JP2002048806A - Dispensing method for specimen testing device and specimen testing device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enhance the test accuracy of a specimen test. SOLUTION: In the operation dispensing method, a dispensing mechanism 40 is provided selectively with a dispensing nozzle 45 which sucks and discharges a liquid sample, a dispensing pump 18 which urges the suction operation and the discharge operation of the dispensing nozzle 45 or tips T1, T2, T3 which are freely attached and removed with reference to the tip part of the dispensing nozzle 45 and which temporarily hold the sucked sample. The method is provided with a mounting process in which the tips T1, T2, T3 are mounted on the tip part of the dispensing nozzle 45, a suction process which sucks the liquid sample via the tips T1, T2, T3, a discharge process which discharges the sucked liquid sample to a prescribed container and a pulling and removing process in which the tips T1, T2, T3 are pulled and removed from the tip part of the dispensing nozzle 45. The pulling and removing process is accompanied by the discharge operation of the dispensing pump 18 when the tips T1, T2, T3 are pulled and removed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a dispensing method for a dispensing mechanism and a sample test apparatus, and more particularly to a dispensing mechanism suitable for a sample test for measuring a reaction between a sample and a reagent such as an enzyme immunoreaction. And a sample test apparatus.

[0002]

2. Description of the Related Art In a reaction test of a sample in a clinical test in the medical field, for example, in an enzyme immunoreaction test, a large amount of a sample is distributed to a reaction container, a reagent is poured into the reaction container, and a predetermined temperature is set as necessary. In addition, a technique has been used in which agitation is performed to equalize the reaction conditions between the sample and the reagent, and thereafter, a reaction according to the characteristics of the reagent is observed. Further, in addition to these steps, there have been cases in which a sample or a reagent is diluted, a new reagent is further added, or a container washing operation is added during these steps.

As described above, a sample test is performed through many steps, and when a test is performed on a large number of samples, each step is too complicated and requires a long working time. Therefore, development for automating each process is being promoted. Similarly, the development of a sample test apparatus capable of performing a plurality of steps of each step is also underway. In addition, among the above-mentioned steps, since the dispensing operation is particularly complicated and requires a long time to be performed manually, the automation is particularly advanced.

[0004]

The dispensing mechanism generally comprises:
A dispensing nozzle for aspirating and discharging the liquid sample, and a dispensing pump for energizing the aspirating and discharging operations of the dispensing nozzle are provided at the tip of the dispensing nozzle to ensure the accuracy of the test. Is equipped with a disposable tip that is replaced for each sample or reagent, and is configured such that the sample or reagent does not directly touch the dispensing nozzle itself.

Further, in the above dispensing mechanism, the operation of exchanging tips is often automated. In order to automate such tip exchange, a dispensing nozzle and a tip are required.
It is desirable that the dispensing nozzle and the tip have a simple structure in which either one of the dispensing nozzle and the tip is attached by being pushed into the other and is detached by withdrawing the other from one. The structure is adopted.

However, in the dispensing mechanism having the above structure, if a liquid sample (sample or reagent) remains inside when the used chip is withdrawn from the dispensing nozzle, the inside of the chip accompanying the withdrawal operation is reduced. Pressure drop, the residual liquid sample is drawn to the dispensing nozzle side, and the droplets of the liquid sample that scatter immediately after withdrawal may adhere to the tip of the dispensing nozzle, which lowers the accuracy of the inspection. There was a risk of inviting.

To cope with such inconvenience, Japanese Patent Application Laid-Open No.
In the analysis device described in Japanese Patent No. 94844, an operation control for detecting the pressure in the dispensing nozzle and reducing the extraction speed when the internal pressure is lower than the atmospheric pressure when the chip is extracted is performed. Is being done. This suppresses a decrease in the pressure inside the chip, and prevents the residual liquid sample from moving toward the dispensing nozzle and being scattered.

However, with such an analyzer,
Inevitably, the operation of removing the chip is delayed, and the speedy effect of the operation, which is an advantage of automation, is reduced. In addition, a special configuration such as a pressure detection sensor is required, and there is also a disadvantage that the productivity of the apparatus is reduced.

[0009]

SUMMARY OF THE INVENTION An object of the present invention is to provide a dispensing method for a sample test dispensing mechanism capable of improving the disadvantages of the prior art and preventing a liquid sample from adhering to the tip of a dispensing nozzle during use. It is an object of the present invention to provide a sample test device.

[0010]

According to the first aspect of the present invention,
A dispensing nozzle for aspirating and discharging the liquid sample, a dispensing pump for energizing the suction and discharging operations of the dispensing nozzle, and a dispensing and detachable liquid sample that is detachable from the tip of the dispensing nozzle. An operation dispensing method of a dispensing mechanism including a tip temporarily held therein, which includes an attaching step of attaching a tip to a tip portion of a dispensing nozzle, and suction for aspirating a liquid sample through the tip. The method includes a process, a discharge process of discharging the sucked liquid sample into a predetermined container, and a withdrawal process of withdrawing the tip from the tip of the dispensing nozzle. The withdrawal step has a configuration in which the withdrawal of the chip involves the discharge operation of the dispensing pump.

In the above configuration, the tip is mounted on the tip of the dispensing nozzle before dispensing. The relationship between the tip and the dispensing nozzle may be such that the inner diameter of the tip and the outer diameter of the tip of the dispensing nozzle are set substantially equal and the tip of the nozzle is inserted into the tip, or the outer diameter of the tip and the dispensing nozzle A configuration in which the inner diameter of the distal end portion is set substantially equal and the tip is inserted into the dispensing nozzle may be adopted. In any case, it is desirable that the chip is mounted by press-fitting one into the other.

Then, in the region where the container in which the liquid sample is placed is arranged, the liquid sample is sucked into the chip by the urging of the suction by the dispensing pump. Such aspiration is not performed beyond the volume of the tip, so that the dispensing nozzle does not touch the liquid sample.

Further, a predetermined amount of the liquid sample sucked into the chip is discharged to the container by, for example, urging the discharge by a dispensing pump in a region where a container for performing a test is arranged. When there are a plurality of such containers, such discharge is performed for each container.

When this is completed, the used chip is withdrawn from the tip of the nozzle and discarded. At the time of such withdrawal, the discharge operation is energized by the dispensing pump.
Therefore, the liquid sample remaining in the chip is on the opposite side (discharge direction) from the dispensing nozzle by the urging of the dispensing pump.
To prevent the residual liquid sample from moving to the dispensing nozzle side due to the pressure drop in the chip at the time of withdrawal, or the liquid sample is moved to the opposite side from the dispensing nozzle in advance, so that the chip is removed. The liquid sample is prevented from scattering on the dispensing nozzle side at the moment of removal.

A second aspect of the present invention has the same configuration as that of the first aspect of the present invention, and in the withdrawal step,
The withdrawal of the chip is performed by a relative separating operation between the dispensing nozzle and the chip, and the discharge operation of the dispensing pump is performed at least after the dispensing nozzle and the chip start moving in the separating direction. The configuration is such that the process is started before the tip is separated from the tip.

In the case of this configuration, the same operation as that of the first aspect of the invention is performed, and the tip is pulled out from the nozzle tip by the operation of separating from the nozzle tip. The above-described urging of the discharge operation by the dispensing pump is started after the chip separating operation is started and before the chip is separated. If ejection is performed during this time, the liquid sample remaining in the chip will be on the opposite side (discharge direction) to the dispensing nozzle.
The liquid sample is prevented from being scattered on the dispensing nozzle side at the moment of chip withdrawal due to the pressure drop in the chip at the time of withdrawal.

According to a third aspect of the present invention, in addition to the configuration of the first aspect of the invention, in the withdrawal step, the withdrawal of the chip is performed by a relative separating operation between the dispensing nozzle and the tip. And the discharge operation of the dispensing pump is performed continuously from the start of the movement of the dispensing nozzle and the chip in the separating direction until the chip is separated from the tip of the dispensing nozzle.

In the case of this configuration, the same operation as in the first aspect of the invention is performed, and the chip is pulled out from the nozzle tip by the operation of pulling it apart. The above-described urging of the discharge operation by the dispensing pump is started at the same time as the chip separating operation, and is continuously performed until the chips are separated. Therefore, the liquid sample continuously remaining in the chip while the chip moves in the separating direction is pressed to the opposite side (discharge direction) from the dispensing nozzle,
Due to the pressure drop in the chip at the time of withdrawal, the liquid sample is prevented from scattering on the dispensing nozzle side at the moment of chip withdrawal.

According to a fourth aspect of the present invention, in addition to the configuration of the first, second or third aspect of the invention, the dispensing pump urges suction and discharge by a change in the internal volume thereof.
A configuration is adopted in which, before the suction step, an empty suction step in which the dispensing pump sucks the atmosphere is provided.

In this configuration, the dispensing pump has a structure in which the suction and the discharge are urged by changing the internal volume. Therefore, in order to perform the discharge at the time of removing the tip, the atmosphere is previously suctioned by the dispensing pump. Then, the atmosphere for the discharge is secured. Other operations are performed in the same manner as in the first, second, and third aspects of the present invention.

According to the fifth aspect of the present invention, a dispensing nozzle for sucking and discharging a liquid sample, a dispensing pump for energizing the suction and discharge operations of the dispensing nozzle, and a state in which the tip of the dispensing nozzle is superimposed. A dispensing mechanism having a chip that is detachably mounted and temporarily holds the aspirated liquid sample inside itself and a lifting unit that raises and lowers the dispensing nozzle, and a chip holder that holds the chip before mounting Unit, a liquid sample disposing unit for disposing a container containing a liquid sample, a discharge container disposing unit for disposing a discharge container from which a liquid sample is discharged, and a chip discarding unit for removing a chip by raising a dispensing nozzle. A transport unit that transports the dispensing nozzle to each of the chip holding unit, the liquid sample placement unit, the discharge container placement unit, and the chip disposal unit, and an operation control unit that controls the operation of each unit.

The operation control section includes a removal / positioning control section for positioning the dispensing nozzle to a predetermined chip removal position of the chip disposal section by the transport section, and a dispensing position at the chip removal position by the lifting / lowering section. A tip removal control unit that raises the nozzle until the chip separates from the dispensing nozzle, and a residual liquid scattering prevention control unit that causes the dispensing pump to perform a discharging operation in accordance with the rising operation are adopted. .

In the above-described configuration, the operation from the time after the ejection of the liquid sample is completed by the dispensing nozzle to which the chip is mounted to the time when the used chip is arranged is targeted. The tip is mounted on a dispensing nozzle. The relationship between the tip and the dispensing nozzle in this case is the same as in the description of the first aspect of the present invention.

First, the dispensing nozzle after ejection is positioned by the withdrawal positioning control unit to the tip withdrawal position of the dispensing nozzle. The chip discarding unit is disposed in advance in the transfer range of the transfer unit, and the transfer unit transfers the dispensing nozzle to a known removal position of the chip discarding unit. The tip disposal section has a structure that locks the tip of the dispensing nozzle.
The chip removal operation is performed by the chip removal controller.
That is, the dispensing nozzle is moved upward by the elevating unit in a state where the chip is locked in the chip disposal unit, and the dispensing nozzle is separated from the chip. Then, at this time, the liquid scattering prevention control unit performs the discharging operation of the dispensing pump in accordance with the rise of the dispensing nozzle.

Therefore, the liquid sample remaining in the chip is pressed to the opposite side (discharge direction) from the dispensing nozzle by the urging of the dispensing pump, and the pressure in the chip at the time of withdrawal is reduced. Movement of the residual liquid sample to the dispensing nozzle side is suppressed, or the liquid sample is moved to the opposite side from the dispensing nozzle in advance, so that the liquid sample scatters to the dispensing nozzle side at the moment of chip removal. Is prevented.

According to a sixth aspect of the present invention, there is provided a dispensing nozzle for sucking and discharging a liquid sample, a dispensing pump for energizing the suction and discharging operations of the dispensing nozzle, and a state in which the tip of the dispensing nozzle is superimposed. A dispensing mechanism that has a tip that is detachably mounted with and that temporarily holds the aspirated liquid sample inside itself, a tip holder that holds the chip before mounting, and a container that contains the liquid sample A liquid sample placement section to be
A discharge container disposition section for disposing a discharge container from which a liquid sample is discharged, a chip disposal section for separating chips by a dispensing nozzle transport operation, a chip holding section, a liquid sample disposition section, a discharge container disposition section, and chip disposal. A transport unit that transports the dispensing nozzle to each of the units and an operation control unit that controls the operation of each unit are provided.

The operation control section includes a removal / positioning control section for positioning the dispensing nozzle to a predetermined chip removal position of the chip disposal section by the transfer section, and a dispensing position at the chip removal position by the transfer section. A tip removal control unit that transports the nozzle until the tip is separated, and a remaining liquid scattering prevention control unit that causes the dispensing pump to perform a discharge operation in accordance with the transport operation for removal are adopted. ing.

In the above configuration, the chip discarding unit removes the chips by using the transfer operation of the dispensing nozzle by the transfer unit. Therefore, the chip removal control unit attempts to remove the chip by controlling the transfer unit, and the remaining liquid scattering prevention control unit performs the discharge operation of the dispensing pump in accordance with the transfer operation during the removal. ing. Other operations are the same as those of the fifth aspect.

According to the seventh aspect of the present invention, the fifth or sixth aspect is provided.
In addition to having the same configuration as the described invention, the remaining liquid scattering prevention control unit starts the discharge operation of the dispensing pump from the start of the withdrawal operation by the chip withdrawal control unit until the chip is separated. It has a configuration.

In the case of this configuration, the same operation as that of the invention according to claim 5 or 6 is performed, and the discharge operation by the dispensing pump is energized after the start of the withdrawal operation of the chip. Is started until is separated. If the liquid is ejected during this time, the liquid sample remaining in the chip is pressed in the direction opposite to the dispensing nozzle (in the direction in which the liquid is ejected). The liquid sample is prevented from scattering on the dispensing nozzle side at the moment of withdrawal.

According to the invention described in claim 8, claim 5 or claim 6
In addition to having the same configuration as the described invention, the above-mentioned remaining liquid scattering prevention control unit continues the discharge operation of the dispensing pump from the start of the dispensing nozzle withdrawal operation by the chip removal control unit until the chip is separated. Is performed.

In the case of this configuration, the same operation as the invention according to claim 5 or 6 is performed, and the urging of the discharge operation by the dispensing pump is started simultaneously with the withdrawal operation of the tip, This is continued until the chips are separated.
Therefore, the liquid sample continuously remaining in the chip while the chip is moving in the separating direction is pressed to the side opposite to the dispensing nozzle (the direction in which the liquid is ejected). Due to the pressure drop in the inside, the liquid sample is prevented from being scattered to the dispensing nozzle side at the moment of tip removal.

According to the ninth aspect of the present invention, the fifth aspect, the sixth aspect,
The dispensing pump has the same configuration as that of the invention described in 7 or 8, and the dispensing pump urges suction and discharge by a change in its internal volume, and the operation control unit determines the dispensing nozzle in advance by the transport unit. A suction positioning control unit for positioning the liquid sample placement unit at the position of the container containing the liquid sample, a liquid suction control unit for performing a suction operation by the dispensing pump, and a suction operation by the liquid suction control unit. An empty suction control unit for performing an air suction operation by a dispensing pump is provided.

In the above configuration, the operation from the time when the tip is mounted on the dispensing nozzle until the suction of the liquid sample is completed is targeted. The tip is mounted on a dispensing nozzle.

First, the dispensing nozzle is positioned by the suction positioning control unit with respect to the container containing the liquid sample. The liquid sample disposition unit is disposed in advance in the transfer range of the transfer unit, and the transfer unit conveys the dispensing nozzle to a known position of the liquid sample container in the liquid sample disposition unit. Then, a liquid sample is suctioned by the liquid suction control unit.
In this case, the dispensing pump is driven to suck, and the liquid sample is sucked from the container containing the liquid sample into the chip by a predetermined suction amount via the dispensing nozzle and the chip.

In addition, in the above-described configuration of the present invention, since the idle suction control section is provided, the dispensing pump is once driven to suck the air before the suction operation of the liquid sample by the liquid suction control section, and the air is stored in the suction pump. Is sucked.

In such a configuration, the dispensing pump has a structure in which the suction and discharge are urged by changing the internal volume thereof. Therefore, in order to perform discharge at the time of later withdrawal of the used tip, The air is suctioned by a dispensing pump in advance to secure the air for discharge.

The present invention is to achieve the above-mentioned object by the above-mentioned respective constitutions.

[0039]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS (Overall Configuration of Embodiment) An embodiment of the present invention will be described below with reference to FIGS.
The present embodiment is an enzyme immunoreaction measurement device 10 as a sample test device for testing an antibody reaction on a sample such as a body fluid, blood, and serum of a subject. For the inspection, an assay microplate (hereinafter, referred to as an assay plate P) having a plurality of wells P1 (see FIG. 3) as a plurality of ejection vessels in which an enzyme immunoreaction between a sample and a reagent is performed is used. FIG. 1 is a perspective view schematically showing an arrangement of each part of the enzyme immunoreaction measurement device 10, and FIG. 2 is a plan view schematically showing an arrangement of each part of the enzyme immunoreaction measurement device 10.

The enzyme immunoreaction measuring apparatus 10 includes a plurality of reagent bottles S each containing a plurality of types of reagents as liquid samples.
(A container containing a liquid sample) and a plurality of sample containers K (containers containing a liquid sample) each containing a plurality of samples as liquid samples, and a reagent / sample tray 20 on which the reagent / sample tray 20 is placed. A base 11 for reciprocating support, a stage mechanism 30 for urging the reciprocating movement of the reagent / sample tray 20, a dispensing mechanism 40 for dispensing a sample or a reagent to each well P1 of the assay plate P, Assay plate P
And a cleaning mechanism 60 for cleaning the inside of each well P1 of the assay plate P.
A reaction measuring mechanism 70 for measuring an enzyme immunoreaction in each well P1 of the assay plate P;
A plate cover 12 for preventing the sample or reagent in each well P1 from drying, and disposable chips T1, T described later.
2, a chip discarding unit 13 for discarding T3, and an operation control unit 100 (see FIG. 19) for controlling the operation of each unit. Reference numeral 14 denotes a power supply for supplying power to each unit of the apparatus, reference numeral 15 denotes an apparatus cover that houses the entire apparatus, and reference numeral 16 denotes a fan that cools the power supply 14 with outside air.

The components will be described below.

(Assay plate and dilution plate)
First, the assay plate P will be described before describing the configuration of each unit. Here, a microplate for diluting a sample or a reagent (hereinafter, referred to as a dilution plate U) having a plurality of wells U1 as a discharge container to be described later is a plate having the same structure as the assay plate P, and will be described at the same time.
FIG. 3A shows an example of a plan view of the assay plate P (dilution plate U), and FIG. 3B shows a sectional view in the front direction.
Shown in The assay plate P (dilution plate U) has a total of 96 wells P1 (U1), 12 × 8, formed in a plane. Each well P1 (U1) has a bottom and an upper opening, and the bottom is flat.
As described above, the assay plate P (dilution plate U) is not limited to the plate having a flat bottom as described above, and may have a bottom formed in a hemispherical shape.

Further, regarding the assay plate P,
It is made of transparent plastic, and it is possible to obtain a measurement result of an enzyme immunoreaction by irradiating light of a predetermined wavelength from above and measuring the absorbance from the transmitted light below the assay plate P. A reagent is applied to the entire inner surface of each well P1 in advance, and a sample or another reagent is dispensed from above. The dilution plate U does not need to be particularly transparent, and no reagent is applied.

(Base) The base 11 is a plate-like member on which the components of the enzyme immunoreaction measuring device 10 described above are mounted and mounted. The base and the components are all contained in a device cover (not shown). Will be accommodated.

(Reagent / Sample Tray) Next, the reagent / sample tray 20 will be described with reference to FIGS. FIG. 4 is a perspective view of the reagent / specimen tray 20 during the test. The reagent / sample tray 20 is mounted on the base 11 via the tray transport mechanism 30. The reagent / sample tray 20 includes a tray main body 27 having a rectangular plate shape, and a group of stockers disposed on the tray main body 27.

The stocker group on the tray body 27
A reagent stocker 21 as a liquid sample placement unit that holds reagent bottles S of a plurality of reagents corresponding to the inspection method, which are sequentially arranged along the reciprocating direction Y by the tray transport mechanism 30;
A sample stocker 22 as a liquid sample placement unit that holds a plurality of sample containers K that individually store a plurality of samples, and a sample chip T1 used when dispensing each sample to a corresponding well P1 of an assay plate P Sample stocker 23 as a chip holding unit for holding a plurality of
A diluting tip stocker 24 as a tip holding unit for holding a plurality of diluting tips T2 corresponding to each one, and a reagent tip for reagent dispensing corresponding to each reagent adjacent to the reagent stocker 21 and the sample stocker 22 It is composed of a reagent chip stocker 25 as a chip holding section for holding T3.

The reagent stocker 21 has seven holes 21a for inserting and holding the reagent bottle S from above, arranged in the X direction perpendicular to the Y direction, but the number is not limited. Absent. That is, more or less may be provided as needed.

The sample stocker 22 is formed in a tray shape, and is provided detachably from the tray body 27. The sample stocker 22 has a hole 22a for inserting and holding a sample container having a bottom and an opening at the top, which is 14 × in the X direction.
A total of 98 are formed at 7 in the Y direction. The total number of the holes 22a is not limited to this.

The sample chip stocker 23 and the dilution chip stocker 24 are arranged adjacent to each other along the X direction, and both are adjacent to the sample stocker 22. Each of these chip stockers 23 and 24 is detachably held by a holder 26 provided on a tray body 27. Each of the chip stockers 23 and 24 has the same structure, and the sample chip T1 and the dilution chip T2 also have the same structure. The chips T1 and T2 are detachably held from the chip stockers 23 and 24.

Here, the chips T1 and T2 will be described in more detail. Each of the chips T1 and T2 has a tubular shape, and the tip portion is thinner than the base portion (see FIG. 15). This chip T1,
The base end of T2 is attached to the tip of a dispensing nozzle of a dispensing mechanism 40, which will be described later, and the sample or diluent is sucked and discharged from the tip of the tip. In order to prevent mixing of each sample, each of the plurality of chips T1 and T2 is attached to each assay plate P
Alternatively, one corresponding to each well P1, U1 of the dilution plate U is used.

The above-described reagent chip stocker 25 is provided at one end of the tray body 27 in the X direction. This reagent chip stocker 25 can hold nine reagent chips T3 in a state of being arranged along the Y direction, and each of these chips T3 is also detachable. The number of chips held is not limited, but is preferably set to be larger than the number of reagent bottles held in the reagent stocker 21.

Here, the chip T3 for a reagent will be described in more detail. The chip T3 is tubular like the chip T1 for a sample, and the tip is thinner than the base (see FIG. 15). ). The base end of the tip T3 is also attached to the tip of a dispensing nozzle of a dispensing mechanism 40, which will be described later, and suction and discharge of a reagent are performed from the tip of the tip.
However, the diameter of the reagent chip T3 is larger than that of the sample chip T1, the length thereof is set longer, and the internal volume is set larger. Also, as the reagent chip T3, an individual chip is used for each reagent bottle S in order to prevent mixing of each reagent.

(Holding Frame) Further, on the tray main body 27 of the reagent / sample tray 20, a holding frame 28 as a holding portion for the assay plate P and the dilution plate U is provided.
It is provided on the tray main body 27 via a vibration mechanism 80. 5A is a plan view of the holding frame 28, FIG. 5B is a cross-sectional view taken along the line WW, and FIG. 6 is an exploded perspective view of the vibration mechanism 80.

The holding frame 28 and the vibration mechanism 80
It is disposed at the end in the X direction on the tray main body 27 and is adjacent to the above-mentioned dilution chip stocker 24. The holding frame 28 has a flat plate shape, and the upper surface thereof has a concave portion 28 as a discharge container arrangement portion for disposing the assay plate P.
a and a concave portion 28b as a discharge container arrangement portion for disposing the dilution plate U. Each recess 28a, 28
b is formed on the tray main body 27 so that each of the plates P, U is formed in a shape and size that can just fit therein, and the longitudinal direction of each of the plates P, U (the direction in which twelve wells are arranged) is along the Y direction. It is arranged in. Further, as shown in FIG. 4, the right half of the holding frame 28 provided with the arrangement area of the assay plate P
It projects in one direction along the direction.

Also, as shown in FIG.
A large hole 28c that penetrates the back side of the holding frame 28 is provided on the bottom surface of 8a. The hole 28c is set to have such a size that substantially the entire surface of the bottom of the assay plate P except for the peripheral portion is exposed below the holding frame 28. The hole 28c is provided in consideration of the fact that the temperature maintaining mechanism 50 described later heats the assay plate P from below, and that the reaction measuring mechanism 70 detects the downward transmitted light of the light irradiated from above. I have.

Further, a cleaning tank 29 for cleaning a tip portion of a suction nozzle of the cleaning mechanism 60, which will be described later, is provided adjacent to the holding section 28a on the upper surface of the holding frame 28 in the Y direction. The cleaning tank 29 is set to have a width substantially equal to the width of the assay plate P in the X direction. During the cleaning, discharge and suction of the cleaning liquid are repeated inside the tank, thereby cleaning the tip of the suction nozzle.

(Vibration Mechanism) As described above, the holding frame 28 is mounted on the tray main body 27 via the vibration mechanism 80. As shown in FIG. 6, the vibration mechanism 80
The base plate 81 fixedly mounted on the tray main body 27 via four legs and the rotation axis are set in a vertical direction (a direction orthogonal to both the X direction and the Y direction, hereinafter referred to as a Z direction). A vibrating motor 82 fixedly mounted on the base plate 81 upward, an eccentric cam 83 mounted on a drive shaft of the vibrating motor 82, and an eccentric shaft 83a of the eccentric cam 83 are rotatably held by a holding frame. A bearing 84 connected to the body 28 and a slider connected to the base plate 81 such that the holding frame 28 can slide freely in any direction along a horizontal plane (a plane parallel to both the X direction and the Y direction). A body 85 and an original position sensor 86 for detecting a reference position of the holding frame 28 with respect to the base plate 81 are provided.

The vibration motor 82 is a servomotor capable of freely controlling the number of rotations and the rotation angle.
Control is performed to end the vibration at a constant rotation angle so that the position of the holding frame 28 with respect to the base plate 81 does not change after the vibration.

The eccentric cam 83 is connected at one end to the drive shaft of the vibration motor 82, and has an eccentric shaft 83a parallel to and eccentric to the drive shaft at the other end. Since the eccentric shaft 83a is connected to the holding frame 28 via the bearing 84, the driving of the vibration motor 82 causes the holding frame 28 to be a circle having a radius corresponding to the eccentric distance of the eccentric shaft 83a about the drive shaft. Exercise will be energized.

A connecting member 85 for connecting the base plate 81 and the holding frame 28 is a combination of two sliders which allow the other member to slide freely along the linear direction with respect to the other member. Turn the sliding direction of the slider in the X direction,
The sliding direction of the other slider is oriented in the Y direction and the base plate 81-
It is provided between the holding frames 28. Therefore, the holding frame 28
Allows sliding in any direction along the horizontal plane without changing the orientation of the frame itself. For this reason, the holding frame 28 performs a circular motion by the driving of the vibration motor 82 described above without changing the direction along the horizontal plane.

A projection 83b is provided on the circumferential surface of the eccentric cam 83, and the above-mentioned original position sensor 86 detects the presence or absence of the projection 83b. The detection signal of the in-situ sensor 86 is based on the enzyme immunoreaction measuring device 1 described above.
The operation control unit 100 determines that the holding frame 28 is at the reference position when the protrusion 83b is detected, and applies the rotation angle at that time. The control of stopping the driving of the vibration motor 82 and ending the vibration operation is performed. Therefore, before and after the vibration operation, the position of the holding frame 28 with respect to the base plate 81 can always be kept constant, and other operations (for example, dispensing of the assay plate P, washing, heat keeping, reaction measurement, etc.) can be performed. In this case, inconvenience due to the displacement of the assay plate P can be prevented.

(Stage device) Next, the stage device 30
Will be described with reference to FIG. 2 and FIG. As described above, since the assay plate P is held on the reagent / sample tray 20 via the holding frame 28, the stage mechanism 30 for transferring the reagent / sample tray 20 functions as a microplate transfer mechanism. .

The stage device 30 has two guide shafts 31 for guiding the reagent / sample tray 20 along the Y direction.
a, 31b, sliders 32a, 32b fixedly mounted on the lower surface side of the reagent / sample tray 20 and slidable along the guide shafts 31a, 31b, and two driven pulleys 33a,
Endless belt 3 stretched along the Y direction by 33b
4, a driving motor 35 which is a driving source for conveying the endless belt 34, a driving pulley 36 provided on an output shaft of the driving motor 35, a reduction pulley 37 connected with the driven pulley 33a on the same shaft, A transmission belt 38 for transmitting the torque of the pulley 36 to the reduction pulley.

Both ends of each of the guide shafts 31a and 31b are fixed to the base 11 (not shown in FIG. 7) along the Y direction. Each slider 32a, 32b
Have built-in linear motion ball bearings (not shown) engaged with the guide shafts 31a and 31b, respectively, so that they can slide freely along the guide shafts 31a and 31b. Also,
Each slider 32a, 32b is mounted on the lower surface side of the tray main body 27 of the reagent / sample tray 20, whereby the entire reagent / sample tray 20 can reciprocate along the Y direction.

Each of the driven pulleys 33a and 33b and the endless belt 34 are arranged close to the guide shaft 31b, and the slider 32b is connected to an intermediate portion of the endless belt 34 via a bracket 32c. Therefore, the transport of the endless belt 34 urges the reciprocating operation of the reagent / sample tray 20 via the slider 32b.

The deceleration pulley 37 and the driven pulley 33a are supported at the opposite ends of the same shaft and are interlocked. The driving pulley 36 has a smaller diameter than the deceleration pulley 37, whereby the rotation speed is reduced and transmitted to the deceleration pulley 37.

The drive motor 35 is a servo motor capable of freely controlling the amount of rotation. By controlling the amount of rotation, positioning of the reagent / sample tray 20 in the Y direction is performed.

(Temperature Maintenance Mechanism) As shown in FIG. 2, the temperature maintenance mechanism 50 is located on the near side (lower end in FIG. 2) in the Y direction on the base 11 and reciprocates the reagent / sample tray 20. It is arranged on the base 11 adjacent to the end side (the right side in FIG. 2) where the holding frame 28 in the area is equipped. This temperature maintaining mechanism 50 is shown in FIG.
A description will be given based on FIG. FIG. 8 shows a lid 56 to be described later.
FIG. 9 is a perspective view showing the relationship between the movement region R of the assay plate and the holding frame and the housing 52 of the temperature maintenance mechanism 50 with the open state.

The temperature maintaining mechanism 50 has a heater 51 as a temperature regulator and a housing 52 containing the heater 51. The temperature of the heater 51 can be set by an operation panel (not shown). Note that the temperature regulator is not limited to the heater, and for example, a Peltier element may be used to enable not only heating but also cooling.

The housing 52 includes a main body 5 for holding the heater 51.
3, four legs 54 supporting the main body 53 on the base 11 (not shown), and an openable and closable lid provided at the upper end of a side wall 55 erected from the upper end of the main body 53 56.

The above-described heater 51 is provided on the upper surface of the main body 53. The lid 56 is provided on the side wall 55 so as to face the heater 51 with the moving region of the assay plate P and the holding frame 28 therebetween in the closed state. That is, the main body 53 and the lid 56 can be inserted through the assay plate P and the holding frame 28 which are conveyed by the movement of the reagent / sample tray 20, and the assay plate P
A gap close to the thickness (height) of the holding frame 28 in the holding state is provided. For this reason, when the assay plate P is inserted between the main body 53 and the lid 56, the heater 51 is opposed to the lower surface of the assay plate P so as to be close to the lower surface of the assay plate P.
Is close to and opposes the upper surface of the assay plate P. As described above, since the recess 28a of the holding frame 28 is provided with the hole 28c, the lower surface of the assay plate P and the heater 51 face each other without any shielding, so that the heat from the heater 51 is efficiently removed. Can communicate well. Also,
A lid 5 is provided at the opening of each well P1 of the assay plate P.
6 are present close to each other, it is possible to prevent evaporation of excessive moisture such as specimens and reagents in each well P1.

FIG. 9 shows the housing 52 with the lid 56 closed. In FIG. 9, reference symbol R indicates a moving area of the assay plate P and the holding frame 28 accompanying the movement of the reagent / sample tray 20. As shown in this figure, the temperature maintaining mechanism 50 is disposed on the base 11 at the end of the moving area R of the assay plate and the holding frame so as to overlap the area R. A portion of the housing 52 that overlaps with the moving region R of the assay plate and the holding frame is notched. That is, the notch 52 is formed at one end face in the Y direction and one end face in the X direction of the housing 52.
a and 52b are provided, and the assay plate P and the holding frame 28 are connected to the housing 52 with the movement of the reagent / sample tray 20.
It is possible to be guided inside.

(Reaction Measuring Mechanism) As shown in FIG. 2, the reaction measuring mechanism 70 is adjacent to the back side (the upper side in FIG. 2) of the temperature maintenance mechanism 50 in the Y direction and the reciprocating area of the reagent / sample tray 20. Are disposed on the base 11 adjacent to the end side (the right side in FIG. 2) where the holding frame 28 is mounted. The reaction measurement mechanism 70 will be described with reference to FIG. FIG. 10A is a front view of the reaction measurement mechanism 70, and FIG. 10B is a side view.

The reaction measuring mechanism 70 includes a halogen lamp 71a as a light source, an irradiating section 71 for irradiating the emitted light to the well P1 of the assay plate P, and a sensor holder 72 having a photodiode 72a as a light receiving sensor.
And a filter holder 73 including a plurality of types of band-pass filters 73 a according to the measurement, a filter selecting unit 74 for driving the filter holder 73, and an irradiation unit 71, a sensor holder 72, and a filter holder 73. A bracket 75 and two legs 7 on a base 11 (not shown in FIG. 10).
6a, a base plate 76 supported by the base plate 76, a guide member 77 mounted on the base plate 76, a slider 78 sliding freely along the guide member 77, and a positioning for urging the slider 78 to reciprocate. And a biasing means 79.

The irradiating section 71 includes a halogen lamp 71a.
And a guide tube 71b through which the emitted light passes, and a mirror 71c that reflects the emitted light toward the sensor holder 72 side. The guide tube 71b is erected from the bracket 75 along the X direction, and the distance from the base end of the guide tube 71b to the mirror 71c provided at the distal end is the width of the assay plate P in the X direction (the shorter width). ) Is set longer.

Further, the halogen lamp 71a and the guide tube 7
1b, a disc-shaped filter holder 73 is interposed, and a plurality of (five in this embodiment) band-pass filters 73 having different pass bands on the same circumference.
a is held. Also, a single through-hole 73b without the band-pass filter 73a is formed on the same circumference of the filter holder 73.

The filter selecting means 74 includes a servo motor 74a for rotating the filter holder 73, an original position projection 74b provided on the outer periphery of the filter holder 73, and an original position sensor 74c for detecting the original position projection 74b. It has. With such a configuration, after the original position projection 74b is detected by the original position sensor 74c, the filter holder 73 is rotated by a predetermined angle by the servo motor 74a.
The desired band pass filter 73a is
a, and a light wave of a predetermined wavelength is emitted from the irradiation unit 71.

On the other hand, the sensor holder 72 is also erected from the bracket 75 along the X direction, and the distance from the base end to the photodiode 72a mounted at the front end is equal to the base end of the guide tube 71b. Mirror 71c from top to bottom
Is set equal to the distance to Further, as shown in FIG. 10, the moving region R of the assay plate and the holding frame is
Are set between the guide tube 71b and the sensor holder 72, and the assay plate is moved between the guide tube 71b and the sensor holder 72 by the movement of the reagent / sample tray 20. When P is guided and light passing through the well P1 is detected by the photodiode 72a, a measurement result can be obtained from the absorbance.

The slider 78 holds a bracket 75, and the guide 77 is mounted on a base plate 76 along the X direction. Therefore, the position detected by the photodiode 72a can be changed along the X direction by the sliding of the slider 78. The positioning urging means 79 for urging the movement of the slider 78 includes a driving pulley 79a and a driven pulley 7a.
9b, an endless belt 79 stretched along the X direction.
servo motor 79d for rotating c and driving pulley 79a
And The slider 78 is connected to the intermediate portion of the endless belt 79c via a small bracket 78a, and the rotation of the servomotor 79d positions the detection position in the X direction by the photodiode 72a via the slider 78 and the bracket 75. That is, the photodiodes 72a are positioned for each array interval of the wells P1 arranged in a line in the X direction of the assay plate P, and the absorbance is measured for all the wells P1 in the line. Further, as described above, since the assay plate P can be transported along the Y direction by moving the reagent / sample tray 20, the transport operation and the photodiode 7
It is possible to measure the absorbance of all the wells P1 of the assay plate P in cooperation with the positioning operation in the X direction of 2a.

(Cleaning Mechanism) As shown in FIG. 2, the cleaning mechanism 60 is provided on the back side in the Y direction of the reaction measuring mechanism 70 (FIG. 2).
Is located on the base 11 adjacent to the end (the right side in FIG. 2) on which the holding frame 28 is provided in the reciprocating movement area of the reagent / sample tray 20. The cleaning mechanism 60 will be described with reference to FIGS. FIG. 11 is a front view of the cleaning mechanism 60, and FIG. 12 is a left side view partially omitted. In FIG. 12, the illustration of a configuration located behind a nozzle cover 65 described later is omitted.

The cleaning mechanism 60 includes a base 11 (FIG. 11,
12 is not shown), a chassis body 61 supported on four feet 61a, a cleaning manifold 62 having eight sets of cleaning liquid discharge nozzles 62a and suction nozzles 62b, and a holder 63 for holding the cleaning manifold 62. The cleaning manifold 62 is connected to the chassis body 6 via the holder 63.
1. A lifting urging unit 64 for raising and lowering the nozzle 1, a nozzle cover 65 for preventing liquid dripping from the nozzles 62 a and 62 b of the cleaning manifold 62, a cleaning liquid tank, a cleaning liquid pressure pump and a suction pump (not shown) are provided. ing.

The cleaning manifold 62 has a rectangular parallelepiped shape whose one direction is set to be long, and a pair of cleaning liquid discharge nozzles 62a and suction nozzles 62b is provided on the lower surface thereof at uniform intervals along the longitudinal direction. This suction nozzle 62
b is set longer than the cleaning liquid discharge nozzle 62a. The interval between each pair of nozzles is set equal to the interval between the wells P1 in the X direction of the assay plate P. Further, on the upper surface of the cleaning manifold 62, each cleaning liquid discharge nozzle 6 is provided.
2a and each suction nozzle 62b
The cleaning liquid pump and the cleaning liquid tank are connected to the former via a hose, and the suction pump is connected to the latter via a hose.

Reference numeral 62e designates a valve which can be opened and closed freely according to a command from the operation control unit 100. Each pump is normally continuously driven, and the cleaning liquid is discharged from the cleaning liquid discharge nozzle 62a only when this valve is opened.

Further, the positioning projections 62 f, 62 for the holder 63 are provided on the front and back surfaces of the cleaning manifold 62.
g is provided. The positioning projections 62f, 62
The g is fitted into a notch provided in the holder 63 so that the cleaning manifold 62 is positioned in the X direction.

The chassis body 61 holds the cleaning manifold via the lifting / lowering urging mechanism 64 and the holder 63 such that the longitudinal direction of the cleaning manifold 62 (the direction in which the pairs of nozzles are arranged) is parallel to the X direction. The nozzle plate is arranged on the base 11 so that each nozzle pair is located above each well P1 arranged in the X direction of the assay plate P passing through the moving region R of the assay plate and the holding frame. More precisely, the chassis main body 61 is set so that the position of each nozzle pair is the center position of the corresponding well P1 in the X direction.
Is set.

The raising / lowering urging mechanism 64 includes a guide member 64a fixedly mounted on the chassis body 61 along the Z direction, a slider 64b slidably supported along the guide member 64a, and a slider 64b along the Z direction. A screw shaft 64c rotatably mounted on the chassis main body 61 and a servo motor 64d for rotating the screw shaft 64c are provided.

The slider 64b fixedly supports the holder 63, and transmits the lifting operation to the cleaning manifold 62 via the holder 63. Also, the slider 64b
It is engaged with the screw shaft 64c via a ball screw (not shown), and the vertical movement is urged in accordance with the rotation of the screw shaft 64c.

In the lifting / lowering urging mechanism 64, the height at which the suction nozzle 62b of the cleaning manifold 62 is separated from the assay plate P and located above (the state shown in FIGS. Of the suction nozzle 62b of the assay plate P approaching the upper part of the well P1 of the assay plate P (hereinafter referred to as a discharge height),
The height of the suction nozzle 62b is adjusted in three stages of a height (a suction height) at which the tip of the suction nozzle 62b reaches the bottom surface of the well P1. Therefore, if a sensor for detecting the slider 64b at each height is provided in the chassis main body 61, a normal drive motor can be used instead of the servomotor 64d capable of controlling the rotation amount.

The holder 63 supported by the slider 64b
Is supported by the slider 64b along the X direction at a length close to the longitudinal length of the cleaning manifold 62.
The holder 63 has a U-shaped cross section as shown in FIG. 12, and its opening is directed upward. The cleaning manifold 62 is inserted into a gap in the cross-sectional shape of the holder 63. At this time, the width of the gap portion of the holder is set slightly larger than the thickness of the cleaning manifold.
There will be some play inside 3. However, since the holder 63 is provided with the spring member 63a that elastically presses the mounted cleaning manifold 62, the cleaning manifold 62 is prevented from rattling in the Y direction. As described above, the holder 63 holds the cleaning manifold 62 with play and pressing force, so that the suction nozzle 62b can be brought into contact with the inner wall surface of the well P1 with pressing force during the suction operation. ,
This makes it possible to more effectively remove the liquid in the well P1.

On the surfaces of the U-shaped holder 63 facing each other, notches 63b corresponding to the positioning projections 62f and 62g provided on the cleaning manifold 62 described above (the other notch is not shown). Are formed. The notch 63b allows the cleaning manifold 62
Are positioned and fixed in the X direction.

Further, the holder 63 is provided with an abutment roller 63c for urging the rotation of the nozzle cover 65 at an upper portion thereof. The contact roller 63c moves up and down together with the up and down operation by the slider 64b.

As shown in FIG. 12, the nozzle cover 65 has a first arm 65a facing the upper surface of the chassis body 61, and a base end connected to one end of the first arm 65a. A second arm 65b, and a tray 65c provided at the tip of the second arm 65b. The first arm portion 65a is rotatably connected to the chassis body 61 via a support shaft 65d parallel to the X direction near one end thereof, and is separated from the upper surface of the chassis body 61 at the other end. Spring 65 for pressing against
e.

The second arm portion 65b is connected to the first arm portion 6
5a is connected at substantially right angles to the first arm 65
When a is oriented in the horizontal direction, the second arm 65
The front end of b faces downward. In such a state,
The receiving tray 65c is slightly shifted from the tip of the second arm 65b to the right side in FIG. 12 so as to be located immediately below each nozzle pair of the cleaning manifold 62.
The receiving tray 65c has a length substantially equal to the length of the cleaning manifold 62 in the X direction, and is supported by the second arm 65b in parallel with the X direction. further,
The bottom of the tray 65c is inclined so that the one end (the right end in FIG. 11) in the X direction is lower, and the residual liquid dripping from the nozzles 62a and 62b is collected and discharged to the one end. A discharge port 65f is formed. A waste liquid collecting container (not shown) is provided below the outlet 65f.

The cleaning manifold 62 and the holder 63 are moved by the lifting / lowering urging mechanism 64 as described above.
The height is adjusted in three stages: retreat height, discharge height, and suction height. The contact roller 63c provided on the holder 63 is configured to move the first arm 65a of the nozzle cover 65 at the retreat height.
Is arranged so as to be horizontal and abut against the pressing spring 65e. Therefore, the cleaning manifold 62
When the holder 63 is lowered to the discharge height or the suction height, the first arm 65a is urged to rotate by the pressing spring 65e, and the receiving tray 65c is retracted from the position immediately below each nozzle pair, thereby performing the cleaning operation. Does not interfere with

(Dispensing Mechanism) As shown in FIG. 2, the dispensing mechanism 40 is disposed on the base 11 adjacent to the back side (upward in FIG. 2) of the cleaning mechanism 60 in the Y direction. The dispensing mechanism 40 includes a dispensing nozzle 4 for dispensing a sample and a reagent.
The dispensing section 41 includes the dispensing section 5 and a nozzle transport section 90 that transports the dispensing section 41 along the X direction.

Each chip T1 on the reagent / sample tray 20
The transport unit that transports the dispensing nozzle 45 to each position of T2, T3, each sample container K, each reagent bottle S, the diluent bottle, and the chip disposal unit 13 is constituted by the nozzle transport unit 90 and the stage mechanism 30 described above. Has been realized. FIG. 13 is a plan view of the nozzle transfer section 90, and FIG. 14 is a front view of the dispensing section 41. The dispensing mechanism 40 will be described based on these drawings.

First, as shown in FIG. 13, the nozzle transport section 90 is provided with a mounting table 91 (FIG. 1) provided on the substrate 11 across the moving area of the entire reagent / sample tray 20 including the holding frame 28. , 2) and the erection table 91 along the X direction.
A guide rail 92 mounted thereon, and a slider 9 that holds the dispensing section 41 and slides freely along the guide rail 92.
3, an endless belt 95 stretched along the X direction by two driven pulleys 94a and 94b, a servomotor 96 which is a driving source for conveying the endless belt 95, and an output shaft of the servomotor 96. And a reduction pulley 98 connected on the same axis as the driven pulley 94a.
And a transmission belt 99 for transmitting the torque of the driving pulley 97 to the reduction pulley 98.

The guide rail 92 is mounted on the front end of the erection table 91 along the X direction. Since the slider 93 is slidable along the guide rail 92 as described above, the dispensing section 41 can be moved to any position in the X direction. Each driven pulley 94a, 94
b and the endless belt 95 are both arranged near the guide rail 92, and the slider 93 is
and is connected to the intermediate portion of the endless belt 95 via a.
Accordingly, the X-direction positioning operation of the dispensing section 41 is urged via the slider 93 by the conveyance of the endless belt 95.

The deceleration pulley 98 and the driven pulley 94a are supported at both ends of the same shaft and are interlocked with each other. The driving pulley 97 has a smaller diameter than the reduction pulley 98, so that the rotation speed is reduced and transmitted to the reduction pulley 98. The servo motor 96 can freely control the amount of rotation, and by controlling the amount of rotation, the dispensing section 41 is positioned in the X direction.

The dispensing unit 41 includes a dispensing nozzle 45 for performing suction and discharge, and the above-described chips T1 and T1 that are detachably provided at the tip of the dispensing nozzle 45 and hold the sucked liquid sample therein. T2, T3 (these are selected as needed) and a dispensing pump 18 for energizing suction and discharge
(See FIG. 2), and an elevating unit 17 for raising and lowering the dispensing nozzle 45 along the Z direction.

The elevating unit 17 includes a housing 42 held by the slider 93 of the nozzle transfer unit 90, a guide member 43 fixedly mounted on the housing 42 along the Z direction, and a guide member 43 along the guide member 43. A slider 44 slidably supported and itself holding a dispensing nozzle 45;
2 and a screw shaft 46 rotatably mounted on the screw shaft 4
And a servo motor 47 for rotating the motor 6.

The casing 42 has a rectangular parallelepiped shape elongated in one direction, and is held by the slider 93 of the nozzle transfer section 90 so that the longitudinal direction is parallel to the Z-axis direction. The slider 44 of the dispensing section 41 is engaged with the screw shaft 46 via a ball screw, and the vertical movement is urged in accordance with the rotation of the screw shaft 46. Since the servo motor 47 can control the amount of rotation, this allows the dispensing nozzle 45 to be positioned in the Z direction via the slider 44.

The dispensing nozzle 45 is a tubular member supported by the slider 44 along the Z direction, and its base end (upper end) is connected to a dispensing pump (not shown) that urges suction and discharge via a hose. It is connected. The tip (lower end) of the dispensing nozzle 45 is a sample tip T1 and a dilution tip T.
2 or the mounting portion 45a of the reagent chip T3.

The mounting portion 45a has a small outside diameter and a small diameter portion 45b, so that the sample chip T1 and the dilution chip T2 having a small inside diameter and the reagent chip T3 having a large inside diameter can be attached. A large large diameter portion 45c is provided. That is, the sample chip T1 or the dilution chip T
15A is attached to the small diameter portion 45b as shown in FIG. 15A, and the reagent chip T3 is attached to the large diameter portion 45c as shown in FIG.

Further, the dispensing nozzle 45 is slidably held in the Z direction with respect to the slider 44, and is constantly receiving a pressing load downward by the coil spring 45d. Such a structure corresponds to each of the chips T described above.
1, T2 and T3. That is, the mounting operation of the chips T1, T2, and T3 is performed by setting the dispensing nozzle 45 to the chips T1, T2, and T3 held in the holders 23, 24, and 25 with the mounting ends facing upward. It is performed by lowering and inserting the mounting portion 45a into the mounting end. At this time, the dispensing nozzle 45
Receives a reaction force upward, the coil spring 45 d is compressed, and the dispensing nozzle 45 moves upward with respect to the slider 44. The amount of upward movement is detected by a sensor (not shown), and when the chips T1, T2, and T3 are mounted, the slider 44 and the dispensing nozzle 45 are controlled until the predetermined amount of movement is reached. T1, T2, T
3 can be made uniform. In other words, the chips T1, T2, and T3 are held in a suitable state without being too tight or too loose, thereby preventing inadvertent dropping or inconvenience that the chips cannot be pulled out. It becomes possible.

The suction / ejection urging means includes a dispensing pump connected to the dispensing nozzle 45 and a servomotor for energizing the dispensing pump. The dispensing pump includes a cylinder communicating with the dispensing nozzle and a piston for changing the internal volume thereof. The piston engages with the servomotor via the screw shaft, and the piston moves forward according to the rotation amount of the screw shaft rotated by the servomotor. The rotation direction and the rotation amount of the servo motor are controlled by the above-described operation control unit 100, thereby making it possible to freely switch between suction and discharge and to set the suction amount and the discharge amount.

(Chip Disposal Unit) As shown in FIG. 2, the transport range of the dispensing unit 41 by the nozzle transport unit 90 of the dispensing mechanism 40 is the tip end (right end in FIG. 2) of the tip. A disposal unit 13 is provided. This chip disposal unit 1
3 will be described with reference to FIG. FIG. 16A is a perspective view of the chip disposal section, and FIG. 16B is a front view.

The chip disposal section 13 includes a collection container 13a for each of the chips T1, T2, and T3 to be discarded, and a chip claw member 13 provided at the upper end of the collection container 13a.
b. The upper end of the locking claw member 13b is bent to face the dispensing portion 41 (the left side in FIG. 2), and the width of the bent portion further changes in two steps. A notch 13c is formed.

This notch 13 c is
Is located on the passing line of the dispensing nozzle 45 conveyed by the. The width of the narrow portion 13d of the notch 13c is set to be larger than the outer diameter of the small-diameter portion 45b of the dispensing nozzle 45 and smaller than the outer diameter of the mounting end of the chips T1 and T2. The width of the wide portion 13e is set to be larger than the outer diameter of the large diameter portion 45c of the dispensing nozzle 45 and smaller than the outer diameter of the mounting end of the tip T3.

The sample chip T1 by the chip disposal unit 13
Will be described. First, the dispensing nozzle 45 with the sample chip T1 mounted thereon is transported toward the chip disposal unit 13. Notch 13c of locking claw member 13b at the destination
Is located, the small-diameter portion 45 of the dispensing nozzle 45 is
b and a portion not covered by the sample chip T1 (a portion near the boundary with the large diameter portion 45c which is the small diameter portion 45b)
Is adjusted so that is inserted into the notch 13c.
The dispensing nozzle 45 is transported until the small diameter portion 45b of the dispensing nozzle 45 fits into the narrow portion 13d of the notch 13c. Then, by moving the dispensing nozzle 45 upward, only the sample tip T1 is caught by the locking claw member 13b, falls off from the mounting portion 45a of the dispensing nozzle 45, and is collected.
Collected in a.

The same operation may be performed when removing the dilution chip T2. In the case of the reagent chip T3, the vicinity of the upper end of the large-diameter portion 45c of the dispensing nozzle 45 is notched 1
3c, the dispensing nozzle 45 is transported until the large-diameter portion 45c of the dispensing nozzle 45 fits into the wide portion 13e of the notch 13c, and then the dispensing nozzle 45 is moved upward. I just need.

(Plate Cover) As shown in FIG. 2, the plate cover 12 covering the upper surface of the assay plate P held by the holding frame 28 serves as a moving area of the assay plate P with the movement of the reagent / sample tray 20. It is formed over almost the entire area. FIG. 17 is an explanatory view for explaining the positional relationship between the plate cover 12 and the assay plate P held by the holding frame 28, and FIG.
It is a perspective view of. The plate cover 12 will be described with reference to FIGS.

The plate cover 12 has a shape of a flat plate that is long in one direction. As shown in FIG. 18, the temperature maintaining mechanism 50 is in a state where its longitudinal direction is parallel to the transport direction (Y direction) of the assay plate P. And a power supply 14. Further, as shown in FIG. 17, the width of the plate cover 12 in the X direction is set to be slightly larger than the width of the assay plate P, and the stirring operation of the vibrating mechanism 80 of the assay plate P is performed below the plate cover 12. It is possible. Also, the plate cover 12
Are bent toward the assay plate P side in the X direction. Furthermore, the flat surface of the plate cover 12 is
It is supported by the temperature maintaining mechanism 50 and the power supply 14 in a state parallel and close to the upper surface of the assay plate P held by the holding frame 28. It is desirable that the distance from the upper surface of the assay plate P to the plate cover 12 is as short as possible, and is set at most 50 [mm] or less, preferably 10 [mm] or less. In the enzyme immunoreaction measuring apparatus 10, the interval is set to 3 [mm].

On the other hand, with respect to the assay plate P, the reaction measurement in the well P1, the washing of each well P1, and the dispensing of the sample / reagent into each well P1 are performed in each part of the moving area. Since each of these operations is performed from above the assay plate P, the plate cover 12 has an opening for each operation. That is, the opening 12a is provided at the location where the reaction measurement mechanism 70 is provided, the opening 12b is provided at the location where the cleaning mechanism 60 is provided, and the opening 12c is provided at the location where the dispensing mechanism 40 is provided. Have been. Each of the openings 12a, 12b, 12c is formed over substantially the entire width of the plate cover 12 in the X direction. In addition, each opening 12a, 12b, 12
The width c in the Y direction is set to be at least larger than the diameter of the opening of the well P1 of the assay plate P (for example, about 1 to 2 times the diameter).

Accordingly, the plate cover 12 does not hinder each of these operations, and the wells P1 of all the wells P1 of the assay plate P being conveyed or the other wells P1 waiting for the operation in each operation. With regard to, since the opened upper portion is covered with the plate cover 12, it is possible to effectively suppress evaporation of water in the sample or the reagent in the well P1.

In particular, in the enzyme immunoreaction measuring apparatus 10, since the fan 16 is mounted on the apparatus cover 15, air convection occurs inside the apparatus cover 15, and the holding frame 28
When each well P1 of the upper assay plate P is exposed to the convection air, the moisture in the well P1 evaporates and tends to dry, but the opening of each well P1 of the assay plate P is covered by the plate cover 12. Therefore, it is possible to effectively avoid such water evaporation and drying.

Here, each of the openings 12a, 12b, 12c
May be equipped with a lid member that can be opened and closed. For example, it is desirable that the lid member be a plate-like member slidably provided along the flat surface of the plate cover 12 and that an opening / closing mechanism for urging the lid member be provided. In this case, the opening / closing mechanism includes a rack provided on the lid member along the sliding direction, a pinion gear engaged with the rack provided on the plate cover 12, a drive motor for driving the pinion gear, and a conveyed assay. When configured with a sensor that detects the plate P, by controlling the drive motor to slide the cover member to open the opening when the assay plate P is detected by the sensor,
The opening can be opened only when the assay plate P is transported.

The opening / closing mechanism may be configured so as to perform the opening / closing operation in accordance with the operation control section 100 for controlling the operation of the enzyme immunoreaction measuring device 10 except for the sensor. That is, by controlling the operation of opening the lid member of any of the openings 12a, 12b, and 12c in synchronization with the timing at which the operation of the cleaning mechanism 60, the reaction measurement mechanism 70, or the dispensing mechanism 40 is performed, 40 of the mechanism,
Since the opening is opened only at the time of operation of 60 or 70, it is possible to further prevent drying in each well P1 of the assay plate P.

(Operation Control Unit) Next, the operation control unit 100 will be described. The operation control unit 100 is composed of a personal computer, and is described below.
And the operation control of the enzyme immunoreaction measuring apparatus 10 based on the configuration are realized by a program stored in a personal computer.

FIG. 19 is a block diagram showing the configuration of the operation control unit 100 and the objects controlled by the operation control unit 100. As shown in this figure, the operation control unit 100 includes a main control unit 101 that controls each operation of the cleaning mechanism 60, the reaction measurement mechanism 70, and the vibration mechanism 80, and controls the operation of transporting the assay plate P by the stage mechanism 30 to them. , Display means 102 for displaying measurement results, elevating unit 17, dispensing pump 18
Dispensing control means 1 for controlling the dispensing operation by the nozzle transport unit 90 and the operation of the stage mechanism 30 accompanying the dispensing operation
10, a position memory 103 for storing position data of a positioning target of the dispensing nozzle 45 in the dispensing operation, and a pump operation storing data of the set discharge amount and the set suction amount of the dispensing pump 18 in the dispensing operation. Quantity memory 104
And input means 105 for updating data stored in the position memory 103 and the pump operation amount memory 104.

In the main control means 101, the entire operation of the enzyme immunoreaction measuring apparatus 10 except for the dispensing operation is set, and the cleaning mechanism 60, the reaction measuring mechanism 70, and the vibrating mechanism 80 are set in accordance with the setting operation procedure. The operation of the stage mechanism 30 is controlled. The specific control operation will be described in detail later in the operation description. The display means 102 is realized by a monitor of a personal computer.

The dispensing control means 110 comprises a main control means 101
, The position data relating to the liquid sample is stored in the position memory 103, and the suction / discharge data relating to the liquid sample is pump operation amount. The dispensing operation control is started with reference to the memory 104.

The dispensing control means 110 positions the dispensing nozzle 45 to the position where the chip corresponding to the target liquid sample is held by the transport unit (cooperation of the nozzle transport unit 90 and the stage mechanism 30). At the same time, a tip mounting control unit 111 for lowering and mounting the dispensing nozzle 45 on the chip by the elevating unit 17 and a dispensing nozzle 4 by the transport unit.
And a suction positioning control unit 112 for positioning the dispensing nozzle 18 at the position of the container containing the liquid sample, and the dispensing pump 18 after the positioning of the dispensing nozzle 18 by the suction positioning control unit 112 and before the suction of the liquid sample. Suction control unit 113 for performing the suction operation of
The liquid dispensing nozzle 45 is lowered by the dispensing pump 45 with respect to the container containing the liquid sample, and the dispensing pump 18 performs the suction operation.
Is dispensed with the dispensing nozzle 45 with respect to the discharge container by the elevating unit 17 by positioning the liquid container to which the liquid sample sucked is discharged.
The discharge control unit 115 causes the dispensing pump 18 to perform a discharging operation while the dispensing pump 18 moves down, and the dispensing nozzle 4
5 is positioned at a predetermined chip removal position of the chip disposal unit 13, and the dispensing nozzle 45 at the chip removal position is separated from the dispensing nozzle 45 by the elevating unit. A tip withdrawal control unit 117 for raising, and a dispensing pump 18 in accordance with this raising operation
And a control unit 118 for preventing the remaining liquid from scattering.

The specific control operation by the dispensing control means 110 will be described in detail in steps S21 to S27 of the operation description to be described later.

The position memory 103 stores the individual chip mounting positions (each sample chip T1, each dilution chip T) when the object of the dispensing operation is each sample, each reagent and diluent.
2, each holding position of each reagent chip T3), suction position (each sample container K, each reagent bottle S, diluent bottle, each position of each well U1 of the dilution plate U in the recess 28b), discharge position (dilution plate) U, each position of each well U1, each position of each well P1 of the assay plate P) and a chip disposal position (a notch 13 of the locking claw member 13b of the chip disposal unit 13).
The position data of each of the narrow portion 13d and the wide portion 13e of (c) is stored. Then, the dispensing control means 110 refers to position data corresponding to the type of the target liquid sample.

The position data is stored as coordinate data in the X, Y, and Z directions. Therefore, at the time of each positioning described above, the nozzle transport unit 90 is driven according to the coordinate data of the corresponding target position in the X direction, and the stage mechanism 30 is driven according to the coordinate data of the corresponding target position in the Y direction. When the dispensing nozzle 45 is moved up and down, the elevating unit 17 is driven according to the coordinate data in the Z direction of the target position. The coordinate data in the Z direction includes, for example, the insertion depth of the dispensing nozzle 45 when mounting the tip, the height of the dispensing nozzle 45 during suction / discharge, and the locking of the tip to the locking claw member 13b when removing the tip. Height, etc., corresponds to this.

The pump operation amount memory 104 stores the suction amount, the discharge amount, the empty suction amount when performing the empty suction, and the discharge amount when the chip is removed according to the type of the object of the dispensing operation. The dispensing control means 110 refers to the position data corresponding to the type of the target liquid sample.

The input means 105 comprises a personal computer keyboard. The input means 105 inputs position data, set discharge amount data, and suction amount data as necessary, and the stored data is updated in the position memory 103 or the pump operation amount memory 104.

(Explanation of Operation of Enzyme Immune Reaction Measuring Apparatus) The operation of the enzyme immunoreaction measuring apparatus 10 will be described with reference to FIGS. 2, 20 and 21. FIG. 20 is a flowchart showing the order of operation of the enzyme immunoreaction measurement device 10. In addition,
Here, for convenience of explanation of the operation, the upward direction in FIG. 2 is referred to as a feed direction, the downward direction is referred to as a return direction, the left direction in FIG. 2 is referred to as a left direction, and the right direction in FIG. Shall be referred to as

The operation of the enzyme immunoreaction measuring apparatus 10 described below is realized by controlling the operation of the enzyme immunoreaction measuring apparatus 10 according to the program executed in the operation control section 100 described above.

As preparation for the enzyme immunoreaction measurement, first, the assay plate P is placed in the concave portion 28a on the holding frame 28, and the dilution plate U is placed in the concave portion 28b. In addition,
When placing the assay plate P, the temperature holding mechanism 5
0 while the holding frame 28 is conveyed inside the temperature holding mechanism 5.
Through 0.

The reagent bottle S containing the reagent used for the measurement and the diluent bottle containing the diluent as the liquid sample are placed in the reagent stocker 21 of the reagent / sample tray 20, and the reagent chip T 3 is placed in the reagent chip stocker 25. set. Further, a sample chip stocker 23 holding the sample chip T1, a dilution chip stocker 24 holding the dilution chip T2,
The sample stockers 22 holding the sample containers K are set on the reagent / sample tray 20, respectively.

When the preparation is completed, the operation of the enzyme immunoreaction measuring device 10 is started. First, the sample is diluted in the first step. At the time of this dilution, first, a diluent is dispensed into each well U1 of the dilution plate U (step S1). Here, the dispensing operation will be described based on the flowchart of FIG. 21 showing the details.

For dispensing such a diluent, a reagent chip T3
Is used, the dispensing nozzle 45 is positioned at the tip position of the reagent chip stocker 25 by the cooperation of the stage mechanism 30 and the nozzle transfer section 90 of the dispensing mechanism 40, and the dispensing nozzle 45 is moved by the elevating section 17. Is lowered to mount the reagent chip T3 (Step S21: mounting step).

Next, the dispensing nozzle 45 is connected to the reagent stocker 21.
(Step S2)
2). Then, a predetermined amount of air is sucked in advance before sucking the diluent (step S23: empty sucking step). This air suction is performed in order to secure the discharge air since the air is discharged almost simultaneously with the subsequent removal of the chip T3. The suction amount is, for example, the inside of the chip to be withdrawn. 100 [%] of the volume is sufficient, preferably 30 [%].
It is set to about 50 [%].

Next, after the dispensing nozzle 45 is lowered, the dispensing pump 18 is driven to suck a fixed amount of diluent into the reagent chip T3 (step S24). Such suction may be performed to near the limit volume of the tip T3 (the level of the sucked diluent does not reach the tip of the dispensing nozzle 45), but the necessary amount (the discharge amount for one well U1 × the number of used wells) Is known, it is aspirated by the required amount.

On the other hand, the plate U for dilution is
By 0, the dispensing nozzle 45 is transported to the moving range. At this time, the dilution plate U is placed in the well U in the front row in the feed direction.
1 is positioned in the movement range of the dispensing nozzle 45. Then, the dispensing nozzle 45 is positioned at the rightmost well U1 in the front row of the dilution plate U by the nozzle transport unit 90 (step S25).

After the positioning, the dispensing nozzle 45 is lowered to the dispensing height, and then the diluent is discharged (step S2).
6). Then, the dispensing nozzle 45 is transported leftward at every arrangement interval of the well U1 in the X direction, and dispensing is performed in the same manner. Further, when the dispensing of the front row is completed, the dilution plate U is transported in the feed direction by the stage mechanism 30 at every arrangement interval in the Y direction of the well U1 in the following rows, and dispensing is performed in the same manner.

In such a dilution operation, since the discharge amount of the diluent for each well U1 is known in advance by the dilution ratio, it is possible to calculate in advance how many wells the diluent in the reagent chip T3 corresponds to. Therefore, if necessary, a replenishing operation may be performed such that the diluent is replenished during the dispensing of the diluent to the dilution plate U.

When the diluent is dispensed to all the wells U1, the dispensing nozzle 45 is transported to the chip discarding unit 13 and the reagent chip T3 is discarded. At this time, the used reagent chip T2 is withdrawn.

To explain this, first, the dispensing nozzle 45 is conveyed to the chip disposal section 13 side and enters the notch 13c of the locking claw member 13b. At this point still chip T3
Is located below the locking claw member 13b.
By transporting the dispensing nozzle 45 upward, the chip T3
Only the hook is caught by the locking claw member 13b and separated from the tip of the dispensing nozzle to drop off.
Around the start of the upward transfer of the dispensing nozzle 45, the discharge operation by the dispensing pump 18 is started.

The start of the upward transfer of the dispensing nozzle 45 and the start of the discharging operation may be simultaneous or before and after, but the separation is performed after the chip T3 starts moving in the direction in which the chip T3 is disengaged from the dispensing nozzle 45. It is necessary to perform the discharge before this, and to suppress a decrease in the internal pressure of the chip T3.

The separation timing of the chip T3 is the same as that of the chip T3 (although the same applies to the other chips T1 and T2).
Is attached to the tip of the dispensing nozzle with a constant pressing force, so that the overlap length (insertion length) is substantially uniform for each tip T3. Therefore, since the overlap length is known in advance, if the upper end of the tip T3 is at substantially the same height as the locking claw member 13b of the tip disposal section 13, the dispensing nozzle 45
Is moved upward by a distance substantially equal to the overlap length, it can be regarded as the separation timing of the chip T3.

It is most preferable that the ejection be performed continuously after the chip T3 starts moving in the direction in which the chip T3 is separated from the chip T3 until the chip T3 is completely separated. Since the pressure drop in T3 is suppressed, the effect of suppressing the residual diluting liquid from scattering toward the dispensing nozzle 45 can be obtained.

[0145] The same can be said for the dispensing of a sample or each reagent, which will be described later. However, the empty suction step in step S23 does not need to be performed immediately before the diluting liquid suction step. Any other timing may be used.

Next, a sample is dispensed into each well U1. The dispensing of the sample is performed in substantially the same process as the dispensing of the diluent described above. That is, the dispensing nozzle 45 is transported to the sample chip holder 26 by cooperation of the stage mechanism 30 and the nozzle transfer unit 90, and the sample chip T1 is mounted at any of the chip positions. After the tip is mounted, the dispensing nozzle 45 is transported to the sample stocker 22, is positioned in any of the sample containers K, sucks a predetermined amount of the sample after the empty suction is performed. At this time, the sample chip T1 and the sample container K may also be sequentially selected from the right in the front row in the feed direction.

After the sample is aspirated, the dispensing nozzle 45 discharges the sample onto the dilution plate U. At this time, the sample is discharged to the well U1 on the left side of the front row in the feed direction of the dilution plate U. After the discharge, the sample chip T1 is discharged to the chip discarding unit 13 while the discharge by the dispensing pump 18 is urged. And is discarded. Then, each sample is discharged to the corresponding well U1 in the same procedure.

When the ejection of each sample to each well U1 of the dilution plate U is completed, the vibrating mechanism 80 operates for a certain period of time to stir the inside of each well U1 (step S).
2).

On the other hand, each well P1 of the assay plate P
, A predetermined amount of diluent is dispensed (step S).
3). The dispensing operation of the diluent at this time is the same as that in step S1. That is, the reagent tip T3 is mounted on the dispensing nozzle 45, the suction is performed, the diluent is sucked, the dispensing nozzle 45 is positioned in each well P1, and the diluent is discharged. It is withdrawn and discharged along with the discharge operation.

Next, the diluted sample in each well U1 of the dilution plate U is transferred to the corresponding well P1 of the assay plate P (step S4). That is, the well row in the front row of each of the assay plate P and the dilution plate U in the feed direction is positioned in the transport area of the dispensing nozzle 45. At this time, the well row of the assay plate P is positioned at a position viewed from the opening 12 c of the plate cover 12.

This transfer operation is performed in substantially the same steps as the above-described dispensing of the diluent. That is, after the diluting tip T2 is attached to the dispensing nozzle 45 and the empty suction is performed, a predetermined amount of the sample in the well U1 is aspirated.
Is transported to the corresponding well P1 of the assay plate P.
The used chip T2 is withdrawn and discarded together with the discharging operation. This operation is repeated for each well U1. Thereby, each specimen is further diluted.

In this transfer step, the well U1 of the dilution plate U functions as a container for holding a liquid sample, and at the same time, the concave portion 28b functions as a liquid sample placement section.

Next, the assay plate P is transported into the temperature maintaining mechanism 50 by the stage mechanism 30. In this temperature maintaining mechanism 50, the assay plate P
The temperature is kept at a more suitable temperature. Furthermore, the assay plate P is agitated by the vibration mechanism 80 in order to homogenize or promote the reaction between the reagent applied in advance to the assay plate P and each sample. The stirring may be performed after the stage is moved outside the temperature maintaining mechanism 50 by the stage mechanism 30 (step S5).

When the temperature is maintained by the temperature maintaining mechanism 50 for a predetermined time, each well P1 of the assay plate P is washed (step S6). First, at the time of cleaning, the cleaning tank 2 provided on the holding frame 28 by the transport of the stage mechanism 30 is used.
9 is positioned directly below the row of each nozzle pair of the cleaning mechanism 60. At this time, the cleaning tank 29 is positioned at a position where the cleaning tank 29 is viewed from the opening 12b of the plate cover 12.

Then, the cleaning manifold 62 is immediately lowered from the retracted height to the suction height, and the cleaning liquid discharge nozzle 6
2a is connected to the operating cleaning liquid pressure pump and the suction nozzle 6 is connected.
Connect 2b to the active suction pump. As a result, the cleaning liquid is discharged into the cleaning tank 29, and the tip of the suction nozzle 62b is cleaned and the cleaning liquid is sucked. And
After a certain period of time, the connection between the cleaning liquid discharge nozzle 62a and the pump is disconnected, and then the connection between the suction nozzle 62b and the pump is disconnected. Thereby, all the cleaning liquid in the cleaning tank 29 is sucked. Then, the cleaning manifold 62
Is returned to the evacuation height.

Next, the assay plate P is transported by the stage mechanism 30 to a position corresponding to the washing mechanism 60.
At this time, the front row in the feed direction of the well P1 of the assay plate P is positioned immediately below the row of each nozzle pair of the cleaning mechanism 60, and the well row is located in the opening 12 of the plate cover 12.
b. Then, the cleaning manifold 62 is lowered from the retracted height to the suction height, and the suction nozzle 62b enters each well P1 through the opening 12b. In this state, the sample in the well P1 in the front row is sucked by connecting the suction nozzle 62b to the operating suction pump. Then, the cleaning manifold 62 is raised to the discharge height, and the cleaning liquid is discharged from the cleaning liquid discharge nozzle 62a. Further, the cleaning manifold 62 is lowered to the suction height, and the cleaning liquid in the well P1 is suctioned. When the discharge and suction of the cleaning liquid are repeated a set number of times, the cleaning manifold 62 is returned to the retracted height, and the assay mechanism P is sent to the next row by the stage mechanism 30, and the same cleaning is performed. By performing this washing operation for all rows, washing is performed for all wells P1 of the assay plate P.

Here, the sample in each well P1 is washed away by the above-mentioned washing. However, since each sample has penetrated into the reagent applied in advance to the well P1, the reaction has already been performed. It does not affect the measurement results performed in later steps.

Next, each well P1 of the assay plate P
Next, the first reagent (enzyme-labeled antibody solution) is dispensed (step S7). The dispensing operation of the first reagent is performed in substantially the same manner as the dispensing operation of the diluent in step S3. That is,
The well row P1 of the assay plate P is the plate cover 1
The reagent tip T3 is mounted on the dispensing nozzle 45, the first reagent is sucked after the empty suction, and the dispensing nozzle 45 is positioned on each well P1 to perform the first dispensing. The reagent is discharged, and then the reagent chip T3
Is removed together with the discharging operation and discarded.

Assay plate P after dispensing the first reagent
In the process, agitation and heat retention are performed by the same operation as step S5 (step S8). Then, after keeping the temperature for a predetermined time, the inside of each well P1 is cleaned by the same operation as step S6 (step S9).

Further, after the washing of the first reagent, the second reagent (color-forming substrate solution) is dispensed by substantially the same operation as in step S7 (step S10), and subsequently, the same operation as in step S8 Agitation and heat retention are performed (step S11).

After keeping the temperature for a predetermined time, the third reagent (stop solution) is dispensed into each well P1 of the assay plate P by the same operation as step S7 (step S1).
2).

Then, when this third reagent is dispensed,
The absorbance of each well P1 is measured for measuring the enzyme immunoreaction (step S13). This absorbance measurement is performed by the reaction measurement mechanism 70. In the reaction measurement mechanism 70, as a preparation for measurement, the irradiation light of the halogen lamp 71a is set in a state where there is nothing between the irradiation unit 71 and the sensor holder 72 and the through hole 73b is selected by the filter selection means 74. Is received by the photodiode 72a. The operation control unit 100 stores the sensor output at this time as blank data for correcting the subsequent measurement data.

Next, the front row of the well P1 in the feeding direction of the assay plate P is irradiated by the irradiation mechanism 71 by the stage mechanism 30.
And the sensor holder 72. At this time, the well row is positioned at a position viewed from the opening 12a of the plate cover 12. Further, the filter selection means 7
In step 4, the band-pass filter 73a corresponding to the measurement is selected, and the positioning urging means 79
Is positioned just below the well P1 located on the rightmost side.

Then, the halogen lamp 71a is turned on to irradiate the well P1 through the opening 12a, and the absorbance is measured by detecting the light transmitted through the well P1 by the photodiode 72a. Each time the slider 78 is moved to the left by one interval of the well P1 by the positioning urging means 79, the absorbance of each well P1 is measured.
By transporting to the next row according to 0, and repeating these, the absorbance measurement is performed for all the wells P1 on the assay plate P.

The above measurement results are all stored in the operation control unit 100, and corrective measurement results can be obtained by performing the above-described correction using the blank data. The obtained measurement result is displayed by the display means 102.

As described above, the enzyme immunological reaction measuring device 10
Is a reagent / sample tray 20, a stage mechanism 30 for transporting the same, a dispensing mechanism 40 for dispensing a sample or a reagent, a temperature maintaining mechanism 50 for the assay plate P, and a well P1.
The washing mechanism 60, the reaction measuring mechanism 70, and the vibrating mechanism 80 for the assay plate P are all provided in a single unit. It has become possible to automate a series of operations of dispensing reagents, keeping the assay plate P warm, washing, stirring, and measuring the reaction.

The dispensing section 41 of the dispensing mechanism 40 can reciprocate crossing the reciprocating movement area of the reagent / sample tray 20, and the holding frame 28
And a temperature maintaining mechanism 5 adjacent to the mounting portion side of the holding frame 28 in the movement area of the reagent / sample tray 20.
0, since the washing mechanism 60 and the reaction measuring mechanism 70 are arranged, the assay mechanism P is transported by the stage mechanism 30 to any of the dispensing mechanism 40, the temperature maintaining mechanism 50, the washing mechanism 60, and the reaction measuring mechanism 70. Is possible.
Therefore, it is not necessary to provide independent transport mechanisms for transporting the reagent / sample tray 20 and transporting the assay plate P, and it is possible to improve the productivity by reducing the number of parts and to reduce the size and weight of the apparatus. is there.

Further, since the transporting section 80 of the dispensing mechanism 40 transports the dispensing section 41 along the direction orthogonal to the reciprocating movement direction of the reagent / sample tray 20, the transfer for the reagent / sample tray 20 and the assay plate P is performed. The positioning of the injection nozzle 45 can be obtained by calculation in a rectangular coordinate system, and the calculation process can be easily performed.

Further, the holding frame 28 is made to protrude from the end of the reagent / sample tray 20, and the housing 52 of the temperature maintaining mechanism 50 is
The structure in which the portion overlapping the moving region R of the assay plate and the holding frame is cut out, so that the assay plate P and the holding frame 28 are moved by the movement of the reagent / sample tray 20 so that the casing 52 of the temperature maintaining mechanism 50 is moved. It can be transported inside. Therefore, when maintaining the temperature,
There is no need to provide an independent mechanism for accommodating and removing the assay plate P with respect to the temperature maintaining mechanism 50, and it is possible to further improve productivity by reducing the number of parts and to reduce the size and weight of the apparatus. is there.

Also, in the enzyme immunoreaction measuring apparatus 10, the vibration mechanism 80 for vibrating the assay plate P via the holding frame 28 is provided on the reagent / sample tray 20, so that the vibration mechanism 80 There is no need to provide an independent transporting means for transporting P, and it is possible to further improve productivity by reducing the number of parts and to reduce the size and weight of the apparatus.

Further, the holding frame 28 has recesses 2, which are regions where the assay plate P and the dilution plate U are arranged, respectively.
Since 8a and 28b are provided, it is possible to dilute to a lower concentration by diluting in advance with the dilution plate U and further diluting with the assay plate P.
Furthermore, since the stirring operation can be performed simultaneously on the assay plate P and the dilution plate U via the holding frame 28, the working time can be reduced, and the dilution plate U can be used. Therefore, it is not necessary to provide an independent vibration mechanism, and it is possible to further improve productivity by reducing the number of parts and to reduce the size and weight of the apparatus.

Further, in the enzyme immunoreaction measuring apparatus 10, since the dispensing pump 18 performs a discharging operation when each of the chips T1, T2, and T3 is withdrawn, each chip T
Even when the pressure drop in T1, T2, and T3 is suppressed, and a liquid sample such as a specimen, a reagent, or a diluent remains in the chip, a phenomenon in which the remaining liquid sample is drawn to the dispensing nozzle 45 side. Can be suppressed. Therefore, it is possible to effectively prevent the residual liquid sample from scattering and adhering to the dispensing nozzle 45 at the moment of withdrawal of each chip, and the adhering liquid sample becomes a new liquid when the dispensing mechanism 40 is used next time. It is possible to prevent the sample itself from being mixed and improve the test accuracy of the sample test.

Further, each of the above-mentioned chips T1, T2, T3
When the discharge operation of the dispensing pump 18 is to be performed continuously from the start of the movement of the tip in the separating direction to the separation of the tip when the tip is withdrawn, the pressure drop in the conventional tip is reduced. The pressure drop in the chip is consistently suppressed until the chip is separated from the point when the test started, and it is possible to more effectively prevent the scattering of the residual liquid sample and more effectively improve the test accuracy. .

Furthermore, since each liquid sample is sucked before suction by the dispensing nozzle 45, the cylinder type dispensing pump 18 for urging suction and discharge by a change in internal volume.
Even in this case, it is possible to secure in advance an atmosphere for urging the ejection at the time of chip removal, and it is possible to always suppress the scattering of the liquid sample at the time of chip removal.

Note that a locking claw member 13f shown in FIG. 22 may be used instead of the locking claw member 13b of the chip disposal section 13 described above. The locking claw member 13f is composed of a pair of a wedge-shaped body 13i having a plane portion 13g parallel to the X and Y directions and an inclined surface portion 13h inclined more than the plane portion 13g. The inclined surface portion 13h is inclined so as to go downward as it goes to the right in FIG. The two wedge-shaped members 13i are supported with a constant gap along the X direction, and the width of the gap is set wider than the outer diameter of the tip of the dispensing nozzle 45 and smaller than the outer diameter of the tip. I have. Further, each wedge-shaped body 13i is supported such that the height of the left end of the inclined surface 13h in FIG. 2 is slightly higher than the upper end of the tip mounted on the dispensing nozzle 45. According to the locking claw member 13f, the raising / lowering operation of the dispensing nozzle 45 can be unnecessary for the chip removing operation. That is, when the dispensing nozzle 45 is transported rightward by the nozzle transport unit 90, the upper end of the chip is placed in each wedge-shaped body 1.
3i comes into contact with the inclined surface 13h, and only the chips are pushed down and fall off from the dispensing nozzle 45 with the conveyance.

In the case of using the chip discarding section provided with the locking claw member 13f, the dispensing operation control means 1 described above is used.
The ten chip removal controller 117 separates the dispensing nozzle 45 located at the chip removal position (immediately before the locking claw member 13f, that is, the left side in FIG. 2) from the dispensing nozzle 45 by the nozzle transport unit 90. The scattering prevention control unit 118 performs an operation control of causing the dispensing pump 18 to perform a discharge operation in accordance with the transfer operation from the withdrawal position.

Since the enzyme immunoreaction measuring apparatus 10 uses two kinds of chips having different outer diameters, the above-mentioned engaging claw member 13f needs to be one corresponding to the outer diameter of each chip. . In this case, the locking claw member 13f corresponding to the chip having a large diameter is arranged on the upstream side in the transport direction (left side in FIG. 2).

[0178]

According to the first, fifth and sixth aspects of the present invention, the discharge operation of the dispensing pump is performed when the chip is withdrawn, so that the pressure drop in the chip due to the withdrawal is suppressed and the inside of the chip is reduced. Even when the liquid sample remains, the phenomenon that the liquid sample is drawn to the dispensing nozzle side is suppressed. Therefore, it is possible to effectively prevent the residual liquid sample from scattering and adhering to the dispensing nozzle at the moment of chip removal, and the adhering liquid sample is mixed with a new liquid sample at the next use of the dispensing mechanism. This makes it possible to improve the test accuracy of the sample test.

Further, according to the present invention, it is possible to carry out a test quickly without having to reduce the chip removal speed as in the prior art, and to provide a pressure detection sensor in the device as in the conventional case. There is no need to improve the productivity of the device.

According to the second and seventh aspects of the present invention, the discharge operation of the dispensing pump is started at least when the chips are withdrawn after the chips are moved in the separating direction and before the chips are separated. Therefore, the pressure drop in the chip is suppressed from the time when the pressure drop in the chip starts to the time when the residual liquid sample is scattered, and the driving time of the dispensing pump is reduced while the same time as in the first aspect of the present invention. It is possible to prevent the liquid sample from adhering to the dispensing nozzle and improve the test accuracy.

According to the third and eighth aspects of the present invention, the discharge operation of the dispensing pump is performed continuously from the start of the movement of the chip in the separating direction to the separation of the chip when the chip is withdrawn. Therefore, the pressure drop in the chip is consistently suppressed from the point when the pressure drop in the chip has begun until the chip separates, preventing the scattering of the residual liquid sample more effectively, and improving the test accuracy more effectively. Can be improved.

According to the fourth and ninth aspects of the present invention, since the liquid sample is sucked empty before the liquid sample is sucked by the dispensing nozzle, the dispensing pump which changes its internal volume to urge suction and discharge is used. Even so, it is possible to secure in advance an atmosphere for urging the ejection at the time of chip removal, and it is possible to always suppress the scattering of the liquid sample at the time of chip removal.

Since the present invention is constructed and functions as described above, according to the present invention, it is possible to provide an unprecedented excellent sample test apparatus.

[Brief description of the drawings]

FIG. 1 is a perspective view schematically showing an arrangement of each part of an enzyme immunoreaction measuring device according to an embodiment.

FIG. 2 is a plan view schematically showing an arrangement of each part of the enzyme immunoreaction measuring device.

FIG. 3 is a view showing an assay plate used in the enzyme immunoreaction measurement device, FIG. 3 (A) is a plan view of the assay plate, and FIG. 3 (B) is a sectional view of the assay plate as viewed from the front. is there.

FIG. 4 is a perspective view of a reagent / sample tray during a test.

5A is a plan view of the holding frame, and FIG. 5B is a cross-sectional view taken along line WW in FIG. 5A.

FIG. 6 is an exploded perspective view of a vibration mechanism.

FIG. 7 is a plan view of the stage device.

FIG. 8 is a perspective view showing the housing with the lid opened.

FIG. 9 is a perspective view showing a relationship between a moving area of an assay plate and a holding frame and a cutout of a housing of a temperature maintaining mechanism.

10 (A) is a front view of a reaction measuring mechanism, FIG.
0 (B) is a side view.

FIG. 11 is a front view of a cleaning mechanism.

FIG. 12 is a left side view in which a part of a cleaning mechanism is omitted.

FIG. 13 is a plan view of a nozzle transfer section of the dispensing mechanism.

FIG. 14 is a front view of a dispensing unit of the dispensing mechanism.

15A and 15B are explanatory diagrams showing attachment of a chip at the tip of a dispensing section, where FIG. 15A shows a state where a sample chip is mounted, and FIG. 15B shows a state where a reagent chip is mounted. Is shown.

FIG. 16 (A) is a perspective view of a chip disposal section, and FIG. 16 (B) is a front view.

FIG. 17 is an explanatory diagram illustrating a positional relationship between a plate cover and an assay plate held by a holding frame.

FIG. 18 is a perspective view of a plate cover.

FIG. 19 is a block diagram showing a control system of the enzyme immunoreaction measuring device.

FIG. 20 is a flowchart showing the order of operations of the enzyme immunoreaction measurement device.

FIG. 21 is a flowchart showing the dispensing operation of the enzyme-linked immunosorbent assay in detail.

FIG. 22 is a perspective view showing another example of the locking claw member.

[Explanation of symbols]

 Reference Signs List 10 Enzyme immunoreaction measurement device (sample test device) 17 Elevating unit 18 Dispensing pump 21 Reagent stocker 22 Sample stocker 23 Sample chip stocker (chip holding unit) 24 Dilution chip stocker (chip holding unit) 25 Reagent chip stocker ( Chip holding portion) 28a Recess (discharge container disposition portion) 28b Recess (liquid sample disposition portion / discharge container disposition portion) 30 Stage mechanism (transport portion) 40 Dispensing mechanism 45 Dispensing nozzle 90 Nozzle transport portion (transport portion) 100 Operation Control unit 112 Suction positioning control unit 113 Empty suction control unit 114 Liquid suction control unit 116 Withdrawal positioning control unit 117 Chip withdrawal control unit 118 Remaining liquid scattering prevention control unit K Sample container (container containing liquid sample) P1 well (discharge) Container) S Reagent bottle (Container containing liquid sample) T1 Sample chip (Chip) T2 Dilution Chip (chips) T3 reagent tip (tip) U1 wells (container dispensing container / liquid sample containing)

Claims (9)

[Claims] 1. A dispensing nozzle for aspirating and discharging a liquid sample, a dispensing pump for urging the aspirating and discharging operations of the dispensing nozzle, and a detachably superimposed equipment at a tip of the dispensing nozzle. A dispensing method for a sample test apparatus, comprising: a tip for temporarily holding a sucked liquid sample inside the dispensing nozzle; and a mounting step of mounting the tip on a tip end of the dispensing nozzle; A suction step of sucking the liquid sample through a tip, a discharge step of discharging the sucked liquid sample to a predetermined container, and a withdrawal step of withdrawing the tip from the tip of the dispensing nozzle, The dispensing method of a sample test apparatus, wherein the withdrawing step involves discharging the dispensing pump when removing the chip. 2. In the withdrawal step, the withdrawal of the chip is performed by a relative separation operation between the dispensing nozzle and the chip, and the discharge operation of the dispensing pump is 2. The specimen according to claim 1, wherein after the dispensing nozzle and the tip start moving in the separating direction, the dispensing nozzle has started at least until the tip is separated from the tip of the dispensing nozzle. Dispensing method of test equipment. 3. In the withdrawal step, the withdrawal of the chip is performed by a relative separating operation between the dispensing nozzle and the chip, and the discharge operation of the dispensing pump is 2. The dispensing method of the sample test apparatus according to claim 1, wherein the dispensing nozzle and the tip are continuously moved from the start of movement in the separating direction until the tip is separated from the tip of the dispensing nozzle. 4. The dispensing pump urges suction and discharge by a change in the internal volume of the dispensing pump. Prior to the suctioning step, an empty suction step in which the dispensing pump sucks air is provided. Claims 1 and 2
Or the dispensing method of the sample test apparatus according to 3. 5. A dispensing nozzle for aspirating and discharging a liquid sample, a dispensing pump for energizing the aspirating and discharging operations of the dispensing nozzle, and a detachably mounted superposedly mounted tip of the dispensing nozzle. A dispensing mechanism having a tip for temporarily holding the sucked liquid sample therein and an elevating unit for elevating the dispensing nozzle, a tip holding unit for holding the tip before mounting, A liquid sample disposing section for disposing a container containing a liquid sample, a discharge container disposing section for disposing a discharge container from which the liquid sample is discharged, and a chip discarding section for removing a chip by raising the dispensing nozzle. A transport unit that transports the dispensing nozzle to each of the chip holding unit, the liquid sample placement unit, the discharge container placement unit, and the chip disposal unit; and an operation control unit that controls the operation of each unit. The department is A withdrawal positioning control unit that positions the dispensing nozzle to a predetermined chip withdrawal position of the chip disposal unit by the transport unit; and the dispensing nozzle that is at the chip withdrawal position by the lifting unit. A sample test apparatus comprising: a tip removal control unit that raises a liquid until it is separated; and a remaining liquid scattering prevention control unit that causes the dispensing pump to perform a discharge operation in accordance with the raising operation. 6. A dispensing nozzle for aspirating and discharging a liquid sample, a dispensing pump for energizing the aspirating and discharging operations of the dispensing nozzle, and a detachably mounted superposedly mounted tip of the dispensing nozzle. Dispensing mechanism having a tip for temporarily holding the sucked liquid sample therein, a tip holding section for holding the tip before mounting, and a liquid sample disposing section for disposing a container containing the liquid sample A discharge container disposition unit for disposing a discharge container from which the liquid sample is discharged, a chip disposal unit for separating chips by a transport operation of the dispensing nozzle, a chip holding unit, a liquid sample disposition unit, and a discharge container A transport unit that transports the dispensing nozzle to each of an arrangement unit and a chip disposal unit; and an operation control unit that controls the operation of each unit. The operation control unit predicts the dispensing nozzle by the transport unit. A withdrawal positioning control unit that positions the chip to a predetermined chip withdrawal position of the chip disposal unit, and a chip withdrawal control by which the dispensing nozzle at the chip withdrawal position is transported by the transport unit until the chip is separated. A sample test apparatus comprising: a dispensing unit; and a residual liquid scattering prevention control unit that causes the dispensing pump to perform a discharging operation in accordance with a transport operation for withdrawal. 7. The dispensing pump according to claim 5, wherein the remaining liquid scattering prevention control section starts the discharge operation of the dispensing pump from the start of the withdrawal operation of the chip to the separation of the chip. 7. The sample test apparatus according to 6. 8. The dispensing pump according to claim 5, wherein the control unit controls the dispensing pump to continuously perform the discharge operation from the start of the chip withdrawal operation until the chip is separated. 7. The sample test apparatus according to 6. 9. The dispensing pump urges suction and discharge by a change in the internal volume of the dispensing pump, wherein the operation control unit is configured to set the dispensing nozzle to a predetermined position by the transport unit. A suction positioning control unit for positioning the dispensing pump at the position of the container containing the liquid sample in the placement unit, a liquid suction control unit for performing a suction operation by the dispensing pump after the positioning, and a suction operation by the liquid suction control unit. 9. The sample test apparatus according to claim 5, further comprising: an empty suction control unit configured to perform an air suction operation by the dispensing pump.