JP2008302322A - Liquid agitation method, and cartridge and liquid agitation system used for it - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid agitation method which enables reliable agitation without causing an increase in cost, and to provide a cartridge and a liquid agitation system used for the method. <P>SOLUTION: In the liquid agitation method for agitating blood and a dilute solution, in a state that blood and the dilute solution are accommodated in a first dilution tank 42A defined by a plurality of inner surfaces including the inner surface 21a of an easily deformable wall 21, the easily deformable wall 21 is deformed so that a part of the inner surface 21a is projected toward the inside of the first dilution tank 42A, and a position of the deformed projected part 21c of the inner surface 21a is sequentially changed to the blood and the dilute solution. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a liquid stirring method suitable for stirring, for example, a very small amount of blood and a diluent or a reagent, a cartridge and a liquid stirring system used therefor.

  In order to grasp the health state of the body, it is widely performed to analyze specific components in blood. In recent years, analysis of the specific component has begun using an analysis apparatus having a relatively compact apparatus configuration without using a large-scale apparatus. In such an analyzer, a process of stirring the liquid is performed in order to dilute the blood with a diluent or to mix the diluted blood and the reagent.

  FIG. 23 shows an example of a conventional liquid stirring method (for example, Patent Document 1). In the figure, a cartridge X used for analyzing a specific component of blood, for example, is shown. The cartridge X is formed with a portion where the introduced blood 94 is diluted or mixed with a reagent. The dilution tank 92 formed in the main body 91 is an example. The blood 94 introduced into the dilution tank 92 is stirred together with the diluent 95. In order to perform this stirring, the dilution tank 92 contains a plurality of magnetic particles 93 in advance. A stirring arm 96 is provided outside the dilution tank 92. The stirring arm 96 is provided with a pair of magnets, and these magnets can be rotated. When the stirring arm 96 is rotated outside the dilution tank 92, the plurality of magnetic particles 93 are caused to move circularly. Thereby, the blood 94 and the diluent 95 are agitated. After the blood 94 and the diluted solution 95 are sufficiently stirred, the diluted blood is sent to an analysis step outside the figure.

  However, the amount of blood 94 used for this type of analysis is generally very small, on the order of μL. For this reason, it is necessary to prepare very fine particles as the plurality of magnetic particles 93. Further, the magnetic particles 93 should not have a property that unreasonably hinders analysis of specific components of the blood 94. Such magnetic particles 93 have caused a significant increase in the cost of the cartridge X. In particular, when the cartridge X is configured as a so-called disposable type that is discarded after one analysis, the above-described increase in cost becomes a major obstacle to practical use.

In addition, the driving force is transmitted to the circular motion of the magnetic particles 93 via the magnetic force. For this reason, when the rotation speed of the stirring arm 96 is increased, the magnetic particles 93 are less likely to follow the movement of the stirring arm 96 due to the resistance force of the blood 94 and the like. This has been a factor that hinders the improvement of the stirring force and thus the time required for analysis.
Japanese Patent No. 3135057

  The present invention has been conceived under the circumstances described above, and provides a liquid stirring method capable of reliably performing stirring without incurring an increase in cost, a cartridge used therefor, and a liquid stirring system. The issue is to provide.

  In order to solve the above problems, the present invention takes the following technical means.

  The liquid stirring method provided by the first aspect of the present invention is a liquid stirring method for stirring a liquid and a substance other than the liquid, and is defined by a plurality of inner surfaces including the inner surface of the easily deformable wall. In the state where the liquid and a substance other than the liquid are accommodated in the stirring space, the deformable wall is deformed so that a part of the inner surface protrudes inward of the stirring space, and the inner surface The position of the deformed protruding portion is sequentially changed with respect to the liquid.

  According to such a structure, according to such a structure, it is not necessary to accommodate what produces stirring energy, such as a magnetic particle, in the said stirring space. This is advantageous in reducing the cost of the instrument used for the liquid stirring method.

  In a preferred embodiment of the present invention, by pressing one or more protrusions against the outer surface of the easily deformable wall, a part of the inner surface of the easily deformable wall protrudes inward of the stirring space. To deform. According to such a structure, there is no possibility that the said deformation | transformation protrusion part will shift | deviate with respect to the said protrusion.

  In a preferred embodiment of the present invention, one or more of the protrusions are moved relative to the outer surface, whereby the deformed protruding portion of the inner surface is moved relative to the liquid. Such a configuration is suitable for promoting the flow of the liquid, and is advantageous for improving the stirring speed.

  In a preferred embodiment of the present invention, the relative movement of the one or more protrusions includes a circular movement. According to such a configuration, it is possible to cause a swiveling motion to occur in the liquid placed in the minute closed space. According to the turning motion, the liquid can be efficiently stirred.

  In a preferred embodiment of the present invention, the trajectories when the relative movement is performed are concentric circles having different diameters. According to such a configuration, it is possible to uniformly stir the liquid in the stirring space.

  In a preferred embodiment of the present invention, the easily deformable wall is a resin sheet. According to such a configuration, it is advantageous to make the deformed projecting portion well shaped along the projection.

  In a preferred embodiment of the present invention, the liquid is selected from blood, a diluent, and a liquid reagent, and the substance other than the liquid is selected as the liquid from among a diluent, a dry reagent, a blood cell component, and a liquid reagent. Substances different from those listed are selected. According to such a configuration, according to such a configuration, for example, blood cell count, hemoglobin (hereinafter referred to as Hb) and C-reactive protein (hereinafter referred to as CRP) measurement of blood can be performed efficiently and with high accuracy. it can. As a combination of the liquid to be stirred and other substances in such a configuration, for example, blood is diluted with a diluent, a dry reagent is dissolved with blood, and a blood cell component (blood clot) is dispersed with the diluent. The dry reagent is dissolved in the diluent, the high-concentration liquid reagent is diluted with the diluent, and the blood and the liquid reagent are mixed (this liquid reagent may be obtained by diluting the high-concentration liquid reagent with the diluent). It is done.

  The cartridge provided by the second aspect of the present invention is a cartridge having a stirring space for stirring a liquid and a substance other than the liquid, and is an inner surface included in a plurality of inner surfaces defining the stirring space. The easily deformable wall is provided, and the easily deformable wall is characterized in that it can be deformed so that a part of its inner surface protrudes inward of the stirring space.

  According to such a configuration, it is not necessary to enclose magnetic particles, for example, in the stirring space. Thereby, the cost of the cartridge can be reduced.

  In a preferred embodiment of the present invention, by pressing a protrusion against the outer surface of the easily deformable wall, the inner surface of the easily deformable wall is deformed so that a part of the protrusion protrudes inward of the stirring space. It is possible to be done. According to such a configuration, a part of the inner surface of the easily deformable wall can be reliably protruded inward of the stirring space.

  In a preferred embodiment of the present invention, a main body having an opening and a sheet for closing the opening are provided, and a portion of the sheet for closing the opening is the easily deformable wall. According to such a configuration, the easily deformable wall is suitable for being a portion having a remarkably small rigidity with respect to a portion other than the easily deformable wall surrounding the stirring space.

  In a preferred embodiment of the present invention, the sheet is made of a resin. Such a configuration is suitable for deforming the easily deformable wall into a shape that closely follows the shape of the pressed protrusion, for example.

  The liquid agitation system provided by the third aspect of the present invention includes a cartridge provided by the second aspect of the present invention, the easily deformable wall, and a part of the inner surface thereof protruding inward of the agitation space. And a liquid agitator having a deformed protrusion portion generating means for sequentially changing the position of the deformable protrusion portion of the easily deformable wall.

  According to such a configuration, the liquid sealed in the stirring space of the cartridge can be sufficiently stirred while being in a non-contact state.

  In preferable embodiment of this invention, the said deformation | transformation protrusion part production | generation means has a 1 or more protrusion. According to such a structure, the said deformation | transformation protrusion part can be reliably protruded toward the inner side of the said stirring space.

  In a preferred embodiment of the present invention, the one or more protrusions are movable relative to the outer surface of the cartridge. Such a configuration is suitable for promoting the flow of the liquid in the stirring space.

  In a preferred embodiment of the present invention, the relative movement of the one or more protrusions includes a circular movement. According to such a configuration, the liquid in the stirring space can be efficiently stirred.

  In a preferred embodiment of the present invention, the trajectory when the relative movement is performed includes a plurality of the protrusions that are concentric circles having different diameters. Such a configuration is suitable for uniformly stirring the liquid in the stirring space.

  Other features and advantages of the present invention will become more apparent from the detailed description given below with reference to the accompanying drawings.

  Hereinafter, preferred embodiments of the present invention will be specifically described with reference to the drawings.

  FIG. 1 shows an example of a cartridge used for analysis using the liquid stirring method according to the present invention. The cartridge A of this embodiment is for analyzing a specific component of blood, and is loaded into the analyzer B shown in FIG. The cartridge A and the analyzer B correspond to an example of the liquid stirring system according to the present invention.

  As shown in FIG. 1, the cartridge A includes a main body 1, a sheet 2, a dilution unit 4, a plurality of analysis units 5 </ b> A, 5 </ b> B, 5 </ b> C, 5 </ b> D, and two flow rate measurement units 6 </ b> A, 6 </ b> B. As will be described later, the liquid stirring method according to the present invention is performed in the diluting means 4 and the analysis units 5C and 5D.

  The main body 1 has a flat rectangular shape and is made of a resin such as acrylic. On the lower surface of the main body 1 in FIG. 1, a plurality of recesses or grooves for forming channels and tanks to be described later are formed. The main body 1 has a plurality of openings H1 to H15. In the present embodiment, the main body 1 has a size of about 70 mm square and a thickness of about 5 mm.

  The sheet 2 is made of a transparent resin such as PET (PolyEthilene Terephthalate) and is relatively thin. In the present embodiment, the thickness of the sheet 2 is about 0.05 mm.

  The opening H1 serves as a liquid inlet for introducing blood to be analyzed into the cartridge A. The diameter of the opening H1 is about 3 mm. As shown in FIG. 4, the opening H <b> 1 is connected to a through hole penetrating the main body 1, and an introduction flow path 43 a is connected to the lower part in the drawing.

  The dilution means 4 is for diluting the blood introduced from the opening H1 to a concentration suitable for various analyses. The first and second dilution tanks 42A and 42B, the blood measurement means 43, and the first sample blood measurement. Means 45 are provided. The diluting means 4 of the present embodiment is of a type capable of two-stage dilution using the first and second dilution tanks 42A and 42B as will be described later.

    The first and second dilution tanks 42A and 42B are tanks in which blood is diluted. As shown in FIG. 2, the first dilution tank 42 </ b> A is surrounded by a through hole formed in the main body 1 and a sheet 2 that closes the through hole. The portion of the sheet 2 that is closed is an easily deformable wall 21. That is, the first dilution tank 42 </ b> A is a stirring space defined by the inner surface 21 a of the easily deformable wall 21 and the inner surface of the through hole of the main body 1. The first dilution tank 42A is connected to the opening H2. The second dilution tank 42B has the same structure as the first dilution tank 42A and is connected to the opening H3. In the present embodiment, each of the first and second dilution tanks 42A and 42B has a diameter of about 6 mm and a depth of about 2 mm, and has a volume of 50 μL or more. 42 A of 1st dilution tanks are connected with the blood measurement means 43, and are the tanks in which the blood measured by the blood measurement means 43 is diluted. The second dilution tank 42B is connected to the first sample blood measuring means 45. In the second dilution tank 42B, the first sample blood measured by the first sample blood measuring means 45 is diluted.

  The blood metering means 43 is disposed between the opening H1 and the first dilution tank 42A, and includes an introduction channel 43a, a metering channel 43c, and an overflow channel 43d. The introduction channel 43a is a channel for introducing blood from the opening H1. A metering flow path 43c and an overflow flow path 43d extend from the introduction flow path 43a via a branching portion 43b. The measuring channel 43c is for temporarily retaining a predetermined amount of blood suitable for analysis. The introduction channel 43a, the metering channel 43c, and the overflow channel 43d have a width of, for example, about 380 μm and a depth of about 380 μm. The measuring channel 43c has a length of about 8 mm and a volume of about 0.5 μL. An orifice 43e is provided between the measurement channel 43c and the first dilution tank 42A. The orifice 43e has a width of about 50 μm, and is intended to intentionally increase the pressure loss resistance from the measuring flow path 43c to the first dilution tank 42A. The overflow flow path 43d is a flow path having a plurality of bent portions, and is connected to the opening H8.

  The first sample blood metering means 45 includes an introduction channel 45a, a metering channel 45c, and an overflow channel 45d. A metering channel 45c and an overflow channel 45d are connected to the introduction channel 45a via a branching portion 45b. The measurement channel 45c is connected to the second dilution tank 42B through the orifice 45e. An opening H10 is connected to the downstream end of the overflow channel 45d.

  The plurality of analysis units 5A, 5B, 5C, and 5D are parts where analysis of specific components in blood is performed. The first and second analysis units 5A and 5B are analysis units using an electrical resistance detection method, and the first analysis unit 5A is for white blood cells and the second analysis unit 5B is for red blood cells. On the other hand, the third and fourth analysis units 5C and 5D are analysis units using an optical technique, and the third analysis unit 5C is for Hb and the fourth analysis unit is for CRP.

  The first analyzer 5A is connected to the first dilution tank 42A via the buffer tank 46, and is a part for counting white blood cells using the sample blood diluted in the first dilution tank 42A. The buffer tank 46 is connected to an opening H9. The first analysis unit 5A includes a pore 52 and a pair of electrodes 51 sandwiching the pore 52, and is configured to be capable of counting using an electrical resistance detection method. The pore 52 has a narrow width of about 50 μm while the width of the flow path before and after the pore is about 200 μm. This width is determined so that the change in electrical resistance between the pair of electrodes 51 becomes significantly large when white blood cells pass. A pair of electrodes 51 are provided in the enlarged flow path portions around the pores 52. The pair of electrodes 51 is made of one or more kinds selected from, for example, gold, platinum, palladium, and carbon.

  The second analysis unit 5B is connected to the second dilution tank 42B and is a part for counting red blood cells using the sample blood diluted in the second time in the second dilution tank 42B. The second analysis unit 5B has substantially the same structure as the first analysis unit 5A.

  The third analysis unit 5C is connected to the buffer tank 46, and the fourth analysis unit 5D is connected to the first dilution tank 42A. The third and fourth analysis units 5C and 5D are parts for measuring Hb and CRP, respectively, by an optical method. The third and fourth analysis units 5C and 5D each have an analysis tank 54. As shown in FIG. 3, the analysis tank 54 is a stirring space connected to the opening H4 or the opening H5. A portion of the sheet 2 surrounding the analysis tank 54 is an easily deformable wall 21. The inner surface 21a of the easily deformable wall 21 is one of inner surfaces that define the analysis tank 54 as a stirring space. A reflective film 55 is formed on the ceiling surface of the analysis tank 54. The reflective film 55 has a high reflectivity suitable for measuring reflected light, such as a metal foil made of one or more kinds selected from gold, platinum, and palladium, and a white pigment layer made of titanium dioxide. What consists of the raw material which has is preferable. In the present embodiment, the reagent 56 is applied to the reflective film 55. The reagent 56 is mixed with the sample blood and can measure Hb or CRP by an optical method, and is in a dry state. Openings H9, H13, H14, and H15 are arranged before and after the third and fourth analysis units 5C and 5D.

  The first and second flow measurement units 6A and 6B are connected to the first and second analysis units 5A and 5B, respectively. The first and second flow rate measurement units 6A and 6B are parts for measuring the flow rate of the sample blood that has passed through the first and second analysis units 5A and 5B, respectively. 62. Openings H11 and H12 are connected to the downstream sides of the first and second flow rate measuring units 6A and 6B, respectively. When the pair of upstream electrodes 62 gets wet with the sample blood, the conduction can be detected. Thereafter, the time until the pair of downstream electrodes 62 becomes conductive is grasped. From this time and the volume that can be retained in the wide flow channel 61, the flow rate of the sample blood flowing in the first and second analyzers 5A and 5B can be accurately measured.

  Next, blood analysis using the cartridge A will be described below, particularly regarding the liquid stirring method according to the present invention.

  First, blood as a sample solution is introduced from the opening H1 using a dropper or the like. Then, as shown in FIG. 5, the cartridge A is loaded into the analyzer B. In this loading, the connector 8 is connected to a connector (not shown) of the analyzer B. The openings H1 to H15 are connected to a valve unit (not shown) connected to the pump (not shown) provided in the analyzer B, for example.

  Next, the blood is measured by the blood measuring means 43. As shown in FIG. 6, the blood S introduced into the opening H1 is sent to the downstream side by applying a high pressure to the opening H1. Among the blood S, the amount of the blood Sa that has accumulated in the measuring channel 43c is accurately defined by the volume of the measuring channel 43c. In the present embodiment, the blood Sa is about 0.5 μL. In addition, in this figure, x attached to opening H3, H14, H15 represents having been made into the closed state, and it is the same also in subsequent figures.

  Next, as shown in FIG. 7, the diluent 40A is introduced into the first dilution tank 42A. With the cartridge A loaded in the analyzer B, the opening H2 connected to the first dilution tank 42A is closed by a nozzle 82 provided in the analyzer B as shown in FIG. The nozzle 82 functions to apply pressure to the first dilution tank 42A and to inject the diluent 40A. And as shown in FIG. 8, the blood Sa which existed in the measurement flow path 43c is sent to the 1st dilution tank 42A by adding a high voltage | pressure again to the opening H1, for example.

  FIG. 9 shows a state immediately after the blood Sa and the diluent 40A are introduced into the first dilution tank 42A. A stirring arm 7 is disposed below the first dilution tank 42A. The stirring arm 7 is provided in the analyzer B and is appropriately controlled by a CPU (not shown) built in the analyzer B. The agitation arm 7 is an example of the deformed protruding portion generating means referred to in the present invention.

  As shown in FIG. 10, the stirring arm 7 includes a shaft 71, a base 72, and three protrusions 73. The shaft 71 is connected to the motor M. The base 72 is attached to one end of the shaft 71 and has, for example, a circular plate shape. The three protrusions 73 are attached to the base 72. The three protrusions 73 have different distances from the center of the base 72. When the stirring arm 7 is rotated by the motor M, the trajectories of the three protrusions 73 are concentric circles having different diameters. In the present embodiment, the motor M and the stirring arm 7 are configured to be able to approach and separate from the cartridge A. A spring is incorporated between the three protrusions 73 and the base 72 or between the base 72 and the shaft 71. Thus, the three protrusions 73 can be slightly retracted when receiving the force in the longitudinal direction of the shaft 71.

  Next, as shown in FIG. 11, the stirring arm 7 is moved closer to the cartridge A. All three protrusions 73 are pressed against the outer surface 21 b of the sheet 21. Since the easily deformable wall 21 is a flexible wall made of, for example, PET, a portion where each protrusion 73 is pressed is deformed along the tip shape of the protrusion 73. As a result, as shown in FIGS. 11 and 12, a deformed protruding portion 21 c appears on the inner surface 21 a of the easily deformable wall 21. The arrangement of the deforming protruding portion 21 c is the same as the arrangement of the two protrusions 73. In FIG. 12, for convenience of understanding, blood Sa, diluent 40A, and nozzle 82 are omitted.

  Next, as shown in FIG. 13, the stirring arm 7 is rotated by the motor M. As a result, the three protrusions 73 move circularly while drawing concentric circles having different diameters. Then, the three deforming projecting portions 21c also make a circular motion while drawing concentric circles having different diameters. Since the three deformed projecting portions 21c have a shape projecting inwardly of the first dilution tank 42A, the blood Sa and the diluted solution 40A are stirred by the three deformed projecting portions 21c. In this stirring, for example, the height of the deformed protruding portion 21c is about 0.1 mm, and the rotation speed of the stirring arm 7 is about 5000 to 15000 rpm. As a result, the blood Sa and the diluted solution 40A are stirred to such an extent that a vortex is generated. As a result, about 0.5 μL of blood Sa and about 50 μL of diluted solution 40A are mixed to obtain first sample blood DS1 as a diluted sample solution diluted 100 times.

  The first specimen blood DS1 obtained by stirring in the first dilution tank 42A is further diluted in the second dilution tank 42B, the white blood cell count in the first analysis unit 5A, the Hb analysis in the third analysis unit 5C, And those used for CRP analysis in the fourth analyzer 5D. In the second dilution tank 42B, the first sample blood DS1 measured by the first sample blood measuring means 45 is further diluted 100 times with the new diluent 40A. As a result, the second sample blood diluted 10,000 times is obtained. The stirring for obtaining the second specimen blood is performed by the same method as that using the stirring arm 7 in the first dilution tank 42A. The second sample blood is used for counting red blood cells in the second analyzer 5B.

  Of the other first specimen blood DS1, the one sent to the third analyzer 5C via the buffer tank 46 is stirred again in the analysis tank 54. As shown in FIG. 14, a reagent 56 is applied to the analysis tank 54. In order to perform Hb analysis in the third analyzer 5C, it is necessary to sufficiently stir the first sample blood DS1 and the reagent 56. Therefore, the stirring arm 7 disposed below the analysis tank 54 is pressed against the outer surface 21 b of the easily deformable wall 21 in a state where the analysis tank 54 is closed by the nozzle 84 provided in the analyzer B. The stirring arm 7 may be moved directly under the analysis tank 54 by providing a slide mechanism or the like for the stirring in the first dilution tank 42A, or may be provided with the stirring arm 7 dedicated to the analysis tank 54. Good. By the pressing of the stirring arm 7, three deformed protruding portions 21c appear.

  As shown in FIG. 15, when the stirring arm 7 is rotated, the three deformed projecting portions 21c are caused to move circularly. Thereby, the first specimen blood DS1 is swirled so as to generate a vortex. By this swirling energy, the reagent 56 is crushed and scattered in the first sample blood DS1. Then, the first sample blood DS1 and the crushed reagent 56 are stirred, and the reagent 56 is dissolved in the first sample blood DS1. Thereafter, for example, as shown in FIG. 16, Hb analysis can be performed by irradiating light L from below the analysis tank 54 and measuring the amount of light L reflected by the reflective film 55. The CRP analysis in the fourth analysis unit 5D is the same as this.

  Next, the operation of the liquid stirring method according to this embodiment, the cartridge A using the liquid stirring method, and the liquid stirring system combined with the analyzer B will be described.

  According to the present embodiment, the first and second dilution tanks 42A and 42B, which are stirring spaces for performing liquid stirring, and each analysis tank 54 need to contain, for example, magnetic particles for stirring. No. The sheet 2 that is one element for realizing the liquid stirring method described above is a general-purpose material made of PET, for example. For this reason, the cost required to realize liquid agitation in the cartridge A can be extremely reduced. Therefore, it is avoided that the cost of the cartridge A is unreasonably high, and it is suitable, for example, for configuring the cartridge A as a disposable type part.

  In addition, the liquid stirring method of the present embodiment is not only advantageous for reducing the cost of the cartridge A, but also the inventors' experiment that stirring performance equal to or higher than that of the liquid stirring method using magnetic force can be obtained. It is revealed by Details are described below.

  As the performance confirmation test, (A) a stirring comparison test corresponding to stirring for dilution in the first dilution tank 42A and (B) a stirring comparison test corresponding to stirring with the reagent 56 in the analysis tank 54 were performed. It was. In the test (A), a test cartridge was prepared, and 63 μL of physiological saline was filled in the stirring space. A solution obtained by gently pouring 7 μL of blood into this physiological saline was stirred. In the test of (B), 14 μL of liquid reagent was applied to the stirring space of the test cartridge, and this was left to stand overnight to produce a dry reagent. A stirring space filled with 70 μL of distilled water was stirred. For each of the tests (A) and (B), (1) When left for 30 seconds, (2) When stirred at 800 rpm for 30 seconds with a plurality of iron balls, (3) With a tool similar to the stirring arm 7 Three cases were verified when stirring at 9000 rpm for 30 seconds. The degree of stirring was quantified by measuring the absorbance at a wavelength of 570 nm for each liquid after stirring. The results are shown in Table 1. The number of measurements in each case is three.

表中の基本吸光度は、試験（Ａ），（Ｂ）に用いた液体および試薬について、攪拌棒を用いて十分に攪拌した予備実験から得られた吸光度である。これを１００％として、各ケースの値を比較した。まず、ケース（１）は、試験（Ａ），（Ｂ）のいずれにおいても低い数値となっている。これは、３０秒間程度の放置では、ほとんど拡散が進行しておらず、攪拌と呼べる現象が生じていないと言える。次に、ケース（２）は、試験（Ａ），（Ｂ）のいずれにおいても９０％近い値となっている。すなわち、鉄球を用いた攪拌を行えば、少なくとも同程度の時間だけ放置した場合と比べてはるかに攪拌がなされ、十分な拡散状態に近づいていると言える。しかしながら、ケース（３）の結果によると、試験（Ａ），（Ｂ）のいずれにおいてもほぼ１００％の値となっている。これは、単に放置したに過ぎないケース（１）ばかりでなく、鉄球を用いて積極的に攪拌を行ったケース（２）よりも良好な攪拌が実現できたことを意味する。

The basic absorbance in the table is the absorbance obtained from a preliminary experiment in which the liquids and reagents used in tests (A) and (B) were sufficiently stirred using a stirring bar. The value of each case was compared with this as 100%. First, case (1) has a low numerical value in both tests (A) and (B). It can be said that, when left for about 30 seconds, the diffusion hardly progresses and the phenomenon called stirring does not occur. Next, Case (2) has a value close to 90% in both tests (A) and (B). That is, it can be said that if stirring using an iron ball is performed, stirring is performed much more than when it is allowed to stand for at least the same amount of time, and it is approaching a sufficient diffusion state. However, according to the result of case (3), the value is almost 100% in both tests (A) and (B). This means that not only the case (1), which is simply left untreated, but also a better agitation than in the case (2) where the agitation was positively performed using iron balls.

About this point, the validity of a result is examined by comparing the stirring energy of cases (2) and (3). The source of agitation energy is the kinetic energy associated with the motion of the iron ball used for agitation or the deformed protruding portion by the agitation arm. This kinetic energy can be estimated at ½ mv ² . In case (2), the mass of water that can be pushed away by an iron ball having a diameter of 1 mm is about 0.52 mg, and the mass of water that can be pushed out by an iron ball having a diameter of 2 mm is about 4.19 mg. When this is rotated at 800 rpm, the rotation radius is 8 mm and the speed is about 335 mm / s. Therefore, the kinetic energy of water displaced by the iron ball is 29000-235000 mg · mm ² / s ² . On the other hand, in the case (3), the mass of water that can be pushed out by the deformed protruding portion whose height is 0.1 mm by the protrusion having a diameter of 1 mm is about 0.079 mg. When this is rotated at 9000 rpm, the rotation radius is 4 mm and the speed is about 1885 mm / s. Therefore, the kinetic energy of water pushed away by the deforming protruding portion is about 140000 mg · mm ² / s ² . It is considered that there is a difference in the conversion efficiency of the liquid into the stirring energy between the kinetic energy due to the iron ball moving in the liquid and the kinetic energy due to the circular movement of the deforming protrusion. Even with this conversion efficiency, the magnitude of kinetic energy in case (3) is not significantly inferior to that in case (2), and this can be said to have appeared in the results of Table 1.

  In particular, since an iron ball or the like and a magnet that drives the iron ball have a relationship of transmitting a driving force by a magnetic force, the iron ball may be delayed with respect to the magnet as the rotation speed increases. On the other hand, the protrusion of the stirring arm and the deformed protrusion cannot be displaced from each other. Therefore, if the stirring arm is rotated at a high speed, the speed of the deformed protruding portion can be easily increased. If the object to be agitated is blood or the like, the amount is generally a minute amount on the order of μL. In order to increase the kinetic energy at the time of stirring such a small amount of liquid, the liquid stirring method according to the present invention having the advantage that the speed can be easily improved is suitable.

  As in the above-described embodiment, the liquid stirring method according to the present invention is effective not only for stirring of liquids in the first dilution tank 42A but also for stirring of liquid and solid in the analysis tank 54. Since sufficiently large stirring energy can be obtained, the reagent 56 necessary for analysis can be applied to the analysis tank 54 in a dry state in advance. This is because when the cartridge A is used as a disposable type, the user is not forced to inject the reagent 56 and the analysis can be easily performed. In addition, there is an advantage that there is little possibility that the reagent 56 is altered.

  In order to stir the liquid stored in the closed stirring space, it is reasonable to circularly move the three protrusions 73, that is, the three deformed protruding portions 21c. This is because if the swirl motion is caused by the circular motion, the entire liquid is efficiently stirred even in the closed stirring space.

  By arranging the three protrusions 73 to draw concentric trajectories having different diameters, the three deformed projecting portions 21c also draw the same trajectory. Thereby, the blood Sa, the diluted solution 40A, or the entire first sample blood DS1 can be uniformly stirred by the three deformed protruding portions 21c.

  FIGS. 17-21 has shown the other example of the liquid stirring method which concerns on this invention, the cartridge used for this, and a liquid stirring system. In these drawings, the same or similar elements as those in the above embodiment are denoted by the same reference numerals as those in the above embodiment.

  In the example shown in FIGS. 17 and 18, the position where the reagent 56 is applied is different from the above-described embodiment. As shown in FIG. 17, in this embodiment, the reagent 56 is applied to the inner surface 21 a of the easily deformable wall 21 in the analysis tank 54. In this case, as shown in FIG. 18, when the stirring arm 7 is pressed against the outer surface 21b, the portion to which the reagent 56 has been applied becomes the deformed protruding portion 21c. Thereby, in the process in which the inner surface 21a swells, the effect of positively peeling the reagent 56 from the inner surface 21a can be expected. Further, the peeled reagent 56 can be reliably stirred by the deformed protruding portion 21c.

  19 and 20 show still another example of the analysis tank 54. As shown in FIG. 19, the analysis tank 54 of this embodiment is not provided with the reflective film 55 shown in FIGS. Further, at least a portion of the main body 1 that forms the ceiling surface of the analysis tank 54 is formed of a transparent resin. The reagent 56 is applied to the ceiling surface of the analysis tank 54. Unlike this, the configuration may be such that the reagent 56 is applied to the inner surface 21a as in the example shown in FIG.

  FIG. 20 shows a step of performing Hb analysis or CRP analysis by an optical method after stirring by the stirring arm 7 described above. In the present embodiment, the light L irradiated from below the analysis tank 54 forms the ceiling surface of the analysis tank 54 of the main body 1 and the first sample blood DS1 stirred together with the easily deformable wall 21 and the reagent 56. , In order. Then, the light quantity of the transmitted light is measured by the light receiving means arranged so as to be positioned above the analysis tank 54, whereby Hb analysis or CRP analysis is performed.

  FIG. 21 shows another example of the stirring arm 7. This embodiment is different from the above-described embodiment in that the rotation axis of the stirring arm 7 is tilted from a posture perpendicular to the easily deformable wall 21. With such an arrangement, when the stirring arm 7 rotates, the three protrusions 73 periodically move while approaching and separating from the outer surface 21b while making a circular motion. As a result, a phenomenon in which the deformed protruding portion 21c appears on the inner surface 21a and disappears after performing the arc motion periodically occurs. As a result, for example, blood Sa and diluent 40A are swung and swung vertically. Thus, by making the movement of the three protrusions 73 a more complicated movement including a circular movement, for example, when the depth of the first dilution tank 42A is deep, an effect of promoting stirring can be expected.

  FIG. 22 shows still another example of the stirring arm 7. In the present embodiment, the stirring arm 7 includes a plurality of protrusions 73 and a protrusion elevator 74. The plurality of protrusions 73 are disposed so as to contact substantially the entire region of the easily deformable wall 21 and are individually supported by the protrusion elevator 74 so as to be movable up and down. The protrusion elevator 74 has a mechanism for moving up and down the plurality of protrusions 73 in a predetermined order using, for example, a driving force by a motor or a magnetic force by an electromagnet. In the present embodiment, the plurality of protrusions 73 are repeatedly raised and lowered by the protrusion elevator 74. At this time, for example, if the plurality of protrusions 73 are sequentially raised along the circumferential direction of a circle centering on the central portion of the first dilution tank 42A, the first sample blood DS1 can be pseudo-rotated. is there. Also according to such an embodiment, liquid agitation can be appropriately performed.

  The liquid stirring method according to the present invention, the cartridge used therefor, and the liquid stirring system are not limited to the above-described embodiments. The specific configuration of the liquid stirring method according to the present invention, the cartridge used therefor, and the liquid stirring system can be varied in design in various ways.

  The arrangement of the protrusions 73 of the stirring arm 7 is not limited to the drawing of concentric circles having different diameters. For example, the arrangement may be such that the mutual locus is the same circle. The number of protrusions 73 may be four or more, or two or less, and may be one when the stirring space is extremely small. The relative motion of the protrusion 73 with respect to the outer surface 21b preferably includes a circular motion, but is not limited thereto, and may be, for example, a reciprocating motion along any direction or a combination thereof.

  In addition to constituting the stirring space and the easily deformable wall according to the present invention by a part of the combined structure of the main body 1 and the sheet 2, for example, a portion corresponding to the main body 1 and the sheet 2 is integrally formed using a resin or the like. May be. Parts such as the easily deformable wall may be transparent or opaque.

  The direction in which the stirring arm 7 is pressed against the outer surface 21b of the easily deformable wall 21 is not limited to the upper side in the vertical direction. For example, the configuration may be such that the stirring arm 7 is pressed in the horizontal direction against the easily deformable wall 21 standing in the vertical direction, or the stirring arm 7 may be pressed downward in the vertical direction. If the inner surface 21a is wetted by the liquid to be stirred, the liquid stirring can be appropriately performed by pressing the stirring arm 7.

  The deformation | transformation protrusion part production | generation means said by this invention is not limited to the structure which has the processus | protrusion for pressing on the outer surface of an easily deformable wall. Any structure having a function of deforming a part of the easily deformable wall to the inside of the stirring space may be used.

  The cartridge according to the present invention is not limited to the counting of blood and can be used for analysis of various sample solutions. In addition, the cartridge according to the present invention does not include an analysis unit, and may be configured to be used only for preparing a diluted sample solution for a blood cell coefficient, for example.

  The liquid stirring method according to the present invention, the cartridge used therefor, and the liquid stirring system are not limited to those intended for blood analysis, and are intended to stir various liquids and other substances. be able to.

It is a top view which shows an example of the cartridge which concerns on this invention. It is principal part sectional drawing in alignment with the II-II line of FIG. It is principal part sectional drawing in alignment with the III-III line of FIG. It is principal part sectional drawing in alignment with the IV-IV line of FIG. 1 is an overall perspective view showing an example of a liquid stirring system according to the present invention. It is a principal part top view which shows the process of measuring the blood in the analysis using the cartridge shown in FIG. FIG. 3 is a plan view of a principal part showing a step of injecting a diluent in the analysis using the cartridge shown in FIG. FIG. 3 is a plan view of a main part showing a step of stirring blood and a diluted solution in the first dilution tank of the cartridge shown in FIG. 1. FIG. 2 is a main part cross-sectional view showing a state in which blood and a diluent are injected in the first dilution tank of the cartridge shown in FIG. 1. It is a perspective view which shows the stirring arm of the analyzer which concerns on this invention. FIG. 2 is a cross-sectional view of a main part showing a state where a stirring arm is pressed against a first dilution tank of the cartridge shown in FIG. 1. It is a principal part perspective view which shows the state by which the stirring arm was pressed on the 1st dilution tank of the cartridge shown in FIG. FIG. 5 is a cross-sectional view of a main part showing a step of stirring blood and a diluted solution in the first dilution tank of the cartridge shown in FIG. 1. It is principal part sectional drawing which shows the state by which the stirring arm was pressed on the analysis tank of the cartridge shown in FIG. FIG. 5 is a cross-sectional view of a main part showing a step of stirring the first sample blood and the reagent in the analysis tank of the cartridge shown in FIG. 1. It is principal part sectional drawing which shows the optical measurement in the analysis tank of the cartridge shown in FIG. It is principal part sectional drawing which shows the other example of a structure of an analysis tank and a reagent. In the example shown in FIG. 17, it is principal part sectional drawing which shows the process of stirring a 1st sample blood and a reagent. It is principal part sectional drawing which shows the further another example of a structure of an analysis tank and a reagent. It is principal part sectional drawing which shows the optical measurement in the example shown in FIG. It is principal part sectional drawing which shows the stirring process in the other example of a structure of a 1st dilution tank and a stirring arm. It is principal part sectional drawing which shows the stirring process using the further another example of a stirring arm. It is principal part sectional drawing which shows an example of the conventional liquid stirring method.

Explanation of symbols

A cartridge B analyzer DS1 first sample blood H1 to H15 opening S blood 1 main body 2 sheet 4 dilution means 5A first analysis unit 5B second analysis unit 5C third analysis unit 5D fourth analysis unit 6A first flow rate measurement unit 6B Second flow rate measuring unit 7 Stirring arm (deformation protruding part generating means)
8 Connector 21 Deformable wall 21a Inner surface 21b Outer surface 21c Deformed protruding portion 40A Diluent 42A First dilution tank (stirring space)
42B 2nd dilution tank (stirring space)
43 Blood measuring means 45 First specimen blood measuring means 46 Buffer tank 51 Electrode 52 Pore 54 Analysis tank (stirring space)
55 Reflective film 56 Reagent 61 Wide channel 62 Electrode 71 Shaft 72 Base 73 Projection 74 Projection elevator

Claims (16)

A liquid stirring method for stirring a liquid and a substance other than the liquid,
In the stirring space defined by a plurality of inner surfaces including the inner surface of the easily deformable wall, the liquid and a substance other than the liquid are accommodated,
The deformable wall is deformed so that a part of the inner surface protrudes inward of the stirring space,
A liquid stirring method, wherein the position of the deformed protruding portion of the inner surface is sequentially changed with respect to the liquid.   The one or more protrusions are pressed against the outer surface of the easily deformable wall to deform the inner surface of the easily deformable wall so that a part of the inner surface protrudes inward of the stirring space. The liquid stirring method as described.   The liquid agitation method according to claim 2, wherein the one or more protrusions are moved relative to the outer surface to move the deformed protruding portion of the inner surface relative to the liquid.   The liquid stirring method according to claim 3, wherein the relative movement of the one or more protrusions includes a circular motion.   The liquid stirring method according to claim 4, wherein the plurality of protrusions are used such that a locus when the relative movement is performed is a concentric circle having different diameters.   The liquid stirring method according to claim 1, wherein the easily deformable wall is a resin sheet. The liquid is selected from blood, diluent, and liquid reagent,
The liquid stirring method according to any one of claims 1 to 6, wherein the substance other than the liquid is selected from a diluent, a dry reagent, a blood cell component, and a liquid reagent that are different from those selected as the liquid. . A cartridge having a stirring space for stirring a liquid and a substance other than the liquid,
Comprising an easily deformable wall having an inner surface included in a plurality of inner surfaces defining the stirring space;
The cartridge according to claim 1, wherein the easily deformable wall can be deformed so that a part of the inner surface protrudes inward of the stirring space.   By pressing a protrusion against the outer surface of the easily deformable wall, the inner surface of the easily deformable wall can be deformed so that a part thereof protrudes inward of the stirring space. Item 9. The cartridge according to Item 8. A body having an opening;
A sheet for closing the opening,
The cartridge according to claim 8 or 9, wherein a portion of the sheet that closes the opening is the easily deformable wall.   The cartridge according to claim 10, wherein the sheet is made of resin. A cartridge according to any of claims 8 to 11,
The liquid agitation having a deformed protruding portion generating means for deforming the deformable wall so that a part of the inner surface protrudes inward of the stirring space and sequentially changing the position of the deformed protruding portion of the easily deformable wall. A liquid agitation system.   The liquid stirring system according to claim 12, wherein the deformed protruding portion generating means has one or more protrusions.   The liquid stirring system according to claim 13, wherein the one or more protrusions are movable relative to the outer surface of the cartridge.   The liquid agitation system of claim 14, wherein the relative movement of the one or more protrusions comprises a circular motion.   The liquid agitation system according to claim 15, comprising a plurality of the protrusions whose concentric circles having mutually different diameters are trajectories when the relative movement is performed.

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