JPH0619362B2 - Method for detecting short sample in automatic pipetting device - Google Patents

Description

The present invention relates to a method for detecting a short sample of an automatic pipetting device, and more particularly to an automatic pipetting device having improved accuracy of detecting an insufficient amount of a liquid sample injected into a sample tube. The present invention relates to a short sample detection method.

[Prior Art] An automatic pipetting device has been developed for the purpose of large-scale pipetting of received samples, pretreatment pipetting such as biochemistry, or pre-inspection pipetting such as RIA / EIA in a biopsy department of a hospital. Cage,
It is very important in various inspection and research fields because it can dispense a large amount of liquid sample with high accuracy and high speed.

For the operation mode of the automatic pipetting device, the nozzle tip at the end of the air hose connected to the suction pump is inserted into each sample tube of the serum rack in which a plurality of sample tubes in which serum etc. have been sucked are aligned. Sequential dispensing is known, in which a predetermined amount of liquid sample (serum) is inhaled and collected, and discharged and transferred to each sample tube of a serum rack in which a plurality of empty sample tubes are aligned. is there.

Further, as another example, there is sorting and dispensing, which is to sort the samples in each liquid tube of the serum rack in the same manner as in the case of the sequential dispensing according to the worksheet information from the personal computer. , Biochemistry and other analytical equipment assortment and RI
A, EIA set inspection dispensing, etc. are mentioned.

In any case, the basic operating principle of the device is the same, but in that case the problem is that the amount of sample pre-inhaled into the sample tube is insufficient, and this is overlooked. Therefore, the error of the experiment / inspection value will occur and the accuracy will decrease.

[Problems to be Solved by the Invention] As a method of detecting such a shortage of a liquid sample, that is, a short sample, a method of conventionally monitoring a pressure in an air hose at the time of inhaling a sample has been adopted.

That is, when the amount of the liquid sample in the sample tube is less than the predetermined suction amount, when the sample in the sample tube is completely sucked, the air hose internal pressure is negative by suction until then. , And the one that showed a continuous decrease suddenly returns to atmospheric pressure,
It is based on the principle of determining that the sample is a short sample when a large pressure change at this time is found.

However, such a method has a problem that the detection sensitivity of a short sample is very low, and its effect can hardly be exerted even when a delicate sample is insufficient.

That is, the above-mentioned conventional method enables reliable detection when the amount of the sample in the sample tube is much smaller than the reference amount, but it seems that the sample is deficient only slightly. Sometimes, not only the amount of sample, but also the temperature and the type of sample and other various conditions may cause a slight difference in the time of returning to atmospheric pressure in the air hose, so it is extremely difficult to draw a boundary line between a normal sample and a short sample. Becomes difficult.

OBJECT OF THE INVENTION The present invention has been made in view of the above-described conventional problems, and an object thereof is to reliably short-circuit by distinguishing this from a normal time even when the sample in the sample tube is very small. An object of the present invention is to provide a short sample detection method for an automatic pipetting device capable of detecting and determining a sample.

[Means for Solving the Problems] In order to achieve the above-mentioned object, the present invention provides an automatic method for inserting a nozzle tip of an air hose tip connected to a suction pump into a sample tube to absorb and collect a predetermined amount of sample sample. In the short sample detection method of the injection device, the pressure level in the air hose that changes with the suction time when collecting the liquid sample in the sample tube is integrated, and when the integrated value is less than or equal to the predetermined reference value, It is characterized in that the liquid sample shortage is detected and determined.

[Operation] According to the method of the present invention configured as described above, whether or not the liquid amount in the sample tube is insufficient, that is, the integrated value of the pressure level in the air hose after the start of the suction operation is used as a parameter for detecting the short sample. Used. This integrated value corresponds to the area of a pressure change graph in which the vertical axis represents the air hose pressure and the horizontal axis represents the suction time. In the case of a short sample, the sample will be exhausted during suction, and in the above graph, the time at which the pressure inside the air hose returns to atmospheric pressure after the start of suction, which decreases with the lapse of time, becomes earlier. Will appear in the form of a decrease in area value.

As a result, according to the method of the present invention, the short sample is not determined simply by the slope of the pressure change in the hose as in the conventional case, but the area amount obtained by integrating the pressure value that changes momentarily is used as the index. Therefore, the normal sample and the short sample can be surely discriminated from each other, and the detection accuracy can be remarkably improved.

[Embodiment] A preferred embodiment of the present invention will be described below with reference to the drawings.

FIG. 1 shows an apparatus configuration for executing the method of the present invention.
A nozzle tip 14 is attached to the tip of an air hose 12 connected to the suction pump 10. The nozzle tip 14 is inserted into a sample tube 16 and a predetermined amount of a liquid sample injected therein is sampled by suction. , And transfer to another container (not shown).

Although not shown in the illustrated example, such a dispensing operation is usually performed by a large number of sample tubes 16 each filled with a liquid sample.
Often done to.

Here, as the first step of dispensing, when the liquid is not injected at the time of dispensing from the parent container to the plurality of sample tubes 16, a sample tube or a short sample in which the injected liquid material does not reach a predetermined value It can occur for a variety of reasons. If these short samples are overlooked and are used as they are for subsequent sample tests, the entire test associated with them will be affected by the fact that their number at least causes a significant error or other adverse effect on the test results and that only one short sample is missing. There is a possibility that he will be blisters.

The conventional short sample detection method monitors the internal pressure of the air hose and pays attention to the fact that when the amount of liquid is below a predetermined suction amount, the time at which the internal pressure of the air hose returns to atmospheric pressure is accelerated, and when this is found, it is a short sample. It was configured to make a decision.

However, this has a problem that it is not possible to delicately discriminate the lack of the sample.

The characteristic of the method of the present invention is that the level of the internal pressure of the air hose after the start of suction is regularly integrated, and the area value change with a graph showing the pressure change with respect to the suction time axis obtained by this is used as the index. is there.

As a result, it becomes possible to clearly separate normal suction and short sample, and the discrimination accuracy of both is increased by increasing the specified suction amount, then once sucking it and projecting it again into the sample tube. Can be easily improved.

In the figure, a pressure sensor 1 for monitoring the internal pressure of the air hose 12 during suction is shown along the way of the air hose 12.
8 is connected, and the output of the pressure sensor 18 is the DC amplifier 2
After receiving the amplifying action at 0, it goes to the limiter 22.

The element array unit consisting of each element of the suction pump 10 to the limiter 22 is referred to as a channel CH, and the apparatus according to the illustrated example has five channels, but only a single channel is shown for simplification. The output of the limiter 22 is ADC (A / D converter) for each channel.
The detection signal input to 24 and converted into a digital value here enters LSU (liquid sensing unit) 26, is subjected to a short sample detection processing operation described later, and the result is transmitted to the host MPU 28.

At the same time, when it is determined that the sample is a short sample as a result of analysis in the LSU 26, a predetermined nozzle-pump stop signal or alarm signal is output to the suction pump 10 control unit (not shown).

Also, a command from the host MPU 28 for instructing one channel to monitor the internal pressure of the air hose 12 is L.
The LSU 26, which is output to the SU 26 and receives this, supplies a channel designation signal to the A / D converter 24, and accordingly, the A / D converter 24 operates one or more predetermined channels to perform suction operation. Then, the internal pressure of the air hose 12 is started to start the short sample finding action.

Next, the operation of the device of the present invention will be described with reference to FIG.

The figure (A) shows the pressure change at the time of controlled suction, that is, when the required amount of the liquid sample is filled in the sample tube 16, and the internal pressure of the air hose 12 changes about two stages with the lapse of time after the start of suction. The nozzle tip 14 is separated from the liquid surface at the same time when a predetermined amount of suction is completed, and the internal pressure of the air hose 12 rapidly returns to atmospheric pressure.

On the other hand, when the amount of the liquid sample filled in the sample tube 16 is insufficient, the pressure changes as shown in FIG.

That is, when the sample is insufficient, the time from the start of suction until the suction port of the nozzle tip 14 separates from the liquid becomes short, and the area surrounded by the dotted line representing the atmospheric pressure and the solid line of the pressure change graph in the drawing decreases. Understand to take.

Further, when there is no sample in the sample tube 16, that is, when the air is sucked, the graph becomes as shown in FIG. 7C, and the internal pressure of the air hose 12 becomes lower by the amount of the action of the suction pump 10, but its change. The proportion of has become very small.

Therefore, it is possible to very accurately detect and determine the sample shortage in the sample tube 16 by calculating such an area value and comparing this with a predetermined value.

The area value can be calculated by accumulating the internal pressure levels of the air hoses 12 that have been accurately sampled and performing the calculation every 5 msec in a 5-unit LSU as shown in the figure. If the area value calculated in this way does not vary between devices, it is possible to detect a short sample by comparing it with the display area or the area during air suction, but in reality there may be variations within the same lot. In addition, the reference area may actually change depending on the viscosity of the liquid sample. Therefore, the boundary between air / short sample suction and short sample / normal sample suction can be specified at the user level. Of these, the former is called the air judgment level and the latter is called the short sample judgment level. If it is below the short sample judgment level, it is judged as short sample, and if it is below the air judgment level, it is judged as air (no sample). .

Furthermore, when the dispensing amount is single, the area value can be used as it is for the determination level, but this cannot cope with a plurality of dispensing amounts. Therefore, it is preferable to obtain the ratio (percentage) to the standard area and set this as the determination level.

With this method, it is not necessary to set the air judgment level and short sample judgment level for each dispensed amount, and it is possible to handle sorting and dispensing, and further increase or decrease the judgment level even if the area value varies depending on the device. Can be dealt with easily.

Further, the display areas of normal, short sample and air may be obtained in advance and tabulated, or a calculation formula may be obtained. Based on these, the standard area can be obtained from the type of the tip 14, the suction speed, the dispensing amount (pulse), and the like.

Further, even if the model is changed by such a method, if the characteristic of the display area is not changed, it can be dealt with only by changing the determination level.

FIG. 3 shows the variation of the area of the pressure waveform, that is, the area frequency of each sample tube 16 in each case when the minimum area value of the pressure waveform during normal suction is 100.

As is clear from the figure, the area values at the time of air suction (B) are greatly different from those at the time of normal suction (A), and it can be seen that there is no problem in determining this.

On the other hand, in the case of the short sample (C), when the shortage of the liquid sample is large, that is, in the case of a large amount of air, it is surely separated from the normal suction (A), so that an accurate determination can be made. , Normal suction as air volume decreases (A)
It can be seen that it becomes difficult to discriminate as it becomes closer to.

Therefore, by adopting a method of setting the suction amount of the liquid sample to be slightly larger than the required amount and returning the increased amount to the sample tube 16 promptly after the normal suction, the suction air amount at the time of the short sample is relatively increased. It has become possible to reliably determine that the sample is a short sample due to a delicate shortage of the liquid sample.

That is, by this excess suction operation, the sample tube 16
In the case of normal aspiration in which the required amount of liquid sample is filled, the amount of the aspirated liquid material increases, so that the area value in FIG. 2 increases.

On the other hand, in the case of the short sample, the time during which the air is sucked in is increased by the time corresponding to the increased suction amount during normal suction, but this does not substantially lead to an increase in the area value.

Therefore, the difference in area value between the normal suction and the short sample becomes large, which makes it possible to reliably discriminate the two. Then, since the excess suction amount at the time of normal suction is quickly returned toward the sample tube 16 after suction, a change corresponding to the excess suction appears in the internal pressure value detected by the pressure sensor 18, but is actually dispensed. It goes without saying that there is no change as a liquid material.

Thus, according to the method of the present invention, the area value is obtained by periodically sampling the pressure level in the air hose and integrating it, and comparing it with the standard value at the time of normal suction and the short sample. It is possible to reliably discriminate between the two, and in order to clarify the distinction between them, by performing the operation of returning the sample tube to the sample tube immediately after excess suction, it is possible to ensure this even if there is a delicate sample shortage. You can realize the discovery.

[Effects of the Invention] As described above, according to the present invention, the area value obtained by periodically sampling the air hose internal pressure and integrating it is used as the parameter for the short sample determination. Even in this case, it is possible to surely find out without missing this, and it is possible to surely avoid the occurrence of an error in the test result due to the mixture of the sample sample less than the predetermined amount.

[Brief description of drawings]

FIG. 1 is a configuration diagram of an apparatus to which the method of the present invention is applied, FIG. 2 is a graph showing a change in internal pressure of an air hose, and FIG. 3 is a graph showing a variation in area value of a pressure waveform. 10 ... Suction pump 12 ... Air hose 14 ... Nozzle tip 16 ... Sample tube 18 ... Pressure sensor 20 ... DC amplifier 22 ... Limiter 24 ... ADC 26 ... LSU 28 ... Host MPU.

Claims (1)

[Claims] 1. A method for detecting a short sample in an automatic pipetting device, wherein a nozzle tip at the end of an air hose connected to a suction pump is inserted into a sample tube to absorb and collect a predetermined amount of liquid sample. The pressure level in the air hose that changes with respect to the suction time at the time of sampling is taken out at a predetermined sampling period and integrated, and when the integrated value is less than or equal to a predetermined reference value, the liquid sample in the sample tube is insufficient. A method for detecting a short sample in an automatic pipetting device, which is characterized in that it is determined that the sample is present.