JP2001242182A - Sample dispenser for automatic analyzer - Google Patents

Abstract

(57) [Summary] [Problem] To detect the degree of clogging of a sample probe when clogged, detect the possibility of the presence of foreign matter in the sample, and verify whether the dispensing operation has been performed correctly. In addition, a sample dispensing device of an automatic analyzer capable of improving the credibility of a measurement result is realized. A differential pressure sensor (10) is connected between a dispensing syringe (4) and a sample probe (1) by T-joints (6a, 6b), and its output is sent to a microcomputer (13) via an amplifier (11) and an A / D converter (12). It is captured. The microcomputer 13 stores the output of the differential pressure sensor 10 during the suction / discharge operation in the memory 14 and
To determine the degree of clogging. The advantage of measuring the pressure difference by the differential pressure sensor 10 is that the pressure difference is “0” when the sample probe 1 is closed, and therefore the pressure difference is measured when the sample probe 1 is not closed. If
The pressure difference between the two points, that is, the normal state and the completely closed state, is obtained, and the degree of clogging of the sample probe can be detected according to the pressure difference.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample dispensing apparatus used for an automatic analyzer for analyzing a sample such as blood or urine.

[0002]

2. Description of the Related Art For example, in an automatic analyzer for biochemistry or the like, a sample dispensing device having a dispensing syringe and a sample probe connected to the dispensing syringe is provided. A predetermined amount of the sample is dispensed from the sample container to the reaction container by sucking and discharging the dispensing syringe so as to be movable to the position.

[0003] Here, in an automatic analyzer, serum or plasma is usually used as a sample. However, since such a sample contains a solid such as fibrin, the solid is used as a sample probe or a sample. The pipeline connected to it may be blocked.

As described above, when the sample probe is clogged, it becomes impossible to dispense a predetermined amount of the sample into the reaction vessel, which has a serious adverse effect on the analysis result.

[0005] In order to solve such a problem,
For example, a pressure sensor is provided in a pipeline including a sample probe, and clogging of the sample probe is detected based on a comparison between an output of the pressure sensor and a predetermined threshold value (actual fairness 2).
And Japanese Patent Application Laid-Open No. 45818/1995) and an apparatus that monitors and integrates the output of a pressure sensor at predetermined time intervals and detects clogging of a sample probe based on a comparison between the integrated value and a reference value. -19362).

Further, the output of the pressure sensor is secondarily differentiated, and clogging of the sample probe is detected based on a comparison between the second derivative signal and a predetermined threshold value (Japanese Patent Laid-Open No. Hei 7-198726). Also, there has been proposed a method in which the output of a pressure sensor after a predetermined time has elapsed from a discharge operation is compared with a predetermined threshold value so that a sample having a high viscosity is not mistaken for a clogged sample probe (Japanese Patent Laid-Open No. 11-83868). ing.

[0007]

By the way, in the sample dispensing apparatus provided with the above-mentioned pressure sensor, if the output of the pressure sensor is monitored during the dispensing operation of the sample, it is determined according to the viscosity of the sample and the degree of clogging of the probe. And a pressure waveform that changes.

In a normal sample dispensing operation, a negative pressure is applied during the sample aspirating operation period T1 and a positive pressure is applied during the aspirated sample discharging operation period T2, and the atmospheric pressure level is maintained while the dispensing syringe is stopped. Return to

In the case of a pressure waveform during the dispensing operation of a highly viscous sample such as a body fluid other than serum such as cerebrospinal fluid or the serum of a dialysis patient, the negative pressure during the sample suction operation period T1 is normal. Period T1
A negative pressure remains afterwards, but returns to atmospheric pressure after a certain period of time. Therefore, in this case, the required amount of sample is aspirated into the probe.

In the case of a pressure waveform during the dispensing operation when fibrin is sucked during suction and the sample probe is completely closed, the pressure is not changed after the sample suction operation period T1 and after the sample discharge operation period T2. Does not return to atmospheric pressure, so no sample is dispensed into the reaction vessel.

If the sample probe has a pressure waveform during the dispensing operation when the fibrin is sucked during the suction and the sample probe is slightly closed, the negative pressure remains after the sample suction operation period T1 and the sample discharge operation period. Since the pressure does not return to the atmospheric pressure level after T2, some samples are dispensed into the reaction vessel, but the reliability of the data is lost.

As described above, some of the samples are simply viscous, and the suction and discharge operations are normally performed. On the contrary, when the sample is clogged immediately before the end of the sample suction operation period T1, Although the negative pressure itself during the sample suction operation period T1 does not increase, dispensing failure may occur.

Therefore, the clogging of the probe is prevented based on the peak value of the negative pressure during the sample suction operation period T1, the pressure level at a certain timing during the period T1, or the integral value of the negative pressure signal during the period T1. When determined, the probe may be determined to be clogged even when the sample is simply a highly viscous sample and is dispensed normally.

Therefore, in the prior art, in order to avoid the above-described problem, the clogging of the probe is determined by comparing the residual pressure in the flow path after a predetermined time from the suction operation with a predetermined value.

However, even if the clogging of the probe is determined by comparing the residual pressure in the flow path after a predetermined time from the suction operation with a predetermined value, the determination is made depending on the degree of clogging of the sample probe and the viscosity of the sample. Depending on the setting of the time and the predetermined threshold, there is a possibility that the determination as to whether or not the dispensing has been performed normally becomes ambiguous.

In such a case, the automatic analyzer does not dispense a predetermined dispensed amount for a sample which is out of the healthy value range in an item such as a drug use amount measurement where the healthy value is near 0. As a result, there is a possibility that a wrong value may be erroneously reported as a normal value, and a wrong drug administration or the like may be performed on the patient.

[0017] These problems are caused by the fact that when determining whether or not clogging is performed based on the absolute pressure measured at a certain point in the flow path, there are variations in sensor sensitivity and flow path resistance in the flow path. This is because the degree of clogging cannot be determined quantitatively and accuracy is lacking because judgment is performed based on comparison with a predetermined value.

In an automatic analyzer for detecting the liquid level of a sample based on the amount of electrical displacement such as resistance or capacitance when the sample and the sample probe come into contact with each other, the sample may have bubbles on its surface. In, there is a possibility that it is determined that the sample probe has reached the liquid level despite being in the bubble layer, the sample is sucked, air is sucked, and an incorrect measurement result is reported.

An object of the present invention is to detect the degree of clogging of a sample probe when it is clogged, detect the possibility of the presence of foreign matter, fibrin, etc. in the sample, and verify whether the dispensing operation has been performed correctly. It is an object of the present invention to realize a sample dispensing device of an automatic analyzer capable of improving the credibility of a measurement result.

Another object of the present invention is to realize a sample dispensing apparatus of an automatic analyzer capable of determining that a sample has not been normally sucked by a suction operation at the time of sample dispensing. is there.

[0021]

In order to achieve the above object, the present invention is configured as follows. (1) An automatic analyzer having a dispensing syringe, a sample probe connected to the dispensing syringe, and a dispensing means for sucking and discharging the dispensing syringe to suck and discharge a sample in a sample container by the sample probe. In the sample dispensing apparatus, a tube connecting the sample probe and the dispensing syringe, a first pressure measurement point in the tube located on the sample probe side of the tube, and a tube located on the dispensing syringe side of the tube A pressure sensor for detecting a pressure difference between the second pressure measurement point in the tube and the pressure difference detected by the pressure sensor,
Clogging determining means for determining whether or not the inside of the sample probe is closed.

(2) A dispensing syringe, a sample probe including a flow path pipe connected to the dispensing syringe, and a suction / discharge operation of the dispensing syringe to suck and discharge a sample in a sample container by the sample probe. A first pressure measuring point located on the sample probe side in the flow path pipe and a second pressure measuring point located on the dispensing syringe side in the flow path pipe.
A pressure sensor for detecting a pressure difference from a pressure measurement point,
Clogging determining means for determining whether or not the inside of the sample probe is closed based on the pressure difference detected by the pressure sensor.

(3) Preferably, (1) or (2) above
Wherein the pressure sensor has a first pressure sensor that measures the pressure at a first pressure measurement point, and a second pressure sensor that measures the pressure at a second pressure measurement point. If the sample probe cannot normally aspirate the sample due to erroneous detection of the liquid level due to bubbles or the like, the absolute value of the pressure at the first pressure measurement point or the pressure at the second pressure measurement point during the sample aspiration operation is The apparatus further includes suction determination means for determining whether or not the sample probe has suctioned the sample by utilizing the fact that the sample probe is smaller than when suction is performed normally.

(4) A dispensing syringe, a sample probe connected to the dispensing syringe, and dispensing means for sucking and discharging the sample in the sample container with the sample probe by sucking and discharging the dispensing syringe. In a sample dispensing device of an automatic analyzer, a tube connecting the sample probe and the dispensing syringe, a pressure sensor for detecting a pressure at a pressure measurement point located on the sample probe side of the tube, and the pressure sensor If the sample probe cannot aspirate the sample normally due to erroneous detection of the liquid level by bubbles in the sample container based on the detected pressure, the absolute value of the pressure at the pressure measurement point during the sample aspirating operation The sample probe aspirated the sample, taking advantage of the fact that And a suction determining means for determining whether.

The dispensing syringe includes a dispensing syringe and a sample probe connected to the dispensing syringe.
In a sample dispensing device having a dispensing means for discharging,
A pressure sensor that detects a pressure difference between two points in a pipe line including the sample probe and a pressure sensor that closes based on the pressure difference output from the pressure sensor and that the pressure difference becomes substantially zero when the sample nozzle is closed. Determining means for determining the degree of clogging of the sample nozzle during the suction operation from the pressure difference in the normal state;

Further, by using these, the pressure difference at the time of suction is compared with that at the time of water / air suction, and it is determined whether or not the sample suction in the dispensing operation has been correctly performed.

[0027]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS (First Embodiment) A first embodiment of the present invention will be described below with reference to the accompanying drawings. FIG.
In the sample probe 1, the inside is filled with a liquid and connected to a dispensing syringe 4 via tubes 2 and 3. The sample probe 1 is moved up and down by the motor 5.

When the sample probe 1 descends and reaches the liquid surface of the sample 7, the motor 8 is driven by the drive circuit 9 so that the syringe 4 performs a suction operation. Similarly, after the sample probe 1 has moved to the sample discharge position, the motor 4 is driven by the drive circuit 9 so that the syringe 4 performs a discharge operation.

The differential pressure sensor 10 is connected to a connection between the dispensing syringe 4 and one end of the tube 2 by a T-joint 6a, and is connected to the other end of the tube 2 by a T-joint 6b. Connected to the connection,
The output is amplified by an amplifier 11 and then taken into a microcomputer 13 via an A / D converter 12.

The microcomputer 13 stores the output of the differential pressure sensor 10 during the suction / discharge operation in the memory 14,
In addition to judging the degree of clogging of the sample probe 1, each measurement value is reported to the higher-level control unit 15 as necessary. This series of operations is controlled by the host control unit 15.

Hereinafter, a method for determining the degree of clogging in the sample probe 1 according to the first embodiment of the present invention will be described.

When the flow path is clogged, the flow of liquid in the flow path accompanying the sample suction operation stops. Whether or not the flow in the flow path has stopped can be detected by the pressure difference between the two points.
As a method of measuring the pressure difference between the two points, there are a method of preparing two pressure sensors and calculating a difference between the outputs of the two sensors, a method of using a differential pressure sensor, and the like.

The advantage of measuring the pressure difference is that when the sample probe is closed, the pressure difference is "0", so that the normal state, that is, the sample probe is opened,
By measuring the pressure difference in the unblocked state, two pressure differences between the normal state and the completely closed state are obtained, and the degree of clogging of the sample probe can be detected according to the pressure difference. FIG. 2A shows a schematic diagram of the flow path.

The pressure difference Pdif between the two points can be expressed by the following equation (1). Pdif = Rt / (Rc + Rn + Rt) × Pd (1) where Rt is the flow path resistance of the tube 2, Rn is the flow path resistance of the sample nozzle 1, Rc is the flow path resistance caused by clogging of the sample nozzle 1, Pd is the suction of the dispensing syringe 4
Discharge pressure.

Flow path resistance Rc caused by clogging of flow path
The pressure difference Pdif between the two points is inversely proportional to the pressure difference Pdif as shown in FIG. 2 (b). Clogging can be detected.

An example of use in an automatic analyzer will be described below. The microcomputer 13 determines whether or not the sample probe 1 is clogged during the ejection operation based on the synchronization signal of the dispensing syringe 4 from the drive circuit 9 and the control command from the higher-level control unit 15. Judge the degree and report the judgment result to the upper control unit.

The higher-level control unit 15 determines the authenticity of the measurement data according to the degree of the clogging. If the clogging is large and the sample dispensing operation may not have been performed correctly, the measurement result is not waited for. The sample dispensing operation is performed again.

FIG. 3 shows a pressure waveform during the dispensing operation. However, FIG. 3A shows a pressure waveform when the sample probe 1 is normal, FIG. 3B shows a pressure waveform when the sample probe 1 is completely closed, and FIG. 3 shows a pressure waveform when the sample probe 1 is not completely but partially closed.

In FIG. 3, the solid line shows a pressure measurement waveform at the T-joint 6a on the syringe 4 side, and the broken line shows a pressure measurement waveform at the T-joint 6b on the sample probe 1 side. The waveform indicated by the differential pressure in FIG. 3 is a waveform of the pressure difference between the pressure of the T-shaped joint 6a and the pressure of the T-shaped joint 6b.

The period T1 is during the suction operation and the period T2
Indicates a discharging operation, and a period T3 indicates a cleaning operation. In addition,
In FIG. 3, the horizontal axis indicates time, the vertical axis indicates pressure, the upper part indicates a positive pressure, and the lower part indicates a negative pressure.

In FIG. 3A, which shows a normal state, the syringe 4 during the suction operation and the discharge operation operates at a constant speed, so that the pressure on the syringe 4 side (T-joint 6a side) is substantially constant. Becomes On the other hand, the pressure on the sample nozzle 1 side (T-joint 6 b side) is a value obtained by dividing the pressure on the syringe 4 side by the flow path resistance from the pressure measurement point to the tip of the sample nozzle 1 and the syringe 4.

Therefore, the pressure difference between the two points, that is, the pressure on the syringe 4 side and the pressure on the sample nozzle 1 side is constant during suction and discharge, as indicated by the differential pressure.

Next, in FIG. 3B showing a completely closed state, the operation of the syringe 4 during the suction operation is constant, but the tip of the sample nozzle 1 is clogged. The negative pressure has a large absolute value. In this case, since the liquid does not flow in the flow path, the pressure on the sample nozzle 1 side also follows the pressure on the syringe 4 side. Thus, the pressure difference between the two points is zero during suction, as indicated by the differential pressure.

During the period from the suction operation to the discharge operation, the pressure in the flow path is maintained, and the pressure difference remains zero. During the discharging operation, the pressure on the syringe 4 side approaches the opening pressure, but the clogging of the sample nozzle 1 still causes no flow of the liquid in the flow path, and the pressure on the sample nozzle 1 side increases. Since the pressure on the side follows the pressure, the pressure difference becomes almost zero.

Next, FIG.
In (c), during the suction operation and the discharge operation, the absolute value of the pressure on the syringe 4 side transiently increases. Although the pressure on the sample nozzle 1 side follows the pressure on the syringe 4 side, since the flow exists in the flow path, the sample nozzle 1
A pressure difference is generated between the two points on the side and the syringe 4 side.

These pressure differences are determined by the suction
It depends on the discharge pressure, flow path resistance, and flow path resistance caused by clogging. Since the suction / discharge pressure and the flow path resistance are determined by design values, the flow path resistance due to clogging is determined from the pressure difference, and the degree of clogging can be calculated.

When clogging occurs during the suction operation,
When clogging occurs, the sample nozzle 1 side and the syringe 4
Since the pressure difference between the two points on the side is reduced, the degree of clogging can be calculated in the same manner.

As described above, according to the first embodiment of the present invention, the pressure difference between the pressure on the syringe 4 side and the pressure on the sample probe 1 side during the suction or discharge operation is detected by the differential pressure sensor. If the pressure difference is substantially zero, it is configured to determine that the sample probe 1 is clogged.

Further, the pressure difference in a normal state of the sample probe 1 is compared with the detected pressure difference to calculate the degree of clogging of the sample probe 1.

Therefore, when the sample probe is clogged, the degree of the clogging can be detected, the possibility of the presence of foreign matter, fibrin, or the like in the sample can be detected, and it can be verified that the dispensing operation has been performed correctly. It is possible to realize a sample dispensing device of an automatic analyzer that can increase the credibility of a result.

Further, it is possible to realize a sample dispensing apparatus of an automatic analyzer capable of determining that a sample was not normally sucked by a suction operation at the time of sample dispensing.

In the case where data becomes incorrect due to clogging of the sample probe, if clogging occurs, it is foreseen at the time of the sample dispensing operation that incorrect data will be output, and the sample dispensing operation is performed again before the measurement result is output. The effect of (1) is that the time required for retesting after an incorrect measurement result appears and the reagent required for retesting can be saved.

(Second Embodiment) Next, a second embodiment of the present invention will be described. In the second embodiment, in a normal state where the sample probe 1 is not closed,
A suction operation of water in contact with the washing tank and the like and an air suction operation in a state of being separated from water are performed, and the pressure in the sample probe 1 in both suction operations is stored and measured at each suction operation. By comparing the measured pressure with the stored pressure, it is possible to determine whether or not the sample has been sucked at each suction operation.

In the above-described first embodiment, the differential pressure sensor 10 is used to detect the pressure difference between the pressure on the sample probe 1 side and the pressure on the syringe 4 side. In the embodiment, a pressure sensor for measuring the pressure on the sample probe 1 side and a pressure sensor for measuring the pressure on the syringe 4 side are separately provided.

When the clogging of the sample probe 1 is detected, the differential pressure between the two pressure sensors is calculated, and when it is determined whether or not the sample probe 1 has sucked the liquid, one of the two is determined. This is performed using the pressure value detected by one pressure sensor.

In order to determine whether or not the sample probe 1 has sucked the liquid, it is more effective to monitor the pressure on the sample probe 1 side.

Hereinafter, an example of use in an automatic analyzer will be described. The microcomputer 13 stores in the memory 14 the pressure difference between the time of water suction and the time of air suction. Then, based on the synchronization signal from the drive circuit 9 of the dispensing syringe 4 and the control command from the higher-level control unit 15, the pressure at the time of the suction operation is compared with the stored data at the time of water suction and at the time of air suction. It is determined whether or not the sample probe 1 was able to suck the sample. (If the sample probe 1 was not able to suck the sample normally, the absolute value of the pressure at the pressure measurement point during the sample sucking operation was normally sucked. Is smaller than the time), and the determination result is reported to the higher-level control unit 15.

When the upper control unit 15 determines that air suction has occurred, the sample dispensing operation is performed again without exceeding the measurement result. In this case, since the bubble layer may continue to exist again during the sample dispensing operation, the upper control unit 15 controls each mechanism so as to increase the amount of the sample probe 1 penetrating the sample.

As described above, according to the second embodiment of the present invention, it is possible to determine whether or not the sample probe 1 has normally contacted the liquid surface and sucked the liquid during the sample suction operation. In addition, it is possible to realize a sample dispensing apparatus of an automatic analyzer that can determine that a sample has not been normally aspirated by a suction operation at the time of sample dispensing.

As a result, in use in an automatic analyzer, there is an effect of avoiding outputting incorrect data by verifying whether or not the sample suction operation has been performed correctly.

In the case where the sample liquid surface is not normally contacted due to air bubbles or the like, it is foreseen that incorrect data will be output during the sample suction operation, and the sample dispensing operation is performed again before the measurement result is output. This has the effect of not reporting incorrect measurement results.

In the example described above, the pressure sensor for measuring the pressure on the sample probe 1 side and the syringe 4
The pressure sensor for measuring the pressure on the sample side is provided separately, but the pressure sensor is arranged only on the sample probe side, and the sample is sampled during the sample suction operation based on the pressure value detected by the pressure sensor. It is also possible to determine whether or not the probe 1 has normally contacted the liquid surface and sucked the liquid. However, in this case, detecting the clogging of the sample probe 1 due to the differential pressure is
It will be difficult.

In the example described above, the sample probe 1 and the dispensing syringe 4 are connected via the tubes 2 and 3, but the sample probe 1 and the syringe 4 are connected without passing through the tubes 2 and 3. 4 may be directly connected (the sample probe 1 also has a function of a flow path pipe). In this case, the pressure is measured at two points on the distal end side of the sample probe 1 and the syringe 4 side, and the pressure difference is detected.

[0064]

According to the present invention, the degree of clogging of the sample probe can be detected, the possibility of the presence of foreign matter or fibrin in the sample is detected, and it is verified whether the dispensing operation has been performed correctly. Thus, it is possible to realize a sample dispensing device of an automatic analyzer that can increase the credibility of a measurement result.

Further, it is possible to realize a sample dispensing apparatus of an automatic analyzer capable of determining that a sample was not normally sucked by a suction operation at the time of sample dispensing.

[Brief description of the drawings]

FIG. 1 is a schematic configuration diagram of a sample dispensing apparatus according to a first embodiment of the present invention.

FIG. 2 is a schematic diagram of a flow channel of the sample dispensing apparatus of the present invention, and a diagram showing clogging dependence characteristics of a pressure difference.

FIG. 3 is a diagram showing a temporal change of a pressure waveform in a dispensing operation.

[Explanation of symbols]

 Reference Signs List 1 sample probe 2, 3 tube 4 dispensing syringe 5 motor 6a, 6b T-joint 7 sample 8 motor 9 drive circuit 10 differential pressure sensor 11 amplifier circuit 12 A / D converter 13 microcomputer 14 memory 15 host controller

 ────────────────────────────────────────────────── ─── Continuing from the front page (72) Inventor Masato Ishizawa 882 Ma, Hitachinaka-shi, Ibaraki F-term in the measuring instruments group of Hitachi, Ltd. (Reference) 2G058 EA02 EA14 EB01 EB22 ED02 GB10 HA00

Claims (4)

[Claims] 1. An automatic dispensing syringe having a dispensing syringe, a sample probe connected to the dispensing syringe, and dispensing means for sucking and discharging the sample in the sample container by operating the dispensing syringe by sucking and discharging. In the sample dispensing device of the analyzer, a tube connecting the sample probe and the dispensing syringe, a first pressure measurement point in the tube located on the sample probe side of the tube, and a tube on the dispensing syringe side of the tube A pressure sensor for detecting a pressure difference from a second pressure measurement point in the located tube; and a clog for determining whether or not the inside of the sample probe is closed based on the pressure difference detected by the pressure sensor. A sample dispensing device for an automatic analyzer, comprising: a determination unit. 2. A dispensing syringe, a sample probe including a flow path pipe connected to the dispensing syringe, and a dispensing device in which the dispensing syringe is operated to suck and discharge a sample in a sample container by the sample probe. A first pressure measuring point located on the sample probe side in the flow path pipe and a second pressure measurement point located on the dispensing syringe side in the flow path pipe. A pressure sensor for detecting a pressure difference from a point, and clogging determining means for determining whether or not the inside of the sample probe is closed based on the pressure difference detected by the pressure sensor. A sample dispensing device for an automatic analyzer. 3. The sample dispensing device according to claim 1, wherein the pressure sensor measures a pressure at a first pressure measurement point, and a second pressure measurement device. A second pressure sensor for measuring the pressure of the point,
If the sample probe cannot normally aspirate the sample due to erroneous detection of the liquid level due to bubbles or the like in the sample container, the pressure at the first pressure measurement point or the pressure at the second pressure measurement point during the sample suction operation Utilizing the fact that the absolute value of the sample is smaller than when the sample is normally aspirated, further comprising suction determination means for determining whether or not the sample probe has aspirated the sample, further comprising: Dispensing device. 4. An automatic dispensing syringe having a dispensing syringe, a sample probe connected to the dispensing syringe, and dispensing means for suctioning and discharging the dispensing syringe to suck and discharge a sample in a sample container by the sample probe. In the sample dispensing device of the analyzer, a tube for connecting the sample probe and the dispensing syringe, a pressure sensor for detecting a pressure at a pressure measurement point located on the sample probe side of the tube, and the pressure sensor are: Based on the detected pressure, when the sample probe can not normally aspirate the sample due to erroneous detection of the liquid level by air bubbles etc. in the sample container,
Suction determining means for determining whether or not the sample probe has suctioned the sample by utilizing that the absolute value of the pressure at the pressure measurement point during the sample suction operation is smaller than when the sample is normally suctioned. A sample dispensing device for an automatic analyzer, comprising: