JP2003004610A - Stirring method, stirring nozzle member and automatic analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To realize very small amount stirring capable of keeping test accuracy without generating carry-over or scattering. SOLUTION: Since stirring is performed by spraying air on the surface of a liquid or on the side surface of a container housing the liquid at a predetermined angle from a plurality of directions, non-contact stirring becomes possible and stirring efficiency is enhanced and, in equal stirring efficiency, the generation of scattering can be eliminated as compared with the spraying of air from one direction. By this constitution, very small amount stirring capable of keeping test accuracy can be realized without generating carry-over or scattering.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a stirring method, a stirring nozzle member and an automatic analyzer, and more particularly to a stirring method, a stirring nozzle member and an automatic analyzer for performing non-contact stirring.

[0002]

2. Description of the Related Art An automatic clinical test analyzer is a device for measuring components contained in human body fluids by using biochemical reactions, immune reactions and the like. When using an automatic clinical test analyzer, a stirring operation for mixing a body fluid component and a reagent or reagents is essential in each measurement step. The homogenization of the reaction solution by stirring is an important factor for improving the reliability of measured values. Conventionally, for this stirring operation, a method of directly stirring the reaction liquid with a stirring element has been adopted.

[0003]

However, in recent years,
In clinical tests, it is difficult to use the direct stirring method from the viewpoint of measurement efficiency. That is, in recent years, the number of samples (samples) measured in one test is large, and there is a demand for shortening the test time. Therefore, the amount of the liquid (reaction liquid) containing the sample is very small (sometimes several times). Microliters) may be tested. At this time, when the reaction solution is stirred by diverting the stirrer element sequentially, the measurement components are mixed from the previous reaction solution to the next reaction solution,
There has been a problem that a phenomenon in which measured values are blurred (so-called carryover) occurs. This tendency becomes more remarkable as the amount of the sample or the reaction solution is reduced.

In particular, in a test for detecting bacteria and viruses, there is a restriction on the inspection process that direct stirring cannot be used in the first place.

There is also a demand for reducing the amount of the reaction liquid from the viewpoint of cost and waste liquid treatment, and the direct stirring method cannot sufficiently stir a small amount of the reaction liquid. was there.

Incidentally, in the prior art, Japanese Patent Laid-Open No. 06-14804
There is known a stirring technique that does not rely on direct stirring, as disclosed in Japanese Patent No. 3, "Method and apparatus for stirring liquid material in small volume container". This method is a non-contact stirring method using air, and has an advantage that carryover does not occur. However, when air stirring is carried out in a very small amount of stirring solution, not only sufficient stirring cannot be obtained, but also the reaction solution may scatter and bubbles may be generated.

If the reaction solution scatters, it cannot be applied to the above-mentioned test for detecting viruses and bacteria, and if bubbles are generated, an automatic analyzer for detecting various reaction states and reaction results by the absorptance. However, there was a problem that it could not be used.

The present invention has been made in view of the above, and it is an object of the present invention to realize a stirring which does not cause carryover or scattering and which can maintain a test accuracy in a minute amount.

[0009]

In order to achieve the above-mentioned object, the stirring method according to claim 1 is to a liquid surface of a liquid or to a side surface of a container for containing the liquid.
It is characterized in that stirring is performed by blowing gas at a predetermined angle from a plurality of directions.

That is, in the invention according to claim 1, non-contact stirring is possible and the stirring efficiency is improved by spraying gas at a predetermined angle from a plurality of directions. In other words, if the stirring efficiency is the same, scattering does not occur as compared with blowing gas from one direction.

A stirring method according to a second aspect is the stirring method according to the first aspect, characterized in that the plurality of directions have a positional relationship of twist. That is, the invention according to claim 2 efficiently generates a liquid flow.

The stirring method according to a third aspect is the stirring method according to the first or second aspect, wherein the angle is 20 ° to 70 ° with respect to the liquid surface. That is, the invention according to claim 3 efficiently generates a liquid flow.

A stirring nozzle member according to a fourth aspect of the present invention is characterized in that an injection port for blowing the gas according to the first, second or third aspect in a predetermined direction is formed. In other words, the stirring nozzle member according to claim 4 is capable of spraying gas at a predetermined angle from a plurality of directions with respect to the liquid surface of the liquid or the side surface of the container in which the liquid is placed. As described above, a plurality of injection ports having a predetermined angle are provided. That is, the invention according to claim 4 can provide low-cost and high-efficiency stirring with a nozzle member having a simple structure.

The automatic analyzer according to claim 5 is
An automatic analyzer used for clinical examination or chemical analysis in the fields of medicine, biology, and chemistry, comprising a pump for blowing the gas and the nozzle member according to claim 4. To do. That is, the invention according to claim 5 can provide low-cost and highly efficient stirring.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below with reference to the drawings. Here, first, an automatic analyzer for carrying out the present invention will be outlined, and then a detailed description will be given focusing on stirring.

(Outline of Automatic Analyzer) FIG. 1 is an explanatory view for explaining the external structure of an automatic analyzer for carrying out the present invention. The automatic analyzer 100 includes an analysis / stirring unit 101, a consumables storage unit 102, an analysis unit 103, and a display unit 104.
And.

The analysis / stirring section 101 performs a colorimetric analysis, a turbidimetric analysis, etc. by spectroscopic analysis, absorptiometry, etc. by dropping a reagent on a sample (reaction solution) contained in a reaction container. further,
The analysis / stirring unit 101 stirs the reaction liquid in various processes such as the dropping process and the spectroscopic analysis. The stirring will be described in detail later. The analysis / stirring unit 101 also automatically conveys the reaction container, and guides and conveys an unused reaction container to the analysis passage as needed. In addition, analysis / stirring unit 1
In No. 01, a cleaning agent stored in advance is used to wash the probe and the like, and the inside of the apparatus is washed so as not to interfere with the next test.

The consumables storage section 102 stores various consumables used for clinical tests or chemical analyses. Consumables are roughly classified into four types (reagents, cleaning agents, sample containers, and regular replacement parts).

The analysis unit 103 analyzes the content of the test item based on the analysis result obtained by the analysis / stirring unit 101. For example, in the analysis / stirring unit 101, when another reagent B (color-developing substrate) is dropped onto a certain reagent A (enzyme-labeled reagent), the antigen present in the sample, the reagent A, and the reagent B form an immune complex. Then, the colored compound c is formed by the action of the enzyme bound to the reagent A, and the antigen in the sample is quantified by colorimetric analysis.
In particular, since there are many test items in the blood test and the reagents in the middle may be common, the results in the middle are stored in order, and the analysis unit 103 collects various results collectively using a predetermined calculation formula. Output.

The display unit 104 outputs and displays various information. Display items include test name, test item, test date, test number (sample number), test progress status (test end time), reagents used (product name, lot number, serial number, expiration date). . In addition, if an error (fault) occurs during the test, the error content, device status, and operation procedure for recovery procedure are also displayed.

(Contents of Analyzing / Agitating Unit 101) Next, the agitating portion of the analyzing / agitating unit 101 will be described in detail. 2 and 3
FIG. 3 is an explanatory diagram showing a state of a reaction tank disk and a reaction tank in the analysis / stirring unit 101. FIG. 2 is a plan view of the reaction tank disc, and FIG. 3 is a sectional view taken along the line AA of the reaction tank disc shown in FIG. As shown in FIGS. 2 and 3, the analysis / stirring unit 101 includes a disc-shaped reaction tank disk 111 and a disposable reaction container 112 attached to a hole (reaction tank) provided in an outer peripheral portion of the reaction tank disk 111.
And a stirring nozzle member 113 for stirring the reaction liquid in the reaction container 112.

FIG. 4 is an enlarged view of the stirring nozzle member 113. The stirring nozzle member 113 is made of stainless steel and is not affected by acid or alkali. The material is not limited as long as it is a member that is not affected by the reagent. The agitation nozzle member 113 has a thin hole formed in the hollow as shown in the drawing.
Make up 14. The air nozzles 114 are alternately arranged and have a twisted positional relationship. That is, the air nozzles 114 are not on the same plane and have a non-parallel positional relationship.

Further, the air nozzle 114 is connected to a pump and is constructed so that air is blown onto the liquid surface at a predetermined pressure. The angle θ of this air nozzle 114
Is preferably 20 ° to 70 °, more preferably 30 ° to 60 °
It has been found that the angle is preferable, and the angle around 45 is most preferable. The gas is not limited to air, and is not particularly limited as long as it can be used for stirring such as a rare gas.

Since the stirring nozzle member 113 is provided with the plurality of air nozzles 114 in this manner,
Allows non-contact stirring with good stirring efficiency. In the illustrated example, the number of the air nozzles 114 is two, but the number of the air nozzles 11 is not limited to this.
By staggering the 4's, efficient agitation is possible.

The stirring nozzle member 113 is attached to the main body side of the automatic analyzer 100 by a predetermined supporting member, and the reaction vessel disk 111 is sequentially rotated so that the reaction vessel 112 is sequentially moved to the stirring position. It will be sent.

(Example) Next, an example of stirring according to the present invention will be described. Here, in addition to the stirring experiment in the case of using two stirring nozzle members 113 for the air nozzle, a comparative experiment was performed for the conventional non-contact stirring with no air nozzle (no stirring) and one air nozzle.

The experiment was conducted by using 1.5% serum as a simulated solution.
Prepare 100 μl of PVA (polyvinyl alcohol) and orange G (OD478 = 1200) as a simulation reagent,
Each is a micro-pump with a probe, and the reaction container 11
Dispensed in 2. Here, the reason why Orange G was used as a simulation reagent is to examine the absorbance after stirring.

After dispensing, without air nozzle, 1 nozzle, 2
The solution in the reaction vessel 112 was stirred with this nozzle for 2 seconds.
The degree of stirring was randomly sampled from arbitrary 5 points in the solution immediately after stirring, the absorbance OD478 was measured, and the CV was measured.
The evaluation was made based on the value (= (deviation / average value) × 100) and the variation in absorbance (RANGE = difference between maximum absorbance and minimum absorbance of 5 point injection). The experiment was performed twice.

FIG. 5 shows that when there is no air nozzle (no stirring), when there is one air nozzle (conventional non-contact stirring),
It is a chart showing a stirring experiment when a plurality of air nozzles are arranged non-intersectingly (non-contact stirring of the present invention). As shown in the figure, it was found that the non-contact stirring of the present invention requires only 2 seconds for stirring, and is very efficient not only in the case of no stirring but also in the case of one air nozzle.

In this experiment, variation was observed in the agitation even in the case of two air nozzles, so the change over time was also measured. FIG. 6 is a diagram showing changes with time of CV% and range for the stirring of the present invention and the conventional stirring with a single nozzle. Of these, FIG. 6A is a table showing a case where two nozzles are used, and FIG. 6B is a table showing a comparative example using one nozzle.

FIG. 7 is a diagram showing a time-dependent change in the range in which the experimental result is analyzed, and FIG. 8 is a diagram showing a CV value in the experimental result analyzed with time. As is clear from the figure, it is understood that the stirring is performed with extremely high efficiency as compared with the conventional example. The automatic analyzer 100 has 1
A large amount of tests such as 1000 samples per hour may be performed. Along with this inspection, it is necessary to perform a large amount of stirring treatment. Since 1 hour is 3600 seconds, 100
When 0 sample is processed in 1 hour, the time required for 1 sample is 3.6 seconds or less.

As is clear from FIG. 7 or FIG. 8, when the automatic analyzer 100 is used, the time for stirring the solution for one sample is saturated in about 2 seconds, so that highly reliable stirring is possible. On the other hand, in the case of the conventional non-contact stirring (one nozzle), it can be seen that stirring for about 10 seconds is necessary. In other words, it can be said that high-speed analysis processing can be realized by using the stirring method of the present invention.

FIG. 9 is an explanatory view schematically showing the liquid flow when the stirring method of the present invention is used. In addition, FIG.
It is explanatory drawing which showed typically the liquid flow at the time of stirring a solution with one nozzle with the same velocity of air. As shown in the figure, in the present invention, it was found that the liquid flow was generated point-symmetrically. In the conventional example, the liquid flow was not uniform, and scattering was also generated.

Generally, it is sufficient to use air for stirring, but in the case of using a virus which is weak to oxygen, a reagent which is rapidly oxidized, etc., it can be dealt with by appropriately using a rare gas. Further, nitrogen gas or the like may be used depending on the mode of use. In the above example, the present invention is applied to the automatic analyzer 100, but the present invention is not limited to this, and can be applied to various fields such as chemical analysis.

[0035]

As described above, the stirring method of the present invention (Claim 1) has a predetermined angle from a plurality of directions with respect to the liquid surface of the liquid or the side surface of the container for containing the liquid. Stirring is performed by spraying a gas with, so that non-contact stirring is possible and stirring efficiency is improved, and if the stirring efficiency is equivalent, scattering is generated compared to blowing gas from one direction. As a result, it is possible to realize agitation that does not cause carryover or scatter, and can achieve a minute amount of agitation that maintains test accuracy.

The stirring method of the present invention (claim 2) is
In the stirring method according to claim 1, since the plurality of directions are arranged in a twisted positional relationship, it is possible to efficiently generate a liquid flow, and thus, the stirring is a test in which carryover or scattering does not occur. It becomes possible to realize a small amount of stirring that can maintain accuracy.

The stirring method of the present invention (claim 3) is
In the stirring method according to claim 1 or 2, since the angle is set to 20 ° to 70 ° with respect to the liquid surface, it is possible to efficiently generate a liquid flow, and thereby carryover and scattering It is possible to realize a small amount of stirring that does not occur and can maintain test accuracy.

Further, since the stirring nozzle member of the present invention (claim 4) has the injection port for blowing the gas according to any one of claims 1, 2 or 3 in a predetermined direction, it is simple. With a nozzle member having a simple structure, it is possible to provide low-cost and highly efficient stirring.

The automatic analyzer of the present invention (claim 5)
Is an automatic analyzer used for clinical examination or chemical analysis in the fields of medicine, biology, and chemistry, and comprises a pump for blowing the gas and the nozzle member according to claim 4. It is possible to provide low-cost and high-efficiency agitation, which makes it possible to achieve a very small amount of agitation that does not cause carryover or scattering and that can maintain test accuracy.

[Brief description of drawings]

FIG. 1 is an explanatory diagram illustrating an external configuration of an automatic analyzer that implements the present invention.

FIG. 2 is a plan view of a reaction tank disc.

FIG. 3 is an AA cut surface of the reaction vessel disk shown in FIG.

FIG. 4 is an enlarged view of a stirring nozzle member.

FIG. 5 shows an agitation experiment when there is no air nozzle (no agitation), when there is only one air nozzle (conventional non-contact agitation), and when multiple air nozzles are arranged in a non-intersecting manner (non-contact agitation of the present invention). It is a chart.

FIG. 6 is a diagram showing changes over time in CV% and range for the stirring of the present invention and the conventional stirring using a single nozzle.

FIG. 7 is a diagram showing a change with time in a range in which experimental results are analyzed.

FIG. 8 is a diagram showing changes over time in CV values obtained by analyzing experimental results.

FIG. 9 is an explanatory diagram schematically showing a liquid flow when the stirring method of the present invention is used.

FIG. 10 shows the same as the velocity of the air shown in FIG.
It is explanatory drawing which showed typically the liquid flow at the time of stirring a solution with this nozzle.

[Explanation of symbols]

100 automatic analyzer 101 Analysis / Agitation Unit 111 Reactor disk 112 reaction vessel 113 Stirring nozzle member 114 air nozzle

Continued front page    (72) Inventor Hisashi Sakamoto             2023-1 Endo, Fujisawa City, Kanagawa Prefecture             Iand Tea Shonan site F term (reference) 2G052 AA29 AD06 AD26 FB02 FB09                       HC32

Claims (5)

[Claims] 1. A stirring method characterized in that stirring is performed by spraying a gas onto a liquid surface of a liquid or a side surface of a container in which the liquid is placed at a predetermined angle from a plurality of directions. 2. The stirring method according to claim 1, wherein the plurality of directions have a twisted positional relationship. 3. The angle is 20 ° to 7 with respect to the liquid surface.
The stirring method according to claim 1 or 2, wherein the stirring method is 0 °. 4. A stirring nozzle member, characterized in that an injection port for blowing the gas according to claim 1, 2 or 3 in a predetermined direction is formed. 5. An automatic analyzer used for clinical examination or chemical analysis in the fields of medicine, biology and chemistry, comprising a pump for blowing the gas, and a nozzle member according to claim 4. An automatic analyzer characterized in that