JP2002131321A - Chemical analysis device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a chemical analysis device further simplified as a whole with the temperature control of a reactant liquid made highly accurate. SOLUTION: A vessel is formed of a soft material easily deformable by external force exerted from the exterior and an active magnetic element supported by a movable mechanism is provided outside the vessel. Thus, agitation and attraction/cleaning of magnetic particles are conducted by one unit. Such a unit is provided within an incubator, thereby avoiding discontinuity of temperature control. This device is simplified as a whole, discontinuity of temperature control is eliminated, and a reaction with higher accuracy can be realized.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a chemical analyzer for analyzing a sample using a reagent containing magnetic particles.

[0002]

2. Description of the Related Art WO 97-44671 discloses that a specific component contained in a sample is chemically bonded to magnetic particles, and only a specific component is extracted by applying an appropriate magnetic field. There has been disclosed a chemical analyzer that analyzes the amount of components contained in a sample by modifying the extracted conjugate with a certain label and counting.

[0003]

Needless to say, if pretreatment operations such as high-purity extraction from a sample and modification of a label are not reliably performed, a high-precision analytical performance can be obtained even if a high-performance counting unit is provided. Can not get.

As described above, each operation unit used for pretreatment operations such as extraction and label modification of a conventional chemical analyzer has extremely simple functions such as dispensing / aspiration, stirring, and magnetic adsorption. The analysis operation is an extremely complicated process combining these basic operations.

[0005] In the course of the reaction, the temperature of the liquid in the reaction vessel is controlled, and the liquid is incubated (constant temperature reaction) in an incubator (constant temperature bath). Conversely, under such conditions, reagent manufacturers develop reagents so that the maximum performance can be obtained. However, when the vessel (reaction vessel) is transported to each unit during stirring, adsorption of magnetic particles, washing, etc., temperature control in the vessel is cut off, which adversely affects the analysis result. It can be a factor.

An object of the present invention is to provide a chemical analyzer using a reagent containing magnetic particles, the function of which can be realized with a simpler configuration, and the processing capacity can be improved. It is still another object of the present invention to provide a chemical analyzer capable of performing a better reaction without interrupting temperature control in a vessel during a reaction process.

[0007]

An object of the present invention is to provide a chemical analyzer using a reagent containing magnetic particles, which is a soft elastic body which is easily deformed by an externally applied force and returns to its original shape when the force is removed. This can be achieved by providing the prepared vessel and means for realizing stirring and adsorption of magnetic particles in one unit in the incubator.

The unit for stirring and adsorbing magnetic particles is provided with a movable mechanism on an object capable of actively generating a magnetic field, such as an electromagnet, and installed outside the deformable vessel. Can be realized.

[0009]

DESCRIPTION OF THE PREFERRED EMBODIMENTS (Explanation of Configuration) One embodiment of the present invention will be described with reference to FIGS. FIG. 1 is a perspective view showing the configuration of the chemical analyzer of the present embodiment. FIG. 2 is a cross-sectional view of a unit for stirring, adsorbing and cleaning magnetic particles, which is provided in the chemical analyzer shown in FIG.

First, the main configuration of the entire chemical analyzer will be described with reference to FIG. The present chemical analyzer comprises a sample cup 101 containing a sample, a sample disk 102 for storing the plurality of sample cups, and a reagent bottle 1.
04, a reagent dispensing unit 106 for dispensing a sample, a reagent dispensing unit 105 for dispensing a reagent, and a vessel 108 for dispensing a sample and a reagent to perform a reaction. And an incubator 107 for controlling the temperature inside the vessel. Although only a part of the figure is shown in the figure,
A unit 114 for stirring and adsorbing magnetic particles (hereinafter, referred to as a stirring / adsorption unit), a dispensing / suctioning mechanism 115 for dispensing / suctioning a diluent when washing the conjugate, and a label modified. Unit 112 for counting the label of the conjugate
And a console 113 for controlling an interface with a user and each unit.

Next, the structure of the stirring / adsorption unit and its surroundings will be described in detail with reference to FIG. The stirring / adsorption unit is installed so as to be embedded in the incubator 107. FIG. 2 is a sectional view of the incubator in the diametric direction at a position where the stirring / adsorption unit is installed.

A groove 202 is dug in the disk-shaped incubator in the circumferential direction, and a vessel 120 formed of a soft elastic material is arranged in the groove. Vessel 1
A flange 201 is provided in the upper opening of
It is inserted and held in a disk-shaped vessel holder 203 having a diameter substantially equal to that of the incubator. Vessel 1
Sample and reagent reaction system 208 filled in 20
In the groove 202, temperature-controlled air is circulated. In order to seal the circulating air, the gap between the incubator 107 and the vessel holder is
Sealed with packing 204.

In the example shown in FIG. 2, the packing 204 is fixed to the incubator 107 side, and is only in contact with the vessel holder 203 side. Therefore, by rotating the vessel holder 203, the vessel is rotated around the incubator. It can move in the groove carved.

The agitating / adsorbing unit includes an electromagnetic magnet 205 disposed on a side surface outside the vessel, a linear motor 206 driven in a horizontal direction, and a shaft 207 transmitting a horizontal motion to the electromagnet 205. The linear motor 206 is driven in the horizontal direction by a command from the console 113, and can deform the vessel 120 formed of an elastic body via the shaft 207 and the electromagnet 205. The electromagnet 205 is connected to the console 113.
It is possible to turn on / off the magnetic field according to the command from.

As shown in FIG. 1, a discharge / suction unit 115 for diluting liquid for washing is installed at a position where the stirring / adsorption unit is installed. The diluent for cleaning can be discharged or sucked from the upper opening.

The operation of the chemical analyzer having the above configuration will be described below.

It is assumed that the sample and the reagent have been set in advance on the sample disk 102 and the reagent disk 103 by the user. In this state, first, the information of the sample and the reagent set on the chemical analysis device (hereinafter simply referred to as the device) is transmitted to the console 11 by the user.
Register from 3. This allows the device to determine which sample is on which sample cup 101 on the sample disk 102.
And which reagent is present in which reagent bottle 104 on the reagent disk 103 (actually, it is recorded on the memory in the console). Next, the analysis items of each sample desired by the user are displayed on the console 1.
Order from 13 for equipment. According to the order, the console automatically generates the most efficient analysis process by referring to the information of the sample and the reagent registered beforehand.

A signal for operating each unit on the apparatus is issued from the console according to the generated analysis process. Each unit operates in response to the signal. A unit of an analysis operation for analyzing one item for a certain sample is simply called a test, and each analysis operation is hereinafter identified by “test (number)”. For example, three samples are set in the device. When the same four types of analysis are performed among the registered reagents, twelve tests are generated with three samples × four types. These are referred to as test 1, test 2,... Test 12.

In this apparatus, the test to be processed is shown in FIG.
As shown in FIG. 7A, after one test is completed, instead of processing the next test, as shown in FIG. 7B, each test is overlapped and processed on a time axis. . By operating as described above, the processing capability of the entire apparatus, that is, the throughput is improved. When such an operation is performed, what is particularly important is the start time interval TL between the tests, and the processing capability of the apparatus is determined by how short this time can be. This TL depends on the period of the repetitive operation that can be imposed on each unit. In the present invention, the functions of agitation and magnetic particle adsorption are combined into one unit, thereby making it possible to shorten the TL, that is, dramatically improve the processing capacity.

Next, in order to provide a detailed description of the operation of the present apparatus, the operation of each unit in one test will be specifically described. In the following description, it is assumed that each unit operates in response to an operation signal from the console and the operation timing is controlled. The sample cup filled with the desired sample rotates 116 to a position 117 where the sample dispensing unit 106 can aspirate. Then, the sample dispensing unit sucks the sample and discharges the sample into the vessel 108 on the incubator 107. During this time, the reagent dispensing unit supplies the reagent to be dispensed (the first reagent containing magnetic particles) to the reagent bottle 1 in the reagent disk 103.
It is awaited that the vessel from which the sample has been ejected and which has been ejected from the sample 04 has rotated as indicated at 119 to the reagent ejection position 118.

The vessel into which the reagent has been dispensed at the reagent discharge position is located at the position 12 where the stirring / adsorption unit is further installed.
Rotating to 0 as in 121, where stirring is performed to mix the sample and reagent. A specific description of this stirring operation will be described with reference to FIG. As described in the description of the configuration using FIG. 2, the electromagnet 205 provided outside the vessel is movable in the horizontal direction by the linear motor 206.

Further, the vessel used in the present apparatus can be easily deformed by an external force from the outside. Therefore, the electromagnet arranged outside the vessel wall is shown in FIG.
By moving as shown in (a), the vessel shape is deformed as indicated by 301, and the liquid filled therein is fluidly deformed. When the position of the electromagnet is returned to the original position as shown in FIG. 3B, the vessel returns to the original shape due to the elasticity of the vessel, and the liquid in the vessel flows and deforms accordingly.

By repeating the operations shown in FIGS. 3A and 3B,
By reciprocating the electromagnet, the liquid in the container always flows. By this flow, the sample and the reagent are mixed, the sample and the reagent containing the magnetic particles start a reaction, and a conjugate of the sample and the magnetic particles is generated. However, during such a stirring operation, the electromagnet is in the OFF state, and it is assumed that no magnetic force is generated. Also, the liquid volume is within a range that does not overflow when the vessel is deformed.

Next, an operation of completing the reaction and adsorbing the combined body in the vessel to the vessel wall by magnetic force will be described. The power is not supplied during the stirring operation, and the electromagnet 205, which is magnetically OFF, is not supplied with power as shown in FIG.
By connecting the power supply source 401 as shown in FIG.
Generates magnetic force. Then, the combined body 402 floating in the liquid 208 in the vessel 102 is attracted to the vessel wall on which the electromagnet magnetized outside is installed, as shown in the figure. Generally, the magnetic force that an electromagnet can generate is
Smaller than permanent magnets. If the magnetic force generated by the electromagnet is insufficient, a linear motor is
By appropriately narrowing the space 404 between the electromagnets as in (b), a strong magnetic field can be generated in the vessel. By such an operation, it is possible to extract the conjugate from the liquid in the vessel.

Next, the operation when the present agitation / adsorption unit is used for washing the extracted conjugate will be described. The cleaning operation is basically a combination of the above-described stirring operation and extraction operation, and only the operation of discharging and sucking the diluent for cleaning is added to these repeated operations.

FIG. 5 is a flowchart when the present unit is performing a cleaning operation. FIG. 5A shows the operation immediately after the first diluent is dispensed. The operation in which the linear motor is driven to reciprocate the electromagnet to stir the liquid in the vessel is illustrated. Is shown. The figure shows an example in which the stirring operation is performed while the electromagnet is turned on, and the liquid is generated by deforming the vessel while keeping the combined body adsorbed on the vessel wall. By operating as described above, the shear stress of the fluid acts greatly near the wall where the combined body is adsorbed, so that the impurities attached to the combined body can be efficiently eliminated. Conversely, the following effects can be obtained even if the stirring operation is performed with the electromagnet turned off.

In the state where the electromagnet is turned off, as a matter of course, since the magnetic field is not acting, the combined substance in the diluent is in a dispersed state. In this state, if the linear motor is driven to perform a stirring operation, the vessel is deformed in the same manner as described above, and the liquid flows with the deformation. Since the binder also convects by the flow, the impurities are sieved off by the shearing action with the liquid. Whether the electromagnet is agitated in the ON state or the OFF state may be determined in accordance with the characteristic value such as the density and viscosity of the diluent used and the particle size and density of the magnetic particles.

FIG. 5B shows the operation of sucking the diluent from which impurities adhering to the conjugate have been washed away. As a matter of course, no matter which of the above stirring operations is performed, the electromagnet must be turned on before starting this operation, and the combined body must be adsorbed on the vessel wall as indicated by 501. FIG. 5C shows the dispensing of a new diluent. If the stirring operation is performed in a state where the electromagnet is turned off, by turning off the electromagnet before starting this operation, the combined body can be dispersed by the flow due to the discharge. The washing operation is performed by repeating the operations of stirring, diluting liquid suction, and diluting liquid discharge once or a plurality of times. The operation after dispensing the second reagent is basically the same as the operation after dispensing the first reagent described above. Hereinafter, an example of the operation of the present apparatus will be described using a time chart.

FIG. 7 (c) is a more detailed time chart of the analysis process of the present apparatus shown in FIG. 7 (b). This figure is an example in which the timing of each operation is assigned on the time chart of each test. In this apparatus, the stirring operation, the extraction operation, and the washing operation are performed by one unit, but an example of a time chart in FIG. 7C shows what operation is performed at which timing.

In this embodiment, the agitation / adsorption unit is agitation,
Extraction and washing are performed. On the time chart of FIG. 7C, operations are represented by black circles, squares, and white circles, respectively. The state of the operation during the parallel processing of each test with a time difference TL is shown. A black circle indicates a stirring operation, a square indicates an extraction operation, and a black circle indicates a washing operation. As in this example, it is necessary to design a time chart so that two or more operations are not assigned to the same time. If multiple operations are inevitably assigned to the same time on the designed time chart due to other restrictions, avoid this by providing multiple stirring / adsorption units and distributing the operations to each unit can do.

After the above pretreatment is completed, the conjugate with the modified label is counted and evaluated as an analytical value. In this embodiment, the reaction system pre-processed to the counting unit 112 is injected as indicated by 123 by means not shown in FIG. 1, counting is performed therein, and the result 122 is transmitted to the console 113. are doing. Then, the reaction system whose counting is completed becomes the waste liquid 111. In order to further simplify the entire apparatus, such a counting unit may be incorporated in an incubator. In this case, counting can be performed even when the sample is placed in the vessel.

In the present apparatus, since the vessel 120 is merely inserted into the vessel holder 203, it can be easily inserted and removed. In the embodiment shown in FIG. 1, the unit for performing the processing after the counting of the samples is not explicitly shown. However, if contamination is a problem, the contamination between samples can be avoided by providing a vessel feeder, a vessel collection grip arm, a vessel collection container, and the like, and replacing the vessel for each test. If the contamination is not a problem, a cleaning unit for the vessel may be provided, and the cleaning process may be performed every time each test is completed. In the case of such a configuration, it is more preferable that the user can exchange the vessel regularly.

As described above, the gist of the present invention is that in a chemical analyzer using magnetic particles, the main operations of pretreatment, such as stirring, extraction, and washing operations, are performed by one unit. In addition, a soft vessel formed of an elastic material or the like is used to make this possible. Another embodiment of the former will be described below.

In the embodiments of the stirring / adsorption unit described above, as shown in FIGS. 2 to 5, the electromagnet 205 and the linear motor 206 and the shaft 207 as means for reciprocating the electromagnet 205 in the horizontal direction. Were provided two. By the way, depending on the conditions such as the volume and shape of the vessel, there is a case where only one is sufficient as shown in FIG. In this case, since the number of parts is reduced, the configuration is simplified and the cost is reduced.

In this embodiment, an electromagnet is used so that a magnetic force can be actively generated. However, the electromagnet may generate heat depending on the supplied power. In this case, a cooling Peltier element 901 or the like may be provided between the electromagnet 205 and the shaft 206 supporting the electromagnet 205, as shown in FIG.

As described above, stirring, extraction, and washing are performed in one unit, and the vessel is rotated on the circumference of the incubator while being held in the vessel holder during the analysis operation. By operating each unit with respect to the vessel, a very simple apparatus configuration can be obtained as compared with the conventional apparatus shown in FIG. In addition, since there is no vessel transport 604, 605, 606 in the reaction process as in the prior art, the problems of poor grip of the vessel and disconnection of temperature control are solved.

[0037]

As described above, according to the present invention, in a chemical analyzer using a reagent containing magnetic particles, its function can be realized with a simpler configuration and the processing capacity can be improved. Also,
Without interrupting the temperature control inside the vessel during the reaction process,
A better reaction can be performed.

[Brief description of the drawings]

FIG. 1 is a perspective view showing the overall configuration of a chemical analyzer according to an embodiment of the present invention.

FIG. 2 is a longitudinal sectional view showing details of a part of the embodiment shown in FIG. 1;

FIG. 3 is an explanatory view showing a stirring operation of the embodiment shown in FIG. 2;

FIG. 4 is an explanatory diagram showing a suction operation of the embodiment shown in FIG. 2;

FIG. 5 is an explanatory diagram showing a cleaning operation of the embodiment shown in FIG.

FIG. 6 is a perspective view showing the general configuration of a typical conventional chemical analyzer.

FIG. 7 is a time chart of the operation of the chemical analyzer according to the embodiment of the present invention.

FIG. 8 is another embodiment of FIG. 2 of the present invention.

FIG. 9 is still another embodiment of FIG. 2 of the present invention.

[Explanation of symbols]

101: sample cup, 102: sample disk,
103: reagent cool box, 104: reagent bottle, 105: reagent dispensing unit, 106: sample dispensing unit, 10
7: incubator, 108: dispensing position of vessel sample, 111: waste liquid, 112: counting unit, 114
... stirring / adsorption unit, 115 ... washing dilution unit,
117 ... sample suction position of sample cup, 118 ...
Vessel reagent dispensing position, 119: rotating direction of incubator, 120: rotating direction of incubator, 121: rotating direction of incubator, 122: information of analysis result, 201: flange attached to vessel, 202: inside of incubator, 2
03: vessel holder, 204: packing, 205: electromagnetic magnet, 206: linear actuator, 207: shaft, 208: liquid, 209: deformation of vessel, 40
1. Illumination source for electromagnets, 402: magnetic particles adsorbed, 404: width of deformed vessel, 501: magnetic particles adsorbed, 901: piezoelectric element for cooling.

 ──────────────────────────────────────────────────続 き Continued on front page (72) Inventor Takao Terayama 882 Ma, Hitachinaka-shi, Ibaraki Pref. Within the Measuring Instruments Group of Hitachi, Ltd. Within the Measuring Instruments Group (72) Inventor: Isao Yamazaki 882 Ma, Hitachinaka-shi, Ibaraki F-term within the Measuring Instruments Group, Hitachi, Ltd. 2G058 BA01 BB02 BB07 BB09 BB12 BB16 BB18 CB04 CC00 CE08 EA02 EA04 ED03 FA03 FB12

Claims (7)

[Claims] 1. A reaction vessel having an opening, and a sample / reagent / diluent supply for supplying a reagent or a diluent containing a sample and magnetic particles from the opening to form a liquid to be measured in the reaction vessel. Means, a means capable of managing the temperature of the reaction vessel during the reaction, and a chemical analysis apparatus comprising means for measuring the physical properties of the liquid to be measured during or after the reaction, wherein the reaction vessel is A support member, which is formed of a material that is easily deformed by an externally applied force and has a magnetic force generating unit that generates a magnetic force in response to an external signal on the reaction container side, and moves the support member to apply a force to the container. A chemical analysis device comprising a drive unit for causing a reaction. 2. A reaction container having an opening, and a sample / reagent / diluent supply for supplying a reagent or a diluent containing a sample and magnetic particles from the opening to form a liquid to be measured in the reaction container. Means, a means capable of managing the temperature of the reaction vessel during the reaction, and a chemical analysis apparatus comprising means for measuring the physical properties of the liquid to be measured during or after the reaction, wherein the reaction vessel is A support member, which is formed of a material that is easily deformed by an externally applied force and has a magnetic force generating portion on the distal end side that generates a magnetic force by an external signal, and moves the support member to apply a force to the container. A chemical analysis device comprising a plurality of drive units for causing a chemical analyzer to operate. 3. The chemical analyzer according to claim 1, wherein the driving unit that moves the support member is incorporated in a part of a temperature management unit that manages a temperature of the reaction vessel during a reaction. A chemical analyzer characterized by the following. 4. The chemical analyzer according to claim 3, wherein said magnetic force generating unit is an electromagnet. 5. The chemical analyzer according to claim 1, wherein the material which easily deforms the reaction vessel by an externally applied force is measured by means for measuring physical properties of a liquid to be measured provided outside. A chemical analyzer characterized by being transparent. 6. A reaction vessel having an opening, and a sample / reagent / diluent supply for supplying a reagent or a diluent containing a sample and magnetic particles from the opening to form a liquid to be measured in the reaction vessel. Means, a means capable of controlling the temperature of the reaction vessel during the reaction, and a means for measuring the physical properties of the liquid to be measured during or after the reaction, a chemical analysis apparatus comprising: A chemical analyzer wherein agitation of a sample and a reagent, adsorption of magnetic particles, and washing operation of magnetic particles are performed by an integrated mechanism. 7. The chemical analyzer according to claim 4, wherein an antigen-antibody reaction is used.