JP3396433B2 - Sample analyzer - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample analyzer and, in particular, to an analysis utilizing an antigen-antibody reaction which is used in the field of clinical testing and also used in food testing, medicine, and the basis of life science. The present invention relates to a suitable sample analyzer.

[0002]

2. Description of the Related Art Analyzing a biological fluid such as serum or urine,
It is well known to detect the presence of an antibody and an antigen or an antigen-antibody immune complex in this biological fluid and to quantify the same, and such a method is generally called immunoassay.

[0003] One common method of immunoassay is to use the binding reaction that occurs between a limited amount of antigen and two antibodies. Both of these antibodies are capable of binding the antigen,
For example, one antibody is labeled, both antibodies are bound using an antigen as a medium, and the ratio of the bound labeled antibody is measured, whereby the amount of the present antigen can be determined.

One of the concrete methods is Japanese Patent Laid-Open No. 8-1460.
No. 02 publication. Among them, the first antibody is immobilized as a solid phase on the surface of the magnetic particles, and the second antibody is bound with the labeling substance and melted in the liquid phase. When a sample derived from a biological fluid is mixed with magnetic particles having a first antibody immobilized thereon to cause an antigen-antibody reaction, the antigen contained in the sample binds to the magnetic particles via the first antibody. And second
When the antibody is reacted, the second antibody binds to the magnetic particles via the antigen and the first antibody. The amount of the second antibody bound increases or decreases depending on the amount of the antigen contained in the sample.

By inserting a sipper probe connected to the inlet of the flow cell into the reaction mixture and aspirating a syringe pump connected to the outlet of the flow cell, the reaction mixture flows into the flow cell to which a magnetic field is applied, so that the magnetic particles are captured by the magnetic field. To be done. The magnetic field is provided by placing the magnet close to the flow cell. When the buffer solution is flown through the flow cell by moving the sipper probe to the buffer solution probe and sucking the solution, the liquid phase of the reaction mixture is flown out of the flow cell while the magnetic particles remain in the flow cell.

[0006] The labeling substance is a substance that electrically generates chemiluminescence. After removing the magnetic field, when an electric field is applied to the flow channel of the flow cell, the labeling substance bound to the magnetic particles emits light. The amount of antigen in the sample is analyzed by detecting the intensity of luminescence. After that, the magnets are moved away from the flow cell, the sipper probe is replaced with a washing liquid bottle, and suction is performed to remove the magnetic particles from the flow cell.

In the case of this conventional example, since an electric field is applied at the place where the liquid phase is removed from the mixture to detect the amount of light emission, there is no loss of magnetic particles. Moreover, since a magnetic field is applied to the magnetic particles to separate them from the liquid phase of the mixture, the particle size of the magnetic particles can be reduced and the reaction rate can be increased. Further, since the cleaning liquid is flown into the flow cell and the magnetic particles are flown away, it is possible to continuously analyze a plurality of samples.

Another conventional technique is disclosed in Japanese Patent Publication No. 6-508203.
It is shown in the publication. Among them, a plurality of magnets composed of permanent magnets or electromagnets are used by arranging north and south poles, that is, S poles and N poles alternately. In the case of this example, almost horizontal magnetic field lines are formed on the electrode surface in the flow cell, and as a result, orientation is formed in the magnetic particles, and the electrochemical energy supplied to the electrode is easily accessible.

[0009]

However, the above-mentioned prior art has the following drawbacks. JP-A-8-1460
In the example described in the publication No. 02, a uniform magnet used for generating a magnetic field for trapping magnetic particles has a strong force of attracting the magnetic particles in the direction of the magnet, but a weak force acting in a direction parallel to the electrode surface. . Therefore, the magnetic particles trapped on the electrode surface are continuously flown into the fluid and are offset toward the downstream side of the electrode surface. Therefore, the magnetic particles do not emit light efficiently and high-sensitivity analysis cannot be performed.

Further, in the case of the example described in Japanese Patent Publication No. 6-508203, since a plurality of magnets are alternately arranged at the north and south poles, the force acting on the magnetic particles in the direction parallel to the electrode surface is strong. However, since a plurality of magnets are adjacent to each other with the north and south poles alternately arranged, the magnetic fields generated by the respective magnets cancel each other, and the force of attracting the magnetic particles toward the magnet is weak. Therefore, it takes time to attract the magnetic particles flowing in the flow cell to the electrode surface, and analysis in a short time cannot be performed. As described above, in the conventional method, high-speed analysis and high-sensitivity analysis are contradictory, and both cannot be realized at the same time.

It is an object of the present invention to provide a sample analyzer which has a high ability to analyze in a fixed time, captures magnetic particles as uniformly as possible, and can perform analysis with high sensitivity.

[0012]

In order to achieve the above object, the present invention provides a flow cell, a magnetic field generating means for capturing a specific substance having magnetic particles attached to magnetic particles of a sample liquid circulated in the flow cell, and the capture. In the sample analyzer provided with a detecting means for detecting the amount of emitted light of the magnetic particles, the magnetic field generating means has a magnetic field strength of a predetermined region in the flow cell.
A switchable, specific materials attached to the magnetic particle state, and are not generating a magnetic field to uniformly capture a predetermined range of the flow cell wall, further wherein the magnetic field generating means originating
The generated magnetic field is generated by the magnetic field generator in the predetermined area of the flow cell.
It has a magnetic field vector almost perpendicular to the wall surface on the step side, and
Even if the magnetic force component in the direction parallel to the wall surface is present in a certain range
It is characterized by. As a result, the efficiency and accuracy of sample analysis can be improved.

More specifically, a flow cell having an inlet and an outlet for circulating a sample solution containing a specific substance and magnetic particles, a magnetic field generating means capable of switching the magnetic field strength of a predetermined region in the flow cell, A pipettor that communicates with the inlet of the flow cell, a pump that communicates with the outlet of the flow cell and that can control the suction amount, and a sample solution in which magnetic particles in which the amount of the luminescent substance attached changes according to the concentration of the specific substance are suspended. A sample container for containing, a reagent container for containing a reagent not containing the magnetic particles, a wash liquid container for containing a wash liquid for the flow cell, a detector for detecting a light emission amount in a predetermined region of the flow cell, the pump, and In a sample analyzer provided with a magnetic field generating means and a controller for controlling the operation of the detector, the magnetic field generated by the magnetic field generating means is A substantially vertical magnetic field vector with respect to the wall surface of the magnetic field generating means side of the predetermined area of Roseru, and characterized in that the presence in a predetermined range in a direction parallel to the magnetic force components on the wall. As a result, a sample analyzer with high analytical ability can be obtained.

Further, the magnetic field generating means is a permanent magnet that directs either the S pole or the N pole toward the flow cell side, and a recess such as a groove or a depression is formed on the surface of the permanent magnet. And The magnetic field generating means is a permanent magnet that directs either the S pole or the N pole toward the flow cell side, and a magnetic substance or a nonmagnetic substance that makes the magnetic field non-uniform is mixed on the surface or inside of the permanent magnet. It is characterized by Further, a magnetic material for making the magnetic field non-uniform is embedded in the wall surface of a predetermined region of the flow cell. By appropriately adopting such a configuration, it becomes possible to trap the specific substance to which the magnetic particles are attached almost uniformly in a predetermined range on the wall surface of the flow cell.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a configuration diagram of a first embodiment of the present invention. The flow cell 11 is fluidly connected to the pipettor 27 and the pump 23 through the tubes 35 and 36. The pipettor 27 is installed on the arm 28, and the suspension container 30, the buffer solution container 31, and the cleaning solution container 32 are installed in the movement range thereof. Tube 3
The heat exchanger 41 is provided in the path of 5. A valve 24 is provided downstream of the outlet of the flow cell 11 and the tube 3
Connect to pump 23 through 6. Further, the tube 36 is branched and connected to the valve 25, and the valve 25 is connected to the waste liquid container 33.

A flow path 18 penetrates the inside of the flow cell 11, and the counter electrode 14 and the working electrode 15 are provided on the side surface of the flow path 18.
Is installed. An optical sensor 13 is installed on the flow cell 11 while being covered by a case 12. Flow cell 11
The upper part of the is made of transparent material. The magnet 20 is supported by the lever 22 connected to the motor 21, and can be driven so as to be close to the lower portion of the flow cell 11. Arm 2
8, the optical sensor 13, the motor 21, and the pump 23 are connected to the controller 40. The flow path 18 has a rectangular cross section, and in this case, the thickness measured in the direction facing the magnet 20 is 0.5 mm and the width is 5 mm. The working electrode has a width of 5 mm in the flow direction.

The suspension container 30 containing the suspension treated in the reaction unit 55 is set at a predetermined position by the guide 56. In the reaction unit 55, a plurality of types of samples to be analyzed and a plurality of types of reagents are selectively combined and reacted, and the reaction product is placed in the suspension container 30 and guided.
There is a function of sequentially sending to a predetermined position in 6.

FIG. 2 is a view showing the shape of the magnet 20.
It is a cube-shaped permanent magnet with one side of 5 mm, and two grooves with a width of 0.5 mm and a depth of 0.5 mm are carved in the upper part. The direction of the magnetic pole is such that the direction of the grooved surface is the N pole and the opposite surface is the S pole. The N pole and the S pole may be reversed. The magnet 20 is attached to the lever 22 so that the grooved surface faces the flow cell 11 and the groove direction is orthogonal to the flow direction of the flow cell flow path 18.

The sample to be analyzed here is a sample derived from a biological fluid such as serum or urine. If the sample is serum, the components to be analyzed are, for example, antigens, peptide hormones,
It is a steroid hormone, drug, or viral antibody, or various tumor markers, antibodies, or antigen-antibody complexes, or a single protein. Here, the specific component is, for example, TSH (thyroid hormone).

In the pretreatment process carried out in the reaction unit 55, the sample to be analyzed is mixed with the bead solution, the first reagent, the second reagent and the buffer solution and allowed to react at a constant temperature (37 ° C.) for a predetermined time. To be Here, the sample to be analyzed is 50 μl, the first reagent is 50 μl, the second reagent is 50 μl,
As the buffer, 100 μl is used. The bead solution is a solution in which magnetic particles (specific gravity 1.4, average particle size 2.8 μm) in which a particulate magnetic substance is embedded in a matrix such as polystyrene are dispersed in a buffer solution. , Streptanidin capable of binding biotin is bound.

The magnetic substance may be a magnetic attractant such as iron, iron oxide, nickel, cobalt or chromium oxide, and the matrix itself may be composed of many synthetic and natural polymerizable substances (in addition to polystyrene). For example, cellulose, polyester, etc.) may be selected.

The first reagent contains a substance that binds magnetic particles to a specific component TSH in a sample, and this contains a TSH antibody whose end is treated with biotin. The second reagent contains a substance that labels a labeling substance that emits light by an electrochemical reaction and that binds to a specific component in the sample.
That is, the second reagent includes a TSH antibody having a terminal treated with biotin and generating chemiluminescence upon excitation, here, ruthenium (II) tris (bipyridyl) bound thereto. The first and second reagents depend on the type of particular component to be analyzed, eg immunoglobulins, antigens, antibodies or other biological substances are used.

The buffer solution container 31 contains a buffer solution containing a substance that induces the electrochemiluminescence of the labeling substance. Specifically, this buffer solution is a substance having a pH of about 7.4 containing a substance that induces the excitation of the labeled compound, such as tripropylamine (TPA), after reduction by applying a voltage. The cleaning liquid container 32 contains the cleaning liquid.

The heat exchanger 41 functions to control the temperature of the liquid flowing through the tube 35 so as to reach a predetermined temperature. The tubes 35, 36 and the flow path 18 in the flow cell 11 are filled with a buffer solution before the operation of analysis.

Next, the operation of this embodiment will be described. One cycle of analysis consists of suspension aspiration period, particle capture period, BF
It consists of a separation period, a detection period, a cleaning period, a reset period, and a preliminary suction period. One cycle starts when the suspension container 30 containing the suspension processed by the reaction unit 55 is set at a predetermined position.

In the suspension suction period, first, the motor 21 is rotated by a signal from the controller 40, and the magnet 20 is moved to a position where it contacts the lower portion of the flow cell 11. Valve 24
Is opened and the valve 25 is set to be closed. The arm 28 operates according to a signal from the controller 40, and the pipette 27 is inserted into the suspension container 30. Subsequently, the pump 23 performs a certain amount of suction operation in response to a signal from the controller 40.
Then, the liquid in the tube is sucked and the suspension in the suspension container 30 enters the tube 35 via the pipettor 27. In this state, the pump 23 is stopped and the arm 28 is operated to move the pipette 27 through the washing mechanism 37 to the buffer solution container 3
Insert into 1. When passing through the cleaning mechanism 37, the tip of the pipettor is cleaned.

During the particle capturing period, the pump 23 sucks at a constant speed in response to a signal from the controller 40. During,
The suspension existing in the tube 35 passes through the flow path 18. Since the magnetic field from the magnet 20 is generated in the flow path, the magnetic particles contained in the suspension are attracted toward the magnet and captured on the surface of the working electrode 15.

During the BF separation period, the valve 24 is opened, the valve 25 is closed, and the pump 23 is sucked. Buffer container 3
The buffer solution is sucked from No. 1 and passes through the flow path 18. At that time, the magnetic particles remain as they are held on the working electrode 15, and only the liquid component is flowed out from the flow path 18. The antibody (B) that is not bound to the antibody (B) that is bound to the magnetic particles but is dissolved in the liquid component is separated.

Between the detectors, the motor 21 rotates to move the magnet 20 away from the flow cell 11. Subsequently, a signal from the controller 40 is applied to the working electrode 15 and the counter electrode 14.
Apply voltage between. At that time, light emission occurs from the magnetic particles on the working electrode 15. The intensity of the light emission is measured by the optical sensor 1.
3 and sends it to the controller 40 as a signal. After a certain period of time, the voltage is removed. Arm 2 during the detection period
8 is operated to insert the pipettor 27 into the cleaning liquid container 32.

During the cleaning period, the pump 23 is sucked to allow the cleaning liquid sucked from the cleaning liquid container 32 to pass through the flow path 18. At this time, since the magnetic field is moving away, the magnetic particles are not retained on the working electrode 15 and flow away together with the buffer solution.

During the reset period, the valve 24 is closed and the valve 25 is opened to discharge the pump 23. The liquid in the pump is discharged to the waste liquid container 33. The buffer solution is sucked during the preliminary suction period, and the tube 35, the flow cell channel 18, and the bypass channel 19 are filled with the buffer solution. After the pre-suction period, the next cycle becomes feasible.

The controller 40 calculates the signal received from the optical sensor 13 during the detection period, calculates the concentration of the specific component in the sample to be analyzed, and outputs it. FIG. 3 shows the result of calculating the attractive force applied to the magnetic particles by the magnet used in this embodiment. The horizontal axis represents the position in the flow direction, and the vertical axis represents the suction force. Fz indicated by the solid line is a component of the attraction force in the direction perpendicular to the surface of the working electrode 15, and the direction toward the working electrode 15 is positive. Fx shown by the broken line is a component in the direction parallel to the electrodes, and the direction opposite to the flow is positive.

Since the magnetic pole of the magnet 20 is directed to the working electrode 15, the magnetic field vector on the surface of the working electrode 15 is substantially perpendicular to the working electrode. Further, since the inside of the magnet 20 is uniformly magnetized in one direction, the magnetic field formed is strong.
Therefore, Fz is very large. Therefore, the magnetic particles passing through the flow cell channel 18 are strongly attracted to the working electrode 15 side. Even if the magnetic particles flow at a high flow rate during the particle capturing period, the magnetic particles efficiently reach the surface of the working electrode 15.
Fx has three positive peaks, and the absolute value of the peak is large. Therefore, it is possible to prevent the magnetic particles attached to the surface of the working electrode 15 from flowing downstream due to the flow.

In the case of this embodiment, since the magnetic force in the direction in which the magnetic particles are not made to flow downstream is dispersed and distributed on the surface of the working electrode 15, BF separation can be effectively performed. That is, since many magnetic particles can be left on the electrode, the emission intensity is increased. Also, since the magnetic particles do not flow away from the electrode even if the flow rate of the buffer solution is increased,
BF separation is performed in a short time, and the analysis time can be shortened. In addition, since the detection inhibitor contained in the liquid phase in the suspension can be effectively removed by increasing the flow rate of the buffer solution, it is possible to perform detection with less noise. Therefore, the concentration of the specific component can be analyzed with high sensitivity.

Further, in the case of the present embodiment, the magnetic force acting in the direction of obstructing the flow of the magnetic particles is divided and dispersed on the working electrode 15, so that the magnetic particles are solidified in one place. Since it is dispersed in a wide range without being applied, the magnetic particles can efficiently emit light when a voltage is applied, and the emitted light can be efficiently detected by the optical sensor 13, so that the concentration of the specific component can be analyzed with high sensitivity.

Further, in this embodiment, since the magnetic force for attracting the magnetic particles toward the electrode is strong, the particles can be efficiently captured even if the flow velocity at the time of capturing the particles is increased, and the particles can be captured in a short time. Can be done. Therefore, analysis in a short time is possible.

In this embodiment, an antibody is used as the substance that binds to the specific component in the first reagent, but a specific nucleic acid can be used instead of the antibody. The specific nucleic acid has a property of binding to a specific target nucleic acid, and binds to the target nucleic acid in the sample to be analyzed. The second reagent contains a substance that labels a labeling substance that emits light by an electrochemical reaction and that binds to a specific component in the sample. in this case,
The presence of a nucleic acid having a specific sequence in a sample derived from a biological fluid such as serum or urine can be detected with extremely high sensitivity.

The number of grooves on the surface of the magnet 20 is not necessarily two, and may be one or three or more. The shape of the groove does not have to be square, and may be semicircular or triangular. The V-shaped triangular shape has the advantage of being easy to process. The semicircular groove has advantages that it is easy to process, stress concentration is less likely to occur, and durability is increased.

Although the depth of the groove is 0.5 mm in the first embodiment, it is not limited to this. If the depth of the groove is deep, the peak of Fx becomes stronger, and it becomes difficult for the magnetic particles to flow downstream. On the other hand, magnetic particles are concentrated in the Fx peak region. If the depth of the groove is shallow, the force that prevents the magnetic particles from flowing downstream is weakened, but the concentration of magnetic particles is less likely to occur. The flowability of particles differs depending on the flow rate at the time of capturing particles, BF separation, the size and properties of magnetic particles, and the properties of suspension liquid. The depth, shape, and number of the grooves can be selected so as to be optimized according to those conditions, so that the magnetic particles are less likely to flow away and the magnetic particles are distributed over a wide area on the electrode surface. You can

Further, it is not necessarily a groove, and a plurality of depressions may be formed on the surface. The grooves and depressions do not have to be voids, and may be filled with a non-magnetic material. It is also possible to fill the grooves or depressions with a non-magnetic material, then flatten the surface and perform plating. The filling and plating of the non-magnetic material can increase the durability against the impact on the magnet and also have the effect of preventing the generation of rust.

FIG. 4 shows a magnet 20 used in another embodiment of the present invention. In this case, the ferromagnetic material 59 and the non-magnetic material 58 are alternately stuck on the magnetic pole surface of the rectangular parallelepiped permanent magnet. The magnetic field generated from the permanent magnet is distorted by the ferromagnetic material, and a force that prevents the magnetic particles from flowing away is generated.
Also in this case, the permanent magnet is magnetized in one direction, the layers of the ferromagnetic material 59 and the non-magnetic material 58 are thin, and the loss of the magnetic field is small, so that the force of attracting the magnetic particles to the working electrode 15 is strong. Therefore, favorable analysis can be performed in a short time.

Further, in the case of the present embodiment, the magnet itself has a simple shape, and the ferromagnetic material and the non-magnetic material are attached to it, so that it is possible to manufacture a magnet having high dimensional accuracy at a low cost and at a low price. It is possible to provide the analyzer.

FIG. 5 shows a magnet 20 used in another embodiment of the present invention. In this case, the non-magnetic body 58 is sandwiched between the plurality of permanent magnets. Also in this case, since the respective permanent magnets are magnetized in the same direction and the magnetic field vector is substantially orthogonal to the working electrode, the force of attracting the magnetic particles to the working electrode 15 is strong. In addition, since magnetic force is generated in the direction that prevents the flow of magnetic particles in the non-magnetic part, it is possible to disperse and distribute the magnetic particles in a wide area on the working electrode, which enables favorable analysis in a short time. Is possible.

FIG. 6 is a diagram showing a main part of another embodiment of the present invention. In this embodiment, the magnet 20 is a rectangular parallelepiped magnet with the N pole facing the working electrode 15. In one form of the embodiment, the magnetic body 60 a is embedded on the back side of the working electrode 15. In this case, the magnetic field generated by the magnet 20 is bent by the magnetic body 60a, and as a result, a force that attracts the magnetic particles attached to the surface of the electrode 15 toward the magnetic body 60a is generated. Thereby, the magnetic particles are prevented from flowing, and the magnetic particles can be widely distributed on the working electrode.

In the case of this embodiment, since the magnet 20 has no groove, the magnetic force is not weakened. Therefore, the force of attracting the magnetic particles to the working electrode 15 side is strong, and the flow velocity at the time of capturing the particles can be increased, so that the analysis can be performed in a shorter time. Further, the magnetic body 60a is connected to the working electrode 15
Since they are very close to each other, the magnetic particles have a strong attracting force, and it is possible to effectively disperse the magnetic particles.

In another embodiment, the magnetic substance is embedded at the position of 60b shown by the broken line in FIG. 6, not at the position of 60a, that is, at the side opposite to the working electrode with the flow path 18 interposed therebetween. Also in this case, the magnetic field generated from the magnet 20 causes the magnetic substance 6
The force of being bent by 0b attracts the magnetic particles toward the magnetic body 60b.

In this case, since no groove is required on the surface of the magnet 20 and no magnetic material is present between the magnet 20 and the flow cell flow path 18, the magnetic field in the flow cell flow path 18 is not weakened and the magnetic field is reduced. The force pulling the particles towards the working electrode 15 is the strongest of the embodiments shown so far. Therefore, even if the suspension is flown at the fastest speed, the magnetic particles can be efficiently captured, and the analysis can be performed in a short time. Further, in this case, since the magnetic body 60b is arranged behind the counter electrode 14, it does not block the light emitted from the magnetic particles.

Although the above-described embodiments have shown analysis using electrochemiluminescence, the present invention is not limited to analysis using electrochemiluminescence, but can be widely applied to analysis of samples using magnetic particles. For example, it can be applied to sample analysis using chemiluminescence. In that case, the flow cell does not require the working electrode 15 and the counter electrode 14. Labeling substance A substance that causes chemiluminescence such as an acridinium ester derivative, an acridinium acylsulfonamide derivative, or an isoluminol derivative is used. An enzyme that promotes chemiluminescence of another substance may be used as the labeling substance instead of the substance that directly emits chemiluminescence. In the buffer solution container 31, a solution containing a luminescence-inducing substance such as hydrogen peroxide solution or microperoxidase is prepared according to the type of chemiluminescent substance.

Also in this case, since the labeled magnetic particles are efficiently captured and dispersed and distributed in a wide area within the flow cell, the efficiency of light emission and light collection is high, and rapid and highly sensitive analysis is possible. Is. The magnets used for these need not be permanent magnets, but electromagnets can be used. In that case, add a groove or depression to the core of the electromagnet,
Alternatively, magnetic force can be unevenly distributed by embedding a magnetic material in the flow cell.

[0050]

As described above, according to the present invention,
By using a uniformly magnetized magnet and applying a magnetic field vector in a nearly vertical direction to the wall surface of the flow cell, magnetic particles can be quickly and efficiently trapped, and the trapped magnetic particles are allowed to flow downstream. Since it can be prevented by uneven distribution of magnetic force, it is possible to provide a sample analyzer capable of high-speed and highly sensitive analysis.

[Brief description of drawings]

FIG. 1 is a system diagram showing a configuration of a first embodiment according to the present invention.

FIG. 2 is a diagram showing a main part of the first embodiment.

FIG. 3 is a diagram showing a distribution of magnetic force in the first embodiment.

FIG. 4 is a diagram showing a main part of a second embodiment.

FIG. 5 is a diagram showing a main part of a third embodiment.

FIG. 6 is a diagram showing a main part of a fourth embodiment.

[Explanation of symbols]

11 flow cell 12 cases 13 Optical sensor 14 Counter electrode 15 Working electrode 18 channels 19 Bypass channel 20 magnets 21 motor 22 lever 23 pumps 24 valves 25 valves 26 outlet 27 pipettors 28 arms 29 pumps 30 suspension container 31 buffer container 32 Cleaning liquid container 33 Waste liquid container 35, 36 tubes 37 Cleaning mechanism 40 controller 41 heat exchanger 55 Reaction Unit 56 Guide 58 Non-magnetic material 59 Ferromagnet 60a, 60b Magnetic substance

─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Tomoharu Kajiyama 1-280 Higashi Koigakubo, Kokubunji, Tokyo Inside Hitachi Central Research Laboratory (72) Inventor Yuji Miyahara 1-280 Higashi Koigakubo, Kokubunji, Tokyo Hitachi Ltd. Central Research Laboratory (72) Inventor Hiroyuki Tomita 1-280, Higashi Koigakubo, Kokubunji City, Tokyo Hitachi, Ltd. Central Research Laboratory (72) Inventor Kenji Yasuda 882 Ichimo, Hitachinaka City, Ibaraki Hitachi Ltd. (72) Inventor Yasushi Niiyama 882 Ichimo, Hitachi, Hitachinaka City, Ibaraki, Hitachi, Ltd., Measuring Instruments Division, Hitachi, Ltd. (72) Masaki Shiba, 882, Ichige, Hitachinaka, Ibaraki, Hitachi, Ltd., Measuring Instruments Division, Hitachi (56) ) References Tokumei Hyo 6-505673 (J , A) Special table 6-508203 (JP, A) Special table 6-509412 (JP, A) Special table 7-508340 (JP, A) Special table 10-509798 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) G01N 33/543 541 G01N 33/543 501 G01N 33/543 597 G01N 33/553

Claims (5)

(57) [Claims] 1. A flow cell, a magnetic field generating means for capturing a specific substance having magnetic particles attached to magnetic particles of a sample liquid circulated in the flow cell, and a detecting means for detecting an emission amount of the captured magnetic particles. In the sample analyzer, the magnetic field generating means is configured to magnetize a predetermined area in the flow cell.
A switchable is field strength, the specific substance adhering magnetic particles, all SANYO for generating a magnetic field to uniformly capture a predetermined range of the flow cell wall surface, further wherein the magnetic field generator
The magnetic field generated by the means is a magnetic field in a predetermined area of the flow cell.
A magnetic field vector almost perpendicular to the wall on the side of the field generation means
The magnetic force component in the direction parallel to the wall surface exists within the specified range
Sample analysis apparatus, characterized in that for. 2. A flow cell having an inlet and an outlet for flowing a sample solution containing a specific substance and magnetic particles, a magnetic field generating means capable of switching the magnetic field strength of a predetermined region in the flow cell, and an inlet of the flow cell. A pipette that communicates with the pump, a pump that communicates with the outlet of the flow cell and that can control the suction amount, and a sample container that contains a sample solution in which magnetic particles in which the amount of the luminescent substance attached changes depending on the concentration of the specific substance are suspended. A reagent container containing a reagent not containing the magnetic particles, a cleaning liquid container containing a cleaning liquid for the flow cell, a detector for detecting the amount of light emission in a predetermined region of the flow cell, the pump, the magnetic field generating means, and In a sample analyzer equipped with a controller for controlling the operation of the detector, the magnetic field generated by the magnetic field generating means is at the location of the flow cell. A substantially vertical magnetic field vector with respect to the wall surface of the magnetic field generating means side of the area, sample analysis apparatus, characterized in that the presence in a predetermined range in a direction parallel to the magnetic force components on the wall. 3. The sample analyzer according to claim 1 or 2, wherein the magnetic field generating means has an S pole or an N pole on the flow cell side.
A sample analyzer, which is a permanent magnet for directing one of the poles, wherein a concave portion such as a groove or a depression is formed on the surface of the permanent magnet. 4. The sample analyzer according to claim 1 or 2, wherein the magnetic field generating means is an S pole or an N pole on the flow cell side.
A sample analyzer, which is a permanent magnet for directing one of the poles, wherein a magnetic substance or a non-magnetic substance that makes a magnetic field non-uniform is mixed on the surface or inside of the permanent magnet. 5. The sample analyzer according to claim 1, wherein a magnetic material that makes the magnetic field nonuniform is embedded in a wall surface of a predetermined region of the flow cell.