JP2016014578A - Automatic analysis device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a liquid level detection device that detects a liquid level position with high sensitivity and high accuracy irrespective of manufacturing variations in a probe or a change in the installed environment.SOLUTION: A liquid level detection device comprises: a plurality of first switches for controlling electrical continuity between a first capacitor and a prescribed voltage; a plurality of second switches for controlling electrical continuity between the first capacitor and a second capacitor; a control unit for controlling the open/close operations of the first and second switches so as to repeat at random; a measurement unit for measuring a voltage that develops in the second capacitor as the charge accumulated in the first capacitor while the first switch is closed moves from the first capacitor to the second capacitor due to that the first switch is opened and the second switch is closed; and a determination unit for comparing the voltage value measured by the measurement unit with a prescribed threshold and determining whether a probe is in contact with a liquid level.

Description

The present invention relates to an automatic analyzer that performs qualitative and quantitative analysis of biological samples such as blood and urine.

  In order to perform qualitative and quantitative analysis of target components in biological samples such as blood and urine, an automatic analyzer that measures the concentration by adding a reagent to the sample (sample) and causing a reaction is used to reproduce the measurement results. It is widely used in large hospitals, inspection centers, etc. because it can improve performance and speed up measurement. One of the reasons is that a dispensing apparatus that can automatically dispense a sample and a reagent necessary for analysis with high accuracy and speed in comparison with a method of use is used.

  In particular, when capturing a certain amount of reagent or sample, the variation in the amount of adhesion to the outer wall of the probe causes a probable carry-in to the dispensing destination container or the sample container after the next time, insufficient cleaning of the outer wall of the probe, etc. There is a possibility of causing a variation in analytical reproducibility and an increase in cross contamination between samples. Therefore, in order to minimize the amount and dispersion of the probe on the outer wall of the probe, the liquid level is high enough to perform dispensing with high accuracy and speed by controlling the amount of probe entry into the reagent or sample to a minimum. As a detection technique, a bridge circuit or differentiation circuit is used to apply an input signal having a specific frequency component to the dispensing probe, and the liquid level position is detected based on the change in capacitance value at that time. Technology is disclosed. (Patent Documents 1 and 2).

Further, Patent Document 3 discloses an automatic analyzer that increases the number of tests that can be processed per unit time by dispensing reagents using a plurality of reagent dispensing probes.

JP-A-8-122126 Japanese Patent Laid-Open No. 2-59619 JP 2004-45112 A

  In the liquid level detection techniques described in Patent Documents 1 and 2, in order to operate these detectors, the detection target and the capacitance value are substantially equivalent, and a circuit network for balancing is required. This means that if there is a variation in the structure that fixes the detector or the detector itself, the balance is physically balanced in order to ensure the maximum dynamic range of the detector and to offset the amount of signal change due to the variation. It is a circuit for holding a trimmer capacity for the purpose.

  On the other hand, as a technical trend in recent years, there has been an increasing demand for improving laboratory efficiency in order to reduce social medical costs. For this reason, there are automatic analyzers in which a large number and many types of reagents are mounted on one reagent disk and dozens of types of target components can be measured. In such an automatic analyzer, the space in which reagent bottles can be installed is limited, and the shape of each reagent bottle is relatively miniaturized, so that the capacitance signal changes when detecting the liquid level. There is a need to reduce the sensitivity of the detector. Further, in order to detect the liquid level by the electrostatic capacity method, it is necessary that a liquid amount of a certain level or more remains in the reagent bottle so as to cause a change in the detectable electrostatic capacity value. Since the ratio of the dead volume remaining in the reagent bottle may inevitably increase with the miniaturization of the reagent bottle, there is a demand for improving the sensitivity of the liquid level detection sensor in order to improve the economy.

  However, in order to improve the sensitivity of the liquid level detection, if the sensitivity of the liquid level sensor is simply increased, the fluctuation due to the variation due to the device structure fixing the detector and the fluctuation of the individual difference of the detector itself are large. It is necessary to adjust the physical trimmer capacity for each device and each detector. This is very troublesome because adjustments are required during the manufacture, installation, and regular maintenance of the automatic analyzer.

Furthermore, when dispensing using a plurality of probes, the charge moves between the probes via the circuit network via the reagent container, and an interference voltage is generated in the detection signal of the detector. As a result, the net signal change due to the capacitance change before and after the liquid level contact becomes unclear, and there is a possibility that the amount of intrusion into the sample or reagent liquid level and erroneous detection may occur.

In view of the above problems, the configuration of the present invention is as follows. That is, a plurality of containers for storing liquid used for analysis, a plurality of probes for sucking liquid from the plurality of containers, and a plurality of first capacitors provided between the plurality of probes and a ground voltage, respectively. A plurality of second capacitors provided between the plurality of probes and the ground voltage, each having a known capacitance value, a specified voltage for applying a voltage to the first capacitor, and the first A plurality of first switches for controlling electrical conduction between a capacitor and the specified voltage; and a plurality of second switches for controlling electrical conduction between the first capacitor and the second capacitor. And a controller for controlling the opening and closing operations of the first switch and the second switch to be repeated at random, and the first capacitor stored in the first capacitor with the first switch closed. The voltage generated in the second capacitor as it moves from the first capacitor to the second capacitor when the first switch is opened and the second switch is closed. And a determination unit that compares the voltage value measured by the measurement unit with a predetermined threshold value and determines whether or not the probe is in contact with the liquid surface. .

According to the present invention, it is possible to detect the position of the liquid surface with high sensitivity and high accuracy by the above-described means even if the manufacturing variation of the probe or the mounting environment changes.

The figure which shows the liquid level detection device and switch opening and closing timing in the single probe The figure which shows the liquid level detection apparatus and switch opening / closing timing in several probes The figure explaining the 1st Example of the liquid level detection apparatus in this patent The figure explaining the 2nd Example of the liquid level detection apparatus in this patent

  Embodiments of the present invention will be described below with reference to the accompanying drawings. Since automatic analyzers are well known, descriptions of functions and the like of each device in the device will be omitted.

  A first embodiment of the present invention will be described with reference to FIGS.

  The reagent probe moves down from the upper part of the reagent container until the tip of the reagent probe contacts the reagent. Whether the reagent probe has come into contact with the reagent is determined by the following operation.

  The controller a controls the opening / closing operation of SWa1 and SWa2. In a state where the reagent probe is not in contact with the liquid surface, the reagent probe a (101) has a capacitor Cpa having an electrostatic capacity Cpa between the apparatus case (GND voltage). In accordance with the opening / closing of SWa1 and SWa2 shown in FIG. 1, when SWa1 is closed while SWa2 is opened, the specified voltage V0 is applied to the capacitor Cpa and the charge Q is accumulated. Next, when SWa1 is opened and SWa2 is closed while the charge Q is accumulated, the charge Q moves to a capacitor Ca having a known capacitance Ca. At this time, the voltage measured by the voltage measuring unit a is V.

  On the other hand, when the probe is in contact with the liquid, the reagent probe has a capacitance Cma between the reagent container and the housing, but the value of the capacitance Cma is larger than the value of the capacitance Cpa. . At this time, when SWa1 is closed while SWa2 is open, the specified voltage V0 is applied to the capacitance Cma and the charge Qa is accumulated, but the value of the capacitance Cma is larger than the value of the capacitance Cpa. Since Qa = CmaxV0 and Q = CpaxV0 can be calculated, Qa is larger than the value of Q. Further, when SWa1 is opened and SWa2 is closed while the charge Qa is accumulated, the charge Qa moves to a known capacitance Ca. At this time, the voltage measured by the voltage measuring unit a, Va is Va = Qa / Ca, so Va is the value of V observed when the reagent probe is not in contact with the reagent, and V = Q / Ca Is also a large value.

  The reagent probe a (101) continues to descend, and the switching operation of the SWa1 and SWa2 is repeated at all times, so that the determination unit a compares the voltage value measured by the measurement unit a with the V value. carry out. When V0 changes and becomes a voltage exceeding a certain criterion V1, it is determined that the probe has come into contact with the liquid, and the lowering of the reagent probe is stopped.

  Since the reagent probe has a capacitance between all the structures holding the probe and the circuit, the voltage V measured in a state where the reagent probe is not in contact with the liquid varies. In this case, variation occurs in the difference from the determination criterion V1, resulting in variation in sensitivity, and there is a concern about influence on dispensing accuracy. Therefore, it is possible to reduce the sensitivity variation by starting up the apparatus power supply, measuring the voltage V after a predetermined time has elapsed, and determining V1 according to the measured value.

  Next, a case will be described in which a plurality of probes are simultaneously lowered to adjacent reagent containers and stopped by liquid level detection in FIG. In order to simplify the description, the case of two reagent probes will be described. In the second reagent probe b (202), the controller b controls the opening / closing operation of SWb1 and SWb2. In a state where the reagent probe b (202) is not in contact with the liquid surface, the reagent probe b (202) has a capacitor Cpb having a capacitance Cpb between the reagent probe b (202) and the apparatus housing. When SWb1 is closed while SWb2 is open, the specified voltage V0 is applied to the capacitor Cpb and the charge Q is accumulated. When SWb1 is opened and SWb2 is closed while the charge Q is accumulated, the charge Q moves to the capacitor Cb having a known capacitance Cb. At this time, V is a voltage measured by the voltage measuring unit b.

  In a state where the probe b (202) is in contact with the liquid, the reagent probe b (202) has a capacitance Cmb between the reagent container and the housing, but the value of the capacitance Cmb is the capacitance Cpb. Larger than the value of. If SWb1 is closed while SWb2 is open at this time, the specified voltage V0 is applied to the capacitance Cmb and the charge Qb is accumulated, but the value of the capacitance Cmb is larger than the value of the capacitance Cpb. Qb = CmaxV0 and Q = CpaxV0, Qb is larger than the value of Q. Further, when SWb1 is opened and SWb2 is closed while the charge Qb is accumulated, the charge Qb moves to a known capacitance Cb. Since the voltage measured by the voltage measuring unit b at this time, Vb is Vb = Qb / Cb, Vb is the value of V observed when the reagent probe is not in contact with the reagent, and V = Q / Cb Is also a large value.

  The reagent probe b (202) always repeats the opening / closing operation of the SWb1 and SWb2 for the time that the descent continues, so that the determination unit b compares the voltage value measured by the measurement unit b with the V value. carry out. When Vb changes and becomes a voltage exceeding a certain criterion V1, it is determined that the probe has come into contact with the liquid, and the descent of the reagent probe is stopped.

  Next, a typical example in which interference occurs in each of the above operations when the reagent probe a (201) and the reagent probe b (202) are simultaneously lowered will be described. Since the reagent probe a (201) and the reagent probe b (202) have the independent control part a and control part b, respectively, the opening / closing timing as shown in FIG. 2 may occur. When both SWa2 and Swb1 reagent probe a (201) and reagent probe b (202) are in contact with the reagent, SWa2 can transfer the charge Qa accumulated in Cm and Cma to Ca. Since the charge accumulation operation is performed on Cm and Cmb by Swb1 while SWa2 is closed, sufficient charge cannot be transferred to the capacitance Ca. In this case, the voltage measured by the measurement unit a does not exceed the determination reference V1 for determining liquid contact by the determination unit a, and contact with the reagent cannot be determined.

  Therefore, in the configuration of the first embodiment, the switching operation as shown in FIG. 3 is performed. The switch ON (closed) time of SWa1, SWa2, SWb1, and SWb2 is shorter than the closed switch OFF (open) time. For example, when the unit of the repeated operation of the switch operation is 200 us, the ON (closed) time of each switch is 1 us. Further, the shorter the operation interval between SWa1 and SWa2, the better. However, there is no problem as long as the time for electrically separating the circuits is ensured, and it may be 1 ns in an extreme case. Further, in order to avoid the case where the operation times such as SWa2 and Swb1 described above overlap, the operation of SWa1 and SWa2, and the operation of SWb1 and SWb2 are repeated at random times within the time of the operation unit. Control part a and control part b control so that it may do.

  In this case, the probability that SWa2 and SWb1 overlap in time is low (about 1%), and the possibility of occurrence of a liquid surface position determination failure is very low. Even if the timing of SWa2 and SWb1 overlap, interference occurs, and even if the detection of the liquid surface position does not operate normally, the probability that SWa2 and SWb1 will overlap in time again within the time of the next consecutive repetitive operation is Further lower (0.01% or less), the probability that interference occurs continuously n times decreases exponentially. By operating the switches at random by the control unit a and the control unit b, it is possible to make the situation in which the probes (301) and (302) become practically impossible to detect in spite of the liquid contact.

  In this embodiment, an example in which the present invention is applied to a reagent dispensing probe has been described. However, the present invention is not limited to the liquid level detection of a reagent, and can be used in an automatic analyzer such as a specimen, a sample, and a washing liquid Applicable to all kinds of liquids.

  FIG. 4 shows a second embodiment of the present invention.

  Reagent probe a (401) and reagent probe b (402) descend from the upper part of the reagent container and move downward until the tip of the reagent probe contacts the reagent. Whether the reagent probe has come into contact with the reagent is determined by the following operation.

  The control unit controls the opening / closing operation of SWa1 and SWa2. In a state where the reagent probe (401) is not in contact with the liquid surface, the reagent probe a (401) has a capacitance Cpa between itself and the apparatus casing. In accordance with the opening / closing of SWa1 and SWa2 shown in FIG. 1, when SWa1 is closed while SWa2 is opened, the specified voltage V0 is applied to the capacitance Cpa and the charge Q is accumulated. Next, when SWa1 is turned off (opened) and SWa2 is turned on (closed) with the charge Q accumulated, the charge Q moves to a known capacitance Ca. At this time, the voltage measured by the voltage measuring unit a is V.

  On the other hand, when the probe is in contact with the liquid, the reagent probe a (401) has a capacitance Cma between the reagent container and the housing, but the value of the capacitance Cma is the value of the capacitance Cpa. Bigger than that. At this time, when SWa1 is closed while SWa2 is open, the specified voltage V0 is applied to the capacitance Cma and the charge Qa is accumulated, but the value of the capacitance Cma is larger than the value of the capacitance Cpa. Since Qa = CmaxV0 can be calculated as Q = CpaxV0, Qa is larger than the value of Q. Further, when SWa1 is turned off (opened) and SWa2 is turned on (closed) with the charge Qa accumulated, the charge Qa moves to a known capacitance Ca. At this time, the voltage measured by the voltage measuring unit a, Va is Va = Qa / Ca, so Va is the value of V observed when the reagent probe is not in contact with the reagent, and V = Q / Ca Is also a large value.

  The determination unit a compares the voltage value measured by the measuring unit a with the V value by repeating the opening / closing operation of the SWa1 and SWa2 at all times while the reagent probe (401) continues to descend. . When V0 changes and becomes a voltage exceeding a certain criterion V1, it is determined that the probe has come into contact with the liquid, and the descent of the reagent probe is stopped.

  Since the reagent probe has capacitance between all the structures that hold the probe and the circuit, the voltage V measured in a state where the reagent probe is not in contact with the liquid varies. In this case, the difference from the determination criterion V1 varies, and the sensitivity varies, which may cause an influence on the dispensing accuracy. Therefore, it is possible to reduce the sensitivity variation by starting up the apparatus power supply, measuring the voltage V after a predetermined time has elapsed, and determining V1 according to the measured value.

  Next, a case will be described in which a plurality of reagent probes a (401) and reagent probes b (402) are simultaneously lowered to adjacent reagent containers and stopped by liquid level detection. In order to simplify the description, the case of two reagent probes will be described. In the second reagent probe b (402), the control unit controls the opening / closing operation of SWb1 and SWb2. In a state where the reagent probe b (402) is not in contact with the liquid surface, the reagent probe b (402) has a capacitance Cpb between itself and the apparatus housing. When SWb1 is closed while SWb2 is open, the specified voltage V0 is applied to the capacitance Cpb and the charge Q is accumulated. When SWb1 is opened and SWb2 is closed while the charge Q is accumulated, the charge Q moves to a known capacitance Cb. At this time, V is a voltage measured by the voltage measuring unit b.

  On the other hand, when the reagent probe b (402) is in contact with the liquid, the reagent probe b (402) has a capacitance Cmb between the reagent container and the housing, but the value of the capacitance Cmb is static. Larger than the value of the capacitance Cpb. At this time, when SWb1 is closed while SWb2 is open, the specified voltage V0 is applied to the capacitance Cmb and the charge Qb is accumulated, but the value of the capacitance Cmb is larger than the value of the capacitance Cpb. Since Qb = CmaxV0 and Q = CpaxV0 can be calculated, Qb is larger than the value of Q. Further, when SWb1 is opened and SWb2 is closed while the charge Qb is accumulated, the charge Qb moves to a known capacitance Cb. At this time, since the voltage measured by the voltage measuring unit b, Vb is Vb = Qb / Cb, Vb is the value of V observed when the reagent probe b (402) is not in contact with the reagent, V = The value is larger than Q / Cb.

  While the reagent probe a and the reagent probe b continue to descend, the voltage value and the V value measured by the measuring unit a and the measuring unit b by repeating the opening / closing operation of the SWa1, SWa2, SWb1, and SWb2 are always performed. Is compared by the determination unit a and the determination unit b. When V0 changes and becomes a voltage exceeding a certain criterion V1, it is determined that the probe has come into contact with the liquid, and the descent of the reagent probe is stopped.

  Next, a typical example in which interference occurs in each of the above operations when the reagent probe a (401) and the reagent probe b (402) are simultaneously lowered will be described. When the opening / closing timing as shown in FIG. 2 occurs, if both SWa2, Swb1 reagent probe a (401), and reagent probe b (402) are in contact with the reagent, SWa2 is originally stored in Cm and Cma. The charge Qa can be transferred to Ca. However, since the charge accumulation operation is performed on Cm and Cmb by Swb1 during the time period in which SWa2 is closed, sufficient charge cannot be transferred to the capacitance Ca. In this case, the voltage measured by the measurement unit a does not exceed the determination reference V1 for determining liquid contact by the determination unit a, and contact with the reagent cannot be determined.

Therefore, in the configuration of the second embodiment, the switching operation as shown in FIG. 4 is performed. The switch ON (closed) time of SWa1, SWa2, SWb1, and SWb2 is shorter than the OFF (open) time. For example, when the unit of the repeated operation of the switch operation is 200 us, the ON (closed) time of each switch is 1 us. Further, the shorter the operation interval between SWa1 and SWa2, the better. However, there is no problem as long as the time for electrically separating the circuits is ensured, and it may be 1 ns in an extreme case. In addition, the common control unit controls the opening and closing of the SWa1 and SWa2 operations and the SWb1 and SWb2 operations so that the operation time does not overlap. Liquid level detection is possible.

101 Probe a
102 Reagent container a
103 Device housing 201 Probe a
202 Probe b
203 Reagent container a
204 Reagent container b
205 Device housing 301 Probe a
302 Probe b
303 Reagent container a
304 Reagent container b
305 Device housing 401 Probe a
402 Probe b
403 Reagent container a
404 Reagent container b
405 Device housing

Claims (4)

A plurality of containers containing liquids used for analysis;
A plurality of probes for sucking liquid from the plurality of containers;
A plurality of first capacitors respectively provided between the plurality of probes and a ground voltage;
A plurality of second capacitors each provided between the plurality of probes and a ground voltage, each having a known capacitance value;
A specified voltage for applying a voltage to the first capacitor;
A plurality of first switches for controlling electrical conduction between the first capacitor and the specified voltage;
A plurality of second switches for controlling electrical conduction between the first capacitor and the second capacitor;
A control unit for controlling the opening and closing operations of the first switch and the second switch to be repeated at random;
The electric charge accumulated in the first capacitor with the first switch closed causes the first switch to open and the second switch to close so that the first capacitor A measuring unit for measuring a voltage generated in the second capacitor as it moves to the second capacitor;
A liquid level detection apparatus comprising: a determination unit that compares a voltage value measured by the measurement unit with a predetermined threshold value to determine whether or not the probe is in contact with the liquid level.
In the liquid level detection apparatus according to claim 1,
The liquid level detection device according to claim 1, wherein the first switch and the second switch are open for a shorter time than the time during which the switches are closed.
In the liquid level detection apparatus according to claim 2,
A liquid level detection device comprising a plurality of control units for individually controlling a plurality of first switches and a plurality of second switches.
  The automatic analyzer provided with the liquid level detection apparatus in any one of Claims 1-3.