unit 35 uses this main computer.
Receiving the signal from 32, according to the program at the time of abnormality,
The operations of the arm, the holding unit 4, the three-way valve 12, and the reagent dispensing pump 20 are controlled. First, the rotor 22 of the three-way valve 12 is set to a position rotated 180 degrees in the direction of the arrow 23 from the position shown in FIG. 1 so that the flow path 25 of the reagent dispensing pump 20 communicates with the cleaning liquid reservoir 17, and The piston 26 of the reagent dispensing pump 20 is moved downward by a predetermined stroke, and the cleaning liquid 19 from the nozzle is sucked into the reagent dispensing nozzle 2.

When the cleaning liquid 19 is sucked and collected into the reagent dispensing nozzle 2, the rotor 22 of the three-way valve 12 is rotated 180 degrees in the direction of the arrow 23 to switch the flow passage, and the connection passage 13 and the reagent dispensing pump 20 flow passage. 25 is made to communicate, and the holding part 4 is raised. Next, the arm is operated to move the reagent dispensing nozzle 2 to the first reagent dispensing position 9. Next, the holding part 4 is lowered to move the piston 26 of the reagent dispensing pump 20 in the direction opposite to the arrow 28, and the cleaning liquid 19 sucked and collected in the reagent dispensing nozzle 2 is drawn.
Are dispensed into the reaction cuvette 10 in which the sample 42 is dispensed.

At the first reagent dispensing position 9, the reaction cuvette 43 into which the first reagent 41 is dispensed moves intermittently along the reaction line,
When the analysis item of the reaction cuvette 43 into which the first reagent is dispensed is a one-reagent system, for the reaction cuvette 43,
While the intermittent movement of the subsequent reaction cuvette rotor 38 is stopped, the absorbance measuring device for the analysis item component rotates to measure the absorbance of the analysis item component together with each reaction cuvette 4 located in the absorption measurement region of the analysis item component. A measurement of the absorbance with respect to wavelength is made.

On the other hand, when the analysis item of the reaction cuvette 43 into which the first reagent is dispensed is a two-reagent system, the reaction cuvette 43 is intermittently moved in the direction of the arrow 39 along the reaction line 5, The second reagent is dispensed from the second reagent container at the second reagent sampling position 30 by the second reagent dispenser when the second reagent is sent to the two-reagent dispensing position.

The reaction cuvette to which the second reagent has been dispensed moves intermittently along with the other reaction cuvettes in the direction of arrow 39 along with the other reaction cuvettes, but during the period during which the intermittent movement of the subsequent reaction cuvette rotor 38 is stopped, analysis is performed. The absorbance measuring device for the item component rotates to measure the absorbance for the absorbance measuring wavelength of the analysis item component together with each reaction cuvette located in the absorbance measuring region of the analysis item component.

In this example, measurement can be performed by rate analysis and the endpoint method, as in the conventional device.

After this measurement, the reaction cuvette is sent to the washing and dehydration area where it is washed and dehydrated to be clean and sent to the sample dispensing position.

Although only the first reagent dispensing apparatus has been described in this example, the second reagent dispensing apparatus is also configured in the same manner as the first reagent dispensing apparatus of the present example, and the first reagent dispensing apparatus runs out of reagents. Alternatively, the diluent may be injected into the reaction container into which the diluent has been injected or the reaction container into which the first reagent has been dispensed due to the reagent running out of the second reagent dispensing device. For example, the third reagent dispensing device after the second reagent dispensing can be configured in the same manner as the first reagent dispensing device of this example.

(G) Effect of the Invention In the present invention, the reagent amount in the reagent container is measured for the reagent to be dispensed at the reagent dispensing position, the shortage of the reagent amount is detected, and the reagent is sent to the reagent dispensing position. Since the diluent is dispensed into the reaction container to be dispensed, even if the amount of reagent in the dispensing reagent container is insufficient and so-called reagent run-out occurs, the amount of liquid in the reaction container that moves in the reaction line Can be maintained at a desired amount, like the conventional continuous analysis method,
The reaction line does not move with a small amount of liquid.

Therefore, according to the present invention, it is possible to prevent the deposit from being firmly attached to the wall of the reaction container when the reagent runs out, so that the influence on the next analysis due to the reagent running out is greater than that in the conventional continuous analysis method. Can be avoided and the accuracy of analysis can be improved.

[Brief description of drawings]

FIG. 1 is an explanatory view showing an outline of a reagent dispensing section in one embodiment of the present invention. Regarding the reference numerals in the drawing, 1 is a reagent dispenser, 2 is a reagent dispensing nozzle, 3 is a liquid level sensor, 4 is a holding portion, 5 is an arrow, 6 is a first reagent sampling position, 7 is a reagent container, and 8 Is an arrow, 9 is a reagent dispensing position, 10 is a reaction cuvette, 11 is a conduit, 12 is a three-way valve, 13 is a connecting conduit, 14 and 15 are connecting conduits, 16 is a conduit, 17 is a washing liquid reservoir, and 18 is a tip. , 19 is a cleaning solution, 20 is a reagent dispensing pump,
21 is a stator part, 22 is a rotor part, 23 is an arrow, 24 is a rotor flow path, 25 is a sample dispensing pump flow path, 26 is a piston, 27
Is a driving device, 28 is an arrow, 29 is a liquid level detecting device, 30 and 31 are conducting wires, 32 is a main computer, 33 is conducting wire, 34 is conducting wire,
35 is a control unit, 36 is a conducting wire, 37 is a conducting wire, 38 is a cuvette rotor, 39 is an arrow, 40 is a first reagent tray, 41 is a first reagent,
42 is a sample and 43 is a reaction cuvette.

Claims (1)

[Claims] 1. A reaction container is sent to a sample dispensing position to dispense a predetermined amount of sample, and the sample dispensed sample container is sent to a reagent dispensing position to dispense a reagent. After measuring the absorbance of the reaction product, after the measurement is completed, the reaction container is sent to the washing position to wash the reaction container, and the washed reaction container is sent to the sample dispensing position to newly dispense a sample. In the continuous analysis method, the amount of the reagent in the reagent container is measured for the reagent to be dispensed, the lack of the reagent amount is detected, and the diluent is dispensed into the reaction container in which the reagent is dispensed at the reagent dispensing position. A continuous analysis method characterized by pouring.