JP2007040833A - Biochemical analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means which surely carries out a stirring operation, while eliminating the influences due to liquid viscosities, capillary forces, static electric charges and the like, under an environment where the space for mixing a small amount of specimen with a solid, such as a reagent or the like, becomes narrower. <P>SOLUTION: A biochemical analysis method is provided, which prevents centrifugal separation from occurring, within a comparatively short time, when two or more different kinds of materials are mixed in a minute space, and applies angular accelerations in order to increase or decrease rotations with the passage of time, such that the number of the rotations gives a required acceleration for a prescribed period. Furthermore, an apparatus is provided, which employs this method. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a carrier having a site showing a biochemical reaction and a biochemical analyzer for measuring the carrier.

Recently, lifestyle-related diseases such as diabetes, cancer, and cerebral infarction are closely related to daily living requirements such as diet and stress, so body fluid components such as blood and urine can be measured quickly and diagnosed across multiple items. There is a demand for a more accessible environment to be realized.
A device that analyzes and diagnoses such body fluids can be diagnosed easily and in a short time even if there is no use or equipment at home, as long as the body fluid components are supplied, even without special operations. Things are preferable.
Further, reducing the burden on patients by reducing the amount of collected body fluid is an important factor in diagnosis at home as well as medical facilities such as hospitals. If measurement is possible with a small amount of sample, the carrier for measurement becomes smaller and the analyzer becomes smaller.
Recently, an increasing number of hospitals, institutions, and organizations use a general-purpose public network such as the Internet as a means of communication and perform health checks by self-collecting blood.
The blood collection and transport process is explained on the Internet in an easy-to-understand manner, blood is collected by itself, transported to the hospital, and blood components and body fluid components are measured to check health.
However, a system including actual blood transport is time-consuming and extremely complicated because it needs to prepare a cold storage environment in advance.
In the situation of body fluid analysis in medical treatment including at home, simplification of the body fluid analysis system, simplification of diagnosis, and speeding-up that are required are moving toward the direction of promoting the reduction of body fluid collection.

JP-T-2001-510568 JP 2001-165939 A JP 09-475932 A

Miniaturization of specimens is preferable for patients and collectors, and the downsizing of carriers and analyzers can be widely used at home and outdoors. In an environment where the space for mixing solids such as reagents becomes narrower, not only stirring operations are difficult, but also actions such as viscosity, capillary force, static electricity, etc. that have not been regarded as problems so far are necessary. In particular, when a solid such as a reagent is mixed with a liquid such as plasma, the difference in specific gravity is large and difficult.
Also, when oxygen is required for a chemical reaction or the like, when the reaction space is narrow and optical measurement is performed in that space, a method for supplying oxygen becomes a problem.

In view of the above, as a result of intensive studies, the present inventors have found that two or more liquids in a micro three-dimensional space can be mixed only by a predetermined rotation mode, and have reached the present invention.
That is, in the present invention, when mixing different substances, the centrifugal separation does not occur in a relatively short time, and the necessary acceleration is increased over time up to a given time, and then in the opposite direction. Centrifugation does not occur in a relatively short period of time, and the necessary acceleration is increased over time to a given speed for a given time, and this can be repeated to facilitate even those with large differences in specific gravity. Realized that it can be mixed.
In the present invention, it is sufficient that the liquid in the minute space to be mixed is given acceleration in one direction or alternately in the other direction periodically and intermittently. As for the driving, rotational driving, linear driving, furiko driving, etc. can be used.
Furthermore, the present invention provides a measuring unit for mixing substances having different specific gravity arranged in the direction of the outer peripheral edge on the rotating body, measuring the result, a quantifying unit for supplying a quantitative sample to the measuring unit, and the quantifying unit A fixed-quantity supply channel extending in the circumferential direction, a finite first recovery channel and a second recovery channel extending in the circumferential direction, and the first recovery channel; By providing a recovery unit that is connected to the quantitative supply channel and connects the second recovery channel and recovers surplus specimen, a solution to be measured on a carrier that performs various rotations and movements, We realized that the surplus specimen solution and so on were made independent without leaking to other configurations.
Furthermore, the present invention is a part for optical measurement, and in the part where the reagent and the sample are mixed, by forming an air reservoir in the center direction of the rotating body, there is no hindrance to the optical measurement by transmitted light or the like, Moreover, a carrier that can sufficiently cope with a reaction that requires oxygen has been realized.

Further, the present invention is a flow path having a capillary force, and at least from the input port, the output port has a straight line portion parallel to the diameter or a flow channel extending in the circumferential direction. Thus, without requiring a complicated flow path such as a so-called siphon, the liquid can be moved and stopped only by adjusting the number of rotations according to the cross-sectional area or length of the flow path.
In the present invention, the aerobic reaction tank has an elliptical shape or a gourd shape having a long axis in the central direction, so that the carrier is rotated and an air reservoir is formed in the central direction portion, and a stable measurement optical path is obtained. It can be secured.
Even if the shape is not elliptical or gourd, there may be a case where a portion protruding slightly toward the center may be formed.

  The present invention makes it possible to perform a simple body fluid test because it enables a large number of tests just by adjusting the number of rotations and the direction of rotation of a mixture of substances having different specific gravities, such as quantitative determination of a small amount of specimen, reagents, etc. Realize body fluid diagnosis in a wide area.

The micro space in the present invention is, for example, a cylindrical reagent reaction tank of a type in which a reagent is accommodated, a quantitative specimen is supplied from the outside, and is colored when mixed, and the upper and lower areas are 0. 0. Although 5 to 2.5φ and a height of about 5 mm or less are exemplified, the present invention is not limited to this, and the present invention can also be applied to a part intended only for mixing.
Examples of substances having different specific gravities include, for example, mixing of body fluids such as blood, body fluid, and urine and solid, powdered, and granular reagents, and other liquids having different concentrations.
Centrifugation does not occur in a relatively short time, and the rotation speed at which acceleration required for stirring is given for a predetermined time indicates a rotation speed at which centrifugation does not occur in a relatively short time, and the predetermined time is approximately 1 Examples are around seconds.
In other words, this rotational speed indicates the vicinity of the rotational speed boundary where separation by centrifugal force occurs in a relatively short time, and the rotational speed at the boundary is the degree of difference in specific gravity, viscosity, distance from the rotational center, etc. However, it is sufficient that the number of rotations is such that at least centrifugal separation does not occur immediately.
The “opposite direction” indicates counterclockwise when the previous rotation is clockwise.
The rotation is increased from the state where the target rotational speed is reached to the rotational speed in which the direction is different and the separation due to the centrifugal force does not occur in a relatively short time. The number of rotations is appropriately adjusted depending on the substance for mixing, the difference in specific gravity, and the mixing time, and is not limited.

Specifically, for example, when the minute space for mixing is about 2 to 3 cm away from the center of rotation on the carrier, the number of revolutions is first increased clockwise from 0 rpm to 2000 rpm, and the number of revolutions is increased to 2000 rpm. After reaching this time, it is continuously changed and increased up to 2000 rpm counterclockwise, and after reaching 2000 rpm, it is switched to reverse rotation again and continuously changed and increased up to 2000 rpm, which is several hundred msec to several This is shown repeatedly at intervals of about sec.
The time from the maximum rotational speed in one direction to the maximum rotational speed in the opposite direction is from 0.1 msec to 2 sec, preferably from 0.5 sec to 1 sec. This is preferable in terms of utilization.
In addition, by devising the shape of the reaction / measurement chamber, for example, when measuring while rotating at 600 rpm or higher, liquid gathers or sticks to a part of the measurement chamber (outer wall). When the rotation is stopped (or the number of rotations is reduced), the liquid spreads to the bottom of the measurement chamber. By repeating this change in the liquid shape, efficient stirring, oxygen supply, and measurement during rotation are possible. enable.

The number of recovery flow paths may be two or more, and is not particularly limited. However, two may be sufficient when the carrier is smaller or depending on the purpose of use.
In the present invention, the “circumferential supply channel” means, for example, a tangential direction with respect to the circumference, and is not limited to being perpendicular to the radial direction, but within a range of approximately ± 30 ° with respect to the perpendicular. If it is good.

In the present invention, “a flow path having a capillary force, and at least from the input port, the output port has a linear portion parallel to the diameter, thereby adjusting the number of rotations of the carrier to move and stop the liquid”. Indicates a flow path on a straight line parallel to the diameter direction. It should be noted that at least near the rotation center of the carrier, it is only necessary to be parallel to the diametrical direction, and there may be bent portions in all directions before and after that.
Further, in the present invention, it is possible to stop and start the movement of the liquid by adjusting the number of rotations even in a configuration in which the flow path has a capillary force and the output port extends in the circumferential direction from at least the input port. To do. Extending in the circumferential direction is a flow path having the same curvature as the circumference, and indicates a state extending on the circumference, but the curvature does not necessarily have to coincide with the circumference. Even when the curvature is somewhat large and vice versa, it can be used as a switch for controlling the flow of liquid.

FIG. 1A is a diagram for explaining an embodiment of the present invention.
Reference numeral 118 denotes a first supply flow path, and a plurality of reagent reaction tanks 116 are connected to each other in the outer peripheral direction via a fixed quantity tank 114 and a fixed quantity supply flow path 115. FIG. 1 shows one of the reagent reaction vessels.
An example of the overall configuration is shown in FIG. At this time, the diameter of the outermost periphery of the carrier 100 is about 60 mm to 70 mm.
Since FIG. 1 is a part thereof, the numbers are common.
Reference numeral 114 shown in FIG. 1 (a) denotes a quantification tank, which is a part for securing a sample of a volume corresponding to the volume of the quantification supply channel 115.
Reference numeral 115 denotes a fixed amount supply channel, which extends in the circumferential direction. The direction of the constant supply flow path is exemplified by a tangential direction, but is not limited thereto, and may have an inclination of approximately + 0 ° to 30 ° with respect to the tangential line.
Reference numeral 116 denotes a reagent reaction tank, in which a dry or liquid reagent SY is enclosed in advance or supplied at the time of use.
Reference numeral 116a denotes a reaction region, which is formed of a cylindrical recess as shown in FIG. 1B, and has a size of, for example, a diameter of about 1 mm and a height of about 3 mm.
Reference numeral 116b denotes an air reservoir, and the height is formed in a range from about half the height of the reaction region to about the same as the reaction region.

FIG. 2 illustrates an example of a state in which the specimen is quantitatively supplied to the reagent reaction region.
First, the carrier rotates in one direction, and the specimen 3A that has flowed through the first supply channel 118 is filled in the quantification tank 114 with the rotational force (FIG. 2 (a)).
The sample 3B is also filled in the quantitative supply channel 115, and a state as shown in FIG. 2B is formed. The volume of the specimen 3B quantified at this time is an amount that fills the reaction region 116a, but may be smaller than an amount that fills all of 116a and 116b.
Depending on the reaction mechanism of the reagent, its properties, or depending on the purpose, a part of the necessary reagent is also enclosed in this quantification tank, and mixing with the supplied specimen or primary reaction is performed in the quantification tank. It can also be done within. As an example, a so-called two-reagent reaction system, which is stored in a physically or chemically separated state in order to prevent a reaction between reagent components during storage, is assumed.
Next, the rotational speed is increased to about 5000 to 6000 rpm.
Thereby, the specimen 3C is filled in the reagent reaction region so as to be pushed (FIG. 2 (c)).

In this state, a sample liquid (unmixed) containing the solid or liquid reagent SY supplied in advance or immediately before use as shown in FIG. 1B is formed.
Next, the carrier is rotated as shown in FIG.
For example, in the rotation as shown in FIG. 3A, the carrier is first rotated clockwise.
When the first clockwise rotation reaches 1500 rpm with a predetermined angular acceleration, the rotational speed is decreased with the predetermined angular acceleration, and when the rotational speed reaches 0, the predetermined angular acceleration is increased counterclockwise to 1500 rpm. After reaching 1500 rpm, the rotational speed is decreased at a predetermined angular acceleration to zero, and then rotated clockwise, and this is repeated. Thereby, sufficient mixing is performed for 10 to 120 seconds.
The period P1 at this time is suitably about 1 to 2 seconds. However, as shown in FIG. 3 (b), even if the period P2 is increased, the time until stirring and mixing is somewhat increased, but sufficient mixing is possible. In some cases, it can be expected, and is appropriately adjusted according to the size of the reaction vessel.
It should be noted that the shift to the above-described rotation speed and the shift to the lower limit rotation speed based on the predetermined angular acceleration may be performed by linear increase, decrease, and exponential increase / decrease.
Moreover, the expression by the angular acceleration is an example, and at least the rotation from the lower limit rotation speed to the upper limit rotation speed or from the upper limit rotation speed to the lower limit rotation speed is caused to reach the rotation of the carrier in the above-described manner in a predetermined time. Anything is acceptable.

Further, as shown in FIG. 3 (c), there may be a case where strength is increased with a predetermined angular acceleration in one of clockwise and counterclockwise directions without alternating.
The waveform indicating the rotation change in FIG. 3 is indicated by a saw-like direct current or alternating wave, but is not limited to this, and is not limited to this, but a rectangular shape, a trigonometric function wave, an intermittent triangular wave shape, an intermittent rectangular wave shape, an intermittent sine wave. It may be a change in the number of rotations corresponding to a waveform such as a wavy direct current or an alternating wave.
FIG. 3 shows a case where the angular acceleration is continuous and constant. After the angular acceleration is increased to a certain fixed rotation, the rotation is once stopped and then increased again to a certain fixed rotation in the reverse direction. It may be good. At this time, the range of acceleration given to the liquid in the reaction tank is preferably 10 to 500 m / s @ 2, but is not particularly limited.
The shape of the embodiment shown in FIG. 1 (a) is not limited to this, and may be a shape like an elliptical reagent reaction tank 116f as shown in FIG. 1 (c), for example.
In the case of the elliptical reagent reaction tank 116f, as shown by 116fa in FIG. 1 (c), the sample amount to be quantified is filled slightly smaller than the volume of 116f, and due to the bias in the centrifugal direction of the liquid mixture due to rotation. An air reservoir can be formed, and an optical path length for optical measurement by an optical unit disposed in the outer peripheral direction can be secured.

Moreover, in this invention, simple stirring can also be implement | achieved by increasing the air which remains in a reagent reaction tank, and increasing / decreasing a rotation speed.
2D and 2E show the YY ′ cross section of FIG.
TA is a carrier, which is the same as the carrier 100 shown in FIG. 6, and is made of transparent, translucent acrylic, PET, PP, polyester resin, or the like.
FT is a lid, made of the same material as the carrier TA, and made of an acrylic thin plate coated with double-sided or single-sided adhesive tape, adhesive, or adhesive.
FIG. 2D shows a state in which the specimen 116fb is supplied to the reagent reaction tank 116f in whole or in part, and is rotated at a low speed (rotation of 600 rpm or less) or is stationary.
116fa is an air reservoir, and SY is, for example, a solid reagent.
Next, the rotational speed is set to 600 rpm or more. The specimen 116fb is biased toward the outer wall surface of the reagent reaction tank 116f by centrifugal force as shown in FIG.
When the rotational speed is lowered again to 600 rpm or less, the state shown in FIG. 2D is obtained.
By alternately repeating these two states, the reagent SY and the specimen 116fb can be efficiently stirred.
Since the influence of the capillary force of the quantitative supply path 115 on the specimen 116fb is low due to the air in the air reservoir 116fa, the specimen is not moved to the quantitative supply path 115, and the specimen is mixed only by centrifugal force. Is called.
FIGS. 2 (d) and (e) show a method of mixing and causing movement of liquid by changing the centrifugal force generated by increasing / decreasing the rotational speed, and the rotational speed is the same as in the other embodiments. After increasing to a predetermined number of rotations, rotation with angular acceleration that rotates in the opposite direction may be given to the carrier, or temporarily stopped.
In this case, the increase / decrease in the number of rotations and the relationship between the increase period and the decrease period may be performed with values similar to those in the other embodiments, and at least the same acceleration may be applied to the liquid.

Next, an embodiment of the present invention will be described with reference to FIGS.
The configuration shown in FIGS. 4 and 5 shows a part of the overall configuration of the carrier shown in FIG.
Reference numeral 118 denotes a first supply flow path, which is formed of a substantially concentric arc-shaped flow path with respect to the disc-shaped carrier. Since it is a substantially concentric arc, it is not always necessary to have a concentric curvature, as long as it can obtain a good distribution of plasma components during carrier rotation.
However, when discharging the surplus specimen or performing quantification in the quantification tank, the outer wall of the first supply channel 118 is preferably concentric with the rotation center of the carrier.
117a is a surplus sample storage unit that stores a surplus sample after each quantification tank 114 is filled with a sample. The surplus sample storage unit 117a has two substantially arcuate shapes, and is a first surplus storage unit 117aa located in the outer circumferential direction. And a second surplus accommodating portion 117ac and a connecting path 117ab that couples these accommodating portions, and is connected to one or both of the end portions of the supply channel via a surplus accommodating portion channel 117ad.
The position of the excessively diluted mixed solution storage portion 117a is not limited to the end of the supply flow path, but may be in the center or the like.
The connection path 117ab is sharpened at a connection point with each surplus accommodating portion, and prevents leakage due to the backflow of the surplus liquid to the first supply flow path 118.

Reference numeral 114 denotes one of the quantification tanks, which are arranged at equal intervals or unequal intervals on the outer peripheral portion of the first supply flow path 118, and the volume thereof indicates the target liquid amount.
Reference numeral 115 denotes a constant supply channel, which extends in the circumferential direction and substantially in the tangential direction.
Reference numeral 116a denotes a reaction region, in which a reagent is disposed, and is connected to the fixed amount supply channel 115 via an air reservoir 116b.
The configuration from the quantification tank 114 to the reaction region 116a has a configuration as shown in FIG.

The operation of the configuration shown in FIG. 4 will be described in detail with reference to FIG.
The sample supplied to the first supply channel 118 is in a state where the carrier is rotating, and the remaining sample that is filled and held in the quantification tank 114 by centrifugal force or the like passes through the surplus storage unit channel 117ad. To the second surplus storage part 117ac, and to the first surplus storage part 117aa via the connecting path 117ab.
In a state where any of the quantification tanks 114 is filled with the sample and the sample supply channel 115 is also filled with the sample, the number of rotations is increased and the sample is supplied to the reaction region 116a.
In order to mix the reagent in the reaction region 116a and the specimen, rotation with the angular acceleration alternately increased or decreased as shown in FIG.
At that time, when the rotation direction is counterclockwise as shown in FIG. 5 (a), the surplus specimens 4a and 4b gather at the left end of the surplus storage part, and the rotation direction is shown in FIG. 5 (b). In the case of clockwise rotation, the surplus specimens 4a and 4b gather at the right end of each surplus storage part.
In this way, even when a centrifugal force is applied due to rotation, even when the rotational direction changes alternately, that is, when the direction of acceleration changes, the surplus specimen is held in the surplus specimen storage section 117a, and the flow path and each tank Depending on the wettability of the surface, a specimen that easily leaks from other parts does not leak to the first supply channel 118, and stable low-speed agitation while maintaining the independence of the liquid in each reagent reaction tank Is possible.

Next, an example of the whole carrier including the embodiment of the present invention is shown.
FIG. 6 is a plan view of a disk-like carrier 100 made of transparent, semi-transparent acrylic, PET, PP, polyester resin, etc., and grooves and recesses are formed so that each component such as a flow path, a reservoir, and an excess storage portion is formed. Formed.
Reference numeral 101 denotes a blood reservoir, which is a portion for supplying blood obtained by collecting blood collected from a human body or the like with a pipette or other holder.
As shown in FIG. 6, blood reservoir 101 has a configuration that does not provide an acute angle on the side surface of the reservoir and has a shape that reduces residual blood.
Reference numeral 102 denotes a diluent storage unit that stores the diluent leaked to the outside by, for example, destroying a sealed diluent pouch.
The blood reservoir 101 has an open upper surface, and the adjacent diluent storage part 102 is accommodated in a pouch in advance, and a lid is disposed on the upper part of the diluent storage part 102. ing.
When used, blood is supplied to the blood reservoir 101 with a pipette or the like, or a porous material in which body fluid is immersed in cancer is inserted, and the lid is slid to cover the upper surface of the blood reservoir 101. And the pouch inside the dilution reservoir 102 is moved and destroyed due to sliding of the lid, so that the diluent can be supplied from the diluent reservoir 102 to the outside. The configuration of Japanese Patent Application No. 2005-168885 is preferably used. Although not numbered, the grooves provided on both side surfaces of the blood reservoir 101 and the diluent reservoir 102 can be used as guide grooves for allowing the lid portion to be slidably fixed.
Reference numeral 103 denotes a blood distribution unit, which includes a blood constant supply channel for supplying blood toward the two blood cell separation units.
Reference numeral 104 denotes a surplus blood reservoir, which is a portion for storing the blood that has overflowed after the blood has filled the first blood cell separator 106 and the second blood cell separator 107.
Reference numeral 105 denotes a surplus part flow path, which is used to flow the overflowed blood to the surplus blood storage part 104 after the first blood cell separation part 106 and the second blood cell separation part 107 are filled with blood. is there.
Reference numeral 106 denotes a first blood cell separation unit, and 107 denotes a second blood cell separation unit, which are formed so that the volume of each space indicates the required amount of liquid.
Reference numeral 108 denotes a first blood cell storage unit, which is connected to the second blood cell separation unit 107 via a relatively thin channel, and 109 denotes a second blood cell storage unit, which separates the first blood cell via a relatively thin channel. Connected to the unit 106. Such a connection by a relatively narrow flow path prevents blood cells from flowing backward when the centrifugal force is weakened, such as when the rotation direction is alternated during low rotation of the carrier.
Reference numeral 111 denotes a first flow path having a bent portion in the central direction, and connects the second blood cell separation unit 107 and the mixing unit 112.

Reference numeral 113 denotes a second flow path having a bent portion in the center direction for connecting the first blood cell separation unit 106 and the adjustment tank 110.
Reference numeral 114 denotes one of each of the quantification tanks, which has the same configuration as that of FIG. 1 and is arranged on the outer peripheral portion of the first supply flow path 118 at equal intervals or unequal intervals, and the volume thereof is a target liquid amount Is shown.
Reference numeral 115 denotes a quantitative supply channel, which has the same configuration as that of FIG. 1 and extends in the circumferential direction for connecting the quantitative tank 114 and the reagent reaction tank 116.
Reference numeral 116 denotes a reagent reaction tank having the same configuration as that shown in FIG. 1, which is formed in a substantially tangential direction of the carrier, and has a reagent disposed therein as shown in FIG. Depending on the type of reagent, when oxygen is required for the color development reaction, the reagent reaction tank 116 may be provided with an air reservoir as shown in FIG.
117a to 117d are surplus dilution liquid mixture storage portions having the same shape and size, respectively, and are configured by connecting concentric first surplus storage portions and second surplus storage portions by connecting portions as shown in FIG. Has been.
Reference numeral 118 denotes a first supply flow path, which is formed concentrically, and a plurality of reagent reaction tanks 116 each having a metering tank 114 are arranged in the outer circumferential direction.
Reference numerals 119, 121, and 127 denote deaeration ports, which are openings for releasing the air in the mixing part and the buffer part to prevent the movement of the liquid in the flow path to the outside.
Reference numeral 120 denotes a third flow path, which has a bent portion in the center direction, and connects the adjustment tank 110 and the first supply flow path 118.
Reference numeral 122 denotes a fourth flow path, which has a bent portion in the center direction and connects the mixing portion 112 and the second supply flow path 130.

Reference numeral 123 denotes a fifth channel, which is a straight channel for connecting the diluent storage unit 102 and the diluent quantification unit 124.
Reference numeral 124 denotes a dilution liquid quantification unit, and one end of the sixth flow path 125 is connected in the central direction, and the other end of the sixth flow path 125 is connected to the surplus dilution liquid storage unit 126.
Reference numeral 126 denotes an excess dilution liquid storage unit that stores the dilution liquid overflowing in the dilution liquid determination unit 124.
Reference numeral 128 denotes a reserve tank for increasing the accuracy of quantification of the liquid quantified at 124 by utilizing the concentricity of the liquid surface remaining at 128 by applying a centrifugal force. Are connected in the outer circumferential direction.
Reference numeral 129 denotes a seventh flow path that extends parallel to the diameter direction and is connected to the mixing unit 112 through two bent portions.
Reference numerals 131 and 131 ′ denote chucking holes, which are parts for connecting to a reading device.

FIG. 7 shows an example of a reading device.
Reference numeral 132 denotes a lower part of the apparatus, in which a recess for accommodating the carrier 100 is formed at the center, and at the center, there are protrusions 135 and 135 ′ for insertion and fixing into the two chucking holes 131 and 131 ′ of the carrier 100. A rotating body 134 is provided. Although not shown, the rotating body 134 is connected to a stepping motor, a transmission gear, and the like.
Reference numeral 133 denotes an upper part of the apparatus, which is connected to the lower part 132 of the apparatus so that one side can be rotated.
Reference numerals 136a to 136c denote primary color light sources, which are formed by laser light, LEDs, infrared light sources, and the like. Reference numerals 137a to 137c denote light receiving elements, which are arranged at portions facing the light sources, respectively.

Next, the operation when blood and diluent are supplied and developed on the carrier of the embodiment shown in FIGS. 6 and 7 will be described.
Blood is supplied to the blood reservoir 101 of the stationary carrier 100 and the diluent is developed into the diluent reservoir 102.
At this time, the chucking holes 131 and 131 ′ of the carrier 100 are inserted into the protrusions 135 and 135 ′ of the rotating body 134 shown in FIG.
The measurement is performed while rotating each reagent reaction tank on the carrier 100 by closing the upper part 133 of the apparatus so as to overlap the storage lower part 132.
The carrier 100 accommodated in the apparatus is rotated at a rotational speed of about 5000 rpm.
The blood in the blood reservoir 101 is supplied to the first blood cell separator 106 and the second blood cell separator 107 via the two flow paths of the blood distributor 103, and the diluent in the diluent reservoir 102 is It is supplied to the diluent storage part 124 via the fifth channel 123.

The blood supplied to the first blood cell separation unit 106 and the second blood cell separation unit 107 fills the first blood cell storage unit 108 and the second blood cell storage unit 109 by centrifugal force, while the first blood cell separation unit 106 and the second blood cell separation unit 109 are filled. The two blood cell separation unit 107 is filled, and the surplus portion is accommodated in the surplus blood storage unit 104 via the surplus portion channel 105. The said structure has two or more fixed_quantity | quantitative_assay parts, and there are few surplus blood storage parts, and the simplified structure is proposed.
The diluent supplied to the diluent quantification unit 124 gradually fills the diluent quantification unit while filling the preliminary tank 128, and the surplus is accommodated in the excess diluent reservoir 126 through the sixth channel 125. The
The blood supplied to the blood cell separation unit attempts to move to be filled with capillary force with respect to the first flow path 111 and the second flow path 113, but the movement is hindered by centrifugal force. Yes.
The diluent also tries to move due to the capillary force of the seventh flow path 129, but the movement is hindered by the centrifugal force.

By continuing the rotation, the blood cells in the first blood cell separation unit 106 and the second blood cell separation unit 107 are moved to the first blood cell storage units 108 and 109 to perform blood cell separation. Since the blood cell separation unit and the blood cell storage unit are connected by a thin flow path, the blood cells that have once entered the blood cell storage unit are held and do not flow backward even at low speed rotation.
After the separation is sufficiently performed and the blood cell separation units 106 and 107 are filled with only the plasma component, the rotation of the carrier 100 is lowered. The centrifugal force is weakened, the blood in the first flow path 111 and the second flow path 113 moves so as to be filled in the flow path, and the diluted liquid in the seventh flow path 129 is also directed toward the mixing unit 112. Moving.
When the number of rotations is increased again, the plasma in the first channel 111 and the second channel 113 moves to the mixing unit 112 and the adjustment tank 110, and the diluted solution also moves to the mixing unit 112.
At this time, since the output port is located farther from the rotation center than the input ports of the first channel 111, the second channel 113, and the seventh channel 129, the blood cell separation units 106 and 107 and the dilution channel are diluted. The plasma and dilution liquid quantified by the liquid quantification unit 124 move to the mixing unit 112 and the adjustment tank 110.
After the movement is completed, the rotation direction is changed over time and mixed. In this case, since the mixing tank has a large volume, mixing is possible only by changing the speed over time or changing the rotation direction.
After the mixing, the rotation speed is decreased, so that the mixed liquid fills the fourth flow path 122 connected to the mixing unit 112, and the plasma fills the third flow path 120.
When the rotational speed is increased again to about 500 rpm to 1000 rpm, the mixed solution is supplied to the second supply channel 130, and the plasma is supplied to the first supply channel 118. Filled. The fixed amount supply channel 115 is also filled, but stays on the connection surface with the reagent reaction tank 116.
After each of the quantification tanks 114 and 114 ′ is filled with the mixed solution and plasma, the surplus is increased to about 2500 rpm in order to be stored in the excess diluted mixed solution storage units 117a to 117d.

Furthermore, in order to supply each liquid of each fixed_quantity | quantitative_assay tank 114,114 'to the reagent reaction tank 116,116', the rotation speed of a support | carrier is further enlarged (5000 rpm-6000 rpm).
After the supply is completed, as shown in FIG. 3, the carrier is caused to rotate alternately up to a predetermined number of rotations over time.
Due to this alternating change in acceleration, the liquid in the reagent reaction tank and the reagent are mixed, and a uniform color reaction is performed.
Next, the primary color light sources 136a to 136c irradiate each reagent reaction tank with laser light, receive the transmitted light with the light receiving elements 137a to 137c, obtain the absorbance electronically, and measure the blood component concentration.
According to the above description, it is possible to easily measure blood components simply by supplying blood to the central blood reservoir 101.

  Since the present invention can quickly obtain more accurate biochemical information in a biochemical analyzer such as a blood test and an infection test, a faster biochemical analyzer can be configured.

The figure which shows one Example of this invention. The figure which shows the other Example of this invention. The figure which shows the other Example of this invention. The figure which shows the other Example of this invention. The figure which shows the other Example of this invention. The figure for demonstrating the other Example of this invention. The figure for demonstrating the other Example of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 100 Carrier 101 Blood storage part 102 Dilution liquid storage part 103 Blood distribution part 104 Surplus blood storage part 105 Surplus part flow path 106 1st blood cell separation part 107 2nd blood cell separation part 108 1st blood cell storage part 109 2nd blood cell storage part 110 Adjustment tank

Claims (14)

When mixing two or more different substances in a minute space, the rotation does not occur in a relatively short time, and the rotation is increased or decreased over time until the required acceleration is given for a predetermined time. A liquid mixing method in which angular acceleration is applied. A carrier having a micro space for mixing two or more different substances, and the carrier does not centrifuge in a relatively short period of time, and the elapsed time until a required acceleration is given for a predetermined time. A liquid mixing apparatus comprising driving means for applying angular acceleration to the carrier so as to increase or decrease rotation. When mixing substances with different specific gravities in a minute space, centrifugal separation does not occur in a relatively short time, and the necessary acceleration for the substance is increased over time up to a given time, 2. The method according to claim 1, wherein the centrifugal separation does not occur in the opposite direction in a relatively short time, and the necessary acceleration for the substance is increased over time to a given speed for a predetermined time, and this is repeated. The liquid mixing method as described. A carrier having a mixing part for mixing substances having different specific gravities, the carrier is rotated, and centrifugal separation does not occur in a relatively short time, and the rotation speed is such that a necessary acceleration can be given to the substance for a predetermined time. A rotation means that repeats this by increasing the number of rotations over time so that the centrifugal separation does not occur in a relatively short time in the opposite direction and the necessary acceleration is given to the substance for a predetermined time. The liquid mixing apparatus according to claim 2. When mixing two or more substances in a minute space in a carrier, a centrifugal separation does not occur in a relatively short time, and a living means having a driving means for driving the carrier to give a necessary acceleration to the substance for a predetermined time. Chemical analyzer. The liquid mixing method and apparatus according to claim 1, wherein the rotational speed is 2000 rpm or less. 6. The liquid mixing method and apparatus according to claim 1, wherein the time from the maximum rotational speed in the one direction to the maximum rotational speed in the opposite direction is 0.5 sec to 2 sec. Mixing substances with different specific gravity arranged in the direction of the outer peripheral edge on the rotating body, measuring the reaction state and results such as absorbance, the quantification unit for supplying the measurement sample to the measurement unit, the quantification A flow path for supplying a sample to the unit, a fixed-quantity supply flow path extending in the circumferential direction, a finite first collection flow path extending concentrically, and another collection flow path, and the first collection flow path, A carrier for a biochemical analysis apparatus comprising a recovery section that is connected to the fixed-quantity supply flow path and that collects surplus specimens by a connection flow path connecting the other recovery flow paths. The biochemical analyzer carrier according to claim 8, wherein a connecting portion between the first recovery channel and the second recovery channel of the connection channel is formed in an acute angle shape. The biochemical analyzer carrier according to claim 8, wherein the measurement unit and the quantification unit are connected by a flow path extending in a circumferential direction. The carrier for a biochemical analyzer according to claim 8, wherein an air storage part is formed in a central direction in the measurement part. The carrier is not centrifuged in a relatively short time, and the necessary angular acceleration is increased over time up to a given time and then centrifuged in the opposite direction for a relatively short time. The biochemical analyzer according to claim 8, further comprising a rotating device for increasing the number of rotations over time until a required angular acceleration is given for a predetermined time and repeating the required angular acceleration. A flow path having capillary force, for a biochemical analyzer that moves and stops liquid by adjusting the number of rotations of a carrier with a configuration in which at least an input port has a linear part parallel to the diameter from an input port Carrier. A carrier for a biochemical analyzer, which has a capillary force, and moves and stops liquid by adjusting the number of rotations of the carrier by a configuration in which at least an input port and an output port extend in the circumferential direction.

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