JP4615342B2 - Stirring method, cell, measuring device using the same, and measuring method - Google Patents

Description

  The present invention relates to a method for stirring a sample solution and a reagent, which is used in a clinical test for chemically analyzing a sample solution such as blood or urine. Furthermore, this invention relates to the cell suitable for the said stirring method, a measuring apparatus using the same, and a measuring method.

In an inspection device such as an immunochemical analyzer or biochemical analyzer, a reaction is efficiently generated in a container such as an analysis cell, and the sample solution and the reagent are agitated to maintain measurement accuracy. Is done.
Conventional stirring techniques include, for example, a technique of rotating a magnetic rotor with a magnetic stirrer (Patent Document 1), a technique of vibrating a stirring blade using a piezo element as a drive source (Patent Document 2), and a reaction cassette. There has been proposed a technique (Patent Document 3) that rotates and moves a liquid by gravity, and agitates it by contacting with a means for disturbing the flow of the liquid provided in the reaction cassette.
JP-A-3-214049 JP-A-4-363665 Japanese Patent Laid-Open No. 3-46566

However, in the conventional agitation techniques shown in Patent Documents 1 to 3, it is necessary to perform the agitation operation by operating the agitation mechanism with a driving source, separately from the operation of injecting the sample solution or the reagent into the reaction system.
Specifically, after injecting the sample solution or reagent into the reaction system, for example, in Patent Document 1, it is necessary to rotate a magnetic rotor by a magnetic generator, and in Patent Document 2, it is necessary to vibrate a stirring blade by a piezo element. In Patent Document 3, it is necessary to rotate the reaction cassette using a stepping motor or the like as a drive source.

Therefore, in the conventional stirring technique, it is necessary to newly provide a driving source for stirring, and there is a problem that the configuration of the inspection device including the stirring device becomes complicated.
In addition, it is necessary to perform a stirring operation separately from the operation of injecting the sample solution or the reagent into the reaction system. Depending on the concentration of the sample solution and the reagent in the reaction system from the injection of the sample solution and the reagent into the reaction system. In addition, there is a problem that it takes a considerable amount of time before an accurate reaction can be measured.

The above-mentioned conventional problems are recognized especially in quantitative type POCT (Point of Care Testing) inspection equipment that requires quick and accurate measurement in the field, and in the future, more and more quantitative type POCT inspection equipment will be available. Considering that it will become widespread, it is expected that the above problems will be solved quickly.
Therefore, the present invention solves the conventional problems as described above, and a stirring method, a cell, a measuring apparatus using the same, and a measuring method that can quickly and easily stir a sample solution and a reagent with a simple configuration The purpose is to provide.

In order to solve the conventional problems as described above, the present invention
A method of stirring a sample solution containing a measurement object and a reagent,
(A) A sample liquid containing a measurement object from the sample liquid supply port to the sample liquid holding part using a cell including a sample liquid holding part having a plurality of particles and the reagent and a sample liquid supply port And (B) stirring the sample liquid and the reagent by the movement of the particles accompanying the flow of the sample liquid generated in the sample liquid holding part by supplying the sample liquid, And a stirring method comprising a step of obtaining a mixed solution containing the reagent and the particles ,
The reagent contains a specific binding substance that can specifically bind to the substance to be measured contained in the sample solution,
In the mixed liquid, a stirring method is provided in which at least the surface charge of the particles and the charge of the specific binding substance have the same polarity .

The present invention also provides:
A sample liquid holding unit having a plurality of particles and a reagent, and a sample liquid supply port;
The particles are held in the sample solution holding unit movably along with the flow of the sample solution supplied from the sample solution supply port into the sample solution holding unit,
A cell in which the sample liquid and the reagent are stirred by the movement of the particles ,
The reagent contains a specific binding substance that can specifically bind to the substance to be measured contained in the sample solution,
In the mixed liquid containing the sample liquid, the reagent, and the particles obtained by supplying the sample liquid, the charge of at least the surface of the particles and the charge of the specific binding substance have the same polarity. A cell is provided in which the particles and the specific binding substance are conditioned .

Furthermore, the present invention provides
Above cell,
Cell holding portion for holding the cell,
A sample solution supply unit for supplying the sample solution to the sample solution holding unit through the sample solution supply port of the cell;
A light source for emitting light incident on the light incident part of the cell, and a light detection part for detecting light emitted from the light emitting part of the cell,
Provided is a measuring device for measuring an object to be measured in a sample liquid based on light detected by the light detection unit.
Furthermore, the present invention provides
In addition to the above stirring method,
Furthermore, using a cell comprising a light incident part for making light incident on the sample liquid holding part, and a light emitting part for emitting light from the sample liquid holding part,
(C) a step of causing light to enter the holding portion through the light incident portion;
(D) detecting the light emitted out of the holding part through the light emitting part, and (E) in the sample liquid based on the light detected after the particles in the liquid mixture have settled. Provided is a measuring method including a step of measuring a contained measurement target substance.

  According to the stirring method, the cell, and the measuring apparatus using the same of the present invention, the sample solution and the reagent can be rapidly and easily stirred with a simple configuration.

  The present invention relates to a method of stirring a sample liquid containing a measurement object and a reagent, and (A) using a cell including a plurality of particles and a sample liquid holding unit having the reagent and a sample liquid supply port, A step of supplying a sample liquid containing an object to be measured from the sample liquid supply port to the sample liquid holding section; and (B) accompanying the flow of the sample liquid generated in the sample liquid holding section by the supply of the sample liquid. A step of stirring the sample liquid and the reagent by the movement of the particles to obtain a mixed liquid containing the sample liquid, the reagent, and the particles;

  The cell of the present invention includes a sample liquid holding unit having a plurality of particles and a reagent, and a sample liquid supply port, and the sample liquid is supplied from the sample liquid supply port into the sample liquid holding unit. The sample liquid holding part is held so as to be movable in accordance with the flow of the liquid, and the sample liquid and the reagent are stirred by the movement of the particles.

If it does in this way, the flow of the liquid can be generated in the sample liquid holding part by flowing the sample liquid into the sample liquid holding part from the sample liquid supply port. As the liquid flows, the plurality of particles held in the sample solution holding part move, so that the sample solution and the reagent can be stirred and uniformized. For this reason, as compared with the case where the operation of adding the sample solution and the reagent to the reaction system and the stirring operation are individually performed, as in the measurement method used in the conventional inspection apparatus for homogeneous reaction measurement, the reaction Therefore, the time required to make the sample solution and the reagent uniform can be shortened. Therefore, when the stirring method of the present invention is applied to a homogeneous reaction measurement inspection apparatus, the measurement time of the reaction between the sample solution and the reagent can be shortened.
In addition, since the stirring operation can be performed using the flow of the liquid into the container when the sample liquid flows, it is not necessary to newly provide a drive source for stirring, and the configuration is simplified.
As described above, according to the present invention, the sample solution and the reagent can be stirred quickly and easily with a simple configuration.

  Examples of the sample solution in the stirring method, the cell, and the measurement device and measurement device using the same according to the present invention include a water-soluble sample solution and a colloid solution containing colloidal particles that can be suspended in water. More specifically, examples include body fluids such as urine, blood, plasma, serum, saliva, cell interstitial fluid, sweat, and tears, or aqueous solutions in which biological components are dissolved.

The reagent only needs to contain a substance having reactivity with the measurement target contained in the sample solution. Examples of the substance having reactivity with the measurement target include an enzyme, an immunoreactive substance that causes an antigen-antibody reaction with the measurement target, and a substance that causes a ligand receptor reaction with the measurement target. Among these, it is preferable that the substance having reactivity with the measurement object is a specific binding substance that can specifically bind to the measurement object substance. Examples of the specific binding substance include an immunoreactive substance and a substance that causes a ligand receptor reaction with an object to be measured.
In particular, antibodies that are immunoreactive substances are preferable because they can specifically bind to low molecular compounds, high molecular compounds such as proteins, bacteria, viruses, and the like.
Moreover, the reagent used in order to measure reaction optically is preferable.

The particles used in the present invention are not necessarily spherical but may be of any shape, but the particles need only be insoluble in water, have a specific gravity greater than 1, and can settle in the sample solution. In addition, it is preferable to use particles that easily float in the sample liquid due to a flow caused by a water pressure of about −1 atm to +1 atm and settle quickly after the movement.
Examples of the material constituting the particles include glass, sea sand, silica, metal, polystyrene, polyethylene, acrylic, polypropylene, and other resins. The particle size of the particles is preferably about 400 to 700 μm. Among them, it is preferable to use glass particles or sea sand having a particle size of about 400 to 700 μm.

Further, in the mixed solution of the sample solution and the reagent, it is preferable that the particles and the specific binding substance are adjusted so that at least the surface charge of the particle and the charge of the specific binding substance have the same polarity.
In this way, since the particles and the specific binding substance are electrostatically repelled when mixed with the sample liquid, this effect can prevent the adsorption of the specific binding substance to the particles. The dissolution of the specific binding substance and the mixing of the sample solution and the specific binding substance can be promoted.

Specifically, when a protein is supported on a particle as a specific binding substance, a functional group or the like that can maintain a constant polarity charge within a pH range of about 4 to 9 may be present on the particle surface.
For example, it is assumed that particles having an amino group on the surface are used as the particles and an antibody is used as the specific binding substance. The amino group is positively charged within a pH range of about 4-9. Therefore, assuming that the isoelectric point pI of an antibody is 6.5 (however, the isoelectric point pI of a general antibody is 6 to 8), a pH smaller than 6.5 (preferably pH 4.5) If the antibody is positively charged over the whole molecule and supported on the particles, the positively charged antibody and the positive charge on the particle surface will repel each other, preventing the antibody from adsorbing to the particles. Can do.
On the other hand, when a protein having an isoelectric point on the acidic side and negatively charged near neutral is used as a specific binding substance near neutral (for example, pH 7.4), a sulfone as a functional group is formed on the surface as particles. What has an acid group or a carboxyl group may be used. In this case, both the functional group and the protein are negatively charged and repel each other.

In the present invention, when the sample solution and the particles are mixed, a buffering agent is included in the reagent so as to cause a pH change in which at least the surface charge of the particles and the charge of the specific binding substance are repelled. It is preferable to keep it.
According to such a configuration, it is easy to set the pH for electrostatically repelling the particles and the specific binding substance during mixing, and the pH can be stabilized. And repulsive electrostatic repulsion between the specific binding substance and the specific binding substance.
The particles may be coated with a reagent so that the reagent is dissolved in the sample liquid supplied from the sample liquid supply port into the sample liquid holding unit. At this time, even if the reagent is coated so as to cover the entire particle surface, the reagent may be coated so as to cover only a part of the particle surface.
If it does in this way, when the reagent which coat | covers a particle will contact a sample solution, it will melt | dissolve in a sample solution and will detach | desorb from a particle.

At this time, a concentration gradient of the reagent is generated from the particle surface toward the periphery (that is, from the vicinity of the particle surface). This reagent concentration gradient becomes high near the particle and becomes an obstacle to the dissolution of the reagent. However, since the particle moves in the liquid, the concentration of the dissolved reagent near the particle is prevented from becoming extremely high. can do. As described above, since the factor that inhibits the dissolution of the reagent can be alleviated, the dissolution of the reagent in the sample solution can also be promoted.
Furthermore, the sample liquid and the reagent can be agitated by the turbulent flow generated by the movement of the particles to obtain a mixed liquid in which the dispersion state of both is uniform.

In the present invention, when the reagent is coated on the particles, the surface of each particle may be individually coated with the reagent, or the surfaces of a plurality of particles may be collectively coated with the reagent. .
Especially, it is preferable to coat | cover the surface of each particle | grain with the said reagent separately. This is because if the individual particles are coated with the reagent, the contact area between the reagent and the sample liquid can be increased, and the fluidity of the particles can be easily secured in the resulting mixed liquid, so that the reagent can be dissolved. This is because it can be promoted.

The reagent is preferably in a dry state. Examples of the method for bringing the reagent into a dry state include air drying and freeze drying. Among these, freeze drying is preferably used from the viewpoint of solubility and activity maintenance of the reagent.
The presence of individual particles coated with the reagent can be achieved by, for example, freeze-drying an appropriate amount of the reagent on one particle. Alternatively, a plurality of particles may be mixed with a reagent, and the resulting mixture may be freeze-dried to obtain a freeze-dried product, and then the freeze-dried product may be pulverized so that the particles can exist individually. The latter method is superior to the former method from the viewpoint of simplicity of the operation of coating the particles with the reagent.

Further, in the present invention, it is preferable that a particle (adsorption inhibiting substance) that inhibits the specific binding substance from adsorbing to the particle is supported on the particle.
According to such a configuration, it is possible to prevent the specific binding substance from adsorbing non-specifically on the particles and not being dissolved in the sample solution, thereby preventing the specific binding substance from being involved in the reaction with the object to be measured. Thus, the reaction between the measurement object and the specific binding substance can be performed more efficiently. Examples of the substance that inhibits the specific binding substance from adsorbing to the particles include silicon and proteins that do not participate in the reaction between the sample solution and the reagent.

Here, it is preferable that the substance that inhibits the specific binding substance from adsorbing to the particles also inhibits the object to be measured in the sample liquid from adsorbing to the particles. The substance that inhibits the specific binding substance from adsorbing to the particle is preferably provided so as to cover the surface of the particle. Furthermore, it is preferable that the substance does not participate in the reaction between the sample solution and the reagent.
For example, when an immunoassay reagent is used, casein, bovine serum albumin, gelatin or the like can be used as a substance that inhibits the specific binding substance from adsorbing to the particles. For example, by incubating glass particles in a solution containing 1% by weight of casein for 1 hour or more, casein can be adsorbed around the particles to inactivate the particle surface.

In the present invention, it is also preferable that a substance that adsorbs a substance (reaction inhibiting substance) that inhibits the reaction between the object to be measured and the specific binding substance is provided on the surface of the particle.
According to such a configuration, since the substance that inhibits the reaction between the measurement target object and the specific binding substance can be removed from the solution in which the sample solution and the reagent are mixed, the measurement target can be performed more efficiently. The reaction between the object and the specific binding substance can be performed. Examples of the substance that adsorbs the reaction inhibitory substance include a receptor molecule for the reaction inhibitory substance and an immunoreactive substance that can specifically bind to the reaction inhibitory substance.

Here, the substance that adsorbs the reaction-inhibiting substance is preferably provided so as to cover the surface of the particles. Furthermore, it is preferable that the adsorbed substance does not participate in the reaction between the object to be measured and the specific binding substance.
For example, in order to use glass particles as particles and to provide the adsorbing material around the glass particles, the glass particles are incubated in a solution containing the adsorbing material, and the adsorbing material is adsorbed around the glass particles. Good.

For example, when the sample solution is human blood, plasma, serum, urine, etc., and reacting with the target substance in the sample solution with an immune reaction measurement reagent using an animal-derived antibody, the sample solution contains There is a known example in which a human-derived antibody against an animal-derived antibody exists, and this human-derived antibody inhibits the reaction between a target substance and a reagent in a sample solution.
In such a case, the glass particles may be incubated in a solution containing about 0.1 mg / ml antibody against human-derived antibody for 1 hour or more to adsorb the antibody against human-derived antibody around the glass particles. .

After binding the human-derived antibody, which is an inhibitor, with an antibody against the human-derived antibody provided around the glass particles, if the glass particles are precipitated, the human-derived antibody, which is an inhibitor, can be localized in the container. it can. In this way, the human-derived antibody against the animal-derived antibody is restricted from binding to the animal-derived antibody in the reagent, and the reaction between the animal-derived antibody in the reagent and the target substance in the sample solution is controlled against the animal-derived antibody. Inhibition of human-derived antibodies can be suppressed.
In addition, when measuring CRP (C-reactive protein) whose content increases in the case of bacterial infection using a blood sample, it is known that rheumatoid factor adversely affects the measurement. By adsorbing and arranging the antibody that binds the factor around the particle, the influence of rheumatoid factor can be eliminated in the same manner as described above.

The material of the container constituting the cell of the present invention is not particularly limited as long as it is insoluble with respect to the sample solution and the reagent, but is preferably a material that is transparent to the extent that the inside is visible. If the inside is visible, the stirring status of the sample solution and the reagent in the container can be easily confirmed, so that the trouble can be dealt with quickly and the reaction between the sample solution and the reagent. Can also be determined visually.
Specific examples include glass, polystyrene, polyethylene, acrylic, and polypropylene.

Moreover, it is preferable that the said container is comprised with the material which a sample liquid and a reagent cannot adsorb | suck nonspecifically. Or you may comprise the said container with the material which performed the process for preventing the nonspecific adsorption | suction of a sample solution and a reagent.
For example, when using a reagent containing protein, peptide, DNA or the like, or a sample solution containing protein, peptide, DNA or the like as an object to be measured, it is preferable to use polypropylene. This is because polypropylene, protein, and DNA are difficult to adsorb nonspecifically.

In addition, when the container is made of glass or polystyrene that is relatively nonspecifically adsorbed with proteins, peptides, DNA, etc., the inner surface of the container is not involved in the reaction between the sample solution and the specific binding substance, Moreover, what is necessary is just to coat with the material which does not inhibit.
Examples of the material used for such coating include silicon and proteins that do not participate in the reaction between the sample solution and the reagent.

In the cell of the present invention, the sample solution supply port is arranged so that the sample solution flowing into the sample solution holding unit from the sample solution supply port moves along the inner wall surface of the sample solution holding unit. It is preferable.
In particular, it is preferable to provide the sample liquid supply port so that the flow of the sample liquid supplied into the sample liquid holding part is a swirling flow along the inner wall surface of the sample liquid holding part. If it does in this way, it will become possible to raise | generate the flow of a sample solution efficiently within a sample solution holding | maintenance part, the floating and movement of particle | grains can be accelerated | stimulated, and the stirring and mixing effect of a sample solution and a reagent can be improved.

Moreover, it is preferable that the diameter of the opening part outside the sample solution supply port is larger than the diameter of the opening part inside the sample solution supply port.
According to such a configuration, the flow rate of the sample liquid from the outside of the container to the inside of the container can be increased, so that a faster flow of the sample liquid can be generated in the container. In addition, the floating and movement of particles can be promoted, and the effect of stirring and mixing the sample solution and the reagent can be enhanced.

In the present invention, the cell preferably includes a light incident part for allowing light to enter the sample liquid holding part and a light emitting part for emitting light from the sample liquid holding part. .
According to such a configuration, it is not necessary to transfer the mixed solution of the sample solution and the reagent to another optical cell for optical measurement, and the reaction caused by the stirring can be quickly spectroscopically measured. Time can be further shortened. Further, particularly when measuring a transient change in the reaction, the time loss is small and the transient change can be reliably captured. Furthermore, since a mechanism for transferring the mixed liquid to another optical cell is not required, the apparatus configuration can be simplified.

  The light incident portion and the light emitting portion are made of a substantially flat and optically substantially transparent material. The surface of the light emitting part may be disposed substantially parallel to the surface of the light incident part. If it does in this way, it will inject into the sample liquid holding part from the light incident part, and the light which permeate | transmitted the liquid mixture of the sample liquid and the reagent accommodated in the sample liquid holding part will be outside the sample liquid holding part through the light emitting part. Can be emitted. Therefore, a cell suitable for measuring absorbance or turbidity can be provided.

  Further, the surface of the light emitting portion may be disposed substantially perpendicular to the surface of the light incident portion. If it does in this way, it will inject into a sample liquid holding part from a light incident part, and will be scattered in the liquid mixture of the sample liquid and reagent accommodated in a sample liquid holding part, or a light incident part will enter into a sample liquid holding part Fluorescence generated in the liquid mixture due to incident light can be emitted out of the sample liquid holding part through the light emitting part. Therefore, a cell suitable for scattering intensity or fluorescence measurement can be provided.

  For example, quartz glass or polystyrene is preferably used as the optically substantially transparent material constituting the light incident part and the light emission part. These materials are excellent in transparency in the visible light region and are suitable for optical measurement in the visible light region.

Furthermore, the measurement apparatus of the present invention includes a cell holding unit that holds the cell, a sample solution supply unit that supplies the sample solution to the sample solution holding unit through the sample solution supply port of the cell, and the cell of the cell. A light source for emitting light incident on the light incident part, and a light detection part for detecting light emitted from the light emission part of the cell, and a sample based on the light detected by the light detection part Measure the object to be measured in the liquid.
Here, the sample liquid supply unit is preferably a sample liquid suction means for sucking the sample liquid into the sample liquid holding unit through the sample liquid supply port. Examples of the sample liquid suction means include a plunger and a syringe.
In addition to the above stirring method, the measuring method of the present invention includes:
Furthermore, using a cell comprising a light incident part for making light incident on the sample liquid holding part, and a light emitting part for emitting light from the sample liquid holding part,
(C) a step of causing light to enter the holding portion through the light incident portion;
(D) detecting the light emitted out of the holding part through the light emitting part, and (E) in the sample liquid based on the light detected after the particles in the liquid mixture have settled. And a step of measuring the contained substance to be measured.
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. However, the present invention is not limited to these embodiments.

[Embodiment 1]
FIG. 1 is a schematic perspective view showing the structure of a stirring device using a cell according to Embodiment 1 of the present invention. As shown in FIG. 1, the stirring device 10 of the present embodiment includes a bottomed cylindrical container 11, and a sample liquid holding unit 13 of the container 11 includes an object to be measured and an antigen antibody contained in the sample liquid. Reagent-coated particles 12 coated with an immune reaction measuring reagent containing an immunoreactive substance (specific binding substance) that causes a reaction are held.
The particles 12 are held in the sample liquid holding unit 13 so that the particles 12 can move as the liquid such as the sample liquid flows in the sample liquid holding unit 13.

The sample solution supply port for containing the sample solution includes an opening 14 of the container 11 and a pipe 15 connected to the opening 14 and penetrating the wall of the container 11. Here, the diameter of the opening 16 of the tube 15 located outside the container 11 is larger than the diameter of the opening 17 of the tube 15 located inside the container 11.
The container 11 is made of transparent polypropylene, and the inside of the container 11 can be visually observed. As the particles constituting the reagent-coated particles 12, particles (polylysine-coated particles) obtained by coating the surface of glass particles having a particle size of about 550 μm with polylysine to be positively charged are used.

The reagent is coated on the particles as follows. A solution containing an antibody that is an immunoreaction measuring reagent with an isoelectric point of 6.5 is mixed with a plurality of polylysine-coated glass particles, and the resulting mixture is lyophilized under the condition of pH 7.5 to obtain a lyophilized product. And the lyophilizate is ground so that the reagent-coated particles can be present individually.
In addition, a citrate buffer prepared in advance is dropped onto the sample solution holding unit 13 so that the pH during mixing of the sample solution and the reagent-coated particles can be maintained at 5.0.

Next, the operation of the stirring device 10 of the present embodiment will be described.
First, urine is introduced as a sample solution from the opening 16 to supply the sample solution into the container 11 through the opening 14 of the container 11. The reagent-coated particles 12 in the sample liquid holding unit 13 are floated and moved by the flow of the liquid inside the container 11 caused by the supply, and the reagent for measuring the immune reaction is dissolved by the movement of the particles 12, The sample solution is mixed with an immune reaction measurement reagent and a citrate buffer and stirred.

According to the present embodiment, the flow of the liquid can be generated in the container 11 by allowing the sample liquid to flow into the container 11 from the opening 14 of the container 11. As the liquid flows, the plurality of reagent-coated particles 12 held in the container 11 move, so that the immune reaction measurement reagent is dissolved, and the sample solution, the immune reaction measurement reagent, and the citrate buffer are dissolved. Can be mixed and stirred to obtain a uniform liquid mixture.
For this reason, as compared with the case where the operation of adding the sample solution and the reagent to the reaction system and the operation of stirring are performed separately as in the conventional stirring device, the time required for making the sample solution and the reagent uniform. Can be shortened.

In addition, since the immune reaction measurement reagent is coated on the particles, the concentration gradient of the reagent in the vicinity of the particles formed by the movement of the particles and dissolution of the reagent for immune reaction measurement by contact with the sample solution (reagent coating) It is possible to prevent an increase in the concentration gradient of the dissolved reagent generated in the vicinity of the particles, and it is possible to promote dissolution of the reagent coated on the particles in the sample solution.
In addition, since the specific binding substance is coated around the particles, the surface area for supporting can be increased compared to the case where the specific binding substance is supported on the wall surface of the container, and the specific binding substance is contained in the sample liquid holding part. Can hold more.

Further, when the reagent-coated particles 12 are prepared as in the present embodiment and the pH at the time of mixing with the sample solution is maintained at 5.0, the isoelectric point of the antibody that is a specific binding substance in the reagent for measuring the immune reaction Is 6.5, the antibody is positively charged, and the polylysine on the particle surface has a positive charge, so the particle surface is positively charged. As a result, the particles and the antibodies coated with the particles are electrically repelled, and the detachment of the antibodies from the particles can be promoted.
Further, since the stirring operation can be performed using the flow of the liquid when the sample liquid flows into the container 11, it is not necessary to newly provide a drive source for stirring, and the configuration is simple.
As described above, according to the present embodiment, the sample solution and the reagent can be stirred quickly and easily with a simple configuration.

  Further, since the diameter of the opening 16 of the tube 15 facing the outside of the container 11 is larger than the diameter of the opening 17 of the tube 15 facing the inside of the container 11, the diameter of the container 11 from the outside of the container 11 is increased. The inflow speed of the fluid into the inside is high, and a faster fluid flow can be generated in the container 11. Thereby, the floating and movement of the reagent-coated particles 12 can be promoted, and the mixing / stirring effect of the sample solution and the reagent for measuring the immune reaction can be enhanced.

[Embodiment 2]
Next, a stirring device using the cell according to Embodiment 2 of the present invention will be described with reference to FIG. FIG. 2 is a perspective view showing the structure of the stirring device according to the present embodiment.
The stirring device 20 of the present embodiment is the same as the measuring device of the first embodiment, except that the position where the tube 25 is arranged is different.
Here, the reagent-coated particles 22 are held in the sample solution holding part 23 of the container 21, and the diameter of the opening part 26 of the tube 25 facing the outside of the container 21 is the opening part of the tube 25 facing the inside of the container 21. Unlike the first embodiment, the sample liquid that has flowed into the container 21 from the opening 24 moves along the inner wall surface of the container 21 as shown in FIG. A tube 25 is provided.

  According to the present embodiment, the same effects as those of the first embodiment can be obtained, but the sample liquid flowing in from the opening 24 forms a swirling flow along the inner wall surface of the container 21. The formed swirling flow can efficiently cause the liquid to flow in the container 21 and promote the floating and movement of the reagent-coated particles 22. Therefore, compared with the first embodiment, the effect of dissolving the reagent in the sample solution and the effect of stirring and mixing the sample solution and the reagent can be further enhanced.

[Embodiment 3]
Next, a stirrer using the cell according to Embodiment 3 of the present invention will be described with reference to FIG. FIG. 3 is a perspective view showing the structure of the stirring device according to the present embodiment.
The stirrer 30 according to the present embodiment is the above-described embodiment except that the stirrer 30 includes a light incident part for allowing light to enter the container 31 and a light emitting part for emitting light to the outside of the container 31. This is the same as the stirrer of form 1.
Here, the reagent-coated particles 32 are held in the sample solution holding portion 33 of the container 31, and the sample solution supply port is connected to the opening portion 34 of the container 31 and a tube penetrating the wall of the container 31. 35. The diameter of the opening 36 of the tube 35 facing the outside of the container 31 is larger than the diameter of the opening 37 of the tube 35 facing the inside of the container 31.

An optical measurement unit 38 including an incident light window 381 that functions as a light incident unit and a transmitted light window 382 that functions as a light output unit is provided on the wall surface of the container 31.
The incident light window 381 and the transmitted light window 382 are made of polystyrene, which is a substantially flat and optically transparent material, and the surface of the transmitted light window 382 is relative to the surface of the incident light window 381. Are disposed at substantially parallel positions.

According to the present embodiment, the same effects as those of the first embodiment can be obtained, but optical measurement can be easily and reliably performed.
After a predetermined time has elapsed since the sample liquid was supplied into the container 31, light from a light source (not shown) is irradiated almost perpendicularly to the incident light window 381. Incident light enters the container 31 from the incident light window 381, passes through the mixed solution of the sample liquid and the reagent stored in the container 31, and then exits the container 31 through the transmitted light window 382. To do. The emitted light is received by a light receiving unit (not shown). After the particles in the liquid mixture settle, measure the reaction between the sample liquid and the reagent produced by stirring by determining the absorbance or turbidity of the liquid mixture based on the intensity of the light received at the light receiving part. Can do.

  As described above, the stirrer 30 according to the present embodiment includes the optical measurement unit 38 including the incident light window 381 that functions as a light incident unit and the transmitted light window 382 that functions as a light output unit. When performing the optical measurement, it is not necessary to transfer the liquid mixture from the container 31 to another optical cell, and the reaction caused by the stirring can be promptly spectroscopically measured. Therefore, the measurement time can be further shortened. Further, particularly when measuring a transient change in the reaction, the time loss is small and the transient change can be reliably captured. Furthermore, since a mechanism for transferring the mixed liquid to the optical cell is not necessary, the configuration of the measuring apparatus can be simplified.

[Embodiment 4]
Next, a stirrer using the cell according to Embodiment 4 of the present invention will be described with reference to FIG. FIG. 4 is a perspective view showing the structure of the stirring device according to the present embodiment.
The stirrer 40 according to the present embodiment is the above-described implementation except that it includes a light incident part for allowing light to enter the container 41 and a light emitting part for emitting light to the outside of the container 41. This is the same as the stirrer of form 2.
Here, the reagent-coated particles 42 are held in the sample solution holding part 43 of the container 41, and the sample solution supply port is connected to the opening 44 of the container 41 and the tube passing through the wall of the container 41. 45. The diameter of the opening 46 of the tube 45 facing the outside of the container 41 is larger than the diameter of the opening 47 of the tube 45 facing the inside of the container 41.

An optical measurement unit 48 including an incident light window 481 that functions as a light incident unit and a transmitted light window 482 that functions as a light output unit is provided on the wall surface of the container 41.
The incident light window 481 and the transmitted light window 482 are made of polystyrene, which is a substantially flat and optically transparent material, and the surface of the transmitted light window 482 is relative to the surface of the incident light window 481. Are disposed at substantially parallel positions.

According to the present embodiment, the same effects as those of the second embodiment can be obtained, but optical measurement can be easily and reliably performed.
After a predetermined time has elapsed since the sample liquid was supplied into the container 41, light from a light source (not shown) is irradiated almost perpendicularly to the incident light window 481. Incident light enters the container 41 from the incident light window 481, passes through the mixed solution of the sample liquid and the reagent stored in the container 41, and then exits the container 41 through the transmitted light window 482. To do. The emitted light is received by a light receiving unit (not shown). After the particles in the liquid mixture settle, measure the reaction between the sample liquid and the reagent produced by stirring by determining the absorbance or turbidity of the liquid mixture based on the intensity of the light received at the light receiving part. Can do.

  As described above, the stirring device 40 according to the present embodiment includes the optical measurement unit 48 including the incident light window 481 that functions as the light incident unit and the transmitted light window 482 that functions as the light output unit. When the optical measurement is performed, it is not necessary to transfer the mixed solution from the container 41 to another optical cell, and the reaction caused by the stirring can be quickly spectroscopically measured. Therefore, the measurement time can be further shortened. Further, particularly when measuring a transient change in the reaction, the time loss is small and the transient change can be reliably captured. Furthermore, since a mechanism for transferring the mixed liquid to the optical cell is not necessary, the configuration of the measuring apparatus can be simplified.

[Embodiment 5]
Next, a stirrer using the cell according to Embodiment 5 of the present invention will be described with reference to FIG. FIG. 5 is a perspective view showing the structure of the stirring device according to the present embodiment.
The stirrer 50 according to the present embodiment is the above-described embodiment except that the stirrer 50 includes a light incident part for allowing light to enter the container 51 and a light emitting part for emitting light to the outside of the container 51. This is the same as the stirrer of form 1.
Here, the reagent-coated particles 52 are held in the sample liquid holding part 53 of the container 51, and the sample liquid supply port is connected to the opening part 54 of the container 51 and a tube passing through the wall of the container 51. 55. The diameter of the opening 56 of the tube 55 facing the outside of the container 51 is larger than the diameter of the opening 57 of the tube 55 facing the inside of the container 51.

An optical measurement unit 58 including an incident light window 581 that functions as a light incident unit and a scattered light window 582 that functions as a light output unit is provided on the wall surface of the container 51.
The incident light window 581 and the scattered light window 582 are made of polystyrene, which is a substantially flat and optically transparent material, and the surface of the scattered light window 582 is in relation to the surface of the incident light window 581. In a substantially vertical position.

According to the present embodiment, the same effects as those of the first embodiment can be obtained, but optical measurement can be easily and reliably performed.
After a predetermined time has elapsed since the sample solution was supplied into the container 51, light from a light source (not shown) is irradiated almost perpendicularly to the incident light window 581. Incident light enters the container 51 from the incident light window 581, scatters in the mixed liquid of the sample liquid and the reagent stored in the container 51, and the scattered light passes through the scattered light window 582. Emits outside. Alternatively, the fluorescence generated in the liquid mixture due to the incident light is emitted out of the container 51 through the scattered light window 582.
The emitted light or fluorescence is received by a light receiving unit (not shown). After the particles in the mixed solution settle, the reaction between the sample solution and the reagent generated by stirring is measured by determining the scattering degree or fluorescence intensity of the mixed solution based on the intensity of light received by the light receiving unit. be able to.

  As described above, the stirring device 50 according to the present embodiment includes the optical measurement unit 58 including the incident light window 581 that functions as the light incident unit and the scattered light window 582 that functions as the light output unit. When performing the optical measurement, it is not necessary to transfer the mixed solution from the container 51 to another optical cell, and the reaction caused by the stirring can be promptly measured. Therefore, the measurement time can be further shortened. Further, particularly when measuring a transient change in the reaction, the time loss is small and the transient change can be reliably captured. Furthermore, since a mechanism for transferring the mixed liquid to the optical cell is not necessary, the configuration of the measuring apparatus can be simplified.

[Embodiment 6]
Next, a stirrer using a cell according to Embodiment 6 of the present invention will be described with reference to FIG. FIG. 6 is a perspective view showing the structure of the stirring device according to the present embodiment.
The stirrer 60 according to the present embodiment is the above-described implementation except that it includes a light incident part for causing light to enter the container 61 and a light emitting part for emitting light to the outside of the container 61. This is the same as the stirrer of form 2.
Here, the reagent-coated particles 62 are held in the sample solution holding part 63 of the container 61, and the sample solution supply port is connected to the opening part 64 of the container 61 and the tube passing through the wall of the container 61. 65. The diameter of the opening 66 of the tube 65 facing the outside of the container 61 is larger than the diameter of the opening 67 of the tube 65 facing the inside of the container 61.

An optical measurement unit 68 including an incident light window 681 that functions as a light incident unit and a scattered light window 682 that functions as a light output unit is provided on the wall surface of the container 61.
The incident light window 681 and the scattered light window 682 are made of polystyrene, which is a substantially flat and optically transparent material, and the surface of the scattered light window 682 is relative to the surface of the incident light window 681. In a substantially vertical position.

According to the present embodiment, the same effects as those of the second embodiment can be obtained, but optical measurement can be easily and reliably performed.
After a predetermined time has elapsed since the sample liquid was supplied into the container 61, light from a light source (not shown) is irradiated almost perpendicularly to the incident light window 681. Incident light enters the container 61 from the incident light window 681, scatters in the mixed liquid of the sample liquid and the reagent stored in the container 61, and the scattered light passes through the scattered light window 682. Emits outside. Alternatively, the fluorescence generated in the liquid mixture due to the incident light is emitted out of the container 61 through the scattered light window 682.
The emitted light or fluorescence is received by a light receiving unit (not shown). After the particles in the mixed solution settle, the reaction between the sample solution and the reagent generated by stirring is measured by determining the scattering degree or fluorescence intensity of the mixed solution based on the intensity of light received by the light receiving unit. be able to.

  As described above, the stirring device 60 according to the present embodiment includes the optical measurement unit 68 including the incident light window 681 that functions as the light incident unit and the scattered light window 682 that functions as the light output unit. When the optical measurement is performed, it is not necessary to transfer the mixed solution from the container 61 to another optical cell, and the reaction caused by the stirring can be quickly spectroscopically measured. Therefore, the measurement time can be further shortened. Further, particularly when measuring a transient change in the reaction, the time loss is small and the transient change can be reliably captured. Furthermore, since a mechanism for transferring the mixed liquid to the optical cell is not necessary, the configuration of the measuring apparatus can be simplified.

[Embodiment 7]
Next, a stirring device using the cell according to Embodiment 7 of the present invention will be described with reference to FIG. FIG. 7 is a perspective view showing the structure of the stirring device according to the present embodiment.
The stirring device 70 according to the present embodiment is the same as the stirring device of the third embodiment, except that the configuration of the optical measurement unit is changed.
Here, the reagent-coated particles 72 are held in the sample liquid holding part 73 of the container 71, and the sample liquid supply port is connected to the opening part 74 of the container 71 and a tube passing through the wall of the container 71. 75. The diameter of the opening 76 of the tube 75 facing the outside of the container 71 is larger than the diameter of the opening 77 of the tube 75 facing the inside of the container 71.

In the third embodiment, the optical measurement unit 38 is provided in the container 31, but in the present embodiment, the bottomed cylindrical optical measurement unit 78 connected to the upper opening 71a of the container 71 is provided. Is provided. An opening that communicates with the upper opening 71 a is provided at the bottom of the optical measurement unit 78, and the liquid can be moved between the optical measurement unit 78 and the container 71.
The optical measuring unit 78 is made of substantially flat and optically transparent polystyrene. Of the surfaces constituting the optical measurement unit 78, two surfaces facing each other function as an optical measurement window 781 that is a light incident portion and an optical measurement window 782 that is a light emission portion.

  According to the present embodiment, the same operational effects as those of the third embodiment can be obtained. Furthermore, by adopting the configuration of the optical measurement unit as in the present embodiment, it is not necessary to perform special processing and polishing so as to be optically transparent with respect to a part of the container wall surface. Configuration becomes easy. For example, it can be formed by joining a container having an opening for containing a sample solution or a reagent and a sample solution holding unit to a lower part of a commercially available optical cell having a hole in the bottom. Further, in this case, a cell that can be adapted to a cell holder of a commercially available spectroscopic measurement device can be configured, so that a highly versatile cell capable of optical measurement can be provided.

  In the present embodiment, of the surfaces constituting the optical measurement unit, two surfaces facing each other function as an optical measurement window that is a light incident unit and an optical measurement window that is a light emission unit, respectively. Although the case has been described, the present invention is not limited thereto, and two surfaces that are orthogonal to each other among the surfaces constituting the optical measurement unit are an optical measurement window that is a light incident unit and an optical measurement window that is a light emission unit, respectively. You may make it function. The number of optical measurement windows is not limited to two, and may be three or more.

[Embodiment 8]
Next, a stirring device using the cell according to Embodiment 8 of the present invention will be described with reference to FIG. FIG. 8 is a perspective view showing the structure of the stirring device according to the present embodiment.
The stirrer 80 according to the present embodiment is the same as the stirrer of the fourth embodiment except that the configuration of the optical measurement unit is changed.
Here, the reagent-coated particles 82 are held in the sample solution holding portion 83 of the container 81, and the sample solution supply port is connected to the opening portion 84 of the container 81 and a tube passing through the wall of the container 81. And 85. The diameter of the opening 86 of the tube 85 facing the outside of the container 81 is larger than the diameter of the opening 87 of the tube 85 facing the inside of the container 81.

  In the fourth embodiment, the container 41 is provided with the optical measurement unit 48. However, in the present embodiment, the bottomed cylindrical optical measurement unit 88 connected to the upper opening 81a of the container 81 is provided. Is provided. An opening that communicates with the upper opening 81 a is provided at the bottom of the optical measurement unit 88, and the liquid can be moved between the optical measurement unit 88 and the container 81.

The optical measuring unit 88 is made of substantially flat and optically transparent polystyrene. Of the surfaces constituting the optical measurement unit 88, two surfaces facing each other function as an optical measurement window 881 that is a light incident unit and an optical measurement window 882 that is a light emission unit.
According to the present embodiment, the same effect as that of the fourth embodiment can be obtained. Furthermore, by adopting the configuration of the optical measurement unit as in the present embodiment, it is not necessary to perform special processing and polishing so as to be optically transparent with respect to a part of the container wall surface. Configuration becomes easy. For example, it can be formed by joining a container having an opening for containing a sample solution or a reagent and a sample solution holding unit to a lower part of a commercially available optical cell having a hole in the bottom. Further, in this case, a cell that can be adapted to a cell holder of a commercially available spectroscopic measurement device can be configured, so that a highly versatile cell capable of optical measurement can be provided.

  In the present embodiment, of the surfaces constituting the optical measurement unit, two surfaces facing each other function as an optical measurement window that is a light incident unit and an optical measurement window that is a light emission unit, respectively. Although the case has been described, the present invention is not limited thereto, and two surfaces that are orthogonal to each other among the surfaces constituting the optical measurement unit are an optical measurement window that is a light incident unit and an optical measurement window that is a light emission unit, respectively. You may make it function. The number of optical measurement windows is not limited to two, and may be three or more.

[Embodiment 9]
Next, a stirrer (analyzer) using the cell according to Embodiment 9 of the present invention will be described with reference to FIGS. FIG. 9 is a schematic perspective view showing the structure of the analyzer according to the present embodiment. FIG. 10 is a diagram for explaining the operation of the analyzer 100 shown in FIG.
The analysis apparatus 100 according to the present embodiment includes a casing 91 and a stirring device (corresponding to a cell of the present invention) 99 configured by a cylinder having a plunger 92. The stirring device 99 is provided in the casing 91. Is provided. In addition, the cylinder has a rectangular cross section, and each side portion functions as an incident light window 933, a transmitted light window 931, and a scattered light window 932. Further, the lower portion of the cylinder has a tapered shape that becomes gradually thinner, and the opening at the tip serves as the sample liquid supply port 98.

A light source 95, a transmitted light detection detector 941, and a scattered light detection detector 942 are provided on a side surface portion of the stirring device 99 in the housing 91. As the transmitted light detection detector 941 and the scattered light detection detector 942, visible photometry photodiodes are used.
Further, the surface of the transmitted light window 931 is parallel to the surface of the incident light window 933, and the surface of the scattered light window 932 is perpendicular to the surface of the incident light window 933. , A transmitted light window 931, a scattered light window 932, and an incident light window 933 are provided.

  In the stirrer 99, reagent-coated particles 96 coated with a reagent for measuring an immune reaction including an immunoreactive substance that causes an antigen-antibody reaction with a measurement target contained in the sample liquid are disposed in the sample liquid supply port 98. .

The incident light window 933, the transmitted light window 931, and the scattered light window 932 are made of substantially flat and optically transparent polystyrene. Further, the surface of the incident light window 933 is arranged to be perpendicular to the light source 95, and the detection surface of the transmitted light detection detector 941 and the detection surface of the scattered light detection detector 942 are respectively transmitted. It is set to be perpendicular to the light window 931 and the scattered light window 932.
The other part of the stirring device 99 is made of polypropylene. Further, as the reagent-coated particles 96, those similar to those in the first embodiment are used.

Subsequently, the operation of the analyzer 100 according to the present embodiment will be described with reference to FIG. As shown in FIG. 10A, first, when the sample solution supply port 98 is immersed in the sample solution 101 in the beaker 102 and the plunger 92 is pulled upward, the sample solution 101 flows from the sample solution supply port 98. The reagent-coated particles 96 are rolled up by the flow. As a result, the reagent is suspended in the sample solution 101 in the stirring device 99 and the reagent coated on the surface of the reagent-coated particles 96 is dissolved in the sample solution 101 by the movement of the reagent-coated particles 96.
When the plunger 92 is pulled and stopped to the position shown in FIG. 10B, the reagent-coated particles 96 float to the positions of the incident light window 933, the transmitted light window 931, and the scattered light window 932. It reaches.

However, since the particle after the reagent is dissolved from the reagent-coated particle 96 has a large specific gravity, as shown in FIGS. 10C and 10D, the incident light window 933, the transmitted light window 931, and the scattered light are scattered. It gradually sinks below the position of the working window 932. Thereby, the turbidity generated by the antigen-antibody reaction between the measurement target object and the reagent in the sample liquid 101 can be optically measured.
After the particles settle, the light from the light source 95 is irradiated almost perpendicularly to the incident light window 933. Light incident from the incident light window 933 passes through the mixed liquid of the sample liquid and the reagent. At this time, light with high straightness is emitted through the transmitted light window 931 and received by the transmitted light detection detector 941. The light scattered by the reactant in the mixed solution exits through the scattered light window 932 and is received by the scattered light detection detector 942.

Based on the intensity of the light received by the transmitted light detection detector 941 and the scattered light detection detector 942, the reaction generated between the sample liquid and the reagent can be measured.
The absorbance or turbidity obtained by the transmitted light detection detector 941 and the scattered light intensity obtained by the scattered light detection detector 942 can be used as a reaction indicator between the sample liquid and the reagent. Any index may be used to measure the reaction between the sample solution and the reagent, but if the degree of turbidity due to the above reaction is low, more sensitive measurement is possible by obtaining the scattered light intensity. .

In the present embodiment, the stirring device 99 can be replaced with another stirring device. For example, it is possible to use a stirring device 110 having the structure shown in FIG.
A stirrer 110 shown in FIG. 11 has a lid 119a disposed on the top of the stirrer according to the seventh embodiment of the present invention shown in FIG. A guide 119c is provided. A plunger 92 is connected to the guide 119c.
Similarly, a stirrer obtained by providing a lid, an opening, and a funnel-shaped guide on the top of the stirrer shown in FIGS.

As described above, according to the analyzer 100 of the present embodiment, the sample solution and the reagent are mixed and stirred rapidly and easily simultaneously with the sampling of the sample solution by attaching the stirring device 99 to the plunger 92. be able to.
In the present embodiment, the stirrer 99 is provided with an incident light window 933, a transmitted light window 931, and a scattered light window 932, and the incident light window 933 is perpendicular to the light source 95. The detectors 941 and 942 for detecting transmitted light and the detector 942 for detecting scattered light are arranged so that their directions are perpendicular to the window 931 for transmitted light and the window 932 for scattered light, respectively.
Therefore, using a mixed solution obtained by mixing and stirring the sample solution and the reagent, the antigen-antibody reaction can be quickly spectroscopically measured, and the measurement time can be further shortened. Further, particularly when measuring a transient change in the reaction, the time loss is small, and the transient change can be reliably captured. Furthermore, a mechanism for transferring the mixed liquid to the optical cell is unnecessary, and the configuration of the measuring apparatus can be simplified.

  The stirring method and cell according to the present invention can stir a sample solution and a reagent quickly and easily with a simple configuration. Therefore, the present invention is useful in an immunochemical analysis test apparatus or a test apparatus (particularly a POCT test apparatus) such as a biochemical analysis apparatus used in a clinical test that chemically analyzes a sample solution such as blood or urine. .

It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 1 of this invention. It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 2 of this invention. It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 3 of this invention. It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 4 of this invention. It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 5 of this invention. It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 6 of this invention. It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 7 of this invention. It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 8 of this invention. It is a perspective view which shows the structure of the stirring apparatus which concerns on Embodiment 9 of this invention. It is a figure for demonstrating operation | movement of the stirring apparatus which concerns on Embodiment 9 of this invention. It is a perspective view which shows the modification of the stirring apparatus in Embodiment 9 of this invention.

Explanation of symbols

10, 20, 30, 40, 50, 60, 70, 80 Stirrer 11, 21, 31, 41, 51, 61, 71, 81 Container 12, 22, 32, 42, 52, 62, 72, 82 Reagent coating Particles 13, 23, 33, 43, 53, 63, 73, 83 Sample liquid holding part 14, 24, 34, 44, 54, 64, 74, 84 Opening part 15, 25, 35, 45, 55, 65, 75 , 85 Tube 16, 26, 36, 46, 56, 66, 76, 86 Opening 17, 27, 37, 47, 57, 67, 77, 87 Opening 38, 48, 58, 68, 78, 88 Optical measurement Part 381,481,581,681 Incident light window 382,482 Transmitted light window 582,682 Scattered light window 781,782,881,882 Optical measurement window 91 Housing 92 Plunger 931 Transmitted light window 932 Turbulent light window 933 incident light window 941 transmitted light detecting detector 942 scattered light detection detector 95 light source 96 reagent-coated particles 98 liquid sample supply inlet 99 stirrer 100 analyzer 101 liquid sample 102 beakers

Claims (11)

A method of stirring a sample solution containing a measurement object and a reagent,
(A) A sample liquid containing a measurement object from the sample liquid supply port to the sample liquid holding part using a cell including a sample liquid holding part having a plurality of particles and the reagent and a sample liquid supply port And (B) stirring the sample liquid and the reagent by the movement of the particles accompanying the flow of the sample liquid generated in the sample liquid holding part by supplying the sample liquid, And a stirring method comprising a step of obtaining a mixed solution containing the reagent and the particles,
The reagent contains a specific binding substance that can specifically bind to the substance to be measured contained in the sample solution,
In the mixed liquid, at least the surface charge of the particles and the charge of the specific binding substance have the same polarity.   The stirring method according to claim 1, wherein the flow of the sample liquid in the step (B) is a swirl flow along an inner wall surface of the sample liquid holding portion. A sample liquid holding unit having a plurality of particles and a reagent, and a sample liquid supply port;
The particles are held in the sample solution holding unit movably along with the flow of the sample solution supplied from the sample solution supply port into the sample solution holding unit,
A cell in which the sample liquid and the reagent are agitated by the movement of the particles,
The reagent contains a specific binding substance that can specifically bind to the substance to be measured contained in the sample solution,
In the mixed liquid containing the sample liquid, the reagent, and the particles obtained by supplying the sample liquid, the charge of at least the surface of the particles and the charge of the specific binding substance have the same polarity. A cell in which the particles and the specific binding substance are conditioned. The reagent further comprises a buffer;
The cell according to claim 3, wherein the buffer adjusts the pH of the mixed solution so that at least the surface charge of the particles and the charge of the specific binding substance have the same polarity in the mixed solution.   The cell according to claim 3, wherein the particles are coated with the reagent so that the reagent is dissolved in the sample solution.   The cell according to claim 3, wherein a substance that inhibits the specific binding substance from adsorbing to the particle is supported on the particle.   The cell according to claim 3, wherein a substance that adsorbs a substance that inhibits a reaction between the object to be measured and the specific binding substance is supported on the particle.   The cell according to claim 3, wherein a diameter of an opening portion outside the sample solution supply port is larger than a diameter of an opening portion inside the sample solution supply port.   The cell according to claim 3, further comprising: a light incident part for causing light to enter the sample liquid holding part; and a light emitting part for emitting light from the sample liquid holding part. The cell of claim 9 ,
Cell holder for holding the cells,
A sample solution supply unit for supplying the sample solution to the sample solution holding unit through the sample solution supply port of the cell;
A light source for emitting light incident on the light incident part of the cell, and a light detection part for detecting light emitted from the light emitting part of the cell,
A measuring apparatus for measuring an object to be measured in a sample liquid based on light detected by the light detection unit. In addition to the stirring method according to claim 1,
Furthermore, using a cell comprising a light incident part for making light incident on the sample liquid holding part, and a light emitting part for emitting light from the sample liquid holding part,
(C) a step of causing light to enter the holding portion through the light incident portion;
(D) detecting the light emitted out of the holding part through the light emitting part, and (E) in the sample liquid based on the light detected after the particles in the liquid mixture have settled. A measurement method comprising a step of measuring a contained measurement target substance.

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