JP2005345160A - Biological information analyzing unit - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a biological information analyzing unit which provides an operation part for arbitrarily performing the separation of blood corpuscles effectively used when a blood analyzer is automated and the transfer and storage of a fluid and enables the highly precise analysis of blood in spite of a small size and a simple constitution. <P>SOLUTION: The biological information analyzing unit has a disc-shaped rotor type analyzing means comprising a combination of a flow channel for transferring a sample and an operation region for performing the operation of the sample and is constituted so that the holding region in the operation region is in an outer peripheral direction, the distance between the outer peripheral end part and center of the operation region is longer than another outer periphery, capillary force is quantitatively arranged while the movement of body fluids is controlled, and the capillary force and the operation region are controlled. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a body fluid information detection unit for measuring body fluid component information.

The measurement of blood components is indispensable for early detection of disease, but in order to actually perform only blood tests, we go to a medical institution or donate blood, and only blood tests in a health checkup of about one month a year. There is no means, and even if such an opportunity is set, there are few people who have time to do only blood tests on weekdays.
In the field of blood analysis, an apparatus for measuring multi-component components such as blood components and urine components using a dry chemistry technique was proposed in the 1970s and has been used in many medical institutions.
Among them, due to the rapid increase of diabetic patients, glucose measuring devices are provided as devices that can be handled by patients themselves.
In addition to diabetes, diseases related to lifestyle such as cerebral infarction and myocardial infarction are rapidly increasing, and the need for multiple blood component tests is increasing. Inspection is desired.

While blood analyzers using dry chemistry have been developed in the market, a unique blood analyzer shown in Japanese Patent Publication No. 5-62304 has been proposed.
This apparatus uses a centrifugal force and capillary force as driving force, and measures a color reaction generated by quantitatively supplying serum and plasma obtained by separating blood cells into a well in which a freeze-dried reagent is arranged.
The blood device shown in Japanese Patent Publication No. 5-62304 is intended for blood tests in space, and can be used under zero gravity by using only centrifugal force and capillary force.

  US Pat. No. 5,160,702 discloses a blood analysis unit using a rotor. On the rotor, a liquid operation region having various shapes and a liquid transport mode utilizing capillary action are described.

Centrifugation is capable of aggregating high specific gravity components in blood in an agglomerated manner. Japanese Patent Application Laid-Open No. 2001-239183 discloses a configuration in which blood cells and clots are separated by precipitation after centrifugation. There are only disclosures limited to single use.
Japanese Patent Publication No. 5-62304 enables a series of operations from centrifuging to supplying quantitative blood cell separated blood to the reagent-containing well, causing color development reaction, and examining the color development value. In order to perform such separation, a certain amount of time is required, and the separated serum component must be transferred to the next processing step. When analyzing the biochemical components in serum by the color reaction between serum and reagent, the color development time between reagent and serum is likely to have a significant effect on the accuracy of the test. Control is considered an important factor.

Japanese Patent Publication No. 5-62304 US Pat. No. 5,160,702 JP 2001-239183 A Special table hei 10-501340 Special table hei 9-504732

In such units that try to use capillary force and centrifugal force effectively, the diameter of the flow path becomes smaller, so the influence of capillary force and surface tension becomes stronger, and the liquid does not move in the desired direction. However, when the surface treatment is performed, the treatment is hydrophobic and hydrophilic, the liquid state changes greatly, and the movement of the liquid becomes more difficult.
In particular, problems that can be considered include the stopping of liquid movement due to the inflow of air into the capillary, the retention of liquid for a certain period of time when wettability is ensured, and the state where the centrifugal force and capillary force are in conflict. Examples include excessive movement and minute movement of liquid caused by differences in capillary force due to differences in liquid viscosity.

The stoppage of the liquid due to the inflow of air in the capillary tube becomes a problem as an increase in the required liquid amount due to the movement of the liquid, a so-called reduction in the recovery rate, and in a severe state, there may be a malfunction due to the stoppage of the liquid.
Regarding the retention of liquid, the liquid moves to an unexpected space through the wall surface in combination with the wettability in the flow path and the surface tension of the liquid. It becomes a problem when it needs to be held in a certain space, such as when measuring.
In addition, when performing operations such as moving these liquids using inexpensive motors, the use of low-priced motors is considered to contribute to the user economically. In a system in which liquid is moved by centrifugal force through a path, if the motor's operating performance is not sufficiently satisfied, or if the motor is not so good, excessive movement or minute movement of the liquid will occur and the desired function will not be obtained Can be considered. Although it may be possible to eliminate the wettability of the surface state by chemical and physical treatment as a method of adjusting the excessive movement and minute movement of the liquid, these methods easily cause high costs in the manufacturing process, resulting in results. This suggests the possibility that it cannot be provided to users as an inexpensive mechanism.
As described above, various cases are observed in which the movement of the liquid occurs depending on the liquid flow path and the surface state of the operation region, and the target liquid cannot be operated or moved while being rotated.

Although the centrifugation time varies depending on the blood volume, it may take longer depending on the configuration.
Especially for automated hematology analyzers, it is expected to provide faster test data to the user by shortening the time from blood injection until measurement results are obtained. It is required to shorten the time to perform.
In addition, when measuring components in blood cells, especially useful measurement items such as hemoglobin A1c, and serum biochemical components in the same measurement unit, it may be necessary to control the blood separation time on the test sequence. is there. The control in this case is considered not only to shorten the time but also to increase the time.

On the other hand, when the amount of collected blood is small, or when other blood components are modified, a step of mixing an auxiliary solution such as a diluent or a cell modifying solution is added. Such a mixing process does not mix just by pouring the two liquids, and it is difficult to simply rotate, so operations such as rotating in a different direction (shaking) are required. It becomes.
For this purpose, since the performance of the drive motor is required, an expensive servo motor with high performance is required.
In addition, depending on the amount of processing liquid and the viscosity of the liquid, problems such as separation of two liquids may occur depending on the specific gravity rather than sufficient mixing by an operation such as shaking. In this case, uniform mixing cannot be realized only by the motor specifications.

The transport of liquid using capillary force is such that the capillary force increases as the cross-sectional area of the flow path becomes smaller. As long as it is pulled by the capillary force in that direction, there is a high possibility that the sample cannot be manipulated due to a complicated force relationship.
In particular, when the capillary force drive unit that draws the sample operation to the final region and the final operation region are combined, it may be very difficult to hold the liquid in the final operation region.
In addition, the final region is often a region for the purpose of quantifying the liquid, and it is conceivable that a liquid quantification error due to air contamination causes mechanism inhibition.
As a means for solving these problems, a method as described in Japanese Patent Application Publication No. 9-504732 has been proposed. In order to reduce the amount of the liquid as much as possible, it is desirable to make the introduction flow path thin so as to reduce the amount of the sample to be measured. It is desirable that the input flow path to the road is narrower than the introduction flow path in order to control the air flow.

  However, there is a possibility that problems may occur due to the quality control for manufacturing the input flow path, the properties of the liquid to be introduced, etc., and these may cause an increase in cost. There seems to be room for this. Further, if the introduction flow path is not taken longer than a certain length, the liquid is moved by the capillary force generated in the input flow path, and even the mechanism for holding it in the operation region for a certain period may be hindered.

In home examinations that have become widespread in recent years, techniques for collecting trace samples, pretreatment techniques to minimize the contents of collected specimens as much as possible, technologies for transporting collected specimens, etc. will be developed and marketed. However, it can be said that there are still few specifications that take the general user into account. However, the current challenge is how to handle these demands in a growing social situation. Among these, the present invention is a method for easily sealing a minute sample and transporting a sample stably without increasing the cost burden of an instrument for operation when the collected liquid is transported to a laboratory. Unit can be provided.
The quantification of the specimen is an indispensable element in various configurations including the operation area for the purpose of analysis. Various methods for quantifying specimens have been devised, but in the case of blood analysis, blood used as specimens has a large content component and is divided into blood cells and plasma or serum components. Of these, plasma or serum components are mostly used for measurement. Therefore, when preparing a sample quantitatively, it is necessary to take two steps: a blood cell separation step and a plasma or serum quantification step. However, the conventional method that requires separate steps requires a large operating area. There is an inconvenience that the measurement and inspection tool is enlarged and the processing time is lengthened due to the fact that it must be taken.

In view of the above, the present invention
It has a disk-shaped rotor type analysis means consisting of a combination of a flow path for sample transfer and an operation area for sample operation,
By setting the desired indwelling region in the outer peripheral direction and the operation region such that the distance between the outer peripheral end and the center is longer than the other outer periphery,
The inventors have found that the position of the sample in the operation region can be a specific position, and have reached the present invention.
According to the present invention, in particular, a sample is transferred to a specific part in one operation region without requiring a shielding object or a guiding structure, and for example, a measurement region or a quantification structure is transferred to the part. If a flow path port for moving to another operation region such as a body is arranged, there is an effect that the target sample can be efficiently transferred.

That is, the present invention focuses on the fact that the liquid in the container forms a liquid surface having an equal distance from the substantially circumferential center by centrifugal force,
By forming the outer peripheral side surfaces having different radii with respect to the shape of the container in the outer peripheral direction, the liquid stays at a farther part of the outer peripheral side surfaces. Therefore, in the present invention, the diameter from the center of the desired part for collecting the sample in the operation area only needs to be longer than the other diameters, and the difference is exemplified by 0.1 mm to 2 mm. However, it is not limited to this because it is different.

Furthermore, after the liquid in the container forms a liquid surface having the same distance from the substantially circumferential center by centrifugal force, when the centrifugal force is reduced, the wall surface of the space in which the liquid sample is held has wettability. We have found that this effect is improved by using a material that can be improved, or by performing a chemical surface treatment or a physical surface treatment to reduce the contact angle of the liquid sample with respect to the wall surface.
As a result, not only can the liquid sample be held in a certain area, but also when the liquid is transferred from the channel port for moving to another operation area, air can be prevented from being mixed in without using a complicated mechanism. It became possible to stably transfer a certain sample to another operation area.

Furthermore, the present invention provides
An operation area for operating a liquid, a supply flow path for supplying a sample liquid to the operation area, and an output flow path for taking out a sample after operation from the operation area, the connection between the supply flow path and the operation area By the combined configuration in which the cross-sectional area of the surface is narrower than the connection cross-sectional area of the output flow path and the operation area, even in the operation area where a plurality of flow paths on the supply side and the output side are connected, It is possible to hold the sample solution in the operation region under conditions in which a force repelling the output or the capillary force of the supply channel such as centrifugal force and gravity acts.

In the present invention, the hole diameter of the supply port is exemplified by 0.04 to ¹ mm ² , and the hole diameter of the output port is exemplified by 0.09 to 2.25 mm ² . These examples are dimension values for which current machining accuracy can be expected. If an inexpensive manufacturing method is established in the future, this value will shift to a smaller value.
The arrangement of the supply port and the output port is not particularly limited. However, in the case where the centrifugal force such as a rotor can be used, the operation liquid after operation of the liquid in the operation region should be located near the supply port. It is preferable in that the movement to the next operation area can be performed by centrifugal force.
In addition, it is possible to recover the liquid held on the outer periphery in the operation region and on the constant area outside in the centrifugal direction by the output circuit.

A liquid operation tool having a flow path for transferring liquid by capillary action and an operation region for storing or operating the liquid temporarily or continuously, at least transferring the liquid to a target site; With a configuration with a narrower flow path around the liquid operation area, it is possible to hold the liquid in the operation area for a certain period of time, and further, the liquid can be quantified in the space of the operation area. For example, even when there is a configuration in which a solid water-soluble substance such as a coloring reagent is held in advance, by introducing forces such as centrifugal force and air pressure into the liquid, the solid water-soluble substance is introduced into the external space. It can be filled without missing, and a certain amount of liquid defined by the space can be stirred and mixed only by changing the rotational speed of the centrifugal force, for example. Even in a system in which the reaction proceeds further, the rotational speed of the centrifugal force is changed on the liquid-gas interface formed by the narrow channel and the space joined to the entrance of the narrow channel. This makes it possible to supply the necessary reaction oxygen in the operation area with a simple operation. This thin channel has a cross-sectional area of 0.04 to 0.25 mm ² connected to the operation area provided at the outlet, and even when the isotonic liquid is filled in the space in contact with the narrow channel inlet, the liquid in the operation area is not The knowledge that movement to outside space was not observed was obtained.

As a constituent requirement in the present invention, a degassing port is not provided, but by applying a force of a certain level or more to the liquid, the liquid having a higher specific gravity than the gas is sufficiently filled in the operation area with almost no air mixing. For example, when a force of 500 G to 1000 G is applied, knowledge has been obtained that filling can be performed in about 10 to 60 seconds, but this is not limited because it varies greatly depending on the amount of processing liquid.
In addition, using a surfactant such as TWEEN 20 to improve the wettability of the surrounding space of the configuration of the present invention, and measuring the change in the amount of movement of the liquid to the wall surface, leave it for 2 hours. Just looking at the gas mixture with a diameter of 0.1μm, this seems to be caused by evaporation rather than liquid movement, so liquid movement is not observed even with improved wettability, etc., making it possible to hold a stronger liquid It is the structure to do. In addition, Brij25 Triton X-100, Span 20, etc. are used as the surfactant.
This has also been found to be more effective when the narrow channel in this configuration is made smaller than the channel cross-sectional area defined by other configurations.

Centrifugal structure

Furthermore, the present invention is a rotating body that performs centrifugal separation, and a bodily fluid storage portion including a bodily fluid supply port and a separated bodily fluid extraction port provided on a predetermined circumference of the rotating body, and a continuous outer circumferential direction of the storing portion. It consists of a centrifugal separator comprising a particle container having a connection port with a convex part, and by adjusting the connection area of the connection port, the separation time of particles such as blood cells and blood clots can be controlled while sufficiently In addition, the present invention has realized a body fluid detection device including a blood cell separation unit that enables easy blood cell separation and that particles once entering the particle storage unit do not diffuse into the body fluid storage unit even if the centrifugal force is reduced.

The present invention includes a bodily fluid storage portion including a bodily fluid supply port and a separated bodily fluid extraction port provided on a predetermined circumference of the rotating body, and a convex portion continuous to a connection site between the bodily fluid storage portion and the particle storage portion. It has centrifugal separation means consisting of a particle container having a connection port, and the predetermined circumference of the rotating body may be at least a region where centrifugal force acts, and the body fluid reservoir portion acts by centrifugal force The size of the region is appropriately adjusted according to the amount of specimen to be handled.
The connection port is a connection connection port between the body fluid storage unit and the particle storage unit, and the size thereof is any of the distance and height of the outer periphery of the body fluid storage unit and the distance and height of the inner periphery of the particle storage unit. The smaller one is the maximum area. The blood cell separation speed may be adjusted by adjusting either the distance or the height of the inner circumference, or both. More preferably, compared to the cross section of the separated body fluid extraction port, the cross section height of the separated body fluid extraction port is preferably lower than the height of the connection connecting port. In addition, in order to increase the separation efficiency after blood cell separation, the connection port needs to secure the surface tension within its cross-sectional area to hold the separated blood cells, so the connection port height is about 2 mm at the maximum, preferably less Should be adjusted between 0.3-1.5mm.

  The bodily fluid storage part has a shape and a bodily fluid in which the distance between the position of the outermost peripheral direction on both sides of the outer peripheral direction and the central axis is different as shown in FIG. It is preferable that the circumference of the body fluid concentration part in the outer peripheral edge part of the storage part is set to be outside as compared with the circumferences of other parts.

For example, liquid or particles gather more outwardly than the specific gravity of the object under centrifugal force, thus separating the body fluid containing the component to be analyzed from normal body fluid components. This is because it is effective when manipulating blood before and after the separation.
The particle container is a space for separating particles such as blood cells, blood clots, and the like, and can be connected to the peripheral part of the body fluid storage part at least in the direction in which centrifugal force acts. What is necessary is just to arrange | position to a site | part.

When using serum or plasma, the particle storage unit is a place for storing unnecessary materials. However, when measuring the physical properties of blood cells, a transfer path for transferring blood cells to other operation areas is used. May be newly provided.
The convex portion in the connection port having the continuous convex portion according to the present invention may have a structure in which particles such as blood cells are likely to enter the particle accommodating portion, but once entering the particle accommodating portion, it is difficult to go outside. ,
In addition, when used under gravity, the depth in the bottom direction of the particle storage unit may be simply set to be deeper than the depth of the body fluid storage unit.
In this case, although it depends on the amount of blood to be processed, the relationship between the depth of the particle container and the distance from the connection port is preferably larger than the depth of the particle container. Even when the depth of the particle containing portion must be larger than the distance of the connection port, the convex shape inside the particle containing portion can be increased by making an angle in the centrifugal direction from the upper side of the convex portion.
This is because when the convex shape becomes longer in the depth direction, the force vector direction due to the centrifugal force cannot work in the vertical direction with respect to the accommodating portion. This is because it may become an obstacle when accommodating large particles.

In general, the depth between the body fluid storage part and the particle storage part is larger than the body fluid storage part. This is because, in the case of a stationary state in which gravity is controlled, a substance having a higher specific gravity can be efficiently accommodated in the lower part when the accommodation part is deeper. In this case, a continuous convex portion having a connection port portion height of about 0.3 to 2 mm and a width of about 1 to 200 mm is preferable. Considering the amount of body fluid treated in the test, usually these are more preferably about 0.5 to 1 mm in height and about 5 to 20 mm in width.
At this time, the following relationship is known from the experimental results.
Separation time = 10 / cross-sectional area (mm ² )
Here, the determination of the completion time of separation varies depending on the viscosity of patient blood, the amount of water, etc., but should be applicable when 60% or less of blood is separated in terms of hematocrit. The resulting 10 varies between approximately 8-12. This is due to factors other than those described by the present invention, such as wettability, material, and roughness of the surface of the rotating body for processed measurements. The centrifugal force at this time is also a number that should be greatly influenced by this constant, but this centrifugal force is a result at 500 to 600 G in the experiment in the present invention, but a similar result is obtained even at 1000 G. The positions of the body fluid supply port and the separated body fluid extraction port are appropriately selected, but at least the body fluid supply port only needs to be provided. For example, the reagent storage well may be directly connected to the body fluid reservoir. .

  Body fluids handled include blood, urine, sweat, bacterial fluid, medium after cell culture, tissue physical fluid, lymph fluid, interstitial lymph fluid, bone marrow fluid, tissue fluid, saliva, gastric fluid, joint fluid, pleural effusion, semen , Bile, ascites, amniotic fluid, etc., and the particles to be separated include red blood cells, white blood cells, blood clots, fungi, cells, tissue sections, mixed substances, interfering substances, etc. It is selected appropriately.

Mixing operation

Furthermore, the present invention is a means for mixing two or more liquids, two or more supply passages for introducing two or more liquids, a storage chamber for mixing, and a liquid collection for recovering the mixed liquid A structure in which one or more output flow paths are configured, and either one or both of the output flow paths or the two or more liquid supply flow paths have a micro cross-sectional area that generates a capillary force In
The amount of liquid introduced into the capillary is changed by using any one or more of air pressure and / or gravity and / or centrifugal force and / or inertial force. Stirring and mixing means by a method of changing the operation according to the
A biological sample provided on the rotating body and a storage chamber for storing the mixing body for mixing with the biological sample in a single space, and a liquid in the central direction of the rotating body, outward from the storage chamber. With a combination of a moving force supply means for applying a moving force to the liquid in the storage chamber, a driving means that rotates around the rotation speed central axis of the rotating body, and can change the rotation speed a predetermined number of times, It is possible to perform quick mixing while reducing the burden on the rotary motor.
That is, the present invention has a configuration in which, for example, a centrifugal force generated when the rotating body rotates and a liquid moving force that generates a force for moving other liquid are provided, and the liquid moving force and the centrifugal force are opposed to each other. By adjusting the centrifugal force, the movement of the liquid introduced into the capillary is reciprocated to mix the liquid in the storage chamber.

In the present invention, the biological sample includes blood, urine, semen, interstitial fluid, sweat, blood components such as serum and plasma, bacterial fluid, medium after cell culture, fluid after physical destruction of tissue cells, lymph fluid, Exemplified lymphatic fluid, bone marrow fluid, tissue fluid, saliva, gastric fluid, joint fluid, pleural effusion, semen, bile, ascites, amniotic fluid, etc. Solution, chemical synthesis reagent solution, partition solution for extraction by partition, chromatographic resin solution capable of adsorbing a specific substance using affinity, radiation marker solution, buffer solution such as pH, surfactant solution, medium, Examples include environmental hormone solutions, specific saturated gas solutions, cell disruptions, DNA extracts, color reagents, marker substances, and coagulation substances.
Examples of the moving force used in the moving force supply means include capillary force, other porous materials such as nonwoven fabric and cotton cloth, suction force generated by volume change, gravity, air pressure, and gas pressure generated by mixing. Power is shown.
The moving force supply means has a part for moving the liquid from the storage part to the outside at least once in the direction opposite to the centrifugal force, but the countermeasure at that time is not necessarily 180 degrees with respect to the centrifugal direction. It is not necessary to have such a direction that the liquid stops moving at least due to the centrifugal force or moves more slowly. Needless to say, it is in the direction of the centrifugal center.

As the moving force supply means, a capillary tube having a bent portion extending toward the central region is preferable in that it can stop the progress of the liquid by centrifugal force, but is not limited thereto.
“The operation of changing the amount of liquid introduced into the capillary tube and changing the amount of liquid in the result storage chamber according to the amount of liquid introduced into the capillary tube” means, for example, the movement of the liquid by the capillary force of the capillary tube as described above. The action to limit the movement of the liquid in the capillary is applied in the direction that inhibits the liquid. Etc.

In addition, in this invention, the combination of the storage part with a deeper depth and the flow path extended from the centrifugal direction may be sufficient, for example.
The flow path is in a state having a force for sucking the liquid in the storage portion in a direction opposite to the centrifugal force from the capillary force, the adsorption force of the separately provided adsorption member, and the like.
In this case, the fluid that has entered the storage portion receives a force attracted by the suction force of the flow path, and is attracted to the flow path, but increases the number of rotations to draw the fluid away from the flow path, The fluid may be mixed by lowering the rotational speed again and drawing the fluid to the flow path, increasing the rotational speed again, pulling the fluid away from the flow path, and repeating this operation.

Furthermore, the present invention comprises a small chamber opened at the outermost periphery in one direction of the primary reaction tank that receives a force in one direction, and a configuration in which an additive is placed in the small chamber in an intermediate process. It is possible to sufficiently cope with cases where the above cannot be obtained or when other processing is required.
The additive in the present invention includes, for example, the first primary reaction tank, mutarotase, glucose oxidase, peroxidase, ascorbate oxidase, phenol, 1-naphthol-3,6-disulfonic acid disodium salt, catalase, L-aspartic acid, α- Ketoglutarate, thiamine pyrophosphate, magnesium chloride hexahydrate, HEPES, lipoprotein lipase, adenosine-5'-disodium triphosphate trihydrate, PIPES (buffer) L-alanine, carbonate buffer, hydroxylation Sodium p-nitrophenyl phosphate disodium, creatinase, sarcosine oxidase, Good buffer, creatininase, sodium azide, 3,5-dinitrobenzoic acid, lithium hydroxide monohydrate, cholesterol oxidase, hexokinase, βNAD , Nitrotetrazolium Blue, L-milk Lithium, βNADPNa, creatine phosphate 2-Na tetrahydrate, glucose 6-phosphate dehydrogenase, magnesium acetate tetrahydrate, nitroblue tetrazolium, glycine buffer, NPP, OCPC, EGTA, CAPS buffer, thiamine pyrophosphate , A reagent such as glycylglycine buffer, Lg-glutamyl-carboxy-4-nitroanilide, and the reagent in the reaction tank for measuring the color reaction from the outside in the next mixing tank is, for example, , Mutarotase, glucose oxidase, peroxidase, ascorbate oxidase, phenol, 1-naphthol-3,6-disulfonic acid disodium salt, phosphate, pyruvate oxidase, oxaloacetate decarboxylase, catalase, N-ethyl-N- (2 -Hydroxy-3-sulfopropyl) -m-toluidine sodium, 4-aminoa Tipilin, L-aspartic acid, α-ketoglutaric acid, thiamine pyrophosphate, magnesium chloride hexahydrate, HEPES, lipoprotein lipase, adenosine-5'-diphosphate disodium trihydrate, glucerol kinase, glucerol -3-phosphate oxidase, 3,5-dimethoxy-N-ethyl-N- (2'-hydroxy-3'-sulfopropyl) -aniline sodium, PIPES (buffer) L-alanine, DAOS, carbonate buffer, Sodium hydroxide p-nitrophenyl phosphate disodium, F-DAOS, uricase, N, N-bis (4-sulfobutyl) -3-methylaniline disodium (TODB), creatinase, sarcosine oxidase, Good buffer, Claire Tininase, sodium azide, 3,5-dinitrobenzoic acid, lithium hydroxide monohydrate, cholesterol oxidase, N, N-bis (4-sulfobutyl) -m-toluic Denni sodium (DSBmT), cholesterol esterase, surfactant, copper sulfate pentahydrate, potassium sodium tartrate, copper sulfate, glucoamylase, BES buffer, α-glycosidase, p-nitrophenylbenzyl-α-maltohentacid (BG5P), benzylidene-p-nitrophenyl maltohephthalate (BG7-pNP), monoethanolamine buffer, methylxinol blue, 8-quinolinol, o-cresolphthalein confexone, hexokinase, βNAD, nitrotetrazolium blue , L-lithium lactate, βNADPNa, creatine phosphate 2-Na tetrahydrate, glucose 6-phosphate dehydrogenase, magnesium acetate tetrahydrate, nitroblue tetrazolium, glycine buffer, NPP, OCPC, EGTA, CAPS buffer , Thiamine pyrophosphate Glycylglycine buffer, L-g- Group Tamil over local Bokishi 4-nitroanilide, and the like.
The force in one direction refers to centrifugal force, air pressure, gravity, and the like, and the outermost periphery in one direction refers to the edge peripheral portion of the primary reaction tank that is farthest from the direction in which the force is applied.
The open chamber is a chamber connected inside the peripheral portion of the primary reaction tank, and the form of the additive disposed therein is enclosed in a solid, liquid, or soluble capsule. And those supported on porous particles.
In addition, by making an opening part into an acute angle, when an additive is a liquid, it becomes possible to hold | maintain inside a small chamber by surface tension.
In the case of a solid shape, it is possible to prevent the additive from coming out of the small chamber by making the opening smaller than the size of the solid.

Manipulating specimens with multiple capillary forces

In view of the above, the present invention provides an operation area having a predetermined depth and a reserve area for preliminarily storing a sample (specimen), and a flow path having a capillary force connecting the operation area and the reserve area. And a pressure generating means that applies a force in a direction that presses or sucks the fluid in the flow path and supplies the fluid to the operation area, so that the flow path having a capillary force is connected to the operation area. After passing through the flow path, the liquid in the operation region is stabilized by the holding force of the liquid held in the capillary, here the capillary force.
More specifically, an operation area having a predetermined depth and a reserve area for preliminarily storing a sample are provided, the operation area, a flow path having a capillary force connecting the reserve areas, and the flow A combination of pressure generating means that presses or sucks fluid in the channel and applies a force in the direction that supplies it to the operation area. Manipulation of the biological sample was made possible while reducing the target appropriately.
In addition, a small amount of liquid can be held by holding a certain amount of liquid in the operation area and adding a filling liquid for sealing the liquid later.
More specifically, the capillary force of the flow path and the surface of the flow path are introduced into the flow path where the capillary force is generated after introducing a predetermined amount of liquid before the preliminary area or the liquid quantified in the operation area. By transporting the filling liquid by tension, it is possible to seal the liquid that has been moved to the operation area in advance.

The operation region in the present invention refers to a final operation region in biological measurement such as a marker substance detection site by causing a reaction with a cell modifying element such as a region that reacts with a reagent. Even a tank may be applicable. In addition to this, it may be a final chamber for transporting the specimen and a storage section for keeping the specimen for a certain period or longer.
The strong capillary force of the present invention is exemplified by a flow path having a caliber cross-sectional area of 0.04 to 0.25 mm ² in consideration of the processing accuracy in the current general product launch.
Examples of the hydrophilic treatment include application of a wetting agent and a surfactant, plasma treatment, excipient application, chromic sulfate mixed solution treatment, adjustment of surface roughness, removal of a hydrophobic film, and the like.
The biological sample in the present invention includes whole blood, serum, plasma, blood components, blood components such as various blood cells, blood clots, and platelets as well as urine, semen, breast milk, sweat, interstitial fluid, fungal fluid, Examples include various body fluids such as a medium after cell culture, a fluid after physical destruction of tissue cells, interstitial lymph, bone marrow, tissue fluid, saliva, gastric fluid, joint fluid, pleural effusion, bile, ascites, amniotic fluid.

Examples of the pressure generating means include air pressure, water pressure, gravity, and inertial force that apply a force parallel to the direction of flow of the flow path. Among them, centrifugal force is preferable when the whole is incorporated in the rotor, but centrifugal force is preferable. It is not limited to power.
It is preferable that the sample solution is used in such an amount that it is not supplied to the operation area, or the sample solution is contained in the flow path where capillary force is generated.
The preliminary region is preferably formed much deeper than the capillary channel, and the wettability of the liquid is improved by hydrophilization, etc., as deep as 1.5-3 mm compared to 0.2-0.5 mm of the capillary channel. However, it is preferable in that the sample holding stability in the operation region is improved because there is no concern about the movement of the liquid due to the surface tension of the liquid acting.

The filling liquid in the present invention is mainly used for sealing a certain amount or a semi-quantitative amount of liquid fed into the operation region more than a certain amount, and is an extra sample or water that does not affect the sample. Or an aqueous solution embodiment such as physiological saline, a liquid having a high boiling point and difficult to evaporate even in a minute amount, for example, an aromatic solvent such as DMSO, DMF, AN, xylene, a self-solidifying adhesive, a sealing agent, moisture Since the substance dissolved by drying is solid at room temperature, those that solidify in the flow path having capillary force, such as starch solution, agar solution, gelatin, collagen solution, etc. are exemplified, The sample itself may be used. The filling liquid is preferably quickly filled after the sample is supplied to the operation region, and is preferably filled into the flow path, and the configuration for this is not limited.
The timing at which the filling liquid fills the flow path is not limited to moving the liquid to another area in the measurement stage, such as filling the sample in the operation area and causing a mixing reaction with the reagent. If you want to keep in the operation area,
When the capillary force of the flow path forms a state where it does not affect the surrounding area and the liquid in the flow path, the contents of the sample are altered or lost due to storage effects before the operation area is introduced. After performing the pre-treatment process necessary for measurement so as not to be active, it may also be indicated if it is necessary to have holding power until it is measured, holding power enough to withstand transportation, resistance to evaporation it can.

Quantitative

Furthermore, the present invention is a method for quantifying a liquid sample, an operation region for operating a liquid provided on a rotating body, a supply channel for supplying a sample liquid to the operation region, and after operation from the operation region An output channel for taking out the sample, and in the operation region, a degassing port is disposed between the supply channel and the output channel, and a cross-sectional area of the channel to the degassing port is The supply channel has a configuration larger than the output channel, and when the sample supplied from the supply channel is filled with the sample in the operation region with respect to the supply, the sample is supplied from the deaeration port. When the air no longer flows out, the present invention has been focused on that the sample cannot be supplied unless a force of a certain pressure or higher is applied to the supply of the sample to the supply channel. According to this method, even when the amount of liquid is small, it is possible to perform quantification using the difference in specific gravity with the gas regardless of the inherent viscosity of the liquid.

That is, the present invention provides a supply channel for supplying the sample to the operation region, for example, when using gravity, centrifugal force, air pressure, inertial force, or the like. When the structure or distribution is set so that the pressure per unit area of the above force on the liquid sample is smaller than the interface where the operation area contacts, When the liquid is supplied from the supply flow path to the operation region by using a elbow structure in which a part of the supply flow path extends to the centrifugal center, the centrifugal force is generated in the supply flow path. Although it is configured to be weakest at the elbow, when such a structure or dynamic vector can be set, the deaeration port, for example, when using centrifugal force, Supply flow path inside, output flow When the set outwardly, it is disposed between the supply channel and the output channel.

When the liquid sample supplied from the supply flow path is supplied by, for example, centrifugal force, the operation region is filled with the liquid sample, but the edge inside the centrifugal direction of the flow path in which the deaeration port is formed. When the liquid is filled with the liquid, the place of the gas component arranged in advance in the space in the operation region to which the liquid sample is supplied as seen in the supply channel is lost. In the rotating body, the pressure increase in the operation region includes a force required for supplying the liquid sample, here, gravity, centrifugal force, air pressure, inertia force, and the like, but these forces are proportional to the force exerted on the operation liquid. .

In the state where the increased pressure is saturated, the inflow of the liquid is stopped, and the liquid supplied into the operation region can be quantified by the stoppage of the inflow of the liquid. For example, in a mechanism that introduces a liquid into an operation region using a centrifugal force, the liquid in the supply channel often has an elbow-type structure. This is due to the capillary force of the liquid. This is because it is necessary to transport the liquid using siphon force, etc., but the supply power is the weakest in this elbow part, so it was held in the front chamber or the operation area at this part As the gas flows out, the liquid can be removed from the supply flow path.

As a quantification method when a definitive surplus such as blood separation is included, separation of the sample surplus by rotation on the combined configuration of blood cell storage units connected in the outer circumferential direction of the quantification chamber, contact between the quantification chamber and the overflow channel Outflow of liquid with the volume defined by the output flow path with siphon effect from the surface to the outer peripheral direction part of the contact opening surface of the quantitative chamber, containing the flowed quantitative liquid, etc. A structure composed of an operation region for performing an operation, and a residual liquid containing separation particles by controlling the surface tension by the protrusions provided on the side surface of the quantitative flow chamber after the outer peripheral direction portion of the opening surface of the output channel By operating the quantitative holding function, separation, quantification, and movement can be performed simultaneously.

  The present invention has an operation region for manipulating a sample by centrifugal force, and by increasing the distance from the center with respect to the target outer peripheral portion of the outer peripheral shape of this operation region, a constant space around the elongated portion is obtained. The sample can be collected, which can be an obstacle to the transition to the operation area next to the sample, for example, stoppage of liquid movement due to air contamination, increase in fluctuation factors of required sample recovery rate due to air contamination, etc. The liquid can be stably transferred, and the effect can be further improved by improving the hydrophilicity of the material forming this structure.

  The present invention is a case where blood cell separation is performed by centrifugal force, and preferably, when performing automatic blood analysis, control of the amount of raw solution including raw blood supplied and the processing time in the measurement sequence is performed. In the rotating body in which the separation unit and the measurement chamber are integrated, the blood cells can be separated in a time suitable for the measurement, and a separation part suitable for automatic blood processing can be formed.

  In the component analysis of a body fluid sample using a rotating body, the present invention provides a method for adding an auxiliary substance such as a diluent to measure a large number of components from a small amount of body fluid, or a special method for dissolving a solid with a biological sample. An automatic analyzer can be realized with a simple configuration simply by giving the strength to the rotational speed without using a simple part. In addition, mixing for realizing chemical reaction, mixing for adjusting component pH in liquid, mechanism to separate specific substance by binding with affinity substance, marking of minute amount of biological substance, unknown quantity more than 2 Methods for calculating the mixing ratio of liquids, separation / extraction methods such as oil-water solutions, introduction of media into cells, extraction methods such as DNA by cell disruption solution and cell mixing, neutralization, redox neutralization, saturated gas This technology is widely used for solution preparation, cell aggregation, chemical coagulation, dilution series preparation kit, cell-derived dilution method such as cell-derived cells, mixing of bacteria and liquids, extraction of internal substances, pretreatment process of component analysis, etc. It can be used. It can also be used for organic chemical reactions, inorganic chemical reactions, coordination reactions, ionic reactions, redox reactions, and the like with chemical substances other than biological substances.

In the operation region, in order to hold a measurement specimen for obtaining biological information for a certain period of time or more in the operation region, by using a strong capillary force, an operation region is set that allows fluid movement operation with reduced external driving force, Thus, a biological information detection unit having a space that can be used for measurement, reaction, holding, transfer / storage, and the like is realized.

Furthermore, the present invention provides a means for quantifying liquid in a rotating body, and can achieve accurate quantification even in an environment where surface tension and capillary force are dominant regardless of the viscosity of the liquid. This is particularly useful when the biological sample is a liquid sample. For example, even in the same structure, even if the viscosity is different for different biological samples such as samples with different viscosity, blood, saliva, etc. In the case where the centrifugal force is set so as to overcome the surface tension that is sufficiently derived from the viscosity, for example, to form the quantitative ridge line in the operation area, there is no difference in the quantitative accuracy. In the invention, various methods for handling and simply quantifying a small amount of liquid have been proposed, but forces such as surface tension and capillary force work in the quantification field. It is useful to carry out a quantitative operation using this capillary force and surface tension antagonism. This is because it is necessary to control the force working inside the structure to be operated in order to efficiently quantify the measurement sample and the like without waste. The use of surface tension is greatly influenced by the viscosity of the liquid, so the structure should be designed according to the liquid to be handled. However, in the case of an aqueous solution system mainly composed of body fluid components, a certain level of viscosity is guaranteed. Therefore, the structure can be determined uniformly. In addition, since the visual confirmation is facilitated by using this method, it is considered that the experiment operator can obtain results while confirming the procedure of the experiment.

The movement of fluid is controlled by adjusting the shape of the operation area.
In the present invention, at least the outer peripheral radius of a part where a sample is to be collected in one operation region may be made longer than a series of continuous outer periphery. For example, the storage unit 121 that performs the blood cell separation operation of FIG. In addition, it is possible to output serum and plasma after separation of blood cells to the output flow channel 151 without shortage by making the outer peripheral radius r1 of the portion where the liquid is desired to move to the next operation region longer than the other radius r2. It is said. The most important reason for the recovery without any shortage is that air can be prevented from being mixed. This effect is further improved in a state in which the wettability of the storage unit 121 is improved.
FIG. 3A shows a case where it is desired to collect the liquid in the output flow path 43, and the outer peripheral radius r1 is longer than the other radii r2.
Although FIG. 2 is the same, both have shown the area | region where operation is performed on the rotating rotor.
In this way, it is possible to collect liquid by making the diameter of the outer circumference where fluid is to be collected 0.1 to 2 mm longer than the diameter of the other outer circumference. It is appropriately selected depending on the amount.

The movement of the liquid is controlled by the size of the area of the supply channel and the output channel connected to the operation region.
In the present invention, at least the flow diameter of the supply flow path supplied into the operation area is made smaller than the particle diameter of the output flow path for outputting the sample to the next operation area, thereby reducing capillary force such as centrifugal force and gravity. On the other hand, when it is necessary to maintain the operation region for a certain period of time in a field where antagonistic or higher force is supplied to the liquid, for example, when the cross-sectional area of the supply flow path is larger than the cross-sectional area of the output flow path, In a place where centrifugal force is generated, there may be a case where excessive restrictions are required on the specifications of the motor that is the source of centrifugal force. This is because when the liquid is moved from the supply flow path to the operation region, a time zone in which the centrifugal force is smaller than the capillary force of the flow path on the output side may be generated in a state where the cross-sectional area shape is not taken into consideration. This hinders holding the liquid in the operation area, causes the liquid to flow out of the output flow path, and makes it difficult to hold the liquid in the operation area for a certain period of time. Of course, by increasing the rotational speed increase acceleration of the motor, the rotational speed of the motor is increased before the supplied liquid reaches the output flow path from the time when the liquid is supplied from the supply flow path and introduced into the operation area. This can be achieved by adjusting to exceed the capillary force generated in the output flow path, but it is not substantial because it requires the motor to increase the number of revolutions in ms.
The difference of the particle size of the output flow path and the supply flow path, that 0.04～0.64Mm ² the area of the supply passage, the area of the output flow path is preferably to 0.16～1Mm ² limited thereto There is no.

Capillary force is used as induction driving force

The present invention has been achieved by finding that the capillary force of a smaller channel area exhibits a stronger liquid suction force.
The area of the channel is preferably smaller, but for example, when a desired structure is constructed by molding, it is shown that one or more channels having an area of about 0.04 to 0.25 mm ² are used, This is a condition for holding about 3 to 10 μl of liquid in the operation area. It should be defined by the viscosity of the liquid and the processing space. In addition, when the cross-sectional area of the main channel is made the smallest among the channels existing in the same structure, this effect is prominent. Has been found to have a greater impact.
The flow path with a strong capillary force is disposed at the tip in the direction in which the liquid is desired to move or is provided in a region where the liquid is desired to be drawn. Here, it is also conceivable that the optical, electrochemical, physical chemistry and biophysical measurement can be performed. This is effective when the mechanism system has a longer processing time or a mechanism system in which the movement of the liquid causes a problem. Since the wettability of the liquid is hardly affected, it is effective in that it can be applied to various materials.

About centrifugal separation structure

The present invention sets an area of a connection port in which a region for storing a body fluid to be centrifuged and a region for storing separated particles are connected via a continuous convex portion in a centrifuge to adjust a separation speed. The configuration is as follows. The maximum value of the area of the connection port may be adjusted as appropriate, with the smaller one of the size of the outer peripheral surface of the body fluid storage region and the size of the inner peripheral surface of the particle containing region being the maximum value.
In addition, when automatically mixing and quantifying diluents after blood cell separation, it is necessary to vary and adjust the separation speed. May be adjustable.
In the automation, one or more input flow paths and output flow paths are provided in the body fluid storage part, the position of the output flow path may be at least connected to the side surface in the outer peripheral direction of the body fluid storage part, Preferably, the direction of the output flow path to be connected and the vertical direction of the opening direction of the connection port for separation coincide with each other. This is because a substance with a specific gravity greater than each separated liquid component moves by arranging the opening in the vertical direction with respect to the direction in which capillary force, air pressure, gravity and other forces necessary for moving the liquid are applied. The accommodating part wall is arranged in the vector direction to be performed to make the accommodation more reliable. This effect also makes it possible to perform separation and recovery stably without giving a complicated structure such as a physical mechanism, and it is also possible to achieve an economic effect. In addition, the body fluid storage part and the particle storage part are generally configured so that the body fluid storage part has a larger surface area and the particle storage part has a deeper structure, but is not particularly limited.

About mixing operations

In the present invention, a storage space for temporarily or continuously storing a biological sample and a mixing body for mixing with the biological sample on a rotor (rotary body) and a flow path extending from the storage space. A configuration or storage unit that can be arranged such that a fluid moving force is applied outward from the storage space, and the moving force is applied to at least a part of the flow path in a direction opposite to the centrifugal force direction. The structure by which the flow path arrange | positioned above is arrange | positioned in a centrifugal force direction is illustrated.
These storage section and flow path are preferably formed by forming a recess on the rotating body and then covering the surface with a lid-like body.
The configuration in the present invention is, for example, used for mixing a blood component after blood cell separation and a dilution liquid for diluting and increasing the blood component to measure a large number of blood components,
When reacting the solid reagent and the quantitative serum, they are preferably used in order to mix them sufficiently.
In the present invention, the surface inside the mixing chamber is preferably subjected to a hydrophilic treatment.

The present invention relates to an operation area for performing operations such as quantification of a sample, color reaction with a reagent, mixing, storage, and the like, and an area before supplying the sample to the operation area. An area and a pressure generating means for pressurizing or sucking the sample in the flow path in order to move the sample solution in the flow path to the operation area,
Supply enough sample to the operation area and supply enough sample to the spare area to move to the measurement stage.
The sample input to the spare area is moved and packed around and inside the capillary force of the flow path,
The pressure generating means applies pressure to the sample in a state of being moved and packed near the flow path to move the sample to the operation area,
Further, the pressure generating means applies pressure to the flow path until the operation area is filled and the sample is also filled in the flow path.
The liquid in the operation area is released from the external force and the like, mixed with the reagent and colored, and can be measured from the outside.
In addition, since the sample is filled in the operation area with respect to the operation area where the operation area has a sufficient distance in the optical path direction, it can be taken sufficiently without changing the optical path length at the time of color measurement and stable. Optical measurement is possible.
In order to reduce the mixing of air for optical measurement, etc., by providing a structure in which the operation area cross section has a contact angle of 90 degrees or less with respect to the flow path cross section having the capillary force. It is possible to fill the operation area without any influence.
Further, when it is desired to move the sample to the operation area more quickly, a method of further increasing the pressure of the pressure generating means and skipping the space in the spare area is possible.
At that time, it is preferable to subject the preliminary region to a hydrophobic treatment.

Quantitative composition

FIG. 22 shows one embodiment of the quantitative configuration of the present invention.
In FIG. 22, 261 is a quantitative flow path, and 260 is a connection port for connecting the quantitative chamber 262 and the quantitative flow path 261.
A locus in which the radius 26R2 connecting the portion in the center O direction of the connection port 260 and the center O draws the inside of the quantitative chamber 262 becomes the liquid level in the quantitative chamber 262.

262 is a fixed-quantity chamber, and 263 is a blood cell storage unit. Since the quantification chamber 262 has a blood cell separation function, the blood cell storage portion 263 is formed with a deeper bottom than the quantification chamber 262.
H.264 is an input-side flow path, and has a configuration in which a bent portion is formed in the center O direction in order to control the flow of liquid due to centrifugal force.
Reference numeral 265 denotes an output channel having a bent portion for controlling the movement of the liquid using centrifugal force.
The quantitative flow path 261 extends so as to be inside the circular arc locus 26A by the radius 26R1 connecting the bent portion of the output flow path 265 and the center O. The degree of the inner side may be the same as or the inner side of the locus 26A. 266 is a deaeration port. The opening direction may be up and down or left and right.
Next, the operation will be described.
The liquid is supplied from the input side flow path and accumulated in the fixed amount chamber 262 due to a siphon phenomenon or the like.
At that time, the liquid is rotated around the center O, and the liquid gradually accumulates from the outer peripheral direction in the fixed amount chamber 262 and the blood cell storage portion 263. The liquid reaches the connection port 260 and the vicinity of the connection port 260. The liquid supplied from the input-side flow path 264 in a state where the liquid fills the entire connection port 260, that is, the liquid has reached the locus 26B, while the liquid is filled in the flow path 261 of The connection 260 is stopped by gas saturation caused by the liquid being blocked.
At this time, the fixed volume of the liquid determined by the fixed volume chamber partitioned by the trajectory 26 </ b> B and the volume in the blood cell storage unit 263 is determined.
The fixed-quantity chamber 262 performs a blood cell separation / accommodation operation in the blood cell accommodating portion 263 by rotation, and the blood cells are accommodated in the blood cell accommodating portion 263 that is lowered in the bottom direction.
This blood cell separation ability is not necessary when the target is blood and the dilution liquid is quantified.
By moving the connection port 260 in the radial direction of the quantitative chamber, the circumferential locus 26A determined by the distance between the center portion of the connection port 260 and the center O and the outermost periphery of the quantitative chamber 262 (here, The liquid having the volume determined by the distance to the blood cell containing portion 263 (including the outermost periphery) is quantified.

Operation area Figure 1 is a diagram showing an embodiment of the present invention, FIG. 1 shows a rotating body R configuration, polypropylene, polycarbonate - DOO, acrylic, ABS, polystyrene, polyethylene, polyethylene terephthalate, PVDF , PTFE, polyvinyl chloride, TPX, POM, UF, SAN, PSU, PPS, PPO, PPA, PEN, PAR, PA, MF, FEP, DAP, ASA, AS, AES, silicon, glass, aluminum plate, etc. The operation region here and the flow path connecting them are formed by recesses, and a sheet is joined from above using a cover using an adhesive, laser, ultrasonic welding, or the like. The manufacturing method includes, for example, a base material formed by cutting using a CAD / CAM technique, and precision processing using a technique such as electroforming, as well as a precision processing method using semiconductor technology and a processing method using stereolithography technology. It is also possible to create it. The rotating body R rotates about the central axis O and applies a centrifugal force to each operation region. FIG. 1 shows only the centrifugation step, but as a whole, the supply port for supplying blood from the outside and the mixing step shown in other figures are connected to the subsequent stage.

Reference numeral 111 denotes a blood cell storage unit, which is a concave tank connected at the outer peripheral surface of the storage unit 121, and is preferably formed with a deeper bottom than the storage unit 121.
Reference numeral 121 denotes a storage unit which is formed in a fan shape in the outer peripheral direction and is connected to the supply flow path 141 and the output flow path 151.
Here, the combination of the blood cell storage unit 111 and the storage unit 121 forms an operation region.
The outer peripheral surface of the storage part 121 forms a fan shape, but the diameter r1 on the output flow channel 151 side is longer than the other diameter r2 by 0.3 mm or more.
131 is a connection port, and is a part for connecting the blood cell storage unit 111 and the storage unit 121. Preferably, blood cells stored in the blood cell storage unit 111 are connected to the storage unit 121 in the connection port 131. A convex portion is formed along the connection side of the connection port 131 that does not disperse.
Reference numeral 141 denotes a supply channel for supplying the sample solution to the storage unit 121.
Reference numeral 151 denotes an output flow path for supplying the sample liquid after the operation to the next operation region. The output flow path 151 is connected at the outer peripheral surface of the storage part 121, and the form of the output flow path 151 extends on a circular arc derived from the outer peripheral surface of the storage part 121 or in a vertical direction with respect to the convex shape. It is preferable in terms of improving the liquid recovery rate. This is because, by arranging the force vector that must be accommodated with respect to the force vector applied to the liquid to be moved in the vertical direction, the force vector applied in the vertical direction is applied to, for example, the wall surface of the accommodating portion. It is used as such force, and based on the theory that the liquid remains in the storage portion by inhibiting the movement of the storage portion liquid as a stress on the wall surface. Therefore, forming the output port with an angle of 180 degrees or more with respect to the storage unit is a means for preventing the substance present in the storage unit from flowing out to the output port, and depends on the amount of processing liquid, When processing ~ 400 μl of liquid, the outflow of the substance in the container can be prevented by disposing the outlet of the output port about 0.1 to 1.5 away from the convex shape from the convex shape.

The operation of this embodiment will be described in detail with reference to FIG.
The raw blood ZK is supplied to the storage unit 121 via the supply channel 141.
When the rotating body (rotor) R is rotated, the whole blood moves in the outer circumferential direction, and the liquid surface tries to draw an arc SF having the same radius (FIG. 2 (a)).
The whole blood ZK tends to move to the outside due to the capillary force of the output channel 151, but the centrifugal force applied to the output channel 151 serves as a stopper and stays in the output channel 151.
This is because when the whole blood ZK is introduced into the reservoir 121 via the supply flow path 141, the centrifugal force is greater than the capillary force of the output flow path 151 that already attempts to suck the whole blood ZK due to the action of the centrifugal force. It will be a phenomenon that can surely happen because of winning. This is because the cross-sectional area of the supply flow path 141 is smaller than the cross-sectional area of the output flow path 151, so that it can theoretically be said that a stronger capillary force works in the supply flow path. Unless the liquid is supplied from the supply flow path 141 to the reservoir 121 unless it is generated, a centrifugal force stronger than the capillary force generated in the output flow path 151 has already been generated. The liquid can continue to exist.

The whole blood ZK remaining in the storage unit 121 is centrifuged by the rotation of the rotor (rotor) R, and the blood cells in the whole blood ZK are stored in the blood cell storage unit 111 beyond the convex portion of the connection port 131. After a few minutes due to the rotation of the rotating body R, the whole blood ZK is almost entirely stored in the blood cell storage unit 111, and a blood component such as serum or plasma remains.
This blood component gathers around the output flow channel 151 because it exhibits a behavior that gathers in a portion having a long radius r1, particularly when the wettability of the surface of the reservoir 121 is improved.
When the blood cell KK is stored in the blood cell storage unit 111 and the separation is almost completed, if the rotational speed of the rotating body R is decreased, the capillary force that has been suppressed by the centrifugal force is increased. (Fig. 2 (b)).
In this state, the rotation of the rotating body R is further strengthened to promote the outward movement of the blood component in the output flow channel 151, the blood cell is stored in the blood cell storage unit 111, and the blood component in the storage unit 121 Is in an empty state via the output flow channel 151 (FIG. 2C).

  As described above, according to the present embodiment, serum or plasma after separation of blood cells can be formed without leaving serum or the like in the reservoir, and without waste. This is due to the fact that the effect of the present invention, which has the action of collecting the liquid in a certain space, prevents the entry of air, which is the greatest factor for reducing the recovery rate.

The movement of the liquid is controlled by the size of the area of the supply channel and the output channel connected to the operation region.
An embodiment of the present invention will be described in detail with reference to FIG.
3 (a) and 3 (b) are operation units each constituted by a recess provided on the rotating body. In FIG. 3A, 41 is a supply flow path, and 42 is an operation unit. 43 is an output flow path, but the connection surface d2 between the operation section 42 and the output flow path 43 is clearly wider than the connection surface d1 between the supply flow path and the operation section 42.
In the figure, d1, d2, and d3 indicate the area of the connection port between each flow path and the operation region.
With respect to the outer periphery of the operation region and the radius of the central axis O, the radius r1 of the portion where the sample is desired to be gathered is made longer than the other radius r2.

In this way, when the force that gathers the sample near the output flow path by rotation works, the capillary force generated by the material is not uniform even in the same cross-sectional area, but the cross-sectional area of the output flow path is 0.25 mm ² , and acrylic material is used. As a result of the experiment, the generated capillary force is about ~ 0.4G (when the centrifugal force is generated, the rotation radius is 11.8mm and the rotation speed is 280rpm. Under this condition, the capillary force and the centrifugal force antagonize and the liquid moves. without being present at the output channel), so the same material, when the supply flow path cross-sectional area of the same wettable material is set to 0.04 mm ^2, when the capillary force of about 40G (centrifugal force generated, the rotation radius 4.3cm The sample can be kept in the operation area by generating a force equivalent to 900 rpm, and the output flow path 43 may be connected in the vicinity thereof.
To output the sample after operation to the output channel 43, for example, a method of introducing the liquid into the other circuit using the siphon principle and centrifugal force while the liquid is filled in the output circuit by capillary force, It can also introduce | transduce using a pressure, decompression force, etc. In the present invention, even if there is an air portion in the operation region, the mechanism is not affected. Therefore, a structure in which the operation liquid does not flow near the supply flow path is based on the method of the present invention. In this way, the capillary force of the supply channel does not interfere with the movement of the liquid to the output circuit. In this case, d1 is preferably 0.04 to 1 mm ² from the viewpoint of production technology that can be precisely produced by current molding or cutting, etc., but it is preferable that a production method using semiconductor technology is used. This minimum cross-sectional area is not limited in a processing region where technological development is expected, such as when used.

FIG. 3B shows an embodiment in which the present invention is applied to the mixing operation region.
Reference numeral 421 denotes a mixing tank, and the radius r1 of the outer periphery and the center of the part where the liquid is to be collected is set to be longer than the other radius r2.
41a is a blood component supply channel for supplying blood components such as serum and plasma, and 41b is a diluent supply channel.
43 is an output flow path for supplying and outputting the mixed liquid to the next operation area after mixing.
The relationship between the area d2 of the output channel 43 and the areas d11 and d12 of the supply channels is as follows:
d2> d11, d2> d12
Or d2> (d11 + d12)
It is represented by
Reference numeral 44 denotes a convex portion for accommodating particles unnecessary for measurement separated by centrifugal force, such as blood cells.
This part is a part for separating the remaining blood cells in the blood cell separation step in advance before mixing, and when the unnecessary particles are sufficiently removed in the previous step, the convex part 44 is It may not be necessary.

The operation of FIG. 3B will be described.
A blood component is supplied from the blood component supply channel 41a to the mixing tank 421, and a diluent is further supplied from the diluent supply channel 41b to the mixing tank 421.
The mixing tank 421 is rotated and shaken around the central axis O of the rotor, and mixed in the mixing tank 421.
Also in this case, the internal solution is attracted by the capillary force of the supply flow paths 41a and 41b, and is not output from the output flow path 43 to the outside.
The mixing is performed by changing the amount of liquid existing in the capillary by changing the number of rotations of the rotating body, and changing the amount of liquid from the output channel 43 or from the mixing channel 421 by changing the centrifugal force generated according to the number of rotations. In this method, a turbulent flow is generated in the mixing tank 421 by being moved and mixed. There is also a method of stirring and mixing by changing the rotation direction and generating turbulent flow in the liquid using the inertial force of the liquid, which is realized by performing these several times.
After mixing to some extent, in order to use the siphon principle, the mixture is rotated at a low speed for a certain period of time, and after the capillary is sufficiently filled with liquid, the rotation speed is further increased and the mixed liquid is output from the output flow path 43.

As described above, the sample liquid can be retained in the operation region by attracting the liquid by the capillary force on the supply channel side, and the liquid can be held and output with a simple configuration.
3C and 3D, the area d1 of the supply flow path 41 connected to the operation unit 42 and the area d2 of the output flow path 43 have a relationship of d1 <d2.
In the case of FIG. 3C, the output flow path 43 is connected to the bottom of the operation area 42, and FIG. 3D shows an example in which the output flow path 43 is arranged at the top of the operation area 42. It was.
Thus, even if the arrangement of the output channel 43 is changed up and down with respect to the operation region 42, the sample liquid is attracted to the supply channel 41 side by reducing the area d1 of the supply channel 41. Can do it.
Reference numeral 45 denotes a distribution channel, which is a channel connected to the previous operation region. H is a lid and is in the form of a sheet, and is connected to the base material of the rotor R by an adhesive and ultrasonic welding.

Next, another embodiment of the present invention will be described in detail with reference to FIG.
In FIG. 4A, reference numeral 71 denotes an operation region. If it is a reagent reaction tank, it is a portion that preferably contains a reagent and forms a final purpose to which a liquid intended for operation reaches.
In addition, it may be a dummy space formed only for connecting the other end of the capillary tube 72.
Reference numeral 72 denotes a capillary channel, and a channel having a cross-sectional area KA of 0.04 to 0.25 mm ² is preferable in view of the current processing accuracy. However, with future improvements in processing accuracy, the possibility of knowing that the numbers shift in the smaller direction is shown. The capillary channel was provided with five radial channels having the same cross-sectional area KA.
Even if the reaction reagent is a reaction that requires oxygen, it is possible to introduce the oxygen at the KA interface between 73 and 72 into the operation region 71 and to proceed the reaction by changing the rotation speed.
It has been found that the cross-sectional area KA is more effective when set to take the minimum value in the cross-sectional areas in all other identical structures.
Reference numeral 73 denotes a distribution channel for moving blood and diluent between the operation areas.
The depth of 73 is desirably sufficiently larger than the cross-sectional area 72, and for example, the depth is preferably 1 mm to 3 mm. Further, it is desirable that the distance between 72 on the opposite side of 73 and 73 on the 72 side is set so that surface tension is not generated by the introduced liquid.

In this embodiment, since each capillary channel 72 has a strong capillary force, by providing five of these, a stronger capillary force can be obtained. Therefore, it can be used as a fluid drive source.
FIG. 4B is a diagram in which the operation region 74 and the distribution channel 73 are combined without using the capillary channel. Area KB binding surface 75, 0.04～0.8Mm ² is illustrated, the contact angle S of the distribution channel and the operation area 74 is illustrated 5-30 degrees.
In this configuration, since the coupling surface 75 holds the liquid by the surface tension generated by the contact angle between the operation region 74 and the distribution channel, the sample that has passed through the distribution channel 73 is held on the coupling surface 75. Since the surface tension varies depending on the viscosity of the liquid, the contact angle between the operation region 74 and the distribution channel is adjusted in a timely range of 5-30 degrees.
The configuration of FIG. 4 (b) is simpler and can form a sample operation region with reduced cost when forming a fluid chip.
The embodiment shown in FIG. 4 is preferably used for a driving source or a function for quantifying and stopping a fluid or for simply stopping a liquid or slowing a flow. It is effectively used when a polymer liquid is operated.

Blood cell separation composition

The blood cell separation configuration according to the present invention will be described in detail with reference to FIG.
FIG.5 (e) is the figure which looked at the centrifugation structure which shows one Example of this invention from the upper surface.

The present embodiment is a blood test unit having a centrifugal separation as one configuration, and includes a supply flow path 14 for supplying processing blood, and an output flow path 15 for outputting processed blood to the next step. It has.
12 is a fluid reservoir, the size will vary depending on the amount of processing blood, when processing a 20 [mu] l-500 [mu] l of blood, in order to cover the measurement of the hematocrit value of 60% of the specimens 8 mm ³ ~ about 200 mm ³ is illustrated. 11 is a particle | grain accommodating part. It is a part mainly for storing blood cells, and its size is 12 mm ^{3 to} 300 mm ³ in order to cover the measurement of a specimen with a hematocrit value of 60% when processing 20 μl-500 μl of blood. Is exemplified.
13 is a convex part, and is uniformly formed with a height (CC) of 0.5 mm to 2 mm at the bottom of the connection port connecting the particle storage unit 11 and the body fluid storage unit 12. FIG. 5A is an XX ′ cross section of FIG.

  The convex portion 13 is formed in a roughly trapezoidal shape or a triangular shape. This is because the blood cells existing in the body fluid storage portion at the start of the division are quickly and efficiently introduced into the particle storage portion. This is for providing a gentle inclination to the housing portion. The direction from the particle storage unit 11 to the body fluid storage unit 12 is preferably a configuration in which blood cells can easily get over by centrifugal force and not easily move in the reverse direction. However, as shown in FIG. In some cases, it is better to make the depth of the particle storage unit 11 deeper than the body fluid storage unit 12, even if it is not characterized. However, even when the depth is simply increased, the above-described problem may occur. Therefore, the ratio between the distance from the connection port to the outermost part of the particle accommodating portion and the depth is preferably 1 or more and 1: 1. Further, since the substance stored in the particle storage part has a higher specific gravity than the substance stored in the body fluid storage part, it is desirable that the particle storage chamber is deeper than the body fluid storage part in consideration of the storage efficiency. It is not limited.

FIG. 5B is a view of the front of the connection port K. FIG. The rectangle a is about 10 mm and b is about 0.5 mm. However, the shape is not limited to this, and any shape can be used as long as it is a connection port.
Here, the area of the connection port K is rectangular so that the area can be easily calculated. FIG. 5C is a diagram in which the state including the blood cell storage portion 11 and the connection port K is regarded as a perspective space. As shown in FIG. 5C, the protrusions 13 do not have to be arranged in a straight line, and may not have a uniform height CC, such as when the connection surface is curved. In particular, when the distance from the output flow path 15 is lower and the closer distance is higher, the blood cell component can be more efficiently accommodated in the blood cell accommodating portion.

Reference numeral 14 denotes a supply channel, which has a supply unit IN which is a connection part with the storage unit 12, and is a channel through which raw blood, a mixture of diluted solution and raw blood is supplied.
The other end of the supply channel 14 is connected to, for example, an external blood input port or a diluent mixing unit.
The other end of the output channel 15 is connected to a quantification unit for quantifying the sample solution after separation of serum and the like, a reagent chamber equipped with a reagent, and the like.
The cross section is, for example, 1 mm ² or less, and is formed to such a size that capillary force can act.
Reference numeral 15 denotes an output flow path, which has a supply port OUT that forms a connection surface with the storage section 12 and has the same size as the supply flow path 14, but the output flow path 15 faces the center portion C. And may have a bent shape.
FIG. 5D is a diagram showing an example of the positional relationship of the embodiment of the present invention on the rotor R.
Rotor R is made from PP (polypropylene) polycarbonate, acrylic, ABS, polystyrene, polyethylene, polyethylene terephthalate, PVDF, PTFE, polyvinyl chloride, TPX, POM, UF, SAN, PSU, PPS, PPO, PPA, PEN, PAR , PA, MF, FEP, DAP, ASA, AS, AES, silicon, glass, aluminum plate, etc. A flow channel, a storage unit, and a blood cell storage unit may be formed, and in some cases, the formed flow channel surface may be subjected to hydrophobic and hydrophilic treatment.

After that, polycarbonate, acrylic, ABS, polystyrene, polyethylene, polyethylene terephthalate, PVDF, PTFE, polyvinyl chloride, TPX, POM, UF, SAN, PSU, PPS, PPO, PPA, PEN, PAR, PA, of the same area An analysis rotor is formed by joining a lid H made of MF, FEP, DAP, ASA, AS, AES, silicon, glass, aluminum plate or the like.

Next, the operation of this embodiment will be described.
When raw blood is injected from the outside, the raw blood is supplied to the storage unit 12 via the supply channel 14. The driving source for supplying the raw blood G to the storage unit 12 is, for example, centrifugal force, gravity, or capillary force. The rotor R is rotated at 1000 to 30000 rpm with respect to the raw blood supplied to the storage unit 12. The number of rotations should be determined by the distance between the storage unit 12 and the centrifugal center C, the separation time, etc., but considering the economic problem and the safety of the user, the separation is performed at about 3000 to 6000 rotations. Although it is desirable to do so, it is not limited.
Further, it may be defined by the centrifugal force obtained at the number of rotations rather than defining the rotation of the rotor. In this case, the centrifugal force is preferably 400 to 1000 G, but is not limited.
The centrifugal force at this time was generally calculated from what can be given by the following equation.
Centrifugal force v = 11.18 x (n rpm / 1000) ² x R (distance from the centrifuge center cm)
The blood cell GK in the original blood G moves in the direction of the convex portion 13 by the centrifugal force v.
As the centrifugal force v increases, the blood cell GK receives a stronger force in the direction of the convex portion 13 than the other liquids, and the blood cell GK gets over when the rotational speed exceeds a certain value.

Such an operation is repeated, and only the blood cell GK is stored in the blood cell storage unit 11.
Blood components such as serum and plasma that have moved the blood cell GK to the blood cell storage unit 11 try to move to the outside through the output channel 15 by capillary force from the output port OUT. Since the progress of the blood component that has reached the bent portion is suppressed, it does not attempt to move outside.

By applying a centrifugal force of a certain level or more in a state where the area of the connection port K is adjusted in this way, the blood cell GK in the blood G is moved to the blood cell storage unit 11 by continuing for a predetermined time, and blood cell separation is performed. The blood component such as serum is made, and then the rotational speed is weakened to weaken the centrifugal force. The separated blood component moves to the outside by the capillary force in the output flow path 15.
In the case of this example, the centrifugation time is 2.5 to 5 mm ^{2 at the} connection port, the rotation speed is 3000 to 5000 rpm, and the raw blood volume supplied from the supply unit IN is 0.14 to 0.25 ml
For example, 1.5 to 3 minutes is exemplified, and when the separation time is desired to be further increased, the hole diameter of the connection port is narrowed.

From the experimental results, it is known that the present embodiment has the following relationship.
Separation time = 10 / cross-sectional area (mm ² )
Here, the determination of the completion time of separation varies depending on the viscosity of patient blood, the amount of water, etc., but should be applicable when 60% or less of blood is separated in terms of hematocrit. 10 varies between approximately 8-12 depending on the component content of such processing liquid. This can also be attributed to factors other than those described by the present invention, such as wettability, material, and roughness of the surface of the rotating body for processed measurements. The centrifugal force at this time is also a number that should be greatly influenced by this constant, but this centrifugal force is a result at 500 to 600 G in the experiment in the present invention, but almost the same result is obtained at 900 G. It was. This number is also affected by the ratio of the blood cell accommodating part depth and the distance from the connection port to the outermost part of the blood cell accommodating part, but in this embodiment, this ratio is effective in the range of 1: 1 to 1: 3.5. . When this ratio becomes smaller when the depth is 1, the number becomes smaller, and when it becomes larger, the constant becomes larger.

Next, embodiments of the present invention will be described in detail with reference to the drawings.
In FIG. 7, reference numeral 61 denotes a mixing storage chamber having a small chamber 65 in the outer peripheral direction and an output flow path 63 extending in the external direction. Further, a sample supply channel 62 and an auxiliary liquid supply channel 64 are connected to the inner peripheral side of the mixing storage chamber 61.
The mixing storage chamber 61 is installed in a state where the distance r1 between the outer peripheral surface at the connection portion with the output flow path 63 and the center OK is longer than the distance r2 between the other outer peripheral portion and the center OK.
62 is a sample supply channel, and is a channel for supplying blood component solutions such as serum and plasma, and 64 is an auxiliary solution for diluting, for example, a diluting solution and performing amplification for measurement. This is an auxiliary liquid supply flow path for supplying water.
Reference numeral 63 denotes an output flow path, which is bent once in the central direction and extends to the next operation region.
The area (0.04 to 0.64 mm ² ) of the connection port between the sample supply channel 62 and the auxiliary liquid supply channel 64 and the mixing storage chamber 61 is the connection surface between the output channel 63 and the mixing storage chamber 61. Is preferably set smaller than the area (0.25 to ¹ mm ² ). This connection cross-sectional area is set within the above range according to the current processing conditions, but if the value is reduced with the progress of processing technology in the future, a smaller amount of liquid can be handled and prescribed is not.

A small chamber 65 is a part for accommodating unnecessary components remaining in the sample by centrifugal separation.
This may not be necessary if the sample supplied from the sample supply channel 62 has no unnecessary components. The size is exemplified by about 0.3 to 6.5 mm ^3, but is not limited thereto.
The size of the mixing storage chamber 61 in this embodiment varies depending on the amount of sample and auxiliary liquid to be supplied, but there is roughly a space of 1.5 times or more of the combined value of the sample and auxiliary liquid. The depth can be further reduced by increasing the depth near the mouth, setting the liquid mixing portion shallower than the depth, and providing a structure that does not return to the connection port once the liquid is introduced. Further, when the introduction portion depth is changed, a convex shape is created at the boundary, and a structure that further increases the surface tension is set, a liquid having a lower surface tension, such as an organic solvent, etc. This is also effective when used, but is not limited to this percentage.
Moreover, these structures are preferably incorporated in a disk-shaped body having a center axis OK, and are preferably provided with a driving device for rotating the disk-shaped body.

Next, the operation of this embodiment will be described in detail with reference to FIG.
The sample solution 6KS is supplied from the sample supply channel 62 without rotating the rotor or in a rotated state (FIG. 6B). Next, the auxiliary liquid 6KK is supplied from the auxiliary liquid supply flow path 64 (FIG. 6C). These introductions may be performed simultaneously. The sample liquid 6KS and the auxiliary liquid 6KK are both attracted by the capillary force of the sample supply flow path 62 and the auxiliary liquid supply flow path 64 when the rotation of the rotor is small or stationary. It is said.
When the rotational speed is increased to a predetermined value, these solutions move so as to be biased toward the connection surface of the output flow path 63, and particles having a large specific gravity are accommodated in the small chamber 65 while unnecessary particles are removed. Enters the output flow path 63 and tries to move outward by capillary force.
The mixed solution 6K to be moved by the capillary force of the output flow path 63 moves (M1) to a site where the centrifugal force (ES) and the capillary force are balanced (FIG. 6 (d)).
Near the threshold at which the centrifugal force becomes weaker than the capillary force, in the case of this test, the rotation speed is reduced from 500 to 1500 rpm, rotation G 1.4 to 125, rotation radius 0.5 to 50 mm, from 3500 to 5000 rpm rotation G 68 to 1400, rotation radius 0.5 to 50 mm Immediately after that, the mixed solution 6K in the output flow path 63 is pushed back (M2) and returned to the mixing storage chamber 61 (e).
Reducing the rotation speed to 3500 to 5000 rpm, rotation G 68 to 1400, rotation radius 0.5 to 50 mm, and again reducing the rotation speed to the predetermined value 500 to 1500 rpm, rotation G 1.4 to 125 rotation radius 0.5 to 50 mm, the capillary force again As shown in FIG. 6D, the mixed solution 6K is moved to the output flow path 63 (M1).
By repeating this 2 to 8 times, the mixed solution is reciprocated, and sufficient mixing is achieved in the process.

Next, another embodiment of the present invention will be described in detail with reference to FIG.
Reference numeral 51 denotes a reagent reaction tank which is a cylindrical body having a depth of 5 t, and a supply capillary 52 is connected to the upper part thereof. The supply capillary 52 preferably has a caliber area of 0.04 to 0.25 mm ² , but may be appropriately adjusted according to the amount of liquid to be measured, and a plurality of supply capillaries may be arranged in parallel. The depth 5t of the reagent reaction tank 51 is preferably 0.3 to 5 mm in terms of performing a mixing operation by repeated movement of the liquid by capillary force and centrifugal force of the sample supply channel, and ensuring the optical path length.
Reference numeral 53 denotes a distribution channel for distributing the sample solution to other reagent reaction vessels, other operation areas, etc., and its aperture area is about 1 to 4 mm ² .
A coloring reagent 54 is dissolved in the sample solution to cause a coloring reaction.
Reference numerals 55 and 56 denote light-transmitting portions for measurement, which are formed of members that transmit light from the outside.
The upper measurement translucent part 55 and the lower measurement translucent part 56 require both in the case of measurement by transmitted light, but may be one in the case of measuring reflected light.

This configuration is formed as a recess on the rotor, and a configuration in which the lid H is joined from the top with adhesiveness is shown as an example, and FIG. 6 shows a part thereof.
In addition, sectional views showing a cut surface of XX ′ in FIG. 7A are shown after FIG.
Next, the operation of this embodiment will be described in detail with reference to FIG.
The sample 5S1 flowing through the distribution channel 53 is held by the capillary force of the supply channel 52 (FIG. 7B), and the sample 5S2 is in a state where the sample flowing through the distribution channel 53 is interrupted. The sample is held in the supply channel 52 and is quantified in practice.
Next, the rotational speed of the rotor R is set to 5000 RPM, and the sample 5S2 in the supply flow path 52 is pushed out into the reagent reaction tank (FIG. 7 (d)).
The extruded sample 5S3 and the reagent 54 come into contact with each other and the dissolution starts. However, after 10 to 60 SEC, when the rotational speed is reduced and the centrifugal force (5CC1) is weakened, the mixed liquid is supplied by the capillary force of the supply channel 52. 5S4 moves so as to be sucked to the connection port between the flow path 52 and the reagent reaction tank (FIG. 7E).

When the rotational speed is increased again after 1SEC, the centrifugal force 5CC2 increases, and the mixed liquid 5S5 moves again to the bottom surface of the reagent reaction tank 51 (FIG. 7 (f)).
By repeating this process 2 to 8 times, the reagent and the sample are sufficiently mixed, and a state suitable for measurement is formed.

The measurement is performed, for example, using an optical path HS in which one of the upper and lower directions is selected as shown in FIG.

Next, another embodiment of the present invention will be described in detail with reference to FIG.
This example is useful when mixing with a plurality of additives such as reagents and examining the color value.
That is, in FIG. 8 (a), 91 is a primary reaction tank, which is disposed on a rotor that rotates about a central axis O9, and the distance r2 of the outermost peripheral edge on the output side of the outermost periphery and other parts. With the distance r1 from the center of
r2> r1
Have the relationship.
92 is a chamber, for example, mutarotase, glucose oxidase, peroxidase, ascorbate oxidase, phenol, 1-naphthol-3,6-disulfonate disodium, phosphate, pyruvate oxidase, oxaloacetate decarboxylase, catalase , N-ethyl-N- (2-hydroxy-3-sulfopropyl) -m-toluidine sodium, 4-aminoantipyrine, L-aspartic acid, α-ketoglutaric acid, thiamine pyrophosphate, magnesium chloride hexahydrate, HEPES, Lipoprotein lipase, Adenosine-5'-Triphosphate disodium trihydrate, Glucerol kinase, Glucerol-3-phosphate oxidase, 3, 5-dimethoxy-N-ethyl-N- (2'- Hydroxy-3'-sulfopropyl) -aniline sodium, PIPES (buffer) L-alanine, DAOS, carbonate buffer, sodium hydroxide p-ni Trophenyl phosphate disodium, F-DAOS, uricase, N, N-bis (4-sulfobutyl) -3-methylaniline disodium (TODB), creatinase, sarcosine oxidase, Good buffer, creatininase, azidation Sodium, 3,5-dinitrobenzoic acid, lithium hydroxide monohydrate, cholesterol oxidase, N, N-bis (4-sulfobutyl) -m-toluidine sodium (DSBmT), cholesterol esterase, surfactant, copper sulfate 5 Hydrate, Potassium sodium tartrate, Copper sulfate, Glucoamylase, BES buffer, α-Glycosidase, p-Nitrophenylbenzyl-α-maltothiode (BG5P), Benzylidene-p-nitrophenylmaltohephthalate (BG7 -pNP), monoethanolamine buffer, methylxinol blue, 8-quinolinol, o-creso Ruphthalein confexone, hexokinase, βNAD, nitrotetrazolium blue, L-lithium lactate, βNADPNa, creatine phosphate 2-Na tetrahydrate, glucose 6-phosphate dehydrogenase, magnesium acetate tetrahydrate, nitroblue tetrazolium, A primary reagent 95 made of glycine buffer, NPP, OCPC, EGTA, CAPS buffer, thiamine pyrophosphate, glycylglycine buffer, Lg-glutamyl-carboxy-4-nitroanilide or the like is accommodated.
The connection surface between the small chamber 92 and the primary reaction tank 91 is the outermost peripheral edge in the centrifugal force direction, and the opening surface 96 of the small chamber 92 has an acute angle.
The acute angle shape may not be a sharp angle, and may be chamfered if there is no requirement as described below.

Examples of the primary reagent 95 include a freeze-dried one, a state in which a liquid is impregnated with porous particles made of ceramics or polymer, and a liquid state.
As shown in FIG. 8A, the connecting portion between the small chamber 92 and the primary reaction tank 91 is set at an acute angle S, so that the liquid reagent in the small chamber forms a state of staying inside due to surface tension.
93 is an input flow path for inputting a sample solution, and 94 is an output flow path for outputting a sample in a mixed reaction state in the primary reaction tank 91 to another reaction tank.
The output flow path 94 has a so-called siphon configuration, and has a function of adjusting the movement of the solution in the primary reaction tank 91 to the outside by controlling the number of rotations.
The configuration is preferably disposed on the rotor illustrated in FIG. 9, but may be disposed on a rotating body such as a rotor as long as at least one direction of force is applied to the sample or the like. is there.

Next, the operation of FIG. 8 will be described in detail with reference to FIGS. 9A and 9B.
When the sample E9 is input from the input flow path 93 to the primary reaction tank 91 and rotated at the rotation speed (3000 to 6000 RPM), the sample is introduced by the centrifugal force, the capillary force of the output flow path 94, and the like. As shown by 9 (b), the air in the small chamber 92 is pushed into the primary reaction tank 91 by a specific gravity difference by centrifugal force.
Next, when the rotational speed is lowered (500 to 1500 RPM), the centrifugal force becomes weak (EN), the reagent solution dissolves in the small chamber (92), and the mixed sample solution flows out into the small chamber 91. As shown in FIG. 9A, the liquid level becomes uniform on the circumference (H10).
Next, when the number of rotations is increased (3000 to 6000 RPM) until the influence of surface tension is given to the liquid level, as shown in FIG. 9B, the liquid level has a concave center (H10). When the rotational speed is lowered, the liquid level becomes uniform on the circumference as shown in FIG. 9B (H9).

In this way, by moving the liquid level up and down in the centrifugal direction, the primary reagent 95 and the sample are mixed to form a mixed solution M9.
After the primary reaction tank 91 is rotated at 500 to 6000 RPM, the mixed solution M9 is moved from the output flow path 94 to the reagent reaction tank by reducing the rotation speed to 100 to 300 rotations or the like.
In this case, on the outermost peripheral surface of the primary reaction tank 91, the mixed liquid M9 is obtained by making the distance r2 between the outermost peripheral part on the output flow path 94 side and the central axis O9 longer than the distance r1 of the other outermost peripheral part. The mixed liquid M9 can be output from the output flow path 94 to the outside without leaving the mixed liquid M9 of the reagent in the primary reaction tank 91 in an attempt to gather to the output flow path 94 side.

Next, an embodiment of the present invention will be described in detail with reference to FIG.
Reference numeral 71 denotes an operation tank in which a lyophilized reagent 76 is arranged. Examples of the reagent include enzymes such as glucose oxidase, but are not particularly limited as long as they are necessary for measurement. Examples of the depth Tb are 0.3 to 5 mm.
Reference numeral 722 denotes a channel group having the same cross-sectional area and the length is the same, but is not particularly limited. This flow path group is only an example, and may be a single flow path.
By using the flow path group 722, when the sample flows into the operation tank 71 through the flow path group 722, the existing air and gas in the operation tank 71 are at least in the flow path group 722. This is effective in that it becomes an air vent channel that goes outside through one channel. In addition, the capillary force to hold the liquid is maximized in relation to the generated force, which varies depending on the gravity generated from the height of the capillary channel S2, the specific gravity of the liquid to be handled, the surface wettability of the structure, etc. In some cases, it may be necessary to introduce a plurality.

Reference numeral 73 denotes a distribution flow path for carrying the supplied sample to various operation tanks.
Reference numeral 74 denotes a spare chamber whose cross-sectional area is 9/1 to 60/1 compared to the S2 capillary channel cross-sectional area.
Reference numeral 75 denotes a first supply flow path, and the cross-sectional area S1 of the flow path is 2 to 25 times larger than the cross-sectional area of each flow path of the flow path group 722. The spare chamber 74 has a configuration in which the connection surface with the flow path group has an arc shape so that the lengths of the flow path groups are equal.
Reference numeral 77 denotes a lower light-transmitting portion, and 78 denotes an upper light-transmitting portion, which is formed with a light-transmitting property for measuring the state in which the reagent 76 and the sample are mixed and colored from the outside.
Specific examples include transparent plastics such as polystyrene, PET, acrylic, polycarbonate, resin materials for contact lenses, and glass, but are not limited thereto.
R is a rotating body, and is preferably a disk-like body that rotates about the central axis OK, and the arrangement of the capillaries preferably extends in the centrifugal force direction.

Next, the operation will be described.
The sample KS that has flowed through the distribution channel 73 is supplied to the reserve chamber 74 via the first supply channel 75 (FIG. 11A).
The sample KS accommodated in the preliminary chamber 74 is attracted to the channel group 722 by capillary force, and flows into and fills each channel (FIG. 11B).
The channel group 722 is filled with the sample (KSG), and the sample (KSG) further remains around the channel group 722 in the preliminary region.
Next, when the rotational force of the rotor is increased to increase the centrifugal force E <b> 1, the sample in the channel group 722 is pushed out to the operation tank 71.
When there is no sample in the channel group 722, the sample in the preliminary chamber 74 sequentially moves to the channel group 722 by capillary force, and the sample in the channel group 722 is pushed out to the operation tank 71 by centrifugal force ( FIG. 11 (c)).
In the state where the operation tank 71 is filled with the sample and the channel group 722 is filled with the sample (FIG. 11D), the rotational speed is lowered or stopped.

The sample in the operation tank 71 and the sample in the channel group 722 are held in a stable state by the capillary force of the channel group and the surface tension in the auxiliary chamber 74.
When the sample tank is filled in the operation tank 71 and the channel group 722, the fixed sample KS in the operation tank 71 can form a stable state without being attracted to the channel group.
The fixed sample KS is determined by the sum of the volume of the operation tank 71 and the total volume of the flow path group 722.
The quantitative sample KS in the operation tank 71 is mixed with the reagent 78 (KSM), undergoes a color reaction, and a color value is measured by transmission of the external measurement light KH.
In the present invention, the combination structure in which the reagent reaction tank and the preliminary region are connected by the flow path having the capillary force is shown as an example. When the sample inside the operation tank is to be stabilized with the capillary and the operation tank connected, it is possible to eliminate the capillary force in the external direction by filling the flow path with liquid. ,
Such a liquid filling method makes it possible to control the movement and stoppage of the sample.

Next, an embodiment when a small amount of specimen is filled in the reagent reaction tank will be described with reference to FIG.
The embodiment described above shows a state (FIG. 11 (d)) in which the reagent reaction tank and the flow path group are fully filled with the sample specimen in order to ensure the measurement optical path length. May be set to a sufficiently small amount.
At this time, the sample may be desirably quantified or semi-quantified in the operation area before the preliminary chamber, but may be quantified by the channel group 722.
A first supply channel 75 is provided in the preliminary chamber 74 so as to extend in the direction of the centrifugal center as close as possible to a certain distance from the channel group 722, and a stream having capillary force is provided upstream of the first supply channel 75. It is assumed that the path group 722 has a structure for supplying a filler that is filled after the specimen is introduced into the operation region.
The supply of the filler is preferably performed quickly after the sample is introduced into the operation region and before the rotation speed is decreased, and before the sample is drawn to the flow path group 722 and refilled. .

That is, after the specimen is moved to the operation area, the filler is guided to the boundary surface between the first supply channel 75 and the preliminary chamber 74 by capillary force, surface tension, gravity, or the like, and the surface of the preliminary chamber 74 is further wetted. The distance from the first supply flow path 75 to the flow path group 722 is moved at a moving speed determined by the nature. The moved filler is filled in the channel group 722 by the capillary force of the channel group 722.
When the filler is introduced into the operation tank 71 by applying a slight force using air pressure, gravity, centrifugal force or the like after the flow path group 722 is filled, the specimen in the operation tank 71 is in a stable state. Mix with reagent to cause color reaction.
In this case, the input channel cross-sectional area needs to be sufficiently larger than one channel cross-sectional area of the channel group 722 in order to suppress the capillary force of the input channel and shorten the movement time of the moving filler. is there.
Specifically, the cross-sectional area of the input flow path depends on the type of filler relative to the cross-sectional area of one flow path group. For example, in the case of DMSO, a value about 30 to 300 times is appropriate. .

FIG. 12 shows another embodiment of the present invention.
FIG. 12 shows a liquid holding kit for the purpose of temporarily holding and storing a liquid.
80 is a substrate, for example, a resin agent that has little influence on a biological sample having a thickness of 1 to 10 mm, and can be produced at low cost. For example, polystyrene, polypropylene, polyethylene, ABS, polycarbonate, acrylic, etc. , Made of glass material. Here, the size of the substrate 80 is exemplified by about several mm ² to several tens mm ^2, but is not limited.

Reference numeral 81 denotes a storage area, which is composed of a cylindrical recess. 82 is a plug flow passageway groups, a plurality of flow paths (cross-sectional area of 0.09mm ² ~2.25mm ²⁾ is 1 or more the same length, for connecting the storage area 81 and a spare area 83.
Reference numeral 84 denotes an input port, which is a flow path for inputting storage solution and stopper solution from the outside.
Reference numeral 85 denotes a supply channel, which is a channel for supplying a storage solution and a stopper solution from the outside.
The supply flow path 85 is curved along the curved surface of the contact area with the plug flow path group 82 in the spare area 83 and further extends to the outside of the spare area 83.
Because the cross-sectional area of the supply channel 85 is larger than the cross-sectional area of the plug flow passageway groups 82, the difference is, 0.21mm ² ~2.2mm ² is movement of the liquid into the plug flow path is smooth, preferable.
Reference numeral 86 denotes a lid, which is formed of, for example, the same member as the substrate 81 and covers the operation region 81 for the stopper channel group 82 formed as a groove on the substrate 81. When covering, an adhesive bonding technique using an adhesive, a technique such as welding, or an adhesion technique using a silicone-containing sheet is used.
The lid 86 is preferably transparent so that the internal state can be grasped.

Next, the operation of FIG. 12 will be described in detail with reference to FIG.
As shown in FIG. 13A, the storage liquid 8B is input from the input port 84 (8A). At that time, it is preferable that the liquid corresponds to the storage amount or is slightly larger.
The storage liquid 8B is pulled by the strong capillary force of the plug channel group 82 and is filled in each of the plug channel groups 82.
Examples of the storage solution include enzyme reagents, other reagents, body fluids such as blood, plasma and serum, tissue bodies such as cells and fungi, and in vivo chemical substance solutions such as DNA and RNA. In addition, although described as a storage solution, there may be a gas other than that.
Since the supply channel 85 is smoothly connected to the curved surface of the contact area between the preliminary region 83 and the plug channel group 82, the storage liquid 8B flows along the curved surface, and sequentially the plug channel group. 82 is filled.
After the stopper channel group 82 is filled with the storage liquid 8B as shown in FIG. 13B, a force (8E) is applied from the outside as shown in FIG. 13C (8E).

Examples of this force include centrifugal force, air pressure, gravity, inertial force, and the like.
By this force (8E), the storage liquid 8B in the stopper channel group 82 moves to the storage area 81. At the time of applying this force, at least when the storage liquid 8B moves to the storage area 81, the plug liquid 8D is input from the input port 84 (8C).
The plug liquid 8D is supplied to the spare region 83 via the supply channel 85 and is filled in the plug channel group 82 that has become empty.
As the stopper liquid 8D, for example, an inert and stable solution is preferable.
The input of the plug liquid 8D from the input port 84 is preferably supplied at least before the storage liquid 8B in the plug channel group 82 moves to the storage area 81.
Through the above operation, the stopper flow path 82 is filled with the stopper liquid 8D, and the storage liquid 8B in the storage area 81 is stored in a state of being blocked from the outside.

At the time of use, the internal storage solution is used by opening the lid 86 or releasing it by sucking the liquid in the stopper channel group 82.
When the plug fluid in the plug channel group 82 is removed without opening the lid 86, the storage liquid is refilled into the plug channel group 82 that has been emptied and has restored its capillary force, Retained. In this state, the internal storage liquid is taken out by being set in a measuring device or the like and applying a force to the stopper channel member 82.
Further, it may be configured to be fitted in the reagent reaction tank in the form of a cassette.
Such a storage solution is suitable, for example, when holding a small amount of collected body fluid at a remote place.

Next, an embodiment showing the overall configuration of the present invention will be described in detail with reference to FIG.
FIG. 14 shows a disk-shaped rotor structure made of acrylic having a radius of 35 mm and a depth of 4 mm. As shown in FIG. The measurement is divided into the component measurement region 23Y and the first diluted serum component measurement region, and the second diluted serum component measurement region whose degree of dilution is different.
The configuration will be described for each section below.

Reference numeral 201 denotes a diluent storage part that is sealed and enclosed in advance, and preferably has a configuration in which the sealed state is released by an external pressure and flows to the outside during use, but is not limited thereto.
Reference numeral 202 denotes a first blood reservoir, which is a part that stores blood collected from a patient or the like.
The first blood storage unit 202 includes triple side walls and includes a storage unit 202a that stores excess blood between the side walls.
Reference numeral 203 denotes a first flow path, which includes two flow paths and connects the first blood storage unit 202 and the blood cell separation / distribution unit 203a.
The blood cell separation / distribution unit 203 a connects the first blood cell separation unit 204, the second blood cell separation unit 206, and the second flow path 208.
The first blood cell separation unit 204 is connected to the first blood cell storage unit 205 via the first continuous protrusion 252. The specific configuration thereof has a centrifugal separation configuration as shown in FIG.
The second blood cell separation unit 206 is connected to the second blood cell storage unit 207 via the second continuous protrusion 251. The specific configuration thereof has a centrifugal separation configuration as shown in FIG.
The second blood cell separation unit 206 is connected to one end of the fifth channel 215 having the bent portion L4.

Regarding the serum component measurement region 23X,
The second flow path 208 is connected to the first quantitative unit 219. The first quantification unit 219 is connected to the third blood cell separation unit 217 and is also connected to the excess blood storage unit 219a, and the excess blood storage unit 219a is connected to one end of the deaeration channel 220. The other end of the deaeration channel 220 is connected to the first deaeration port 221.
FIG. 16 specifically shows the vicinity of the third blood cell separation unit 217.
The distance DD4 between the outermost right edge of the third blood cell separation part 217 and the central axis O is longer than the other edge part DD3, and is a form for efficiently moving the separated serum.
The third blood cell separation unit 217 is configured to be connected to the third blood cell storage unit 218 via the third continuous protrusion 250.
Reference numeral 216 denotes a third flow path, which has a bent portion L8 and is connected to the third blood cell separation portion 217 and the third continuous portion as shown by a dotted line EO in FIG. The distance between the left connection point of the protrusion 250 and the central axis O is set to be on the same circumference.
The third flow path 216 is further connected to the fourth blood cell separation unit 222, and the fourth blood cell separation unit 222 is connected to the fourth blood cell storage unit 223.
The depth of the fourth blood cell separation unit 222 is shallower than that of the fourth blood cell storage unit 223, so that residual blood cells stored in the fourth blood cell storage unit 223 do not flow out to the fourth blood cell separation unit 222.

The fourth blood cell separation unit 222 is further connected to a sixth channel 224 having a bent portion L6.
The fourth blood cell separation unit 222 is used when the third blood cell separation unit 217 cannot perform sufficient blood cell separation, and is unnecessary depending on the ability of the third blood cell separation unit 217, measurement components, or the like. There is also.
The sixth flow path 224 is connected to the first distribution flow path 241, and the first distribution flow path 241 is provided with a flow path group 243 having the same shape and the same size at equal intervals on the outer side surface. Six 1 reagent reaction parts 242 are arranged.
As shown in FIG. 4A, the flow path group 243 is configured in a state where fine flow paths having the same cross-sectional area of 0.04 to 0.09 mm ² are radially arranged at equal intervals, and has a configuration that exerts a strong capillary force. .
Reference numeral 242 denotes a first reagent reaction unit in which different lyophilized reagents are accommodated. Reference numeral 244 denotes a first recovery area, and a specific configuration is shown in FIG. FIG. 15 shows the second collection region 239, which has the same size and shape.
The first recovery region 244 is composed of a flow channel network having the same cross-sectional area SS1 in a lattice shape, and the cross-sectional area SS1 of the flow channel network is three times the cross-sectional area SS2 of each flow channel in the flow channel group 243. It's getting bigger. 245 is a 2nd deaeration port. The channel group 243 is configured to face the centrifuge light from the first distribution channel 241.
The serum component measurement region 23X is used for measuring the color development reaction without diluting and supplying the serum after blood cell separation to each reagent reaction tank. When sufficient, etc., it may be sufficient as a component measurement configuration.
Each deaeration port penetrates upward and communicates with the atmosphere.

First dilution component measurement area 23Y
The fourth flow path 212 having the bent portion L1 connects the first blood cell separation unit 204 and the first mixing unit 225.
Reference numeral 247 denotes a first dilution channel, which is composed of two channels having the same size and shape, and is connected to the diluent distributor 247a.
The diluent distributor 247a is connected to the first diluent quantifier 210 and the second diluent quantifier 209, respectively. It is preferable that both corners in the outer circumferential direction of the first diluent quantification unit 210 are formed with gentle curved surfaces.
One end of the second dilution channel 211 is connected in the central axis direction of the first dilution quantification unit 210, and an excess liquid storage unit 246 that stores the excess of the dilution liquid is formed at the other end. .
A third deaeration channel 248 for connecting to the third deaeration port 249 is connected to the surplus liquid container 246.
A fourth dilution channel 213 having a bent portion L <b> 2 is connected to the outer peripheral direction of the first dilution liquid determination unit 210. A first diluent quantification unit 210; The fourth dilution channel 213 is preferably connected in the same manner as the connection relationship between the third blood cell separator 217 and the third channel 216 shown in FIG.
The fourth dilution channel 213 is connected to the first mixing unit 225.
The first mixing unit 225 is formed so as to form a first accommodation chamber 226 in the outer circumferential direction and draw an arc around the first accommodation chamber 226.
A first mixing channel 227 having a bent portion L5 is connected to the outer peripheral left edge of the first mixing unit 225.

The distance between the vicinity of the connection with the first mixing channel 227 at the outer peripheral edge of the first mixing portion 225 and the central axis O is longer than the distance between the other outer peripheral edge and the central axis O. The other end of the first mixing channel 227 is connected to the second distribution channel 236.
Six second reagent reaction parts 237 having the same shape and the same size of the flow path group 238 are arranged at equal intervals on the outer side surface of the second distribution flow path 236.
As shown in FIG. 4A, the flow path group 238 is configured in a state where fine flow paths having the same cross-sectional area of 0.04 to 0.09 mm ² are radially arranged at equal intervals, and has a configuration that exerts a strong capillary force. .
Reference numeral 237 denotes a second reagent reaction unit, in which different lyophilized reagents for diluted serum are accommodated. Reference numeral 239 denotes a second recovery region, and a specific configuration is shown in FIG. The second recovery region 239 is formed of a channel network having the same grid-like cross-sectional area SS1, and the cross-sectional area SS1 of the channel network is three times the cross-sectional area SS2 of the individual channels of the channel group 238. It's getting bigger. Reference numeral 240 denotes a fourth deaeration port.
The first dilution component measurement region 23Y shows a configuration in which the diluted solution and serum quantified by the volume of the first dilution region are mixed, and each of the second reagent reaction units 237 performs a color reaction with the reagent. Depending on the reagent, the degree of dilution may differ, and a measurement system having a different dilution process from the degree of dilution performed in the first dilution component measurement region is shown in the second dilution component measurement region 23Z of FIG. The configuration will be described.

Second dilution component measurement area 23Z
As with the first diluent quantifier 210, the second diluent quantifier 209 connected to the diluent distributor 247a is formed with gentle curved surfaces at both corners in the outer circumferential direction.
The volume of the second diluent quantification unit 209 is different from that of the first diluent quantification unit 210, and the dilution of the diluent corresponding to the volume of the second diluent quantification unit 209 is performed.
One end of the second dilution flow path 211 is connected in the central axis direction of the second dilution liquid determination unit 209.
A fifth dilution flow path 214 having a bent portion L3 is connected to the outer peripheral direction of the second dilution liquid quantifying unit 209. The connection between the second dilution liquid quantifying unit 209 and the fifth dilution channel 214 is preferably the same as the connection relationship between the third blood cell separation unit 217 and the third channel 216 shown in FIG. .
The fifth diluent channel 214 is further connected to the second mixing unit 228.

The second mixing unit 228 is formed so as to form a second accommodating chamber 229 in the outer circumferential direction and draw an arc around the second accommodating chamber 229.
A second mixing channel 230 having a bent portion L7 is connected to the outer peripheral left edge as viewed in the drawing of the second mixing portion 228. The other end of the second mixing channel 230 is connected to the third distribution channel 231.
The distance between the vicinity of the connection with the second mixing channel 230 at the outer peripheral edge of the second mixing portion 228 and the central axis O is longer than the distance between the other outer peripheral edge and the central axis O.
Six third reagent reaction parts 233 having the same shape and the same size of the channel group 232 are arranged at equal intervals on the outer side surface of the third distribution channel 231.
As shown in FIG. 4A, the flow path group 232 is configured in a state where fine flow paths having the same cross-sectional area of 0.04 to 0.09 mm ² are arranged radially at equal intervals, and has a configuration that exerts a strong capillary force. .
Reference numeral 233 denotes a third reagent reaction unit in which different lyophilized reagents for diluted serum are accommodated. Reference numeral 234 denotes a third recovery region, and a specific configuration is shown in FIG. The third recovery region 234 is composed of a flow path network having the same cross-sectional area SS1 in a lattice shape, and the cross-sectional area SS1 of the flow path network is 3 than the cross-sectional area SS2 of each flow path in the flow path group 232. It is more than doubled. Reference numeral 235 denotes a fifth deaeration port.

The rotor R is provided with fitting ports T1 and T2 for fitting and mounting to an installation convex portion on the measuring device when the rotor R is installed on the measuring device.
The fitting ports T <b> 1 and T <b> 2 are formed so as to penetrate up and down the rotor R, and may be formed as convex portions on the lower surface.
The rotor R is formed by forming a concave portion in each area on the substrate, and then putting a freeze-dried reagent in the square reagent reaction tank, and then a transparent sheet and a lid formed by a hard film plate on the adhesive. Used in a bonded state by self-adhesion or other methods. The lid (for example, H shown in FIG. 3C) is formed with each deaeration port, blood supply port, fitting port, and a diluent discharge operation member and the like are formed on the substrate. For example, a through region is formed.

Next, the operation of the embodiment shown in FIG. 14 will be described in detail with reference to FIG. 17 and subsequent drawings.
In a state where the rotor R is stationary and, in some cases, taken out from the outside alone, as shown in FIG. 17, 35 to 250 μl of blood collected into the first blood reservoir 202 is supplied by a dropper or pipette.
The supply amount is sufficient, and the excess is held in the accommodating portion 202a formed by the peripheral grooves. The blood 22A in the first blood storage unit 202 moves so as to be drawn to the first flow path 203.
When blood is supplied to the first blood storage unit 202, the diluent 22B enclosed in the diluent storage unit 201 is released to the outside and moved so as to be drawn by the first dilution channel 247. To do.
The rotor R is placed on the measuring device and rotated.
By the first rotation 2500 to 4000 RPM, the blood moves to the blood cell distribution / separation unit 203a and also moves to the first blood cell separation unit 204 and the second blood cell separation unit 206.
When the blood supplied to the first blood cell separation unit 204 and the second blood cell separation unit 206 overflows, the overflowed amount is supplied to the third blood cell separation unit 217 via the second flow path 208 and the first fixed amount unit 219. Is done. The third blood cell separation unit 217 is filled with blood, and the excess is stored in the adjacent excess blood storage unit 219a via the first fixed amount unit 219 (22E).
When blood is stored in each blood cell separation unit, centrifugation starts at each separation unit with rotation of 3000 to 6000 RPM.
The dilution liquid in the dilution liquid storage unit 201 moves to the dilution liquid distribution unit 247a by the rotation and is filled in each of the first dilution liquid quantification unit 210 and the second dilution liquid quantification unit 209 (22F) (22G). The excess 22H is accommodated in the excess liquid storage portion 246 via the second dilution channel 211.

By the rotation, as shown in FIG. 18, the blood cells 22J separated by the first blood cell separation unit 204 are stored in the first blood cell storage unit 205. Become.
The blood cells 22I separated by the second blood cell separation unit 206 are stored in the second blood cell storage unit 207, and the inside of the second blood cell separation unit 206 is in the serum 22A2 state.
Furthermore, the blood cell 22D separated by the third blood cell separation unit 217 is stored in the third blood cell storage unit 218, and the inside of the third blood cell separation unit 217 is in the serum 22C state.

After 30 to 240 SEC, by reducing the rotation of the rotor R to 100 to 300 RPM,
Due to the so-called siphon phenomenon,
The serum 22A1 whose movement has been suppressed by the centrifugal force in the vicinity of the bent portion L1 of the fourth channel 212 flows into the first mixing unit 225 beyond the bent portion L1.
Further, due to the same phenomenon, the serum 22A2 whose movement has been suppressed by the centrifugal force in the vicinity of the bent portion L4 of the fifth flow path 215 flows into the second mixing portion 228 beyond the bent portion L4.
Furthermore, the serum 22C, whose movement has been suppressed by the centrifugal force in the vicinity of the bent portion L8 of the third flow path 216 due to the same phenomenon, flows into the fourth blood cell separator 222 beyond the bent portion L8.
The number of rotations of the rotor R is increased to 2000 to 6000 RPM again when each serum exceeds each bending portion, and the formation in each blood cell separation portion is determined by the first mixing portion 225, the second mixing portion 228 and the fourth mixing portion. All move to the blood cell separation unit 222.
This change in the number of rotations causes the fixed dilution liquid in the first dilution liquid fixed part 210 to move to the first mixing part 225 via the fourth dilution flow path 213 and the bent part L2, thereby separating the first blood cell. A state is formed so as to overlap with the serum that has moved from the unit 204 (22M), and this change in the rotational speed is caused by the flow of the quantitative dilution liquid of the second dilution liquid quantitative part 209 to the fifth dilution flow path 214 and its bending. It moves to the 2nd mixing part 228 via the part L3, and the state which overlaps with the serum which moved from the 2nd blood cell separation part 206 is formed (22K) (FIG. 19).
As the rotation continues, residual blood cells in serum that flow into the first mixing unit 225 are stored in the first storage chamber 226, and residual blood cells in serum that flow into the second mixing unit 228 are stored in the second storage chamber 229. Accommodated and more precise blood cell separation is performed, and sufficient blood cell separation is also performed on the serum 22L flowing into the fourth blood cell separation unit 222, and residual blood cells are stored in the fourth blood cell storage unit 223. .

Next, the increase / decrease is repeated at a cycle of 5-40 SEC in the range of 500-1500 and 3000-6000 RPM.
The quantitative serum and the quantitative diluent in the first mixing unit 225 reciprocate between the bent portion L5 of the first mixing channel 227 and the first mixing unit 225 due to the increase and decrease of this rotation, and a stirring operation is performed. Thorough mixing is performed.
The quantitative serum and the quantitative diluent in the second mixing unit 228 reciprocate between the bent portion L7 of the second mixing channel 230 and the second mixing unit 228 due to the increase / decrease of this rotation, and a stirring operation is performed. Thorough mixing is performed.
Subsequently, the blood cell separation is performed on the serum 22L that has flowed into the fourth blood cell separation unit 222, and the operation of storing the remaining blood cells in the fourth blood cell storage unit 223 is repeated.
Specifically, an operation as shown in FIG. 6 is performed.

After 2 to 6 cycles, after sufficient mixing is performed in each mixing section, the rotational speed of the rotor R is lowered to 100 to 300 RPM.
As the number of rotations decreases, the serum of the fourth blood cell separation unit 222 passes through the bent portion L6 of the sixth flow path 224 and then increases the rotation again to 3000 to 6000 RPM in some cases, thereby returning to the first distribution path 241. Flows in. The fourth blood cell storage unit 223 stores residual blood cells (22Y).
As shown in FIG. 20, the serum 22T is attracted and filled by the capillary force of each flow path group 243 (22U), and is further attracted by the capillary force of the first recovery region 244. Each channel is filled with the liquid mixture (22V).
The mixed liquid in the first mixing section 225 is supplied to the second distribution flow path 236 by passing the bent portion L5 of the first mixing flow path 227 and then increasing the rotation again to 3000 to 6000 RPM in some cases. As shown, the mixed liquid 22Q is attracted by the capillary force of each flow path of the flow path group 238, and the mixed liquid is filled in each flow path group 23 (22R), and further in the second recovery region 239. Also drawn by the capillary force, each flow path in the second recovery region 239 is filled with the mixed liquid (22S). The first storage chamber 226 stores residual blood cells 22W by rotation, and the second storage chamber 229 stores residual blood cells 22X by rotation.
The mixed liquid in the second mixing unit 228 is supplied to the third distribution channel 231 by exceeding the bent portion L7 of the second mixing channel 230 and then increasing the rotation again to 3000 to 6000 RPM as the case may be. As shown in FIG. 6, the mixed liquid 22N is drawn and filled by the capillary force of each flow path group 232 (22O), and is further drawn to the capillary force of the third recovery region 234, and each of the third recovery regions 234 The mixed solution is filled in the flow path (22P).
Serum or mixed serum filled in each recovery unit is a surplus, but when a part of each channel group becomes a gap, the capillary force of each channel group is strong, so it is held in each recovery unit. The surplus that has moved moves there, and each channel group is always maintained in a state of being filled with serum or a mixture thereof.

Thereafter, the rotational speed is again increased to 3000 to 6000 RPM.
As shown in FIG. 21, the serum filled in the flow path group 243 in the serum component measurement region 23X is supplied to the first reagent reaction unit 242 so as to be pushed out by centrifugal force, and is supplied into the flow path group 243. The serum in one recovery region 244 is moved and filled by capillary force and extruded by centrifugal force, the first reagent reaction unit 242 is filled with serum, and the flow path group 243 is filled with serum 22U. Rotation continues until.
The serum that has flowed into the first reagent reaction unit 242 is in a state where the internal reagent is dissolved and mixed (22Z), causes a color reaction, and is irradiated with measurement light from the top and bottom or the outer peripheral direction of the reagent reaction tank. Thus, the color value is measured. At this time, the shape of the reagent reaction part is more effective against the escape of air when it is tapered upward.

Further, in the first diluted component measurement region 23Y, the diluted mixed serum that has been filled in the flow path group 238 is supplied to the second reagent reaction unit 237 so as to be pushed out by centrifugal force, and is supplied into the flow path group 238. 2 The diluted mixed serum in the recovery region 239 is moved and filled by capillary force, pushed out by centrifugal force, the second reagent reaction unit 237 is filled with the diluted mixed serum, and the channel group 238 is serum. The rotation is continued until it is filled by 22R.
The serum that has flowed into the reagent reaction tank 237 is in a state where the internal reagent is dissolved and mixed (23B), causes a color reaction, and is irradiated with measurement light from the top and bottom or the outer peripheral direction of the reagent reaction tank. The color value is measured.

Further, in the second diluted component measurement region 23Z, the diluted mixed serum that has been filled in the flow path group 232 is supplied to the third reagent reaction unit 233 so as to be pushed out by centrifugal force, and the third mixed reaction serum is supplied into the flow path group 232. The diluted mixed serum 22P in the recovery region 234 is moved and filled by capillary force, pushed out by centrifugal force, the third reagent reaction unit 233 is filled with diluted mixed serum, and the flow path group 232 is serum. This rotation is continued until it is filled with 220.
The serum that has flowed into the third reagent reaction unit 233 is in a state where the internal reagent is dissolved and mixed (23A), causes a color reaction, and is irradiated with measurement light from the top and bottom or the outer peripheral direction of the reagent reaction tank. Thus, the color value is measured.
The time from the first supply of blood to the first blood reservoir 202 until the contact with the reagent of each reagent reaction unit and the measurement of the color reaction is exemplified as 180 to 300 SEC. It is adjusted as appropriate according to the items.

Next, the overall configuration including the quantitative configuration shown in FIG. 22 will be described with reference to FIG.
FIG. 23A is a ZZ ′ cross section of FIG.
2R is a rotor, and consists of a disk-shaped body having a radius of 25 to 50 mm and a thickness of 3 to 7 mm. The material of the rotor 2R is made of a transparent plastic such as polystyrene, PET, acrylic, polycarbonate, a resin material for contact lenses, or a transparent plastic such as glass, and each component is formed by a groove as shown in FIG. Has been. The rotor R shown in FIG. 14 has a similar configuration.
In the example shown in FIG. 23, two reagent areas having different dilution ratios are provided, which are 30X and 30Y, respectively.
In the first dilution region 30X,
Reference numeral 301 denotes a diluent storage unit that has the same configuration and operation as those shown in FIG. 302 is a 1st buffer area | region and is a part which stores a dilution liquid temporarily. The size of the first buffer region 302 may be at least larger than the quantitative value, but a volume close to the quantitative value is preferable.
Reference numeral 303 denotes a reference channel, which is used for flowing a diluted solution for the reference to the reference storage unit 304.
Reference numeral 305 denotes a deaeration channel, and reference numeral 306 denotes a deaeration port.
Reference numeral 307 denotes a first fixed amount deaeration part, which is formed by a flow path extending in the central direction and a deaeration port arranged in the central direction.
Reference numeral 308 denotes a first flow path, which is a flow path connecting the first buffer region 302 and the first diluent quantification unit 309, and a bent portion is formed toward the center in order to exert a siphon action. Yes.
Reference numeral 309 denotes a first diluent quantification unit, and a first quantification deaeration unit 307 is connected to a side surface in the central direction.

This connection relationship is the same as the configuration shown in FIG. Reference numeral 310 denotes a second flow path, which connects the first diluent quantification unit 309 and the first mixing chamber 319. The flow path also forms a bent portion with respect to the central direction.
Reference numeral 311 denotes a blood storage unit that supplies blood collected from the outside and temporarily stores the blood.
Reference numeral 312 denotes a blood distribution path, which is a flow path for distributing necessary blood to the blood cell separation unit according to the reagent and the dilution rate.
Reference numeral 313 denotes a first blood cell separation unit which is connected to the first blood cell storage unit 314 in the outer peripheral direction and has an internal configuration as shown in FIG.
Reference numeral 314 denotes a first blood cell storage unit, which is formed deeper than at least the first blood cell separation unit, and its size may be equal to or smaller than that of the first blood cell separation unit 313.
Reference numeral 315 denotes a third flow path for connecting the first blood cell separation unit 313 and the first fixed amount unit 316 and has a bent portion toward the center.
316 is a 1st fixed_quantity | quantitative_assay part, and since it has the structure similar to FIG. 21, it connects with the deaeration part 317 for 1st fixed_quantity | quantitative_assay.

The first fixed amount deaeration unit 317 has the same configuration as the first fixed amount deaeration unit 307, and the flow path extends in the center direction from the bent portion of the fourth flow path 318, and is degassed at the tip thereof. A mouth is formed.
Reference numeral 318 denotes a fourth flow path for connecting the first fixed amount unit 316 and the first mixing chamber 319.
Reference numeral 319 denotes a first mixing chamber having an outwardly curved shape and a blood cell storage portion 322 provided at the center, which is provided to accommodate residual blood cells and the like during mixing and stirring.

Reference numeral 320 denotes a first mixing chamber deaeration port, which is a portion communicating with the outside, and is formed on the center side of the first mixing chamber 319 by a combination with the flow path 321.
Reference numeral 323 denotes a fifth flow path for connecting the first mixing chamber 319 and the first distribution path 324, and a bent portion directed in the central direction is formed in the middle.
Reference numeral 324 denotes a first distribution path which is formed by drawing a partial arc on the circumference, and a plurality of flow path groups 325 are connected at equal intervals in the outer circumferential direction, and the first recovery region 327 is connected to one end. .
Reference numeral 325 denotes a flow path group having a configuration as shown in FIG.
Reference numeral 326 denotes a reagent reaction tank, which forms an elliptical cylindrical body having a major axis in the radial direction. The reason for the oval shape is to cope with physical deviations when the rotating body is attached to the rotary motor and to minimize measurement errors due to centrifugal deviation.
Reference numeral 327 denotes a first recovery region, which is configured by arranging channels larger than the diameter of the channel of the channel group 325 in a lattice shape, and is connected to the first recovery region deaeration port 328. The specific configuration and operation are as described in FIG.

329 is a 2nd buffer area | region and is a part which stores a dilution liquid temporarily. The size of the second buffer region 329 may be at least larger than the quantitative value, but a volume close to the quantitative value is preferable.
Reference numeral 330 denotes a blood discharge channel for collecting blood overflowing from the first and second blood cell separation units and flowing the blood to the excess blood storage unit 331. Considering the user's ease of use during blood spotting, blood spotting within a certain range is required, contributing to a mechanism for eliminating troublesome quantitative spotting.
Reference numeral 332 denotes a deaeration port for the excess blood storage unit, which has a combined configuration of a flow path extending in the center direction and the deaeration port.
Reference numeral 335 denotes a second degassing part for constant quantity, which is formed by a flow path extending in the central direction and a deaeration port arranged in the central direction.
Reference numeral 333 denotes a sixth flow path, which is a flow path connecting the second buffer region 329 and the second diluent quantification unit 334, and has a bent portion formed in the central direction in order to exert a siphon action. Yes.
Reference numeral 334 denotes a second diluent quantification unit, and a second quantification deaeration unit 335 is connected to a side surface in the central direction.

This connection relationship is the same as the configuration shown in FIG. Reference numeral 342 denotes a tenth flow path that connects the second dilution liquid quantifying unit 334 and the second mixing chamber 336. The flow path also forms a bent portion with respect to the central direction.
Reference numeral 337 denotes a second blood cell separation unit which is connected to the second blood cell storage unit 338 in the outer circumferential direction, and has an internal configuration as shown in FIG.
Reference numeral 338 denotes a second blood cell storage unit which is formed deeper than at least the second blood cell separation unit 337 and has a size equal to or smaller than that of the second blood cell separation unit 337.
Reference numeral 339 denotes an eighth flow path for connecting the second blood cell separation unit 337 and the second fixed amount unit 340, and has a bent portion toward the center.
340 is a 2nd fixed_quantity | quantitative_assay part, and since it has the structure similar to FIG. 21, it connects with the 2nd deaeration part 352 for 2nd fixed_quantity | quantitative_assay.
The second quantitative deaeration unit 352 has the same configuration as the first quantitative deaeration unit 307, and the flow path extends in the center direction from the bent portion of the ninth flow path 341, and the degassing part 352 has a degassing at its tip. A mouth is formed.
Reference numeral 341 denotes a ninth flow path for connecting the second quantitative unit 340 and the second mixing chamber 336.
Reference numeral 336 denotes a second mixing chamber, which has a curved shape in the outer direction and a blood cell reservoir in the center, and is provided to accommodate residual blood cells and the like during mixing and stirring.
In the central direction of the second mixing chamber 336, a degassing port 349 is formed together with a flow path connecting the two.

Reference numeral 342 denotes a tenth flow path, which connects the second diluent quantitative unit 334 and the second mixing chamber 336 while having a bent portion in the center direction.
Reference numeral 343 denotes an eleventh flow path, which has a bent portion in the center direction, and is used to connect the second mixing chamber 336 and the second distribution flow path 344.
Reference numeral 344 denotes a second distribution channel, which forms an arc shape extending on the circumference, and has a channel length twice that of the first distribution channel 324.
In the outer peripheral direction of the second distribution channel 344, a channel group 345 having one end connected to the reagent reaction tank 346 is provided at equal intervals. The region 347 and the third recovery region 350 are connected.
The second recovery region 347 is connected to the second recovery region deaeration port 348, and the third recovery region 350 is connected to the third recovery region deaeration port 351.
Since the configurations of the second recovery region 347 and the third recovery region 350 are the same as those of the first recovery region 327, description of the specific configuration is omitted.
In the present embodiment, the second collection region 347 and the third collection region 350 are connected to both ends of the second distribution channel 344, which is a long-distance distribution channel and more channel groups are connected. In this case, the liquid can be replenished more rapidly and sufficiently to each flow path group.

Next, the operation of the embodiment shown in FIG. 22 will be described.
Since the operation basically similar to that of the embodiment of FIG. 14 is performed, a part of explanation of the same operation is omitted.
First, blood is supplied to the blood reservoir 311. The amount of blood to be supplied may be an approximate guide, and blood may be supplied using a dropper or the like.
After supplying the blood to the blood storage unit 311, the diluent is held in advance or newly supplied to the diluent storage unit 301 at a timing of shutting off the outside by closing the lid or the like.
In this state, the rotor 2R is rotated at a rotational speed of 3000 to 6000 RPM.
In the first dilution region 30X, the blood in the blood reservoir 311 moves to the blood distribution path 312 by centrifugal force and is supplied to the first blood cell separator 313 and the second blood cell separator 337, respectively. After any blood cell separation unit is filled with blood, the excess blood is stored in the excess blood storage unit 331 via the blood discharge channel 330.
The air previously present in the surplus blood reservoir 331 passes through the surplus blood reservoir degassing port 332 to the outside.

The diluted solution released in the diluted solution storage unit 301 moves to the first buffer region 302 and the second buffer region 329 by centrifugal force.
The diluted solution supplied to the first buffer region 302 and the second buffer region 329 becomes full, and the overflow is stored in the reference storage unit 304 via the discharge channel 303.
At that time, the air in the reference reservoir 304 is discharged to the outside from the deaeration port 306 via the deaeration channel 305.
The blood moved to the first blood cell separation unit 313 is rotated at a rotational speed of 3000 to 6000 RPM to perform blood cell separation.
Blood cells with heavy specific gravity are stored in the first blood cell storage unit 314.
The second blood cell separation unit 337 performs the same centrifugation, and the second blood cell storage unit 338 stores the blood cells.
After 60 to 240 SEC has elapsed, after sufficient blood cell separation, the rotational speed is reduced to 100 to 150 RPM.
The serum from which the blood cells have been separated is supplied to the first diluent quantification unit 309 via the bent portion of the third flow path 315 due to a decrease in centrifugal force. The serum of the second blood cell separation unit 337 is supplied to the second fixed amount unit 340 through the bent portion of the eighth flow path 339.
The diluent is supplied to the first diluent quantification unit 309 via the first channel 308 and is supplied to the second diluent quantification unit 340 via the sixth channel 333.

The rotation speed is increased to 1000 to 4000 RPM, the supply of serum to the first quantification unit 316, the supply of serum to the second quantification unit 340, the supply of the dilution liquid from the first dilution liquid quantification unit 309, and the second dilution liquid The supply of the diluent to the quantification unit 334 is accelerated.
When the serum supplied to the first quantitative unit 316 is supplied to the first quantitative deaeration unit 317 and the connection port of the first quantitative unit 316, the serum is supplied at the bent portion of the third flow path 315. Stops.
The serum in the first quantitative unit 316 whose supply has been stopped becomes a quantitative substance in effect.
Similarly, serum is quantified by the second quantification unit 340, and quantification is also performed by the first dilution liquid quantification unit 309 and the second dilution liquid quantification unit 334.
The first quantification unit 316 and the second quantification unit 340 preferably also perform separation of residual blood cells by blood cell separation.
The serum is supplied to the first mixing chamber 319 by lowering the rotational speed to 100 to 150, causing the quantified serum to exceed the bent portion of the fourth flow path 318, and increasing the rotational speed. Similarly, serum is supplied to the second mixing chamber 336 through the ninth flow path.
Furthermore, the diluent in the first diluent quantification unit 309 is supplied to the first mixing chamber 319 via the second channel 310, and the metered diluent in the second diluent quantifier 334 passes through the tenth channel 342. Then, it moves to the second mixing chamber and is supplied.

As shown in FIG. 6, the serum and the diluent that have moved to the respective mixing chambers are rotated at a rotational speed of 3000 to 6000, preferably 1000 to 2000 RPM in a cycle of 1 to 5 SEC, and the fifth flow path 323 and the first liquid are diluted. The mixing is performed by reciprocating between the mixing chambers 319, and similarly, the mixing is performed by reciprocating between the eleventh flow path 343 and the second mixing chamber 336.
After 4 to 30 SEC, the number of revolutions is lowered to move the mixed liquid in the first mixing chamber 319 to the first distribution path 324 via the fifth flow path 323, and the mixed liquid in the second mixing chamber 336 is moved to It moves to the 2nd distribution flow path 344 via the 11th flow path 343, increases a rotation speed again, and promotes a movement.
The mixed liquid that has moved to the first distribution path 324 is sequentially filled into the flow path group 325 having a strong capillary force, and the excess mixed liquid is filled into the capillaries in the first recovery region 327.
The mixed liquid that has moved to the second distribution flow path 344 is also filled into the flow path group 345 close to the 11th flow path, while sequentially filling the next flow path group, and the second recovery region 347, 3 An excess liquid mixture is filled in the recovery area 350.
When all the channel groups are filled with the mixed solution, the rotational speed is increased to 2000 to 6000 RPM, the mixed solution in each channel group is moved to the reagent reaction tanks 326 and 346, and the mixed solution in the channel group is When there is no more, the state where the excess liquid mixture in the recovery region moves by the capillary force of the flow channel group and is refilled into the flow channel group is repeated.
In a state where the reagent reaction tank is filled with the mixed solution, the internal reagent and the mixed solution are dissolved and mixed by a rotational force or the like, thereby generating a color reaction.
The developed color value in the reagent reaction tank is measured by measuring transmitted light and reflected light from the outside. In addition, by arranging the recovery regions on both sides of the second distribution channel 344 and supplying the liquid from the center, it is possible to uniformly fill the channel group with the liquid from the center to both sides. As a result, the timing of filling the sample reaction solution in the channel group into the reagent reaction tank can be made easy.
In addition, although the present Example formed the dilution serum which has two different dilution ratios, two or more may be sufficient and it is defined and selected.

Next, another embodiment of the present invention will be described in detail with reference to the drawings.
The present embodiment mainly shows an example of a liquid quantitative configuration. FIG. 23 shows a blood quantitative separation part of a disk-shaped rotor.
Reference numeral 401 denotes a blood reservoir, which is constituted by a recess formed on the rotor R. Reference numeral 402 denotes a first flow path that connects the blood reservoir 401 and the blood distribution flow path 422.
Reference numeral 403 denotes a second flow path that connects the blood reservoir 401 and the blood distribution flow path 422.
These flow paths are formed on the left and right sides of the blood distribution flow path 422 toward the arrangement direction of the blood quantitative distribution section that supplies blood first.
Reference numeral 404 denotes a first blood quantification / separation unit, which is connected to the blood distribution channel 422 and has a surface (shown by a broken line in the figure) that connects the first projections 404a and 404b formed in an acute angle shape in the outer circumferential direction. The space partitioned by the connection surface with the blood distribution channel 422 becomes the quantitative space.
The first convex portions 404a and 404b are preferably acute-angled, and their tips are preferably directed in the outer circumferential direction, for example.
The first convex portions 404a and 404b move the liquid using the siphon principle when the blood cells stored in the first blood cell storage unit 405 move the serum through the first bent flow channel 410. It acts as a stopper that prevents the liquid from moving together by moving the liquid in the capillary direction due to the surface tension generated in the liquid when the number of rotations of the motor is decreased. Therefore, the 1st convex part 404a installed in the other side of a capillary flow path may be unnecessary.

Reference numeral 405 denotes a first blood cell storage unit which is connected to the first blood quantitative separation unit, and has a continuous projection as shown in FIG. Blood cells separated by centrifugation based on are contained.
Reference numeral 406 denotes a second blood quantitative separation unit, which is connected to the blood distribution channel 422 and has a surface (indicated by a broken line in the figure) connecting the second convex portions 406a and 406b formed in an acute angle shape in the outer circumferential direction. The space partitioned by the connection surface with the blood distribution channel 422 becomes the quantitative space.
The second convex portions 406a and 406b are preferably acute-angled, and their tips are preferably directed in the outer circumferential direction, for example.
The second protrusions 406a and 406b are arranged so that the blood cells stored in the second blood cell storage unit 407 move the liquid using the siphon principle when the serum moves through the second bent flow path 411, and then the motor. When the number of rotations is decreased, the liquid moves in the capillary direction due to the surface tension generated in the liquid, and functions as a stopper that does not move together. Therefore, the 2nd convex part 406b installed in the other side of a capillary channel may be unnecessary.
Reference numeral 407 denotes a second blood cell storage unit, which is connected to the second blood quantitative separation unit, and has a continuous projection as shown in FIG. Blood cells separated by centrifugation based on are contained.

Reference numeral 408 denotes a third blood quantitative separation unit, which is connected to the blood distribution channel 422 and has a surface (shown by a broken line in the figure) connecting the third convex portions a and b formed in an acute angle shape in the outer circumferential direction. The space partitioned by the connection surface with the blood distribution channel 422 becomes the quantitative space.
It is preferable that the 3rd convex part 408a, 408b is acute-angle shape, and it is preferable that the front-end | tip faces the outer peripheral direction, for example.
The third protrusions 408a and 408b are arranged in such a manner that the blood cells stored in the third blood cell storage unit 409 move the liquid using the siphon principle when the serum moves through the third bent flow path 412. When the number of rotations is decreased, the liquid moves in the capillary direction due to the surface tension generated in the liquid, and functions as a stopper that does not move together. Therefore, the third convex portion 408a installed on the opposite side of the capillary channel may be unnecessary.
Reference numeral 409 denotes a third blood cell storage unit which is connected to the third blood quantitative separation unit, and has a continuous projection as shown in FIG. Blood cells separated by centrifugation based on are contained.
Reference numeral 410 denotes a first bent flow path, which is formed with a bent portion toward the central direction, one end of which is connected to the upper portion of the first convex portion 404b and the other end is the center of the first processing portion 414. Connect to the direction plane.
Reference numeral 411 denotes a second bent flow path, which is formed with a bent portion toward the central direction, one end of which is connected to the upper portion of the second convex portion 406a, and the other end is the center of the second processing portion 416. Connect to the direction plane.
Reference numeral 412 denotes a third bent flow path, which is formed with a bent portion toward the central direction, one end of which is connected to the upper portion of the third convex portion 408b, and the other end is the center of the third processing portion 418. Connect to the direction plane.

In particular, when moving serum, etc., in each of the channels 410, 411, and 412 by performing R processing on the end so as not to provide an edge in each channel, the liquid can be prevented from running ahead and air can be mixed in. Can be prevented and the mechanism is reliably met, but is not limited.
Reference numeral 413 denotes a surplus blood storage unit that stores the blood overflowing from the third blood quantitative separation unit 408 via the surplus blood distribution channel 413a. The surplus blood distribution channel 413a is connected in the center direction of the third blood quantitative distribution unit 408, and the connection surface between the surplus blood distribution channel 413a and the third blood quantitative distribution unit 408 is the third blood quantitative distribution unit 408. It becomes the interface for quantifying blood.
Reference numeral 414 denotes a first processing unit that performs processing such as mixing of the separated blood quantified by the first blood quantitative separation unit 404 with a diluent, secondary blood cell separation, and reagent reaction.
The circumferential direction of the first processing unit has a curved shape, and a convex portion 414a for accommodating blood cells and reagents is formed at the center.
Reference numeral 415 denotes a deaeration part, which is formed by a deaeration port connected to the outside at one end and a flow path where the other end is also connected to the first processing part 414.
Reference numeral 416 denotes a second processing unit, which performs processing such as mixing of the separated blood quantified by the second blood quantitative separation unit 406 and a diluent, secondary blood cell separation, and reagent reaction.
The circumferential direction of the second processing unit has a curved shape, and a convex portion 416a for accommodating blood cells and reagents is formed at the center.

Reference numeral 417 denotes a deaeration unit, which is formed by a deaeration port connected to the outside at one end and a flow path where the other end is also connected to the second processing unit 416.
Reference numeral 418 denotes a third processing unit that performs processing such as mixing of the separated blood quantified by the third blood quantitative separation unit 408 with a diluent, secondary blood cell separation, and reagent reaction.
The circumferential direction of the third processing part has a curved shape, and a convex part 418a for accommodating blood cells and reagents is formed at the center.
Reference numeral 419 denotes a deaeration unit, which is formed with a deaeration port connected to the outside at one end and a flow path connecting the other end to the third processing unit 418.
Reference numeral 420 denotes a supply channel, one end of which is connected to the outer peripheral direction of the third processing unit 418, and the other end is not shown, but is connected to a reaction tank containing a reagent.
Reference numeral 421 denotes a deaeration part, which is formed with a deaeration port connected to the outside at one end and a flow path connected to the surplus blood storage part 413 at the other end.

Next, the operation of the embodiment shown in FIG. 23 will be described in detail with reference to FIGS.
After supplying blood to the blood cell storage unit 401, a sealed state is formed so as not to leak outside. After the sealing, when the rotor R is rotated at a rotational speed of 2500 to 6000 RPM, the blood BL1 in the blood storage unit 401 passes through the first flow path 402 and the second flow path 403, respectively, and the first blood quantitative separation section 404. , And supplied to the second blood quantitative separation unit 406 (FIG. 24 (a)).
The blood supplied to the first blood quantification separation unit 404 is further filled into the first blood cell storage unit 405, and the blood supplied to the second blood cell quantification separation unit 406 is filled into the second blood cell storage unit 407 ( BL3).
Since the volume of the first blood quantitative separation unit 404 is smaller than that of the other separation units, the blood first overflows from the first blood quantitative separation unit 404, and the overflowing blood BL4 flows into the blood distribution channel 422 and the excess blood distribution channel. It is supplied to the third blood quantitative separation unit 408 via 413a.
Next, the second blood quantitative separation unit 406 is filled with blood (BL2), and the blood overflowing from the second blood quantitative separation unit 406 passes through the blood distribution channel 422 and the excess blood distribution channel 413a. 3 is supplied (BL4) to the blood quantitative separation unit 408 (FIG. 24B).

The blood supplied to the third blood quantification / separation unit 408 flows into the third blood cell storage unit 409 and is filled therein, and as shown in FIG. 25 (a), each of the separation unit and the storage unit is filled with blood. In this state, the overflowed blood is stored in the excess blood storage unit 413.
Next, the number of rotations is set to 3000 to 7000 RPM, and centrifugation operation is performed. Blood cells having a large specific gravity are accommodated in the blood cell separation unit in the outer circumferential direction, and separation of the blood cells proceeds.

Next, the rotational speed of the rotor R is lowered to 50 to 200 RPM.
The blood from which the blood cells in the first blood quantitative separation unit 404 have been separated, that is, serum, moves by capillary force so as to fill the first bent flow path 410.
Next, when the rotation speed of the rotor R is increased to 1000 to 7000 rpm, blood, plasma or serum filled in the first bent flow path 410 moves in the direction of the first processing unit 414 by a so-called siphon phenomenon.
When the movement of the serum proceeds and reaches the line BB1 shown by the dotted line in FIG. 23 connecting the first convex portions 404a and 404b, the connection port of the first bent channel 410 is released from the serum, and the movement of the serum stops.
The volume of blood from the connecting surface of the first blood quantitative separation unit 404 and the blood distribution channel 422 to the surface connecting the first convex portions 404a and 404b has moved to the first processing unit while the movement of the serum has stopped. become.

The blood from which the blood cells in the second blood quantitative separation unit 406 have been separated, that is, serum, moves by capillary force so as to fill the second bent channel 411.
Next, when the rotation speed of the rotor R is increased to 1000 to 7000 rpm, blood, plasma, or serum filled in the first bent flow path 410 moves in the direction of the second processing unit 416 by a so-called siphon phenomenon.
When the movement of the serum proceeds and reaches the line BB2 shown by the dotted line in FIG. 23 connecting the second convex portions 406a and 406b, the connection port of the second bent flow path 411 is released from the serum, and the movement of the serum stops.
The volume of blood from the connecting surface of the second blood quantitative separation unit 406 and the blood distribution channel 422 to the surface connecting the second convex portions 406a and 406b has moved to the second processing unit while the movement of the serum has stopped. become.

The blood from which the blood cells in the third blood quantitative separation unit 408 have been separated, that is, serum, moves by capillary force so as to fill the third bent flow path 412.
Next, when the rotation speed of the rotor R is increased to 1000 to 7000 rpm, blood, plasma, or serum filled in the first bent flow path 410 moves in the direction of the third processing unit 418 by a so-called siphon phenomenon.
When the movement of the serum proceeds and reaches the line BB3 shown by the dotted line in FIG. 23 connecting the third convex portions 408a and 408b, the connection port of the third bent flow path 412 is released from the serum, and the movement of the serum stops.
With the movement of the serum stopped, the volume of blood from the connection surface between the surplus blood distribution channel 413a and the third blood quantitative separation unit 408 to the surface connecting the third convex portions 408a and 408b to the third processing unit 418 It has moved.
This state is shown in FIG. BL9 indicates the blood cells stored in the first blood cell storage unit 405, BL10 indicates the blood cells stored in the second blood cell storage unit 407, and BL11 indicates the blood cells stored in the third blood cell storage unit 409.
BL12 is serum quantified by the first blood quantification separation unit 404, BL13 is serum quantified by the second blood quantification separation unit 406, and BL14 is quantified by the third blood quantification separation unit 408. Each blood is shown. BL15 is excess blood.
The operation in each processing unit is performed, for example, in a state where the operation shown in FIGS. 6 and 8 is set with the rotation speed and the like.

Such a quantification method can be used for quantification of other liquids such as quantification of a diluted solution without requiring a combination with a blood cell separation unit.
That is, if a flow path (preferably having a bent part facing the central direction) having an opening in the outer peripheral direction of the liquid storage part is disposed, the surface of the liquid storage part and the opening surface of the flow path Among these, the space sandwiched between the circumferential lines passing through the outermost peripheral portion can form a fixed area.

  The present invention proposes a device that makes it possible to perform multi-body fluid testing more simply and more quickly, and makes it possible to realize a highly accurate fluid testing device that can be used not only in medical institutions but also at home. .

  The present invention has a shape suitable for use as a blood cell separation unit when blood components are measured by blood cell separation and integrated as a blood analyzer.

  The present invention proposes, for example, a device that makes it possible to carry out multi-body fluid testing more simply and more quickly, and realize a highly accurate fluid testing device that can be used at home, including medical institutions. And

It is a figure which shows one Example of this invention. It is a figure explaining operation | movement of one Example of this invention. It is a figure which shows the other Example of this invention. It is a figure which shows the other Example of this invention. It is a figure which shows the other Example of this invention. It is a figure which shows the other Example of this invention. It is a figure which shows the other Example of this invention. It is a figure which shows the other Example of this invention. The figure for demonstrating operation | movement of the Example shown in FIG. It is a figure which shows the other Example of this invention. The figure for demonstrating operation | movement of the Example shown in FIG. It is a figure which shows the other Example of this invention. The figure for demonstrating operation | movement of the Example shown in FIG. The figure which shows the Example of the whole this invention. The figure which shows a part of Example shown in FIG. The figure which shows a part of Example shown in FIG. The figure for demonstrating the operation | movement of the Example shown in FIG. The figure for demonstrating the operation | movement of the Example shown in FIG. The figure for demonstrating the operation | movement of the Example shown in FIG. The figure for demonstrating the operation | movement of the Example shown in FIG. The figure for demonstrating the operation | movement of the Example shown in FIG. It is a figure which shows one Example of the fixed_quantity | assay structure of this invention. It is a figure which shows one Example of the fixed_quantity | assay structure of this invention. It is a figure explaining the operation | movement of the Example shown in FIG. It is a figure explaining the operation | movement of the Example shown in FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 11 Blood cell accommodating part 12 Reserving part 13 Convex part 14 Supply flow path 15 Output flow path 111 Blood cell accommodating part 121 Reserving part 131 Connection port 141 Supply flow path 151 Output flow path

Claims (52)

It has a disk-shaped rotor type analysis means consisting of a combination of a flow path for sample transfer and an operation area for sample operation,
The biological information detection unit in which the indwelling site in the operation region is in the outer peripheral direction and the distance between the outer peripheral end and the center is longer than the other outer periphery.   The biological information detection unit according to claim 1, wherein a surface treatment for improving wettability is applied to an indwelling site in the operation region.   The output flow path connected to the indwelling site in the operation area is connected to the outer circumferential direction and the distance between the outer peripheral edge and the center is longer than the other outer circumferences. The biological information detection unit according to 1. The biological information detection unit according to claim 1, wherein a flow path connected to the indwelling site in the operation region is connected 0.1 to 1.5 mm inside from the outer peripheral end.   An operation area for operating a liquid, a supply flow path for supplying a sample liquid to the operation area, and an output flow path for taking out a sample after operation from the operation area, and connecting the supply flow path and the operation area The biological information detection unit which makes the cross-sectional area of a surface narrower than the connection cross-sectional area of the said output flow path and the said operation area | region.     The biological information detection unit according to claim 5, wherein the operation region and the various flow paths are arranged on a centrifugal rotor.   A liquid operation tool having a flow path for transferring liquid by capillary action and an operation region for storing or operating the liquid temporarily or continuously for holding the liquid at least at a target site. A liquid operation tool having a configuration in which a narrower flow path is arranged around.   The liquid operation tool according to claim 7, wherein the narrow channel is provided with a plurality of narrow channels.   The liquid operating tool according to claim 7, wherein the narrow channel is the smallest compared to all other channel cross sections. 8. The narrow channel is smaller than a cross-sectional area of a supply channel connected to a region connected to the thin channel connected to the storage and holding region. Liquid operation tool   8. The liquid operation tool according to claim 7, wherein a distance between an area depth connected to the thin flow path connected to the storage and holding area and a wall surface on the opposite side from the thin flow path is 1 mm or more.   A flow path for transferring liquid by capillary action, and a liquid operation tool that temporarily or continuously stores liquid and has an operation area, wherein a side surface of the operation area and a side surface of the flow path A liquid operation tool that is connected at an angle of 90 degrees or less.   From the region where the side surface of the operation region is connected to the side surface of the flow channel at an angle of 90 degrees or less, the side surface of the operation region, and the region where the side surface of the flow channel is connected at an angle of 90 degrees or less The liquid operating tool according to claim 12, wherein the distance from the opposite wall surface is 1 mm or more.   The said operation area | region is a liquid fixed_quantity | quantitative_assay part, the storage part for storing a liquid temporarily or continuously, a mixing part with a diluent, a reagent mixing chamber, etc. Biological information detection unit.     A centrifuge means comprising a liquid storage section provided on the rotating body and a particle storage section having a connection port continuous in the outer peripheral direction of the storage section, the connection port being a convex portion at the boundary between the liquid storage section and the particle storage section A biological material information detection unit having an upper structure.   The biological material information detection unit according to claim 15, wherein a centrifugation time is determined based on a cross-sectional area of the connection port.   The biological material information detection unit according to claim 15, wherein the convex portions are arranged in a bottom surface direction.   The biological material information detection unit according to claim 15, wherein the body fluid reservoir includes a body fluid supply port and a separated body fluid extraction port.   The biological substance information detection unit according to claim 15, wherein the separation body fluid extraction port is formed so as to be arranged on the extension of the convex portion or in parallel with the extension line.   The biological substance information detection unit according to claim 15, wherein the opening height of the connection port formed by the convex portion is equal to or greater than the height of the cross section forming the separated body fluid extraction port.   16. The biological material information detection unit according to claim 15, wherein the convex portion is higher in the bottom surface direction and in the separated body fluid extraction port direction. A means for mixing two or more liquids, two or more supply channels for introducing two or more liquids, a storage chamber for mixing, one or more for collecting mixed liquids The output flow path is configured, and either one or more of the output flow path or the two or more liquid supply flow paths is made of a structure having a micro cross-sectional area that generates a capillary force. Air pressure, gravity, centrifugal force, A method of performing an operation of changing the amount of liquid introduced into the capillary using one or more of inertial forces, and changing the amount of liquid in the result storage chamber according to the amount of liquid introduced into the capillary. A means for mixing two or more liquids, two or more supply channels for introducing two or more liquids, a storage chamber for mixing, one or more for collecting mixed liquids By changing the amount of liquid introduced into the capillary using any one or more of the output flow path, air pressure, gravity, centrifugal force, and inertial force, the liquid amount in the result storage chamber is also the liquid introduced into the capillary tube. A biological information detection unit having a pressurizing means for changing according to the amount, wherein one or more of the output flow path or the two or more liquid supply flow paths generate a capillary force.
  A storage chamber for storing at least two of a biological sample provided on the rotating body and a mixing body for mixing with the biological sample, and an outward direction with respect to the storage chamber, and the centrifugal force of the rotating body Biological information detection comprising: a moving force supplying means for applying an opposing force to the liquid in the storage chamber; and a driving means capable of rotating around the rotation speed central axis of the rotating body and changing the rotation speed a predetermined number of times. unit.   In a direction opposite to the centrifugal force with respect to the storage chamber for storing at least two of the biological sample provided on the rotating body and the mixing body for mixing with the biological sample, and the mixing liquid in the storage chamber A biological information detection unit comprising: a moving force supply means for applying a force; and a driving means capable of rotating around the rotation speed central axis of the rotating body and changing the rotation speed a predetermined number of times.   A biological sample mixing method in which a rotation having periodic strength is given to a combination of a space supplied with a biological sample and an auxiliary liquid and a flow path having a capillary action in the central direction connected to the space.   27. The living body information detection unit according to claim 24, further comprising a flow path having a bent portion extending at least once in the central axis direction.   27. The biological information detection unit according to claim 24, 25, or 26, wherein the biological sample is a blood-related component such as blood, serum, or plasma.   27. The biological information detection unit according to claim 24, 25, or 26, wherein the rotation number is changed in a range of 0.3 to 10 SEC in a range of 100 to 10000 rpm. 27. The biological information detection unit according to claim 24, 25, or 26, wherein a cross-sectional area of the flow path is 4 mm ² or less.   27. The biological information detection unit according to claim 24, 25, or 26, wherein the auxiliary liquid is intended for dilution.   A biological information detection unit comprising: a small chamber opened at the outermost periphery in one direction of a primary reaction tank receiving a force in one direction, and a configuration in which an additive is placed in the small chamber.   The biological information detection unit according to claim 32, wherein the opening of the small chamber has an acute angle.   The biological information detection unit according to claim 32, further comprising a reagent reaction tank in which other additives connected to the mixing tank through a flow path are installed and capable of measuring components.   An operation area having a predetermined depth and a reserve area for preliminarily storing a sample are provided, and the operation area, a flow path having a capillary force connecting the reserve areas, and a fluid in the flow path are pressed. Alternatively, a biological information detection unit having pressure generating means for applying a force in the direction of suction and supply to the operation area. The pressure generating means pressurizes or sucks fluid that is input into the preliminary region and is attracted to the flow path by capillary force intermittently or continuously until the inside of the operation region is filled with fluid. 35. A biological information detection unit according to 35.
An operation area having a predetermined depth and a reserve area for preliminarily storing a sample are provided, and the operation area, a flow path having a capillary force connecting the reserve areas, and a fluid in the flow path are pressed. Or a biological information detection unit having pressure generating means for applying a force in the direction of suction and supply to the operation region, wherein the fluid in the operation region is held by a flow path having capillary force. 35. A biological information detection unit according to 35. Using a flow path having a capillary connected to the operation area and the operation area, a force is applied to supply the fluid in the flow path to the operation area, and the fluid is connected to the operation area and the pressure generation means. 36. The biological information detection unit according to claim 35, wherein the biological information is quantified by being introduced into a flow path having a capillary force.   The biological information detection unit according to claim 34, wherein the pressure generating means is a centrifugal force.   36. The biological information detection unit according to claim 35, wherein the operation region and the spare region are subjected to a hydrophilic treatment. Biometric information detection unit of claim 35 cross sectional area of the flow path is 0.01 to 0.25 mm ^2. 36. The biological information detection unit according to claim 35, wherein a plurality of the flow paths are connected to the operation region. 36. The biological information detection unit according to claim 35, wherein a ratio of a cross-sectional area of the channel having capillary force and the preliminary chamber is 1: 9 or more. 36. The biological information detection unit according to claim 35, wherein a cross-sectional area of the flow path having the capillary force is the smallest among all the cross-sectional areas of the flow paths that communicate with each other.   An operation area for operating a liquid, a supply flow path for supplying a sample liquid to the operation area, and an output flow path for taking out a sample after operation from the operation area, and the supply flow path in the operation area And a biological information detection unit characterized in that a sample liquid is quantified by providing a deaeration port between the output channel and the output channel.   An operation area for operating a liquid provided on the rotating body, a supply flow path for supplying a sample liquid to the operation area, and an output flow path for taking out a sample after operation from the operation area. A path is arranged in the direction of the centrifugal center with respect to the operation region, and the sample liquid is quantified by providing a deaeration port between the supply channel and the output channel in the operation region. A biological information detection unit.   An operation region for operating a liquid provided on the rotating body, a supply channel for supplying a sample liquid to the operation region, and an output channel for taking out a sample after operation from the operation region, A passage is disposed in a centrifugal center direction with respect to the operation region, and a deaeration port is provided between the supply channel and the output channel in the operation region, and a position of the deaeration port of the deaeration port is A biological information detection unit characterized in that the sample liquid is quantified by being arranged on the inner side in the centrifugal direction than the output flow path.   48. The biological information detection unit according to claim 45, 46, 47, wherein a capillary tube is used as a flow path to the deaeration port.   An operation area for operating a liquid provided on the rotating body, a supply flow path for supplying a sample liquid to the operation area, and an output flow path for taking out a sample after operation from the operation area. A degassing port is disposed between the supply channel and the output channel, and a cross-sectional area to the degassing port is larger than the supply channel and the output channel. The biological information detection unit according to claim 45 to 48. At least a metering chamber with an output channel in the outer peripheral direction, connected to an overflow channel through which overflowed liquid flows in the central direction, and an output channel for outputting liquid to the outside in the outer peripheral direction Is a liquid quantification chamber comprising protrusions in the area sandwiched between the overflow channel and the quantitation chamber connection surface, and the connection between the previous output channel and the quantitation chamber.
At least a metering chamber with an output channel in the outer peripheral direction, connected to an overflow channel through which overflowed liquid flows in the central direction, and an output channel for outputting liquid to the outside in the outer peripheral direction Is connected to the overflow channel and the metering chamber, and the region sandwiched between the output channel and the connecting portion of the metering chamber is quantified by the volume between the overflow channel and the projection. Quantitation room.
The liquid after quantification is introduced into the output flow path by surface tension, and a first protrusion is provided at a position below the quantification unit so as not to impede quantification accuracy using the siphon principle. Liquid quantification chamber.

Images