JP2005195418A - Short sample or detection method of automatic dispensing device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To detect the foaming state or the clogging state by a simple method by using thresholds. <P>SOLUTION: In this automatic dispensing device, a tip attached to a nozzle on the air hose end connected to a suction pump is inserted into a specimen tube, and a prescribed quantity of a liquid sample is sucked and collected. The device has a constitution wherein the thresholds for regarding suction by the tip as in the normal state, in the foaming state or in the clogging state at each of both points of time, namely, the point of time of a pressure sensor output peak at the liquid sample collection time in the specimen tube and the point of time after elapse of a fixed time from suction stop of the suction pump, are determined beforehand, and when the foaming state or the clogging state is detected by the thresholds at either of both points of time, the device is discriminated to be in the foaming state or in the clogging state. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a short sample of an automatic dispensing device such as an automatic immune measuring device, that is, a detection method.

Related technology

Conventionally, as an immunoassay utilizing an antigen-antibody reaction, a one-step and two-step non-competitive sandwich method and a competitive method are known.

A method for measuring the amount of antigen contained in a sample such as blood collected from a patient as a sample by the one-step non-competitive sandwich method will be described. For example, an antibody (label) that binds to an insoluble simple substance (solid phase) such as an inner wall or particle (particle) made of a synthetic resin and a labeling substance such as a radioactive substance, a fluorescent substance, or oxygen The sample to be measured is added to the reaction tube to which the antibody is added in advance.

As a result, in the reaction tube, the antigen contained in the specimen reacts with the solid-phase antibody in an antigen-antibody reaction (immune reaction) to produce an antigen-antibody complex. Thus, a complex in which three components of solid phase antibody-antigen-labeled antibody are sandwiched is generated. In this manner, the label of the labeled antibody is bound to the solid phase using the antigen in the specimen as a mediator.

Next, other than the label bound to the solid phase, the excess labeled antibody that did not bind to the antigen added in the reaction tube and the antibody component that did not participate in the immune reaction were separated by washing. (B / F separation) is performed, and finally, the amount of label proportional to the amount of antigen bound to the solid phase is quantitatively measured by a physical or chemical technique using the property of the label, Obtain the antigen concentration.

On the other hand, in the two-step non-competitive sandwich method, first, a sample is added to a reaction tube to which only a solid phase antibody is added in advance, and then a labeled antigen is added to the second reaction. This is a method in which a reaction is performed and measurement is performed.

In addition to these non-competitive sandwich methods, there is also a method referred to as a competitive method in which an antigen (labeled antigen) previously labeled with a labeling substance and the antigen in a specimen are competitively reacted with the solid phase antibody described above. Are known.

As an apparatus for automatically performing measurement in such an immunoassay, an automatic analyzer such as an automatic immunoassay apparatus is known.

  As an apparatus for automatically performing measurement in such an immunoassay, an automatic analyzer such as an automatic immunoassay apparatus, for example, an automatic dispensing apparatus is known. In this automatic dispensing device, in order to transfer the sample from the sample tube containing the collected sample to the reaction tube, and to insert a reagent or the like into the reaction tube, a sample is attached to a nozzle having suction and discharge functions. Aspirate the sample from the tube and discharge the sample into the reaction tube. Reagents are sucked and discharged into the reaction tube. When the series of suction and discharge operations of the nozzle is completed, the dirty chip is removed from the nozzle and discarded.

  Conventionally, when a sample is aspirated with a tip attached to a nozzle, bubbles may be aspirated, and solid substances such as fibrin in the sample fluid may become clogged with the absorption port of the tip. It may not work.

There are various proposals because there is less inspection data (short sample) and normal test values cannot be obtained if this bubble is sucked.
For example, in an automatic dispensing device, the pressure level in the air hose that changes with respect to the suction time at the time of sampling a liquid sample more than necessary once from the nozzle tip is taken out at a predetermined sampling period, and this is integrated. When it is below the reference, it is assumed that the liquid sample is insufficient, and after that determination, the excess suction amount is discharged.
In addition, various proposals have also been made regarding the blockage.
A method has been proposed in which the air hose internal pressure level, which changes with respect to the suction time during the collection of a liquid sample in the sample tube, is sampled at a predetermined period, and detected at the rate of change of the detected pressure value.
Furthermore, there are some which determine a threshold value at various points when collecting a liquid sample and determine bubbles, short samples, and the like.

  The above-described conventional method has to perform complicated calculations for discrimination. In addition, accurate results could not be obtained for complicated calculations. Furthermore, the detection rate of each state was also low.

The present invention proposes a method that can expect a fairly accurate result by an easy method.

As described in claim 1, in the automatic dispensing apparatus for sucking and collecting a predetermined amount of liquid material by inserting a tip attached to a nozzle at the tip of an air hose connected to a suction pump into the sample tube, the liquid in the sample tube Predetermine threshold values for the tip suction to be in the normal state, the bubble state, that is, the state at both the peak point of the pressure sensor output at the time of data collection and the point after a certain period of time has passed since the suction pump stopped. When the bubble state, that is, the state is detected by the threshold value at either time point, the short sample or the automatic dispensing device that detects the clogging of the chip, which is determined to be the bubble state or the state, is detected. Sample, detection method.

FIG. 1 shows voltage conversion of the normal output of the pressure sensor from when the nozzle tip starts sucking the liquid in the sample tube after the liquid level is detected and after which a predetermined time has passed. The threshold value represents a threshold value for discriminating each state at the time of the output peak of the pressure of the pressure sensor after the nozzle tip starts normal suction, and further, when a certain time has passed since the suction stop of the suction pump.
At the time of the suction pressure peak, Ya is the threshold value between the normal state and the bubble state, Yb is the threshold value between the bubble state and the bubble state, and after a certain time (400 mS) has elapsed since the suction stop, Yc is the normal state. This is the threshold value for the bubble state. Yb has the same value at the time of the peak of suction and after the stop of suction.

FIG. 2 is a system diagram of the automatic dispensing apparatus of the present invention.
10 is a suction pump, 11 is an air hose, 12 is a nozzle, 13 is a detachable chip attached to the nozzle 12, 2 is a pressure sensor that converts air pressure into voltage, 3 is an amplifier that amplifies the voltage, and 4 is analog to digital The A / D converter 5 for conversion converts the obtained value with a threshold value, instructs the next process work if normal, or stops the operation if abnormal. This is a control unit that generates an alarm.

FIG. 1 shows the bubble detection rate for each liquid amount. The first judgment point shows the output peak value of the pressure sensor during suction, and the second judgment point shows a certain time (400 mS) after the suction stops. The set time of 400 mS is the time until the internal pressure in the air hose fluctuates immediately after the sample or the like is aspirated and the fluctuation stops and stabilizes.

  The operation of the control unit 5 will be described. First, the nozzle 12 is moved and the chip 13 is loaded. Next, the sample tube to be aspirated moves, and the nozzle tip 13 also moves directly above this sample tube and descends. After detecting the liquid level, the tip of the nozzle tip 13 advances into the sample and starts aspiration of the sample. The output peak voltage value of the pressure sensor when performing the suction set here is compared with the threshold value of the first determination. Next, when the suction by the suction pump is finished, the voltage output of the pressure sensor 2 is compared with the threshold value of the second determination after 400 mS has elapsed since the suction stop. Thereafter, the nozzle tip 13 rises and stops at a predetermined position away from the liquid level. Further, after moving to the upper side of the reaction tube, the sample that is lowered and sucked is discharged into the reaction tube.

Next, the threshold value of the first determination of the output peak voltage value of the pressure sensor when performing suction will be described.
If the pressure sensor output peak voltage value is greater than -70 mV, bubbles, less than -70 mV and greater than threshold Ya, normal, less than threshold Ya, greater than threshold Yb In the case of the bubble, it is determined that the bubble is smaller than the threshold Yb. The actual threshold value Ya is as shown in Table 1.

This can be expressed as a mathematical expression 1. X represents the amount of liquid set to be sucked.
(Equation 1)
Ya =-(2.33X + 253)

The actual threshold value Yb is as shown in Table 2.

This is expressed by the following mathematical expression 2. X represents the set amount of liquid to be sucked.
(Equation 2)
Yb = − (2.33X + 253) X = less than 20 μl Yb = − (3.33X + 463) X = 20 μl or more

In other words, the threshold value is the same value Yb at both the first determination time and the second determination time.
Next, when the suction by the suction pump 10 is finished, the threshold value for the second determination, which is the voltage output of the pressure sensor 2 after 400 mS has elapsed since the suction stop, will be described.
If the output peak voltage value of the pressure sensor is larger than -50 mV, it is bubble, if it is smaller than -70 mV and larger than the threshold value Yc, it is normal, smaller than the threshold value Yc and smaller than the threshold value Yb. When it is large, it is determined that it is a bubble, and when it is smaller than the threshold value Yb, it is determined that it is clogged. The actual threshold value Yc is as shown in Table 3.

  This can be expressed in mathematical formula 3. X represents the set amount of liquid to be sucked.

(Equation 3)
Yc =-(2.14X + 203)

Next, by combining the first determination and the second determination, it is possible to detect bubbles (short samples) or clogging with an accuracy that can be used by a method that is easier than before. The combined effect of the first determination and the second determination represents a comparison between the conventional model that makes a determination as shown in Table 4 and the method of the present invention. As shown in this table, the detection rate of the present invention is greatly improved over the entire set suction amount.

Although the present invention has been described by detecting bubbles (short samples) or clogging of an automatic dispensing device, the present invention is also applicable to those using similar functions.

The figure which shows the time of performing 1st determination and 2nd determination of this invention Configuration diagram of the present invention

Explanation of symbols

10 Suction pump 11 Air tube 12 Nozzle 13 Chip 2 Pressure sensor 3 Amplifier 4 A / D converter 5 Control unit

Claims (1)

Pressure sensor output peak point when collecting a liquid sample in the sample tube in an automatic dispensing device that sucks and collects a predetermined amount of liquid sample by inserting a tip attached to the nozzle at the tip of the air hose connected to the suction pump into the sample tube In addition, a threshold value that is considered to be normal, foam state, that is, a state where the suction of the chip is normal at each time point after a certain period of time from the suction stop of the suction pump is determined in advance, and the foam state at either time point That is, when a state is detected by a threshold value, a short sample that is determined to be a bubble state or in other words a state, or a short sample of an automatic dispensing device characterized by detecting clogging of a chip, that is, Detection method.

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