JPH11242032A - Sample analysis device and method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sample analysis device for speedily and sensitively achieving analysis without allowing a magnetic particle to flow by stopping the flow in a flow cell in a short time. SOLUTION: A bypass channel 19 is provided in parallel with a flow cell channel 18 for switching flow by a valve. A suspension liquid where a magnetic particle being connected to a luminous substance is suspended is sucked and the magnetic particle is captured onto an operation electrode 15 by a magnet 20. The valve is switched and a buffer solution is sucked through a bypass channel 19 while the flow in the flow cell has been stopped completely. The valve is switched again, the buffer solution is allowed to flow to the flow cell channel 18, an antibody B that is connected to the magnetic particle is separated from an antibody F that is not connected to the magnetic particle and is dissolved in a liquid constituent, and the amount of emission from the magnetic particle is detected by a photo sensor 13, thus analyzing the concentration of a specific substance in a sample.

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 a sample analysis method, and more particularly to an antigen-antibody used in the field of clinical testing, and used in the basic fields of food testing, medicine, and life science. The present invention relates to a sample analyzer and a sample analysis method suitable for analysis using a reaction.

[0002]

BACKGROUND OF THE INVENTION Analyzing biological fluids such as serum or urine,
A method for detecting and quantifying the presence of an antibody and an antigen or an antigen-antibody immune complex in a biological fluid is generally called immunoassay.

One common method of immunoassay is to use the binding reaction that occurs between a limited amount of antigen and two antibodies. Since both of these antibodies can bind to the antigen, for example, by labeling one of the antibodies, binding both antibodies via the antigen, and measuring the ratio of the bound labeled antibodies, the amount of the present antigen can be determined. .

One of the specific techniques is disclosed in, for example,
No. 146002. In this example, the first antibody is immobilized as a solid phase on the surface of the magnetic particles, and the second antibody has a label attached thereto and is melted in the liquid phase. When the magnetic particles on which the first antibody is immobilized and the sample derived from the biological fluid are mixed to generate an antigen-antibody reaction, the antigen contained in the sample binds to the magnetic particles via the first antibody. Further, when the second antibody is reacted, the second antibody binds to the magnetic particles via the antigen and the first antibody. The amount of the second antibody to be bound increases or decreases depending on the amount of the antigen contained in the sample. When a sipper probe connected to the flow cell inlet is inserted into the reaction mixture, and aspirated by a syringe pump connected to the flow cell outlet, and the reaction mixture flows through the flow cell to which a magnetic field is applied, magnetic particles are captured by the magnetic field. This magnetic field gives the magnet close to the flow cell. When the sipper probe is moved to the buffer probe and aspirated, and the buffer is allowed to flow through the flow cell, the liquid phase of the reaction mixture flows out of the flow cell while the magnetic particles remain in the flow cell.

[0005] A labeling substance is a substance that generates chemiluminescence electrically. When an electric field is applied within the flow channel of the flow cell after removing the magnetic field, the label attached to the magnetic particles emits light. The luminescence intensity is detected, and the amount of the antigen in the sample is analyzed. Thereafter, the magnet is moved away from the flow cell, the sipper probe is replaced with a washing liquid bottle, and suction is performed to remove 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. In addition, 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 speed can be increased. Further, since the washing liquid is flowed into the flow cell to remove the magnetic particles, a plurality of samples can be continuously analyzed. Since the sample, buffer, and washing solution are sucked by a syringe pump capable of accurately controlling the flow rate, errors in the sample amount and the reagent amount are small, and highly accurate analysis can be performed.

[0007]

However, the above prior art has the following disadvantages. The magnetic field created by moving the magnet close to the flow cell captures the magnetic particles by passing the reaction mixture, and then the buffer solution flows, so the magnetic particles do not sufficiently adhere to the walls of the flow cell and flow out of the flow cell together with the liquid phase. leave. Or move on the wall of the flow cell,
The distribution becomes uneven. Therefore, even when an electric field is applied, the amount of light emission is small, and the sensitivity for measuring the amount of antigen is low.

To avoid this, if a period in which the flow is stopped is provided between the time when the magnetic particles are captured in the flow cell and the time when the buffer solution is passed, the time required for one analysis becomes longer, and the analysis can be performed in a fixed time. Ability becomes small.

An object of the present invention is to provide a sample analyzer and a sample analysis method which have a high ability to perform analysis in a fixed time, can uniformly capture magnetic particles, and can perform high-sensitivity analysis.

[0010]

To achieve the above object, the present invention provides a flow cell having an inlet and an outlet, a magnetic field generating mechanism for switching a magnetic field in a predetermined area in the flow cell between a strong magnetic field and a weak magnetic field, A pipette communicating with the inlet of the flow cell, a pump communicating with the outlet of the flow cell and capable of controlling the suction amount, and a sample in which magnetic particles to which a luminescent substance whose luminescence varies depending on the concentration of the specific substance are attached are suspended. A first sample container containing a liquid, a second sample container containing a sample liquid containing no magnetic particles, a cleaning liquid container containing a cleaning liquid, and a pipetter selectively moving the pipetter to the positions of the plurality of sample containers and the cleaning liquid container. A sample analysis device having an arm for controlling the operation of a pump, a moving mechanism, a magnetic field generating mechanism, a detector, and the like; In the flow cell, in the vicinity of the inlet portion, one has a flow path branching part connected to a flow cell flow path communicating with the predetermined area, and the other has a flow path branch part connected to a bypass flow path not communicating with the predetermined area, and the flow of the fluid sucked from the pipettor The present invention proposes a sample analyzer in which flow path selection means for selectively flowing a flow through at least one of a flow cell flow path and a bypass flow path is provided between a flow cell and a pump.

A heat exchange means may be provided in the flow path between the pipetter and the inlet of the flow cell.

After the first sample is sucked into the flow cell channel by setting the predetermined area to a strong magnetic field, a predetermined amount of the second sample is sucked in the bypass channel, and the flow is switched to the flow cell channel to suck the second sample. be able to.

While detecting the amount of light emission, the flow in the flow cell flow path is stopped, the cleaning liquid is sucked from the cleaning liquid container using the bypass flow path, and after the detection is completed, the cleaning liquid flows into the flow cell flow path.

Immediately after switching the flow of the fluid from the flow cell flow path to the bypass flow path, it is desirable to switch the predetermined area from a strong magnetic field to a weak magnetic field.

According to the present invention, in order to achieve the above object, a flow cell having a flow path communicating from an inlet to an outlet, and having a magnetic field generating part capable of changing the strength of a magnetic field in a part of the flow path is specified. A first sample in which magnetic particles having a luminescent substance whose light emission amount changes according to the concentration of the substance and a second sample containing no magnetic particles are alternately flown, and the magnetic particles are captured in a magnetic field generating portion. In a sample analysis method for detecting the amount of light emission at a magnetic field generation site and analyzing the concentration of a specific substance,
The present invention proposes a sample analysis method in which a first sample is caused to flow through a flow cell and then a second sample is caused to flow after a particle fixing period in which the flow is stopped.

[0016]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Next, an embodiment of a sample analyzer and a sample analysis method according to the present invention will be described with reference to FIGS.

Embodiment 1 FIG. 1 is a system diagram showing a configuration of a sample analyzer according to Embodiment 1 of the present invention. The flow cell 11 includes a pipettor 27, a tube 35, and a tube 3.
6, fluidly connected through a pump 23. The pipetter 27 is mounted on an arm 28, and a suspension container 30, a buffer solution container 31, and a washing solution container 32 are arranged in a moving range thereof. A heat exchanger 41 is provided in the path of the tube 35. In the vicinity of the inlet of the flow cell 11, there is a branch portion 39. In this branch portion 39,
The flow path is divided into the inside of the flow cell and the bypass flow path 19. A valve 43 is provided downstream of the outlet of the flow cell 11, and a valve 44 is provided in the bypass flow path 19. Valve 43 and valve 44 are both tubes 3
6 and connected to a pump 23. Tube 3
6 is branched and connected to a valve 25, and from the valve 25, a pipe is connected to a waste liquid container 33. A flow channel 18 penetrates the inside of the flow cell 11, and a side surface of the flow channel 18
The counter electrode 14 and the working electrode 15 are provided. An optical sensor 13 is provided on the flow cell 11 so as to be covered by a case 12. The upper part of the flow cell 11 is made of a transparent material. Lever 22 connected to motor 21
Supports a magnet 20 and can be driven to be close to the lower part of the flow cell 11. The arm 28, the optical sensor 13, the motor 21, and the pump 23 are connected to a controller 40.

The cross section of the flow path 18 is rectangular, and in this case, the thickness measured in the direction facing the magnet 20 is 0.5 m.
m and a width of 5 mm. Working electrode is 5 in the flow direction
mm width. The magnet 20 is a cubic permanent magnet having a side of 5 mm.

The suspension container 30 containing the suspension treated in the reaction unit 55 is set at a predetermined position by a 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.
Has a function of sequentially sending to a predetermined position.

Here, the sample to be analyzed is a sample derived from a biological fluid such as serum or urine. When the sample is serum, the components to be analyzed include, for example, antigen, peptide hormone,
It is a steroid hormone, a drug, or a virus antibody, or various tumor markers, antibodies, or an antigen-antibody complex, or a single protein. Here, the specific component is, for example, TSH (thyroid hormone). In the pretreatment process performed 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, and reacted at a constant temperature (37 ° C.) for a fixed time. . Here, the sample to be analyzed is 50 μl,
50 μl of the reagent, 50 μl of the second reagent, 100
Use μl. 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. And streptanidine capable of binding. The magnetic substance may be a magnetic attraction substance such as iron, iron oxide, nickel, cobalt, chromium oxide, etc. The matrix itself is made of many synthetic and natural polymerizable substances (eg, cellulose, polyester) in addition to polystyrene. Etc.). The first reagent contains a substance that binds the magnetic particles to the specific component TSH in the sample, and includes:
Includes TSH antibodies whose ends have been treated with biotin. The second reagent contains a substance that labels a labeling substance that emits light by an electrochemical reaction and binds to a specific component in the sample. That is, the second reagent includes a labeling substance whose terminal is treated with biotin and emits chemiluminescence upon excitation, in this case, a TSH antibody bound with ruthenium (II) tris (bipyridyl). The first reagent and the second reagent differ depending on the type of the specific component to be analyzed, and for example, immunoglobulins, antigens, antibodies, and other biological substances are used.

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

The heat exchanger 41 functions to control the temperature of the liquid flowing through the tube 35 to a predetermined temperature.

The tube 35, the tube 36, and the channel 18 in the flow cell 11 are filled with a buffer solution in advance.

FIG. 2 is a time chart showing an operation sequence of the sample analyzer of the first embodiment. One cycle of the sample analyzer of the first embodiment includes a suspension suction period, a particle capturing period, a stop period, a BF separation period, a detection period, a washing period, a reset period, and a preliminary suction period. In addition, BF
Is a symbol in which the antibody (B) bound to the magnetic particles and the antibody (F) unbound and dissolved in the liquid component are omitted. One cycle starts when the suspension container 30 containing the suspension processed in the reaction unit 55 is set at a predetermined position. During the suspension suction period, first, the motor 21 is rotated by the signal of the controller 40 and the magnet 2
0 moves to a position where it contacts the lower part of the flow cell 11. The valve 43 is opened, and the valves 44 and 25 are set in a closed state. The arm 28 is operated by a signal from the controller 40 to insert the pipettor 27 into the suspension container 30. Subsequently, the pump 2
3 performs a certain amount of suction operation. Then, the suspension in the suspension container 30 is sucked by the liquid in the tube, and
Via 7, it enters the tube 35. In this state, the pump 23 is stopped, and the arm 28 is operated. Pipettor 2
7 is inserted into the buffer solution container 31 via the washing mechanism 37. The tip of the pipettor is cleaned when passing through the cleaning mechanism 37.

During the particle capturing period, the pump 23 sucks at a constant speed according to a signal from the controller 40. Meanwhile, the suspension existing in the tube 35 passes through the flow path 18. Since a 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 are captured on the surface of the working electrode 15.

During the stop period, the pump 23 is sucked at a constant speed with the valve 43 closed and the valve 44 opened. At this time, the fluid in the flow cell channel 18 has stopped. During the BF separation period, the valve 43 is opened and the valve 44 is opened.
Is closed, and the pump 23 is sucked. The buffer solution is sucked from the buffer solution container 31 and passes through the flow channel 18. At that time, the magnetic particles are left while being held on the working electrode 15,
Only the liquid component flows away from the channel 18. The antibody (F) dissolved in the liquid component without binding to the antibody (B) bound to the magnetic particles is separated.

The motor 21 rotates between the detectors, and the magnet 20 is moved away from the flow cell 11. Subsequently, the working electrode 15 and the counter electrode 1 are
Apply voltage during 4. At that time, light is emitted from the magnetic particles on the working electrode 15. The intensity of the light emission is measured by the optical sensor 13.
And sends it to the controller 40 as a signal. After a certain period of time, the voltage is removed. Arm 28 during the detection period
To work. The pipetter 27 is inserted into the cleaning liquid container 32 via the cleaning mechanism 37. Close valve 43,
The valve 23 is opened and the pump 23 is sucked. Thereby, the buffer solution filled in the tube 35 is replaced with the washing solution.

During the cleaning period, the valve 43 is opened and the valve 44 is opened.
Is closed, the pump 23 is sucked, and the cleaning liquid passes through the flow path 18. At this time, since the magnetic field is moving away, the magnetic particles are not held on the working electrode 15 but flow away with the buffer.

During the reset period, the valve 43 and the valve 44 are closed, the valve 25 is opened, and the pump 23 is operated to discharge. The liquid in the pump is discharged to a waste liquid container 33.

During the preliminary suction period, the buffer solution is sucked, and the tube 35, the flow cell channel 18, and the bypass channel 19 are filled with the buffer solution. After the preliminary suction period, the next cycle can be executed.

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 is a diagram showing the distribution of magnetic particles on the working electrode immediately after the end of the particle capturing period in the flow cell of the sample analyzer of Example 1, and FIG. 4 is a flow cell of the sample analyzer of Example 1. FIG. 4 is a diagram showing a magnetic particle distribution on a working electrode after a stop period in FIG.

FIG. 3 shows the distribution of the magnetic particles 51 on the working electrode 15 immediately after the end of the particle capturing period. At this time, the magnetic particles 51 are dispersed on the working electrode 15 separately.
In this state, the magnetic particles easily roll on the electrode.

FIG. 4 shows the distribution of the magnetic particles 51 on the working electrode 15 after the stop period. During the suspension period, a plurality of magnetic particles are aggregated due to a suction force between the magnetic particles.
In this state, even if a flow occurs, the magnetic particles are unlikely to roll. Even if a relatively high-speed flow occurs in the flow cell flow channel 18 during the BF separation period, the magnetic particles do not roll, but stay at the spot, and only the liquid phase is flown to be replaced with the buffer.

In the case of the first embodiment, the suspension period is provided after the capture of the particles, so that the magnetic particles hardly flow,
F separation can be performed effectively. That is, many magnetic particles can be left on the electrode, and the emission intensity increases. Since the detection inhibitory substance contained in the liquid phase in the suspension can be effectively removed by increasing the flow rate of the buffer solution, detection with low noise can be performed. Therefore, the concentration of the specific component can be analyzed with high sensitivity.

Since the tube 35 is connected to the pipettor 27 moved by the arm 28 and the heat exchanger 41 is also provided, the flow path from the pipetter 27 to the pump 23 is very long. Therefore, even if the operating speed of the pump 23 is changed, a time delay occurs until the speed at which the liquid flows changes.
However, since the bypass flow path 19 branches off a short portion of the flow path, the flow can be quickly switched from the flow cell flow path 18 to the bypass flow path 19 by switching between the valve 43 and the valve 44. Therefore, the flow in the flow cell flow channel 18 can be stopped quickly and completely during the stop period, and the particles can be made difficult to flow during the short stop period, so that the time required for analysis can be shortened.

Since the flow path to the inlet of the flow cell 11 is long, even if the liquid to be sucked by the pipettor 27 is changed, the tube 3
Mix in 5. Therefore, at the end of the particle capture period, the tube 35 is filled with the buffer mixed with the suspension, and the liquid phase can be efficiently removed even if the buffer 35 is allowed to flow through the flow cell channel 18 as it is. Can not. However, since the buffer solution is sucked from the buffer solution container 31 using the bypass flow path 19 during the stop period, the branch portion 39
The internal liquid up to this is replaced with a high-purity buffer, and efficient liquid phase removal is possible during the subsequent BF separation period. Therefore, the BF separation period can be shortened, and the time required for analysis can be shortened.

Similarly, during the detection period, it is necessary to stop the flow in the flow cell flow path 18, but during that time, the cleaning liquid may be sucked into the tube 35 using the bypass flow path 19. Yes, during the washing period after the end of the detection period,
From the beginning, a highly pure cleaning liquid can be flown into the flow cell flow path 18, and efficient cleaning is possible. For this reason, the carry-over that affects the analysis of the next sample can be reduced, with the sample remaining in the previous analysis remaining, and high-sensitivity analysis can be performed. In addition, the time required for analysis can be reduced by shortening the washing time.

After the BF separation, the valves 43 and 44
Is switched, the flow in the flow cell flow path 18 stops quickly. Therefore, even if the magnet 20 is immediately moved away, the magnetic particles do not flow out. Therefore, BF
There is no need to provide a waiting time until the magnet is moved away after the separation is completed, and the analysis can be performed in a short time.

At the time of preliminary suction, the valve 43 and the valve 44
Are alternately switched, so that both the flow cell channel 18 and the bypass channel 19 are filled with the buffer solution. For this reason, even when a small amount of liquid is mixed in the branch portion 39 from the bypass channel 19 when sucking the suspension, it is a buffer that does not affect the analysis, so that highly accurate analysis can be performed.

Since the valves 43 and 44 for switching between the flow cell flow path 18 and the bypass flow path 19 are located downstream of the flow cell and no valve is provided upstream of the flow cell flow path 18, the flow path is simple. Therefore, it is possible to carry out analysis with high accuracy without the sample remaining in the middle of the flow path and causing carry-over, or the air bubbles remaining and disturbing the flow.

The pressure difference applied to both ends of the valve 43 is only the pressure loss of the bypass flow path 19, and the pressure difference applied to both ends of the valve 44 is only the pressure loss of the flow cell flow path 18. . Therefore, the valves 43, 44
Can provide a low-cost and highly reliable analyzer without leakage.

In the case of the first embodiment, the pressure loss can be reduced by simultaneously opening the valve 43 and the valve 44 when sucking the buffer solution or the like. Since it is unlikely to occur, suction can be performed in a short time, and the time required for analysis needs to be shortened.

Although an antibody is used as the substance that binds to the specific component in the first reagent, 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 a target nucleic acid in a sample to be analyzed. Second
The reagent contains a substance that labels a labeling substance that emits light by an electrochemical reaction and binds to a specific component in a 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.

Embodiment 2 FIG. 5 is a time chart showing an operation sequence of Embodiment 2 of the sample analyzer according to the present invention. The difference from the first embodiment is that the operation for switching the valves 43 and 44 is performed during the BF separation period and the cleaning period, and that the closed one is first opened and then the other is closed when the valves 43 and 44 are switched. It is a point that has been.

In the case of the second embodiment, since the valve is switched during the BF separation, the flow in the flow cell flow path 18 is intermittently stopped. This has the effect of generating turbulence in the flow and efficiently replacing the liquid phase around the magnetic particles with a buffer. For this reason, even if the time of BF separation is shortened, highly accurate analysis is possible, and the analysis time can be shortened.

In order to switch the valve during suction of the cleaning liquid,
The flow in the flow cell channel 18 stops intermittently.
As a result, turbulence can be generated in the flow, and there is an effect that the magnetic particles are applied with a relatively constant force to efficiently wash the magnetic particles.
For this reason, even if the washing time is shortened, highly accurate analysis is possible, and the analysis time can be shortened.

In the second embodiment, since the closed valve is first opened and then the other valves are closed when switching the valves, the flow is not suddenly shut off. Therefore, a sudden increase in pressure due to the inertial force of the fluid can be prevented. Therefore, leakage does not occur in the middle of the flow path, and the sample does not enter the middle of the flow path, so that the reliability of analysis can be improved and the life of the apparatus can be extended.

<< Embodiment 3 >> FIG. 6 is a diagram showing the configuration of Embodiment 3 of the sample analyzer according to the present invention. The difference from the case of FIG. 1 is that a pump 29 for sucking the bypass flow path 19 is provided separately from the pump 23, and the bypass flow path 19 is not connected to the tube 36.
Another difference is that the branch portion 39 is not provided inside the flow cell 11 but is provided in the middle of the tube before the inlet of the flow cell 11.

Embodiment 4 FIG. 7 is a system diagram showing the configuration of Embodiment 4 of the sample analyzer according to the present invention. Example 4
However, the difference from the first embodiment is that the reaction reagent container 34 is provided, and the counter electrode 14 and the working electrode 1
5 is missing. Further, a semiconductor sensor which is hardly affected by a magnetic field is used as the optical sensor 13. In Example 4, a substance that produces chemiluminescence is used instead of a substance that produces an electrochemical reaction as a labeling substance. Substances that generate chemiluminescence include acridinium ester derivatives, acridinium acylsulfonamide derivatives, and isoluminol derivatives.
Instead of a substance that directly emits chemiluminescence, an enzyme that promotes chemiluminescence of another substance can be used as the labeling substance. In the reaction reagent container 34, a solution containing a luminescence inducing substance such as aqueous hydrogen peroxide or microperoxidase is prepared according to the type of the chemiluminescent substance.

After the BF separation, the flow cell channel 18 is stopped, and the reaction reagent is sucked from the reaction reagent container 34 using the bypass channel 19. After the inside of the tube 35 is replaced with the reaction reagent, the valves 43 and 44 are switched,
The flow is changed to flow cell channel 18. At this time, the magnet 20 is kept close to the flow cell. In the flow cell channel 18, the magnetic particles and the reaction reagent are rapidly mixed, and the chemiluminescent substance bound to the magnetic particles reacts with the luminescence-inducing substance in the reaction reagent to generate chemiluminescence. The amount of chemiluminescence is detected by the optical sensor 13 and analyzed.

In the fourth embodiment, since the reaction reagent is sucked up to just before the flow cell by using the bypass flow path, the strong reaction reagent can be rapidly reacted with the chemical reactant.
It is possible to generate strong chemiluminescence in a short time and detect with high sensitivity.

Even if the chemiluminescent substance and the reaction reagent remaining in the tube 35 are mixed to generate luminescence, the luminescence is caused to flow away through the bypass channel 19, so that the luminescence is generated in the flow cell channel 18. And is not detected by the optical sensor 13. Therefore, high-precision analysis is possible without being affected by the chemiluminescent substance left in the tube 35. Since light emission occurs in a state where the magnetic particles are uniformly and widely distributed on the wall surface of the flow channel, the particles can be detected with high efficiency without hindering transmission of light.

[0054]

According to the present invention, after capturing the magnetic particles on the working electrode, the flow can be switched to the bypass flow path to provide a period for completely stopping the flow in the flow cell.
Since the magnetic particles aggregate on the working electrode and are difficult to roll, efficient BF separation is possible without particles flowing away, and high-sensitivity and high-speed analysis is possible.

Further, while the flow in the flow cell is stopped, the buffer solution and the washing solution can be sucked up to just before the flow cell through the bypass flow path.
By performing separation and washing, the time required for analysis can be reduced.

[Brief description of the drawings]

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

FIG. 2 is a time chart illustrating an operation sequence of the sample analyzer of the first embodiment.

FIG. 3 is a diagram showing a magnetic particle distribution on a working electrode immediately after the end of a particle capturing period in a flow cell of the sample analyzer of Example 1.

FIG. 4 is a diagram showing a distribution of magnetic particles on a working electrode after a stop period in a flow cell of the sample analyzer of Example 1.

FIG. 5 is a time chart illustrating an operation sequence of the sample analyzer according to the second embodiment of the present invention.

FIG. 6 is a system diagram showing a configuration of a sample analyzer according to a third embodiment of the present invention.

FIG. 7 is a system diagram showing a configuration of a sample analyzer according to a fourth embodiment of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 11 Flow cell 12 Case 13 Optical sensor 14 Counter electrode 15 Working electrode 18 Flow cell channel 19 Bypass channel 20 Magnet 21 Motor 22 Lever 23 Pump 26 Outlet 27 Pipetter 28 Arm 29 Pump 30 Suspension container 31 Buffer solution container 32 Cleaning solution container 33 Waste liquid container 34 Reaction reagent container 35 Tube 36 Tube 37 Washing mechanism 39 Branch 40 Controller 41 Heat exchanger 51 Magnetic particles 55 Reaction unit 56 Guide

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Masaki Shiba 882 Ma, Oaza-shi, Hitachinaka-shi, Ibaraki Pref.

Claims (6)

[Claims] 1. A flow cell having an inlet and an outlet, a magnetic field generating mechanism for switching a magnetic field in a predetermined area in the flow cell between a strong magnetic field and a weak magnetic field, a pipetter communicating with an inlet of the flow cell, and an outlet of the flow cell. A pump that can control the amount of suction that is communicated, a first sample container that houses a sample solution in which magnetic particles having a luminescent substance that changes in luminescence amount according to the concentration of a specific substance are suspended, A second sample container containing a sample liquid that is not included, a cleaning liquid container containing a cleaning liquid, an arm for selectively moving the pipetter to a plurality of sample containers and a position of the cleaning liquid container, and a light emission amount in a predetermined area of the flow cell. The flow cell, wherein the flow cell comprises: a detector for detecting the flow rate; and a controller for controlling operations of the pump, the moving mechanism, the magnetic field generating mechanism, and the detector. In the vicinity of the inlet portion, one has a flow path branching part connected to the flow cell flow path communicating with the predetermined area, and the other has a flow path branch part connected to a bypass flow path not communicating with the predetermined area, and the flow of the fluid sucked from the pipetter A flow path selecting means for selectively flowing the flow through at least one of the flow cell flow path and the bypass flow path between the flow cell and the pump. 2. The sample analyzer according to claim 1, wherein a heat exchange unit is provided in a flow path between the pipetter and an inlet of the flow cell. 3. The sample analyzer according to claim 1, wherein the predetermined area is set to a strong magnetic field, the first sample is sucked into the flow cell channel, and then the second sample is sucked in a predetermined amount in the bypass channel. A sample analyzer for sucking a second sample by switching a flow to a flow cell flow path. 4. The sample analyzer according to any one of claims 1 to 3, wherein the flow of the flow cell flow path is stopped while detecting the amount of luminescence,
Aspirating the cleaning liquid from the cleaning liquid container using the bypass flow path,
A sample analyzer, wherein the washing solution is caused to flow through the flow cell channel after the detection is completed. 5. The sample analyzer according to claim 1, wherein the predetermined area is changed from a strong magnetic field to a weak magnetic field immediately after the flow of the fluid is switched from the flow cell flow path to the bypass flow path. A sample analyzer characterized by switching. 6. It has a flow path communicating from an inlet to an outlet,
A first sample is prepared by suspending magnetic particles in which a luminescent substance whose luminous intensity changes according to the concentration of a specific substance is suspended in a flow cell having a magnetic field generating portion capable of changing the magnetic field strength in a part of the flow path. In a sample analysis method of alternately flowing a second sample containing no particles, capturing magnetic particles at a magnetic field generation site, detecting a light emission amount at the magnetic field generation site, and analyzing a concentration of a specific substance, the first sample is supplied to a flow cell. Flowing a second sample after a particle fixing period in which the flow is stopped.