JPH08114604A - Automatic analyzer - Google Patents

Abstract

(57) [Summary] [Purpose] It is an object to provide an automatic analyzer capable of accurately aspirating a sample (sample) and a reagent solution. [Structure] An automatic analyzer that dispenses a sample and a reagent solution contained in a liquid container using a sampling probe into a reaction container to cause a reaction, and observes the result of the reaction to perform analysis. A sensor that detects that the probe has come into contact with the sample and reagent in the container, and determines whether the contact has been continuously detected by the sensor from the time the sampling probe starts suctioning until the end of suctioning. It is characterized by having a judging means and a notifying means for notifying the operator of the contact when it is judged that the contact is not continuously detected.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic analyzer for dispensing a sample and a reagent solution contained in a liquid container into a reaction container using a probe and observing the reaction result for analysis. .

[0002]

2. Description of the Related Art For example, when examining blood collected during a periodic health examination, an automatic analyzer is used because the number of samples is very large. The automatic analyzer sucks an appropriate amount from a container accommodating a sample using a probe for suction, and dispenses into a reaction container. Then, an appropriate amount of the reagent liquid is dispensed from the container in which the reagent liquid is contained in the container by using the aspiration probe, the sample and the reagent liquid are reacted, and the reaction result is observed. Then, analyze.

In such an automatic analyzer, the sample and the reagent solution must be contained in a predetermined amount in the container, and if the predetermined amount is not contained, accurate analysis cannot be performed. Therefore, conventionally, in order to detect whether a sample or a reagent solution is contained in the container, a sensor is provided at the tip of the probe to detect whether the sample or the reagent solution is present. . An analyzer using such a method is disclosed in, for example, JP-A-62-21881.
No. 8, JP-A-63-259420, and JP-A-2-59619.

However, each of the conventional methods described above is
Although different detection methods are used, it is possible to detect whether or not a sample or reagent solution is present at the start of aspiration, and when it is found that it is aspirated by the probe, an appropriate amount cannot be aspirated. Even if the sample and the reagent solution are exhausted, it cannot be detected. Therefore, an accurate analysis could not be performed and it was often necessary to reexamine.

Therefore, in order to detect the idle suction, there is known one which detects whether or not a sample and a reagent solution are reliably sucked by using a pressure sensor as described in Japanese Patent Publication No. 40403/1992. Has been.

[0006]

However, the method using such a pressure sensor cannot obtain a sufficient pressure change when the suction amount is very small, and it is difficult to accurately detect the pressure change.

The present invention has been made to solve such a conventional problem, and an object thereof is to provide an automatic analyzer capable of reliably sucking a sample and a reagent solution by a probe. Especially.

[0008]

In order to achieve the above object, the first invention of the present application is to dispense a sample and a reagent solution contained in a liquid container using a sampling probe into a reaction container. In an automatic analyzer that reacts and observes the result of this reaction for analysis, a sensor that detects that the sampling probe has contacted the sample and reagent in the container, and aspiration after the sampling probe starts aspiration Determination means for determining whether or not contact is continuously detected by the sensor until the end of, and a notification for notifying the operator of this when it is determined that contact is not continuously detected by the determination means It is characterized by having means.

The second invention of the present application is an automatic analysis in which a sample contained in a liquid container and a reagent solution are dispensed and reacted using a sampling probe, and the reaction result is observed and analyzed. In the apparatus, a sensor that detects that the sampling probe has come into contact with the sample and the reagent in the liquid storage container, and a determination is made as to whether or not the contact has been continuously detected by the sensor for a predetermined time after the sampling probe started suctioning. It is characterized by having a judging means and a notifying means for notifying the operator of the contact when it is judged that the contact is not continuously detected.

[0010]

According to the first aspect of the present invention configured as described above, it is detected by the sensor whether or not the tip of the sampling probe comes into contact with the sample or the reagent solution, and this detection signal sucks the sample and the reagent solution. It is determined whether or not it continues during the period. Then, when it is determined that the detection signal is continuing, it is notified that an appropriate amount of the sample and the reagent solution have been dispensed into the reaction container. Therefore, it is possible to always perform a highly accurate analysis and to immediately know this when an empty suction occurs.

Further, according to the second aspect of the present invention, it is determined whether or not an appropriate amount of sample or reagent solution has been dispensed, depending on whether or not the detection signal of the sensor is continuously obtained for a predetermined time. Therefore, similarly to the first aspect of the invention, it becomes possible to immediately know the idle suction.

[0012]

Embodiments of the present invention will be described below with reference to the drawings.

FIG. 1 shows an embodiment of an analyzer having a liquid level detecting function according to the present invention. In order to avoid complication, FIG. 1 mainly shows the device components relating to the sampling operation. In the figure, a sampling probe 2 attached to a vertically and rotatably movable arm 1 is equipped with a liquid level detection device 10 according to the present invention. When the sampler 3 is driven and the sample container 4 containing the predetermined sample is set at the sample suction position A, the sampling probe 2 moves to the sample suction position A, and then descends until the sample liquid level is detected. .

When the sample liquid level is detected, the probe 2
Stops descending and a predetermined amount of sample liquid corresponding to the measurement item is sucked by a syringe (not shown). When the suction of the sample is completed, the probe moves up and then moves to the sample discharge position B on the reaction tube 5 mounted on the rotatable reaction line 6. After the probe 2 descends for a predetermined distance at the sample discharge position B, the syringe discharges a predetermined amount of sample into the reaction tube 5. When the ejection is completed, the probe 2 moves up to prepare for the next sample suction. Then, the probe 2 repeats the above operation for each cycle.

FIG. 2 is a block diagram showing the principle of the electrostatic capacity type liquid level detection device 10 of the present invention. The structure of the liquid level detection device 10 is as follows. That is, a sine wave with an angular frequency ω made by the oscillator 11 is added to the bridge circuit 12,
One end of the pair wire is connected to the probe 2 through the pair wire 17 shielded from both ends thereof, and the other end is opened.

Then, after differentially amplifying the voltage corresponding to the change in electrostatic capacitance at both ends connected to the probe 2 of the bridge circuit 12 by the instrumentation amplifier 14, it is averaged by the full-wave rectifier 15 and the low-pass filter 16. The value is taken out and used as the sensor signal 18. Then, the TTL signal 19 is sent to a system control unit (not shown) by the signal comparison circuit 30 which will be described later in detail. The system control unit sends the reset signal 20 and resets the signal comparison circuit 30 when necessary such as the initial operation of the device.

Further, in order to displace the initial state of the bridge circuit 12 from the equilibrium state to the probe side by a predetermined amount, a compensation capacitor 13 having a predetermined value is attached to the bridge circuit terminal connected to the release side pair wire 7. .

FIG. 3 is a block diagram showing a detailed structure of the signal comparison circuit 30. As shown in the figure, the signal comparison circuit 30 includes an addition circuit 31, a first comparison circuit 32, a flip-flop (F / F) circuit 33, a sample hold 34 and a second comparison circuit 35. ing.

Next, the operation of this embodiment will be described with reference to FIG. The signal comparison circuit 30 includes an addition circuit 31.
The first comparison circuit 32 compares the sensor signal TP3 biased to decrease by the predetermined threshold value V _TH with the sensor signal TP2 that has passed through the integrating circuit having the predetermined RC time constant.
To compare. The output TP4 of the comparison circuit 32 is input to the “set” of the F / F circuit 33.

In the initial state, the flip-flop (F /
The Q (-) output of the F) circuit 33 is HIGH, and the sample hold (S / H) circuit 34 is in the sampling state. Since TP3 is lower than TP2 by the threshold value V _TH , the output TP4 of the first comparison circuit 32 maintains the HIGH state.

After that, when the probe 2 comes into contact with the liquid surface and the sensor signal TP1 changes such that the sensor signal TP1 exceeds the threshold value V _TH , the output TP4 of the comparison circuit 32 is the F / F circuit 3
Set 3. In the S / H circuit 34, the S / H gate is LO
It becomes W, and the rising voltage value V _H of the sensor signal TP1 at the time of contact with the liquid surface is held. At this point, the input voltages TP3 and TP5 of the second comparison circuit 35 are inverted in magnitude, so that the output TP6 of the second comparison circuit 35 is HIGH.
Changes from LOW to LOW. At this time, the TTL signal 19 is F
Since it is Q (-) of the / F circuit 33, it similarly changes from HIGH to LOW.

The probe 2 is a sample solution (sample).
While the sensor signal TP3 is in contact with, the sensor signal TP3 maintains a state larger than the held voltage value V _H. Here, when a predetermined suction operation is completed and the probe 2 rises and separates from the liquid surface, or when a shortage of the sample solution occurs during suction,
The sensor signal TP3 sharply decreases to V _H or less.
Then, the output TP6 of the second comparison circuit 35 changes from LOW to H.
Inverts to IGH and F / F with the rising slope
The circuit 33 is reset and the Q (-) output, that is, the TTL signal 19 becomes HIGH again. And the S / H gate is HI
Since it becomes GH, the S / H circuit 34 enters the sampling state, and TP3 becomes smaller than TP5 by the threshold value V _TH, so that the output TP6 of the second comparison circuit 35 maintains the HIGH state.

In this way, the TTL signal 19 can be maintained in the inverted state while the probe 2 is in contact with the liquid surface. Therefore, by observing whether or not the TTL signal 19 accompanies the operation of the probe 2, it is possible to determine whether or not the suction of the sample is accurately performed.

In the above embodiment, the sensor signal TP1 is continuously output from the time when the probe 2 is lowered to detect the contact of the tip end with the liquid surface of the sample until the probe 2 is raised. Although the method of determining whether or not the sample is present is used, in some cases, the minimum required sample may be aspirated without actually aspirating until the probe rises. In this case, the analysis result is not affected. Therefore,
By measuring the suction time after the tip of the probe 2 comes into contact with the liquid surface of the sample and detecting whether or not suction is continued for a predetermined time without idle suction, it is possible to determine whether or not the suction has been reliably performed. You may judge.

A specific circuit configuration example of the signal comparison circuit 30 is shown in FIG. In this example, the adding circuit 51 and the inverting circuit 52
Then, the adder circuit 31 shown in FIG. 3 is configured, and a negative voltage of −V _TH is required as a threshold voltage.

FIG. 6 is a block diagram showing a modified example.
In this example, the point where the sensor signal 18 is integrated by the RC circuit and this signal is compared with the threshold value V _B by the comparison circuit 61 is shown in FIG.
Different from the example. Then, this comparison result is supplied to the “set” of the F / F circuit 33 that detects the presence / absence of contact with the liquid surface.
Further, the adder circuit 51 requires a negative voltage of -V _TH as a threshold voltage.

FIG. 7 is a block diagram showing another modification. In this example, the positive threshold value V _TH and the characteristics of the operational amplifier (threshold value setting circuit 71) are used to add the adder circuit 5 in FIG.
1. It has a function equivalent to that of the inverting circuit 52.

FIG. 8 is a block diagram showing another modification. In this example, the signal voltage obtained by adding the threshold V _TH to the sensor signal that has passed the RC time constant is used as the sample / hold circuit 34.
Is connected to the plus input of the comparison circuit 81 via, and the magnitude is compared with the sensor signal connected to the minus input. Then, the F / F circuit 33 is set with the minus slope of the output of the comparison circuit 34, and the F / F circuit 33 is reset with the plus slope. The Q (-) output of the F / F circuit 33 is connected to the S / H gate to control the operation of the S / H circuit 34.

Next, the operation sequence at the time of sampling of the analyzer having the liquid level detecting function of the present invention will be described with reference to the apparatus configuration of FIG. 1 and the flowchart of FIG. First,
The probe 2 is at the home position A for sample suction of the sampler 3.
To start the descent to the lower limit position (step ST
1). If the liquid level of the sample is not detected until the lower limit position is reached (YES in step ST2).
S), a predetermined error processing routine is executed assuming that a sample shortage has occurred (step ST3). If the sample liquid level is detected on the way (step ST4), the descending of the probe 2 is stopped (step ST5), and then the syringe pump (not shown) of the probe 2 is driven to start the sample suction (step ST6). Then, during sample suction, it is checked whether or not the probe 2 is in contact with the sample liquid surface. If the syringe pump finishes sucking a predetermined amount of sample while maintaining contact with the sample surface (YE in step ST7).
S), the probe 2 moves up to the home position A and executes the next operation sequence. On the other hand, when there is no contact with the sample liquid surface of the probe 2 during the suction of the syringe pump (NO in step ST8), driving of the syringe pump is stopped (step ST9). Then, the effective suction amount is calculated from the moving distance of the syringe pump until the stop (step ST10). If the effective suction amount is equal to or larger than the determination reference amount (YES in step ST11), the effective suction amount is discharged when the sample is discharged into the reaction tube. If it is less than or equal to the judgment reference amount, a predetermined error processing routine is executed (step S
T12). Several can be selected as the criterion. For example, the dummy amount or the dummy amount + fixed sample discharge amount can be selected. Furthermore, dummy amount + (predetermined sample ejection amount / n) or (dummy amount + predetermined sample ejection amount) /
It may be n. Here, n is a real number with n> 1.

FIG. 10 shows the ion exchanged water 2 in the sampling operation of the analyzer having the liquid level detection function of the present invention.
It is a state of change of the sensor signal waveform when 0 μl is sucked. FIG. 11A shows a change signal when the suction is normally completed, and FIG. 11B shows a change signal when the sample is deficient during the suction and the air is sucked. As is clear from the figure, the TP5 continuously outputs the “H” level during the suction period during the normal suction, but becomes the “L” level when the sample shortage occurs in the middle. This notifies the operator of the lack of sample.

In this embodiment, the example in which the sample is sucked by the probe 2 has been described. However, even when the reagent solution is sucked, the empty suction can be similarly detected.

In this way, in this embodiment, it is detected whether or not idle suction has occurred from the time when the tip of the probe 2 comes into contact with the sample and the reagent solution until the suction is completed. Therefore, highly accurate analysis is possible.

[0033]

As described above, according to the present invention,
In addition to detecting whether the tip of the sampling probe is in contact, it is also determined whether this contact or suction is completed, or whether it has continued for a predetermined time, and whether a proper amount of sample or reagent solution has been aspirated. To confirm. Therefore, when the sample and the reagent solution are insufficient, this can be immediately known, and an effect that an accurate analysis can always be performed is obtained.

[Brief description of drawings]

FIG. 1 is a block diagram schematically showing an automatic analyzer according to the present invention.

FIG. 2 is a block diagram showing the configuration of a liquid level detection device applied to the automatic analyzer of the present invention.

FIG. 3 is a block diagram showing a detailed configuration of a signal comparison circuit according to an embodiment of the present invention.

FIG. 4 is a timing chart showing the operation of each signal in FIG.

FIG. 5 is a block diagram showing a specific configuration of a signal comparison circuit.

FIG. 6 is a block diagram showing a modified example of a signal comparison circuit.

FIG. 7 is a block diagram showing another modification of the signal comparison circuit.

FIG. 8 is a block diagram showing another modification of the signal comparison circuit.

FIG. 9 is a flowchart showing the operation of this embodiment.

FIG. 10 is a characteristic diagram showing how TP1 and TP2 change during a sampling operation.

[Explanation of symbols]

1 arm 2 sampling probe 3 sampler 4 sample container 5 reaction tube 6 reaction line
7 Release-side pair wire 10 Liquid level detection device 11 Oscillator 12 Bridge circuit 13 Compensating capacitor 14 Amplifier 15 Rectifier circuit 16 Low-pass filter 17 Shielded pair wire 18
Sensor signal 19 TTL signal 20 Reset signal 31 Addition circuit 32 First comparison circuit 33 Flip-flop circuit 34 Sample hold circuit 35 Second comparison circuit 51 Addition circuit 52 Inversion circuit 61, 81 Comparison circuit 71 Threshold setting circuit

Claims (3)

[Claims] 1. An automatic analyzer for dispensing a sample and a reagent solution contained in a liquid container using a sampling probe into a reaction container for reaction, and observing the reaction result for analysis. A sensor that detects that the sampling probe is in contact with the sample in the container and the reagent, and whether or not the contact is continuously detected by the sensor until the sampling probe starts suctioning and ends suctioning An automatic analyzer comprising: a determination unit for determining, and a notification unit for notifying the operator of the contact when it is determined that the contact is not continuously detected. 2. An automatic analyzer for dispensing a sample and a reagent solution contained in a liquid container using a sampling probe to cause a reaction, and observing the reaction result for analysis, wherein the sampling probe is A sensor for detecting contact with a sample or a reagent in the liquid storage container, a determination unit for determining whether or not the contact is continuously detected by the sensor for a predetermined time after the sampling probe starts suction, and the determination unit When the contact is determined not to be continuously detected in, the automatic analyzer is provided with a notifying means for notifying the operator of this. 3. An automatic analyzer which dispenses a sample and a reagent solution contained in a liquid container using a sampling probe into a reaction container to cause a reaction, and observes the reaction result for analysis. A sensor that outputs a voltage signal of a predetermined magnitude as a sensor signal when the sampling probe comes into contact with a sample or a reagent in a liquid storage container; a subtraction unit that subtracts a predetermined voltage value from the sensor signal; An integration circuit that delays the rise time of the signal and outputs it as an integration signal; a first comparison circuit that compares the sensor signal from which the predetermined voltage value has been subtracted with the integration signal; A flip-flop circuit that outputs a gate signal when it is determined that the subtracted sensor signal is large and holds the output, and the flip-flop circuit when the gate signal is supplied. A sample and hold circuit that holds the value of the sensor signal, and the output signal of the sample and hold circuit and the sensor signal from which the predetermined voltage value is subtracted are compared, and when the output signal of the sample and hold circuit becomes large, An automatic analysis device, comprising: a second comparison unit that supplies a reset signal to the flip-flop circuit.