JP2001108688A - Automatic extraction apparatus for component substances in liquid sample, automatic concentration measurement apparatus for component substances in liquid sample, and method for extracting component substances in liquid sample - Google Patents

Abstract

(57) [Summary] [PROBLEMS] To measure the concentration of a specific component substance contained in a liquid sample by extracting the solvent with a solvent, shaking an extraction container into which the liquid sample and the organic solvent are injected, and shaking the liquid sample. Provided a device equipped with a shaker that does not form an emulsion in the extraction vessel regardless of the type of the liquid sample and the organic solvent when extracting component substances into organic solvents from, and improves the extraction efficiency of component substances I do. The shaker 194 is a mechanism for shaking the extraction container 30 so as to draw a figure 8 in a horizontal plane.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an operation for solvent extraction of a specific component substance contained in a liquid sample such as a homogenate (supernatant) of serum, plasma, whole blood, urine, living tissue and the like, and a reaction mixture. Automatic extraction device, which can automatically perform
And an automatic concentration measurement device capable of automatically performing all operations from extracting a specific component substance contained in a liquid sample to a solvent and measuring the concentration thereof, and specifying the substance contained in the liquid sample. The present invention relates to an extraction method for solvent-extracting the component materials of

[0002]

2. Description of the Related Art In order to measure the concentration of a drug contained in a biological sample, for example, blood, an organic solvent is used, and a drug component is dissolved in an organic solvent from blood and separated (solvent extraction).
After concentrating a sample separation solution in which a drug component is dissolved in an organic solvent as necessary, the sample separation solution is injected into an analytical instrument such as high performance liquid chromatography. One example of this series of measurement operations is as follows.
Discharge of a blood sample to a centrifuge tube (dispensing of a blood sample) → dispensing of an organic solvent for extraction to a centrifuge tube → attaching a cap to the centrifuge tube → shaking the centrifuge tube → centrifugation → centrifuge tube Removal of the cap from the tube → Inhalation of the sample separation liquid from the centrifuge tube (liquid separated into the organic solvent layer and the target substance dissolved) and discharge of the sample separation liquid to the concentration test tube (sample separation liquid Dispensing) → concentration → inhalation of the concentrated sample separated liquid from the test tube and injection of the concentrated sample separated liquid into the high performance liquid chromatography sequentially perform the measurement of the drug concentration in the blood. An automatic extraction device and an automatic concentration measurement device that automatically perform all of these series of operations are disclosed in, for example, Japanese Patent Application Laid-Open No.
No. 6,086,045.

By the way, the operation of shaking a centrifuge tube is usually
In the conventional shaker, the centrifuge tube is held in an upright posture by a container holder, and the container holder is rotated by a rotary drive mechanism so as to draw a circle in a horizontal plane. The tube was shaken.

[0004]

As described above, when a component substance in a liquid sample is subjected to solvent extraction using an organic solvent, a centrifuge tube into which the liquid sample such as blood and the organic solvent are respectively dispensed is used. By shaking with a shaker, the component substances contained in the liquid sample are transferred to the organic solvent,
The component substances are dissolved in an organic solvent and separated from the liquid sample. In this case, the water-insoluble organic solvent and the liquid sample such as blood are usually separated into two layers in the centrifuge tube. However, when a centrifuge tube held by a container holder is circularly moved in a horizontal plane to shake the centrifuge tube as in a shaking operation using a conventional shaker, the liquid sample is, for example, a homogenate (eg, a biological tissue). When the number of revolutions exceeds a certain value or the shaking time exceeds a certain time, the solution in the centrifuge tube may mix uniformly in appearance to form an emulsion (emulsion). is there. When the emulsion is formed in the centrifuge tube, it is no longer possible to dissolve the component substances in the organic solvent and separate them from the liquid sample.

In order to prevent the formation of an emulsion in the centrifuge tube, the number of revolutions of the centrifuge tube in the shaking operation may be reduced or the shaking time may be shortened. However, if the rotation speed of the centrifuge tube is reduced or the shaking time is shortened, the extraction efficiency of the component substances will decrease.

[0006] The present invention has been made in view of the above circumstances, and includes serum, plasma, whole blood, homogenate,
When extracting a specific component substance such as a drug contained in a liquid sample such as a reaction mixture with a solvent and measuring its concentration,
When extracting the components from the liquid sample into the organic solvent by shaking the container such as the centrifuge tube into which the liquid sample and the organic solvent are respectively injected, regardless of the type of the liquid sample and the organic solvent, Provided are an automatic extraction device for a component substance in a liquid sample and an automatic concentration measurement device for a component substance in a liquid sample that do not form an emulsion and also improve the extraction efficiency of the component substance. Further, it is an object of the present invention to provide a method for extracting a component substance in a liquid sample, in which no emulsion is formed in the container and the extraction efficiency of the component substance can be improved irrespective of the type of the organic solvent.

[0007]

The invention according to claim 1 is
A sample holding unit for holding a plurality of sample containers containing a liquid sample, an extraction container holding unit for holding a plurality of extraction containers, and a sample taken out of the sample holding unit or held in the sample holding unit A predetermined amount of a liquid sample is sucked from the container, and the sucked liquid sample is
Sample dispensing means which is taken out of the extraction container holding part or discharged into the extraction container held by the extraction container holding part, and extraction which discharges a predetermined amount of the organic solvent for extraction into the extraction container Solvent dispensing means, shaking means for shaking the extraction container, and transferring the target component substance in the liquid sample contained in the extraction container to the organic solvent for extraction, and a plurality of storage containers And a predetermined amount of a sample separation liquid in which the target component substance is dissolved in an organic solvent and separated in the extraction container, and the sucked sample separation liquid is stored in the storage container. A separation liquid dispensing unit that is taken out of a holding unit or is discharged into a storage container held by the storage container holding unit.In the apparatus for automatically extracting a component substance in a liquid sample, the shaking unit includes: The output container, characterized in that the mechanism for shaking so as to draw a figure eight in a horizontal plane.

According to a second aspect of the present invention, in the automatic extracting apparatus according to the first aspect, a container holder for holding the extraction container in an upright posture, a rotary drive motor having a rotation axis arranged in a vertical direction, and Connected to the rotating shaft of the drive motor,
An eccentric shaft arranged eccentrically from the rotation shaft, and disposed in a horizontal direction, one end of which is rotatably engaged with the eccentric shaft,
The other end is connected to the container holder, and at the other end, a long hole is formed along a straight line connecting the center position of the eccentric shaft and the center position of the container holder, and the eccentricity of the rotation drive motor with respect to the rotation shaft is formed. A horizontal oscillating member that oscillates in a horizontal plane with the revolving motion of the shaft and shakes the container holder, and a detent that is fixed to the device fixing portion and slidably engages with the elongated hole of the horizontal oscillating member. The shaking means from the member, the distance between the center position of the container holder and the center position of the detent member when the container holder is most separated from the detent member, the rotation axis of the rotation drive motor and the So that it is smaller than twice the eccentric distance with the eccentric shaft,
A detent member is disposed.

According to a third aspect of the present invention, there is provided the automatic extraction device according to the first or second aspect, further comprising an evaporating and drying means for evaporating the sample separation liquid contained in the storage container and drying the sample separation liquid. The invention according to claim 4 is characterized in that the automatic extraction device according to claim 3 further includes a dissolving solvent dispensing means for discharging a predetermined amount of the dissolving organic solvent into the storage container. And a dissolving means for dissolving the dried residue in an organic solvent for dissolution in the storage container.

According to a fifth aspect of the present invention, in the automatic extracting apparatus according to the first or second aspect, the organic solvent of the sample separation liquid contained in the container is partially evaporated to concentrate the sample separation liquid. And a concentrating means for causing the concentration.

According to a sixth aspect of the present invention, in the automatic extraction device according to any one of the first to fifth aspects, a predetermined amount of the sample separation liquid contained in the extraction container is sucked from a lower end of the extraction container. A dispensing nozzle that discharges a sample separation liquid from a lower end port, a nozzle holding unit that holds the dispensing nozzle, and a nozzle holding unit that connects the lower end port of the dispensing nozzle to the sample separation liquid in the extraction container. Nozzle raising and lowering means for raising and lowering between a lower position immersed in the container and an upper position in which the lower end of the dispensing nozzle is separated upward from the extraction container; and Nozzle displacing means for moving the sample separation liquid in the extraction container into the dispensing nozzle from a lower end thereof by a predetermined amount, and dispensing the sample in the dispensing nozzle at the dispensing position. By providing a syringe for discharging a liquid from the lower end port thereof, a syringe driving means for driving the syringe, and a syringe control means for controlling the syringe driving means, separation liquid dispensing means is constituted. .

According to a seventh aspect of the present invention, in the automatic extraction apparatus according to any one of the first to sixth aspects, the target component substance is transferred from the liquid sample into the organic solvent for extraction by shaking means. A centrifuge for centrifuging the obtained liquid is provided.

According to an eighth aspect of the present invention, there is provided an automatic extraction apparatus according to any one of the first, second or fourth to seventh aspects, and a concentration measurement for measuring the concentration of a component substance in a liquid sample. Means, and a liquid injecting means for inhaling a component solution obtained by dissolving a target component substance in an organic solvent from the storage container and injecting the inhaled component solution by a predetermined amount into the concentration measuring means. And a device for automatically measuring the concentration of the component substances in the liquid sample.

According to a ninth aspect of the present invention, there is provided a sample holding section for holding a plurality of sample containers each containing a liquid sample, a container holding section for holding a plurality of containers, A predetermined amount of a liquid sample is sucked from the sample container held by the holding portion, and the sucked liquid sample is taken out of the container holding portion or discharged into the container held by the container holding portion. Injection means, extraction solvent dispensing means for discharging a predetermined amount of extraction organic solvent into the container, and shaking the container to extract a target component substance in a liquid sample contained in the container. Shaking means for transferring into an organic solvent, concentration measuring means for measuring the concentration of a component substance in a liquid sample, and a sample in which the target component substance is separated and dissolved in the organic solvent in the container A separating liquid injecting means for inhaling syneresis and injecting a predetermined amount of the inhaled sample separating liquid into the concentration measuring means, wherein the shaking means is provided. And a mechanism for shaking the container so as to draw a figure 8 in a horizontal plane.

According to a tenth aspect of the present invention, in the automatic concentration measuring apparatus according to the ninth aspect, a container holder for holding the container in an upright posture, a rotary drive motor having a rotation axis arranged in a vertical direction, and the rotary drive Connected to the rotating shaft of the motor,
An eccentric shaft arranged eccentrically from the rotation shaft, and disposed in a horizontal direction, one end of which is rotatably engaged with the eccentric shaft,
The other end is connected to the container holder, and at the other end, a long hole is formed along a straight line connecting the center position of the eccentric shaft and the center position of the container holder, and the eccentricity of the rotation drive motor with respect to the rotation shaft is formed. A horizontal oscillating member that oscillates in a horizontal plane with the revolving motion of the shaft and shakes the container holder, and a detent that is fixed to the device fixing portion and slidably engages with the elongated hole of the horizontal oscillating member. The shaking means from the member, the distance between the center position of the container holder and the center position of the detent member when the container holder is most separated from the detent member, the rotation axis of the rotation drive motor and the So that it is smaller than twice the eccentric distance with the eccentric shaft,
A detent member is disposed.

According to an eleventh aspect of the present invention, there is provided the automatic concentration measuring apparatus according to the ninth or tenth aspect, wherein the target component substance is transferred from the liquid sample to the organic solvent for extraction by the shaking means. A centrifugal separator for centrifuging the water.

The invention according to claim 12 is a method for extracting a component substance contained in a liquid sample with an organic solvent, wherein at least a container containing the liquid sample and the organic solvent is placed in a horizontal plane by 8 It is characterized by shaking to draw letters.

According to a thirteenth aspect of the present invention, in the extraction method according to the twelfth aspect, the liquid sample is serum, plasma, whole blood,
It is a homogenate such as urine or living tissue.

According to a fourteenth aspect of the present invention, in the extraction method according to the twelfth or thirteenth aspect, an organic solvent having a higher specific gravity than water, for example, chloroform is used as the organic solvent.

In the apparatus for automatically extracting a component substance in a liquid sample according to the first aspect of the present invention, a predetermined amount of the liquid sample is sucked from the sample container by the sample dispensing means, and the liquid sample is stored in the extraction container. Is discharged to Next, a predetermined amount of the organic solvent for extraction is discharged into the container for extraction by the solvent dispensing means for extraction, and the intended component substance in the liquid sample contained in the container for extraction is discharged by the shaking means. It is transferred into an organic solvent. At this time, the extraction container should be 8 in the horizontal plane.
Shake to draw the letter For this reason, air is less likely to be mixed into the liquid phase in the extraction container than in the case where the extraction container is shaken so as to draw a circle in a horizontal plane as in the related art. Regardless of the type, no emulsion is formed in the extraction container, so that it is possible to set a desired rotation speed and shaking time. Moreover, when the extraction container is shaken so as to draw a figure 8, the stirring efficiency is improved and the extraction efficiency of the component substances is improved. After the shaking operation, a predetermined amount of the sample separation liquid separated in the extraction container is aspirated by the separation liquid dispensing means, and the sample separation liquid is discharged into the storage container. In this way, the target component substance was dissolved (migrated) in the organic solvent for extraction.
A sample separation is obtained automatically.

In the automatic extracting apparatus according to the second aspect of the present invention,
When the rotary drive motor is started, the eccentric shaft arranged eccentrically from the rotary shaft makes a circular motion about the rotary shaft in a horizontal plane. When the eccentric shaft makes a circular motion, a horizontal rocking member whose one end is rotatably engaged with the eccentric shaft rocks in a horizontal plane. At this time, the other end of the horizontal swing member is slidably engaged with the rotation preventing member fixed to the device fixing portion via the long hole formed on the other end side, so that the horizontal swing member swings. While reciprocating, it reciprocates in the direction connecting the rotation shaft of the rotation drive motor and the rotation preventing member. The container holder connected to the other end of the horizontal swinging member also reciprocates while swinging in a horizontal plane, but when the container holder is most separated from the detent member, that is, with the rotation shaft of the rotary drive motor. The distance between the center position of the container holder and the center position of the detent member when the eccentric shaft and the detent member are located on a straight line is smaller than twice the eccentric distance between the rotary shaft of the rotary drive motor and the eccentric shaft. By being made
The container holder connected to the other end of the horizontal swing member makes a figure-eight movement in a horizontal plane. Therefore, the extraction container held in the container holder is also shaken so as to draw a figure eight.

In the automatic extraction device according to the third aspect of the present invention,
By the evaporating and drying means, the organic solvent of the sample separation liquid contained in the container is evaporated and the sample separation liquid is dried to obtain a dried residue containing the target component substance. In the automatic extraction device according to the fourth aspect of the invention, a predetermined amount of the dissolving organic solvent is discharged into the storage container by the dissolving solvent dispensing means, and the residue dried to the organic solvent by the dissolving means is dried. The sample is dissolved to obtain a sample solution in which the target component substance is dissolved in the organic solvent for dissolution.

In the automatic extracting apparatus according to the fifth aspect of the present invention,
The concentration means evaporates a part of the organic solvent of the sample separation liquid contained in the storage container, thereby concentrating the sample separation liquid, and obtaining a concentrated sample separation liquid.

In the automatic extracting apparatus according to the invention according to claim 6,
The dispensing nozzle held by the nozzle holding means is moved to a position immediately above the extraction container by the nozzle moving means,
It is lowered by the nozzle elevating means, and the lower end is immersed in the sample separation liquid in the extraction container. In this state, when the syringe is driven by the syringe driving means, a predetermined amount of the sample separation liquid contained in the extraction container is sucked into the dispensing nozzle. Next, the dispensing nozzle is moved up to the dispensing position by the nozzle moving means after being raised by the nozzle elevating means. When the syringe is driven by the syringe driving means, the sample separation liquid is discharged into the container from the lower end of the dispensing nozzle.

In the automatic extracting apparatus according to the invention according to claim 7,
By centrifuging the liquid with a centrifugal separator, the sample separation liquid in which the target component substance is dissolved in the organic solvent is separated in a short time and surely in the extraction container. At this time, when extracting a component substance in the liquid sample using an organic solvent having a lower specific gravity than water, for example, ethyl acetate or diethyl ether, the organic solvent layer is on the upper layer side, and an organic solvent having a higher specific gravity than water, for example, When extracting component substances in a liquid sample using chloroform or dichloromethane, the organic solvent layer is on the lower layer side.

In the apparatus for automatically measuring the concentration of a component substance in a liquid sample according to the invention of claim 8, the liquid dissolving means is a component solution obtained by dissolving a target component substance obtained by an automatic extraction apparatus in an organic solvent. A sample separation liquid, a sample solution, or a concentrated sample separation liquid) is sucked from the container, and a predetermined amount of the component solution is injected into the concentration measuring means, and the concentration of the component substance in the liquid sample is measured by the concentration measuring means. Is done.

According to the ninth aspect of the present invention, in the apparatus for automatically measuring the concentration of a component substance in a liquid sample, a predetermined amount of the liquid sample is sucked from the sample container by the sample dispensing means and the liquid sample is introduced into the container. Discharged. Next, a predetermined amount of the organic solvent for extraction is discharged into the container by the solvent dispensing means for extraction, and the target component substance in the liquid sample contained in the container is poured into the organic solvent for extraction by the shaking means. Will be migrated. At this time, the container is shaken so as to draw a figure 8 in a horizontal plane. For this reason, compared to the conventional case where the container is shaken so as to draw a circle in a horizontal plane, air is less likely to be mixed into the liquid phase in the container, and as a result, regardless of the type of the liquid sample and the organic solvent, Since no emulsion is formed in the container, it is possible to set a desired rotation speed and shaking time. Moreover, when the container is shaken so as to draw a figure 8, the stirring efficiency is improved and the extraction efficiency of the component substances is improved. After the shaking operation, a predetermined amount of the sample separation liquid separated in the container is aspirated by the separation liquid injection means, and the predetermined amount of the sample separation liquid is injected into the concentration measurement means. The concentration of the component substances is measured.

In the automatic concentration measuring device according to the tenth aspect of the present invention, the container held by the container holder draws a figure eight by the same operation as that of the automatic extracting device according to the second aspect of the present invention. Shaking.

[0029] In the automatic concentration measuring apparatus according to the eleventh aspect, the liquid is centrifuged by a centrifugal separator.
A sample separation liquid in which a target component substance is dissolved in an organic solvent is separated in a short time and surely in a container.

According to the extraction method of the twelfth aspect of the present invention, the container containing the liquid sample and the organic solvent is shaken so as to draw a figure 8 in the horizontal plane, so that the circular shape is formed in the horizontal plane as in the conventional case. Air is less likely to be mixed into the liquid phase in the container compared to the case where the container is shaken so as to draw, as a result, regardless of the type of the liquid sample and the organic solvent,
Since no emulsion is formed in the container, it is possible to set the desired rotation speed and shaking time. Moreover, when the container is shaken so as to draw a figure 8, the stirring efficiency is improved and the extraction efficiency of the component substances is improved.

In the extraction method according to the thirteenth aspect of the present invention, when measuring the concentration of a drug contained in a homogenate such as serum, plasma, whole blood, urine, or biological tissue, a component such as a drug in a biological sample is measured. The substance is extracted with an organic solvent.

In the extraction method according to the fourteenth aspect of the present invention, when the liquid sample and the organic solvent are mixed in the container, the organic solvent, for example, chloroform becomes a lower layer liquid, and the lower layer liquid contains the lower layer liquid. The solvent-extracted component material dissolves.

[0033]

Preferred embodiments of the present invention will be described below with reference to the drawings.

First, three examples of a series of operation steps for measuring the concentration of a drug contained in a liquid sample, for example, blood will be described with reference to FIGS.

First, as shown in FIG. 8A, for example, a frozen serum (sample) obtained by centrifuging blood collected by administering a drug to an animal is stored in a sample tube 10 with a lid. After the frozen serum contained in the sample tube 10 has been thawed, the cap 12 of the sample tube 10 is removed, and a disposable disposable tip (hereinafter, referred to as a “disposable tip”) attached to the tip of the dispensing nozzle of the liquid dispensing device. Chips "
For example, 0.1 ml of a sample solution (serum) is sucked into the sample tube 10 (not shown) from the sample tube 10 (FIG. 8B), and the sucked sample solution is discharged into the centrifuge tube 14. Further, an organic solvent, for example, ethyl acetate, for example, 4 ml, a pH buffer solution (0.5 ml) and methanol (0.1 ml) are dispensed into the centrifuge tube 14 (FIG. 8 (c)). Next, after attaching the cap 16 to the centrifuge tube 14 ((d) in FIG. 8), the centrifuge tube 14 is shaken by a shaker ((e) in FIG. 8). Ensure that the target component (drug) is sufficiently transferred into the organic solvent. Subsequently, the centrifuge tube 14 containing the sample solution and the organic solvent is set in the centrifuge 18,
The liquid is centrifuged ((f) in FIG. 8). By this centrifugation, the liquid in the centrifuge tube 14 is separated into an upper layer A and a lower layer B, and the sample separation liquid in which the target component substance is dissolved in the organic solvent forms the upper layer A (FIG. 8). (G)).
Then, after removing the cap 16 of the centrifuge tube 14, the centrifuge tube 14 is inserted into the disposable tip 22 (see FIG. 8 (h)) attached to the tip of the dispensing nozzle (not shown) of the liquid dispensing device. For example, 3 ml of the sample separation liquid in the upper layer A is
It inhales and discharges the inhaled sample separation liquid into the test tube 24 ((h) in FIG. 8). Next, the test tube 24 is heated from the periphery thereof, and nitrogen gas is blown from the gas supply nozzle 26 into the inside of the test tube 24 through its upper opening to evaporate the organic solvent of the sample separation liquid in the test tube 24. To dry the sample separation solution (FIG. 8).
(I)). Finally, an organic solvent, for example, methanol (0.1 ml) is dispensed into the test tube 24 and stirred to dissolve the residue. Then, the sample solution is sucked from the test tube 24 through the nozzle 28 (see FIG. 8). (J)) The inhaled sample solution is injected, for example, in an amount of 20 to 30 μl into an analytical instrument such as high performance liquid chromatography, and the concentration of the component substance is measured. FIG. 9 shows a flowchart of this series of operations.

Next, in the example shown in FIG. 10, when the liquid in the centrifuge tube 30 is separated into an upper layer A and a lower layer B by centrifugation, the target component substance is dissolved in the organic solvent. This is an operation example in which the sample separation liquid forms the lower layer B, the sample separation liquid in the lower layer B is sucked from the centrifuge tube 30, and the sucked sample separation liquid is discharged into the test tube 24. The operation other than dispensing the sample separation liquid in the lower part B from the centrifuge tube 30 is the same as the example shown in FIG. Also,
In the operation example shown in FIG. 10, the sample separation liquid in the lower layer B is sucked without removing the cap 31 from the centrifuge tube 30. In this case, a special structure is used as the centrifuge tube 30, which will be described later in detail.

FIG. 11 shows an example of a blood analysis operation by the direct protein removal method. First, as shown in FIG. 11 (a), after the frozen serum (sample) contained in the sample tube 10 with the lid is thawed, the cap 12 of the sample tube 10 is removed, and the dispensing nozzle of the liquid dispensing device is dispensed. A sample liquid, for example, 0.1 ml is sucked from the sample tube 10 into a disposable chip (not shown) attached to the tip of the sample (FIG. 11 (b)), and the sucked sample liquid is centrifuged with a lid. Then, a predetermined amount of an organic solvent, for example, 0.2 ml of methanol or 0.5 ml of acetonitrile is dispensed into the centrifuge tube 32 (FIG. 11 (c)). Next, after attaching the cap 34 to the centrifuge tube 32 ((d) in FIG. 11), the centrifuge tube 32 is shaken by a shaker ((e) in FIG. 11). Subsequently, the centrifuge tube 32 containing the sample solution and the organic solvent is set in the centrifuge 18 and the solution is centrifuged ((f) in FIG. 11). By this centrifugation, the liquid in the centrifuge tube 32 is separated into a liquid layer and a precipitation part. Then, since the target component substance is dissolved in the liquid layer, after removing the cap 34 of the centrifuge tube 32, the sample separation liquid is sucked from the liquid layer in the centrifuge tube 32 by the nozzle 28 (see FIG. 11 (g)), the inhaled sample separation liquid is injected into an analytical instrument such as high performance liquid chromatography, for example, in an amount of 20 to 50 μl, and the concentration of the component substance is measured.

Next, referring to FIGS. 12 and 13, an example of the configuration of an automatic concentration measuring device for component substances in a liquid sample will be described. FIG. 12 is a perspective view showing the entire configuration of the automatic concentration measuring device, and FIG. 13 is a plan layout diagram thereof.

This automatic concentration measuring apparatus automatically extracts a specific component substance (eg, drug) contained in a sample liquid such as blood by a solvent.
6, a syringe pump unit 40 for sending an organic solvent and the like to the automatic solvent extraction unit 36, a plurality of storage containers 42 for storing the organic solvent and the like, A drainage unit 38 and an analytical instrument for automatically measuring the concentration of the component substances extracted by the solvent in the automatic solvent extraction unit 36. On this side, high-performance liquid chromatography (hereinafter, referred to as
“HPLC”) 44. The automatic solvent extraction unit 36 is disposed on the upper surface of the apparatus, and the liquid supply / drainage unit 38 and the HPLC 44 are housed in a cabinet below the automatic solvent extraction unit 36, respectively. An operation panel 46 is provided on the front of the apparatus.
Although not shown, the automatic solvent extraction unit 36 is covered with a transparent cover that can be freely opened and closed.

It is to be noted that an apparatus for automatically extracting a component substance in a liquid sample with a solvent is not provided with an analytical instrument such as an HPLC as shown in the figure as an integral type, and the apparatus is finally obtained by the automatic extracting apparatus. It is also possible to adopt a configuration in which the obtained liquid is injected into an attached analytical instrument or into a separate analytical instrument. Such an apparatus having a configuration in which the analytical instrument is omitted from the automatic concentration measuring apparatus is the automatic extracting apparatus according to the first to seventh aspects of the present invention.

The automatic solvent extraction unit 36 includes a circular turntable 48, a processing turntable 50, a sample dispensing unit 52 (the structure is not shown in FIG. 12), a sample suction stage 54, a solvent dispensing unit 56, and a shaking stage 5.
8, the centrifuge 60, the separated liquid dispensing unit 62 (FIG. 12)
The structure is not shown in the drawing), the separated liquid suction stage 64, the evaporation to dryness stage 66, the solvent dispensing stage 68, the injection unit 70, the disposable chip rack 72,
It is composed of a waste pot 73 and the like.

The circular turntable 48 holds a number of sample tube holders 74 for holding a sample tube 10 with a lid (for example, a 1.5 ml microtube) containing a sample such as frozen serum, and a disposable chip. It has a large number of disposable chip holding portions 76, and is rotated by a rotation driving mechanism (not shown) to control the stop position. Further, the processing turntable 50 has a number of centrifuge tube holding portions 78 for holding the centrifuge tubes (for example, 7 cc centrifuge tubes) 14 and a number of cap holding portions 80 for holding the centrifuge tube caps 16. Also, a large number of test tube holders 8 holding the glass test tubes 24 on the outer periphery.
The stop position is controlled by being rotated by a rotation drive mechanism (not shown).

The sample dispensing unit 52 has an arm 84 that reciprocates in the front-rear direction (Y-axis direction), and a dispensing head 86 that is supported by the arm 84 and reciprocates in the left-right direction (X-axis direction). In addition, the dispensing head 86 is provided with a sample dispensing nozzle 88 and a cap chuck unit 90 that reciprocate in the vertical direction (Z-axis direction). The dispensing nozzle 88 is connected through a tube 89 to a syringe (not shown) driven by a motor. The dispensing nozzle 88 is shown in a front view in FIG.
As shown in a left side view of FIG.
Is held in. The dispensing nozzle 88 is driven by a forward / reverse rotatable drive motor 94 fixed to the dispensing head 86.
As a result, the driving force is transmitted through a pinion 96 fixed to the motor rotation shaft and a rack 98 fixed to the vertical slide member 92, and reciprocates in the vertical direction. The reference numeral 100 in FIG.
Ascending limit sensor for detecting the ascending limit position of
Reference numeral 102 denotes a vertical origin sensor for detecting the vertical origin position of the dispensing nozzle 88, reference numeral 104 denotes a descending limit sensor for detecting a descending limit position of the dispensing nozzle 88, and reference numeral 106 denotes a sensor detection plate. , 108 are compression coil springs. Further, reference numeral 110 in FIG. 15 denotes a slide bearing, and 112 denotes a vertical slide guide.
14 is the disposable tip 11 at the lower end of the dispensing nozzle 88.
6 is a chip presence / absence sensor for confirming that it is attached.

The cap chuck unit 90
Is a pair of chuck claws 118, an opening / closing mechanism 1 for opening and closing the pair of chuck claws 118, 118.
20 and a tubular solenoid 122 for driving the opening / closing mechanism 120. The chuck unit 90 is held by a vertical slide member 124 which is engaged with and supported by the dispensing head 86 and reciprocates in the vertical direction. The chuck unit 90 is driven by a forward / reverse rotatable drive motor (not shown) fixed to the dispensing head 86, and a pinion 126 fixed to the motor rotation shaft and a rack fixed to the vertical slide member 124. Driving force is transmitted via 128 to reciprocate up and down. Reference numeral 130 in FIG. 14 denotes an ascending limit sensor for detecting an ascending limit position of the chuck unit 90, 132, an upper and lower origin sensor for detecting an origin position in the vertical direction of the chuck unit 90, and 134, a chuck unit. A lower limit sensor 136 for detecting the lower limit position 90 is a sensor detection plate.

As shown in FIGS. 12 and 13, the sample suction stage 54 is provided with a cap attaching / detaching mechanism 138. Sample tube 1 with lid containing sample liquid
0 is the chuck unit 9 of the sample dispensing unit 52
0 indicates that the sample tube holder 7 of the circular turntable 48
4, the sample tube 10 is placed on the sample suction stage 54, and the cap 12 of the sample tube 10 fixed on the stage 54 is removed by the cap attaching / detaching mechanism 138. Further, the cap 12 is attached to the sample tube 10 after suction of the sample by the cap attaching / detaching mechanism 138, and the sample tube 10 is moved from the sample suction stage 54 to the sample of the circular turntable 48 by the chuck unit 90 of the sample dispensing unit 52. It is returned to the tube holding section 74.

The solvent dispensing unit 56 has a dispensing arm 140 that rotates in a horizontal plane about one end, and a nozzle 142 is provided at the tip of the dispensing arm 140 as shown in FIG. Is provided. A plurality of, for example, three liquid feeding tubes 144 and 146 are provided in the nozzle portion 142.
The tip of one liquid feed tube is not shown is fixed. The three liquid supply tubes 144 and 146 are used for supplying liquid.
A syringe 150 for supplying methanol, a syringe 152 for supplying ethyl acetate (organic solvent), and a syringe 154 for supplying a pH buffer solution of the syringe pump unit 40 of the drainage section 38.
(Refer to FIG. 12). Each of the syringes 150, 152, and 154 has a flow path connected to a storage container (not shown) in which a required liquid is stored. It is connected.

As shown in FIG. 16, the lower surface of one end of the dispensing arm 140 is fixed to the arm support shaft 156. The arm support shaft 156 is connected to the ball spline shaft 15.
8 and is supported so as to be rotatable about a vertical axis and to be vertically movable along the vertical axis.
The arm support shaft 156 is reciprocated in the up and down direction by the elevation drive mechanism, and is rotated by the rotation drive mechanism.
The dispensing arm 140 fixed to 6 moves up and down and rotates. The lifting drive mechanism includes an upper mounting plate 160.
Motor 162 fixed to the drive motor 162
A timing shaft fixed to the vicinity of an upper end of the screw shaft 168 whose upper end and lower end are rotatably supported by the timing pulley 164 fixed to the rotating shaft of the upper shaft and the upper mounting plate 160 and the lower mounting plate 166, respectively. The pulley 170, the timing belt 172 stretched between the timing pulleys 164 and 170, the change nut 174 screwed to the screw shaft 168, connected to the change nut 174, the arm support shaft 156 is allowed to rotate and Elevating member 1 engaged so as to move integrally in the vertical direction
76, and the upper mounting plate 160 and the lower mounting plate 1
The upper end and the lower end are fixed to the
The guide rod 180 is slidably engaged with the lifting member 176 via the guide rod 180. Although not shown, an ascending limit sensor and a descending limit sensor for detecting the ascending limit position and descending limit position of the dispensing arm 140, respectively, and an up and down sensor for detecting the origin position of the dispensing arm 140 in the up and down direction. An origin sensor and a sensor detection plate are provided. In addition, the rotation drive mechanism includes a drive motor 18 fixed to the lower mounting plate 166.
2, a timing pulley 182 fixed to a rotation shaft of the drive motor 182, a support block 184 fixed to the lower mounting plate 166, and a rotatable support of the ball spline shaft 158 by the support block 184. 186 having a boss hole in which a key groove is formed so as to allow the rotation and integral rotation thereof, a timing pulley 188 integrally rotating with the rotation member 186, and a bridge between the timing pulleys 182 and 188. And a positioning sensor 192 for detecting a rotation angle position of the dispensing arm 140.

The solvent dispensing unit 56 having the above configuration
Then, the dispensing arm 140 is rotated by the rotation drive mechanism, and the nozzle 142 at the tip of the dispensing arm 140 is moved to the centrifuge tube holding portion 78 (see FIG. 16) of the processing turntable 50 as shown by the solid line in FIG. 13) centrifuge tube 14
Then, the dispensing arm 140 is lowered by the lifting drive mechanism, and the nozzle 142 at the tip of the dispensing arm 140 is moved into the centrifuge tube 14 as shown by the two-dot chain line in FIG. Insert into Then, the syringes 150, 152, 154 (see FIG. 12) of the syringe pump unit 40 are driven, and the methanol, ethyl acetate (organic solvent) and the pH buffer are distant from the discharge ports at the tips of the liquid sending tubes 144, 146. The liquid is discharged into the sink tube 14.

The shaking stage 58 is provided with a shaking machine 194. Further, the centrifuge 60 is installed inside the annular processing turntable 50 in order to effectively use space and to make the apparatus compact. The centrifuge tube 14 into which the sample solution and the organic solvent have been dispensed is shaken, and then the centrifuge tube 14 is allowed to stand still.
In the case where the liquid of No. 4 is rapidly separated into layers, the centrifugal separator 60 may not be particularly provided. The centrifugal separator 60 has been conventionally used, and illustration and description of its detailed structure are omitted, and a configuration example and operation of the shaker 194 will be described.
A description will be given based on FIGS. 1 to 7.

FIG. 1 is a longitudinal sectional view showing an example of the entire structure of the shaker 194, and FIG. 2 is a view showing a part of the shaker 194 viewed from the side. The shaker 194 includes a centrifuge tube holder 200 that holds the centrifuge tube 30 in an upright posture, and a groove 202 is formed at the bottom of the centrifuge tube holder 200. On the bottom surface of the centrifuge tube holder 200, a horizontal rocking plate 204 disposed horizontally is integrally connected. As shown in the perspective view of FIG. 3, the horizontal rocking plate 204 has a long hole 206 formed in the longitudinal direction thereof. The centrifuge tube holder 200 and the horizontal rocking plate 204 are formed respectively. The groove 202 and the elongated hole 206 are joined so as to overlap each other. In addition, the horizontal swing plate 204 includes
A circular hole 208 is formed at a position on a straight line passing through the center of the long hole 206 on the opposite side of the long hole 206.

A rotary drive motor 210 is provided below the centrifuge tube holder 200, and the rotary drive motor 210 is
The rotating shaft 212 is arranged upward and vertically, and is fixed to the horizontal mounting plate 214. Horizontal mounting plate 2
14 is connected to a horizontal support plate 218 via a connecting support 216, and the horizontal support plate 218 is connected and fixed to a base plate 222 via a connecting support 220. The upper end of the rotary shaft 212 of the rotary drive motor 210 is connected to the lower shaft 22 vertically fixed to the center of the lower surface of the horizontal rotary disk 228.
9 is connected coaxially via a coupling 227. A boss 224 is fixed to the center of the horizontal support plate 218, and a lower shaft 229 of a horizontal rotating disk 228 is inserted through the boss 224, and the lower shaft 229 is rotatably supported by the boss 224 via a bearing 226. Have been. On the upper surface side of the horizontal rotating disk 228, a connecting shaft 230 is vertically fixed at a position eccentric from the center of the horizontal rotating disk 228, and an eccentric shaft 234 is connected to the connecting shaft 230 via a horizontal connecting arm 232. Have been. The eccentric shaft 234 extends vertically through the circular hole 208 of the horizontal rocking plate 204, and is provided with a bearing 238 on an engaging member 236 integrally fixed to the upper surface on one end side of the horizontal rocking plate 204. And are rotatably engaged via the. The eccentric shaft 234 is eccentrically arranged from the rotary shaft 212 of the rotary drive motor 210.

The eccentric shaft 234 and the centrifuge tube holder 200 are connected to each other by an engaging member 236 and a horizontal rocking plate 204, and the elongated hole 206 formed on the horizontal rocking plate 204 on the centrifuge tube holder 200 side. And horizontal support plate 2
A rotation preventing member 240 vertically provided from 18 is slidably engaged. When the rotation drive motor 210 is started, the eccentric shaft 234 revolves in a circular orbit with respect to the rotation shaft 212, so that the horizontal rocking plate 20 is rotated.
4 is swung in a horizontal plane, and the swinging movement at that time is regulated by the detent member 240 to a constant state.

The rotation preventing motor 240 is fixed when the horizontal distance between its center position and the center position of the centrifuge tube holder 200 is the largest, that is, the rotation driving motor 210 is fixed.
When the rotary shaft 212, the eccentric shaft 234, and the long hole 206 of the horizontal rocking plate 204 are aligned (the state shown in FIG. 1).
The maximum value of the horizontal distance is the rotation shaft 212 and the eccentric shaft 2
The position is set so as to be smaller than twice the eccentric distance with respect to. Thus, the centrifuge tube holder 200 is shaken so as to draw a figure 8 in a horizontal plane. This will be described with reference to FIG.

In FIG. 6, the point O is the center position of the rotary shaft 212, and the circle c including the points A to F is the locus of the eccentric shaft 234. The point X is the center position of the detent pin 240, and the points A 'to F' are the trajectories of the center position of the centrifuge tube holder 200 corresponding to the points A to F. Detent member 2 on locus A'-F 'of center position of centrifuge tube holder 200
When the centrifugal tube holder 200 moves so as to pass through the central position of the detent member 240 when the centrifugal tube holder 200 moves through the central position of the centrifugal tube holder 40, the centrifugal tube holder 200 moves in a figure-eight shape with the circular movement of the eccentric shaft 234. Will be shaken so as to draw. That is, when the maximum value 1 of the horizontal distance between the center position of the centrifuge tube holder 200 and the center position of the rotation preventing member 240 is smaller than twice the eccentric distance r between the rotation shaft 212 and the eccentric shaft 234, 2r Holder 200 is 8
Will be exercising.

FIG. 7 is a plan view showing a state in which the centrifuge tube holder 200 makes a figure eight movement. (A) of FIG.
(E) shows a state when the eccentric shaft 234 is located at points A to E in FIG. 6, respectively. As described above, by shaking the centrifuge tube holder 200, and thus the centrifuge tube 30 held by the centrifuge tube holder 200, so as to draw a figure 8, compared with the case where the centrifuge tube is shaken simply to draw a circle. As a result, a solution obtained by mixing a sample solution such as a molten serum and an organic solvent is less likely to be emulsified (emulsified), and the stirring efficiency is improved to increase the extraction efficiency.
Next, a comparative experiment performed on this point will be described.

In the experiment, 0.5 cc of rat brain homogenate was used as a sample solution, and the sample solution mixed with the compound to be extracted was injected into the centrifuge tube 30. 0.1 cc of methanol and 0.1 ml of buffer were added to the sample solution. 5 cc was added, and 4 cc of chloroform was further injected into the centrifuge tube 30 as an extraction solvent. This centrifuge tube 30 is connected to centrifuge tube holder 2.
Set to 00 and a rotation speed of 1,000 rpm for 5 minutes (the rotation speed and the shaking time at which no emulsion is formed in the conventional rotary shaking), the conventional rotary shaking and the 8-shaking according to the present invention for the centrifuge tube holder 200. Was executed respectively. At this time, the extraction efficiency of the compound from the sample liquid into the organic solvent was measured. Table 1 shows the results.

[0057]

[Table 1]

As can be seen from the results shown in Table 1, the centrifuge tube 30 was 8 times smaller than when the conventional centrifuge tube 30 was shaken under the condition that no emulsion was formed by rotary shaking.
The extraction efficiency is improved by shaking.

As shown in the perspective view of FIG. 4, a balancer 242 having a long hole 244 is rotatably mounted on the connecting shaft 230 via a bearing 246 and is supported in a cantilever manner. In addition, a detent member 248 suspended from a horizontal support plate 218 is slidably engaged with a long hole 244 formed in the balancer 242. Then, the rotation shaft 212 of the rotation drive motor 210 rotates and the horizontal rotation disk 228 fixed to the upper end thereof rotates, so that the connection shaft 230 eccentrically fixed on the horizontal rotation disk 228 in a horizontal plane. The balancer 242 accompanying the circular motion
Of the balancer 242 is regulated by the detent member 248 so that the center of gravity of the balancer 242 is always
12 is opposite to the position of the center of gravity of the centrifuge tube holder 200. In addition, the rotation drive motor 210
A balancer 250 having a shape as shown in FIG.

In the shaker 194 having the above-described configuration, when the rotary drive motor 210 is started, the eccentric shaft 234 eccentrically arranged from the rotary shaft 212 is moved.
A circular motion about the rotation axis 212 is performed in a horizontal plane. When the eccentric shaft 234 makes a circular motion, the horizontal rocking plate 204 engaged with the eccentric shaft 234 via the engaging member 236 rocks in a horizontal plane, and the centrifugal tube holder 200 connected to the horizontal rocking plate 204 is moved. As shown above, the figure 8 moves in the horizontal plane. Then, the centrifuge tube 30 held in the centrifuge tube holder 200 is shaken so as to draw a figure of eight.

The separation liquid dispensing unit 62 is moved in the front-rear direction (Y
Arm 196 that reciprocates in the axial direction)
A dispensing head 198 that is supported by 96 and reciprocates in the left-right direction (X-axis direction) (the reciprocating drive mechanisms are not shown). A separation liquid dispensing nozzle 252 that reciprocates in the vertical direction (Z-axis direction) is provided.
Through a tube 254, a flow path is connected to a syringe (not shown) driven by a motor (see FIG. 18). A nozzle elevating mechanism for reciprocating the dispensing nozzle 252 in the vertical direction includes a drive motor (stepping motor) fixedly mounted on a mounting plate 256 fixed to the dispensing head 198.
258, a timing pulley 260 fixed to the rotation shaft of the drive motor 258, and a screw shaft rotatably supported at the upper and lower ends of the upper mounting plate 262 and the lower mounting plate 264 fixed to the dispensing head 198, respectively. 26
6, the timing pulley 268 fixed to the lower end of the screw shaft 266, the timing belt 270 stretched between the timing pulleys 260 and 268, and screwed to the screw shaft 266 to rotate the screw shaft 266 forward and reverse. The change nut 272 reciprocating in the vertical direction with the change nut 272 and the dispensing nozzle 2 connected to the change nut 272
The lifting member 274 that moves in the vertical direction integrally with the change nut 272 and the dispensing nozzle 252 by engaging with the
It is composed of Although not shown, an ascending limit sensor and a descending limit sensor for detecting the ascending limit position and descending limit position of the dispensing nozzle 252, and an up and down sensor for detecting the origin position of the dispensing nozzle 252 in the vertical direction. An origin sensor and a sensor detection plate are provided, and a tip presence / absence sensor for confirming that the disposable tip 276 is attached to the lower end of the dispensing nozzle 252 is provided. Disposable tip 2 attached to the lower end of dispensing nozzle 252
76 is held by a large number of disposable chip holding portions 278 of the disposable chip rack 72.

Although not shown, the dispensing head 198 has a remote control having the same configuration as the cap chuck unit 90 (see FIG. 14) provided on the dispensing head 86 of the sample dispensing unit 52. A chuck unit for transferring the sediment tube is provided.

Although not shown, a cap removing unit and a centrifuge tube fixing unit are fixed to the mounting substrate on the separated liquid suction stage 64.

A method for dispensing the sample separation liquid in the centrifuge tube 14 using the dispensing unit having the above configuration will be described with reference to FIG. In this example, the sample separation liquid 280 separated into the upper layer in the centrifuge tube 14 is sucked into the disposable tip 276 of the dispensing nozzle 252.

The dispensing nozzle 252 is moved to a position immediately above the centrifuge tube 14 and dispensed as shown in FIG. 18A (only the disposable tip 276 of the dispensing nozzle 252 is shown in FIG. 18). The nozzle 252 is lowered. Then, as shown in FIG. 18B, the lower end of the disposable chip 276 is connected to the sample separation liquid 28 stored in the centrifuge tube 14.
Then, the sample separation liquid 280 in the centrifuge tube 14 is sucked into the disposable chip 276 from the lower end port thereof. The suction speed at this time depends on the diameter of the lower end of the disposable chip 276 and the viscosity of the sample separation liquid 280. For example, the lower end of the disposable chip 276 has a diameter of 1 mm.
When the organic solvent of the sample separation liquid 280 is ethyl acetate, diethyl ether, or a material having properties similar thereto, the flow rate is 0.2 to 0.3 cc / sec.

When a predetermined amount of the sample separation liquid 280 is sucked into the disposable chip 276, the suction operation is temporarily stopped, and the dispensing nozzle 252 is raised. Dispensing nozzle 252
In the process of pulling the lower end of the disposable chip 276 out of the sample separation liquid 280 in the centrifuge tube 14, when the lower end of the disposable chip 276 comes out above the liquid surface as shown in FIG. The suction operation is started again. As a result, a small amount of air continues to be sucked into the disposable chip 276 through the lower end thereof, and the air becomes fine bubbles 281 as shown in FIG. The liquid 280 floats toward the liquid surface and flows to the gas portion above the sample separation liquid 280 in the disposable chip 276. The suction speed at this time is, for example, 0.04 to
Although it is 0.2 cc / sec, about 0.1 cc / sec is appropriate.

The minute flow rate is sucked into the disposable chip 276 until the dispensing nozzle 252 moves to a position above the centrifuge tube 14 and then to the position above the test tube 24 at the dispensing position, or further dispenses. The nozzle 252 is lowered to continue until the lower end of the disposable tip 276 is inserted into the test tube 24. During this time, the disposable chip 27
Since the upward suction force always acts near the lower end of the sample separation liquid 6, the sample separation liquid 280 drips from the lower end port of the disposable chip 276 even if the sample separation liquid 280 is of a type that is easily dripped. It doesn't fall. When the lower end of the disposable tip 276 is inserted into the test tube 24, the dispensing nozzle 252 passes through the tube 254.
The sample separation liquid 280 in the disposable chip 276 is pushed down and discharged from the lower end port into the test tube 24.

The above description relates to the case where the sample separated liquid separated into the upper layer in the centrifuge tube 14 is sucked into the disposable tip 276 of the dispensing nozzle 252.
In the case where the sample separation liquid separated to the lower layer side in the centrifuge tube 14 is sucked into the disposable tip 276 of the dispensing nozzle 252, it is possible to suck only the lower layer sample separation liquid without causing any contamination. A preferred centrifuge tube will be described with reference to FIGS.

FIG. 19 is a longitudinal sectional view of a centrifuge tube, and FIG.
0 is a perspective view showing a state in which the centrifuge tube is separated into components.

The centrifuge tube 30 has a bottomed cylindrical shape with an open upper surface, and has an inner cylinder 282 inserted therein. A cap 31 is attached to the upper end of the centrifuge tube 30. Is done. A screw portion 284 is formed on the outer peripheral surface of the upper end of the centrifuge tube 30, and the inner peripheral surface of the cap 31 is
A screw portion 286 that is screwed into the screw portion 284 of the centrifuge tube 30 is formed. The cap 31 has a through hole 288 formed in the center of the upper surface. And cap 31
And the inner cylinder 282 are connected to each other and integrated by a connection ring 290 inserted inside the cap 31.

The inner cylinder 282 has an outer diameter smaller than the inner diameter of the centrifugal tube 30 and has a cylindrical shape in which the lower part is gradually reduced in diameter. A flange 292 is formed at the upper end of the inner cylinder 282, and when the inner cylinder 282 is inserted into the centrifuge tube 30, the flange 292 becomes a liquid-tight member, for example, the O-ring 2.
The upper end of the centrifugal tube 30 is engaged with the intermediate member 94 so as to come into close contact therewith. In addition, the flange part 292 is the centrifuge tube 30
The O-ring 294 need not be particularly inserted as long as the O-ring 294 can be in close contact with the upper end edge of the. By inserting the inner cylinder 282 into the centrifuge tube 30, the inner peripheral surface of the centrifuge tube 30 and the inner cylinder 28
A centrifugal separation chamber 296 is formed between the outer peripheral surface 2 and the outer peripheral surface. Further, when the inner cylinder 282 is inserted into the centrifuge tube 30, there is an extremely small gap between the upper outer peripheral surface of the inner cylinder 282 and the upper inner peripheral surface of the centrifuge tube 30 so as to allow ventilation. . The length of the inner cylinder 282 is such that the lower end is located near the inner bottom surface of the centrifuge tube 30 when the inner cylinder 282 is inserted to the innermost part of the centrifuge tube 30.

At the lower end of the inner cylinder 282, a closing plug 298 is inserted upward at the lower end, and the lower end of the inner cylinder 282 is liquid-tightly closed. The obstruction plug 298 is easily dropped by a downward pressing force, that is, a force pressed downward by the lower end of the dispensing nozzle. The obturator plug 298 has a conical or pyramid-shaped lower surface.

Next, an operation of extracting the lower layer liquid by centrifuging the liquid using the centrifuge tube having the above-described structure will be described with reference to FIG.

First, with the cap 31 removed from the centrifuge tube 30 and the inner cylinder 282 pulled out, a mixed liquid to be separated by centrifugal force is injected into the centrifuge tube 30. For example, when extracting a drug contained in serum with chloroform, for example, 0.5 cc of serum, 0.5 cc of buffer, and 3.
5 cc of chloroform is sequentially injected into the centrifuge tube 30.
Next, after inserting the inner cylinder 282 deeply into the centrifuge tube 30 and inserting it into the liquid, the cap 31 is put on the upper end of the centrifuge tube 30 and screwed to the end. Thus, the flange 292 at the upper end of the inner cylinder 282 is pressed against the upper end of the centrifuge tube 30 by the peripheral edge of the through hole 288 on the upper surface of the cap 31 with the O-ring 294 interposed therebetween. Then, the flange 292 of the inner cylinder 282 and the upper edge of the centrifuge tube 30 come into close contact, and the centrifuge tube 30
A centrifuge chamber 296 formed between the inner peripheral surface of the inner cylinder 282 and the outer peripheral surface of the inner cylinder 282 is hermetically and liquid-tightly sealed. The centrifuge tube 30 in this state is shaken to transfer the drug in the serum into chloroform, and then centrifuged. As a result, as shown in FIG. 21A, the liquid contained in the centrifugal separation chamber 296 is moved by the difference in the specific gravity to the upper liquid (aqueous layer) 30.
0 and a lower layer solution (chloroform) 302. At this time, as shown in FIG.
Since the lower end thereof is located near the inner bottom surface of the centrifuge tube 30, the lower end of the inner cylinder 282 is
2 is located below the boundary surface 304. Therefore, the vicinity of the lower end of the inner cylinder 282 is in a state of being inserted into the lower liquid 302.

When the centrifugation operation is completed, the centrifuge tube is taken out of the centrifuge, and only the lower layer liquid is extracted from the centrifuge tube 30 by the separation liquid dispensing unit 62. To do this, first, the cap 31 put on the upper end of the centrifuge tube 30 is twisted and loosened. Thereby, the flange portion 292 of the inner cylinder 282 and the centrifugal tube 3
0 is released, the gap between the inner peripheral surface of the upper part of the centrifuge tube 30 and the outer peripheral surface of the upper part of the inner cylinder 282, and the flange 292 of the inner cylinder 282 and the upper edge of the centrifuge tube 30 are removed. A centrifuge chamber 296 communicates with the outside air through a gap between the centrifuge chamber 296 and the air. After fixing the centrifuge tube 30 in this state, the dispensing nozzle 2
52 is lowered, and as shown in FIG.
The disposable chip 276 that forms the lower end of 52 is inserted deeply into the inner cylinder 282 through the through hole 288 of the cap 31. Then, as shown in FIG. 21A, the closing plug 298 at the lower end of the inner cylinder 282 is pressed downward by the lower end of the disposable tip 276, so that as shown in FIG. Is dropped from the lower end of the inner cylinder 282, and the lower end of the disposable chip 276 is inserted into the lower layer liquid 302. At this time, the centrifugal separation chamber 296 communicates with the outside air as described above,
Is dropped from the lower end of the inner cylinder 282, the liquid does not flow into the inner cylinder 282 vigorously due to the gas pressure of the gas phase.

The obstruction plug 2 that has fallen from the lower end of the inner cylinder 282
98 is settled just below the lower end of the inner cylinder 282,
The obstruction plug 298 that has reached the inner bottom surface of the cylinder 0 falls down to the left or right because its lower surface is formed in a conical shape. For this reason, as shown in FIG. 21C, even if the lower end of the disposable tip 276 is inserted until it comes close to the inner bottom surface of the centrifuge tube 30, the closing plug 298 is pushed away by the lower end of the disposable tip 276, or Chip 27
6, the lower end surface of the disposable tip 276 is in close contact with the plug 298, and the entire lower end port is not closed by the plug 298. .

The lower end of the disposable chip 276 is
2, the dispensing nozzle 252
The lower liquid 302 is sucked into the disposable chip 276 through the lower end of the disposable chip 276 by driving a syringe (not shown) connected to the disposable chip 276. At this time, since the lower end of the disposable chip 276 is not closed by the closing plug 298 as described above, the lower layer liquid 302 is reliably sucked into the disposable chip 276. Further, at this time, since the lower end of the disposable chip 276 is located far below the boundary surface 304 between the upper liquid 300 and the lower liquid 302, a part of the upper liquid 300 is mixed with the lower liquid 302 to cause contamination. There is no worry that it will occur.

In the above embodiment, the inner cylinder 282
Although the cap 31 and the cap 31 are separated, the inner cylinder and the cap may be integrated or integrally formed. Further, in the above-described embodiment, the lower surface side of the stopper plug 298 is formed in a conical shape, but the shape of the lower surface side of the stopper plug is such that the stopper plug falls off from the lower end of the inner cylinder and the inner bottom surface of the container main body. The shape may be a shape other than a conical shape, for example, a bar-shaped protrusion may be formed at the center of the lower surface of the obstruction plug, as long as it falls down to the left or right from the dropping position when it reaches.

Although not shown, a shaker 194 installed on the shaking stage 58 is provided on the solvent dispensing stage 68.
A similar shaker is provided.

The injection unit 70 shown in FIG.
As shown in FIG. 7, the injection arm 306 has an injection arm 306 that rotates in a horizontal plane with one end as a center. The nozzle holding shaft 310 is resiliently supported at the distal end of the injection arm 306 by a compression coil spring 312. A chuck 314 is provided at the lower end of the nozzle holding shaft 310, and the injection nozzle 316 is held by the chuck 314. One end of the injection arm 306 is fixed to the arm support shaft 318. The arm support shaft 318 is connected to a ball spline shaft (not shown), and is supported so as to be rotatable about a vertical axis and to be vertically movable along the vertical axis. The arm support shaft 318 is
The injection arm 306 fixed to the arm support shaft 318 is raised and lowered and rotated by being vertically reciprocated by the lifting drive mechanism and rotated by the rotation drive mechanism.
The structure of the lifting drive mechanism and the rotation drive mechanism is the same as the lift drive mechanism and the rotation drive mechanism of the solvent dispensing unit 56 shown in FIG.

After evaporating the sample separation liquid dispensed into the test tube 24 to dryness, an organic solvent for dissolving the residue and injecting it into the analytical instrument, for example, methanol, is added to the test tube 2.
4 and a test tube 2
Although an injection unit for sucking the sample separation liquid from inside 4 may be provided separately (see the operation steps shown in FIGS. 8 and 9), in this embodiment,
The operation of dispensing the organic solvent into the test tube 24 is also performed by the injection unit 70.

Next, an example of an operation of automatically measuring the concentration of a specific component substance (for example, a drug) contained in a sample, for example, a frozen serum by the automatic concentration measuring device having the above-described configuration will be described. I do.

First, a plurality of the sample tubes with lids 10 containing the frozen serum are set in the sample tube holding portion 74 of the circular turntable 48 of the automatic solvent extraction unit 36. And
After the frozen serum has been thawed, the sample tube 10 is moved from the circular turntable 48 onto the sample tube suction stage 54 by the chuck unit 90 of the sample dispensing unit 52, and the sample tube 10 is fixed on the sample suction stage 54. I do. Then, the cap 12 of the sample tube 10 is removed by the cap attaching / detaching mechanism 138. Next, the arm 84 of the sample dispensing unit 52 is moved in the Y-axis direction, the dispensing head 86 is moved in the X-axis direction, and the dispensing nozzle 88 is moved in the Z-axis direction. Disposable chip 11 held at 76
6 is attached to the tip of the dispensing nozzle 88. Next, the arm 84, the dispensing head 86, and the dispensing nozzle 88 of the sample dispensing unit 52 are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, respectively, so that the tip of the disposable tip 116 of the dispensing nozzle 88 ( The lower end) is immersed in the sample liquid (melted serum) in the sample tube 10 fixed on the sample suction stage 54 (see the two-dot chain line in FIG. 14).
The sample liquid is sucked into the disposable tip 116. Then, the arm 84, the dispensing head 86, and the dispensing nozzle 88 of the sample dispensing unit 52 are respectively moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, so that the tip of the disposable tip 116 of the dispensing nozzle 88 is moved. , Processing turntable 5
Then, the sample liquid is inserted into the centrifuge tube 14 held by the centrifuge tube holding unit 78 (see the two-dot chain line in FIG. 15), and the sample liquid sucked into the disposable chip 116 is discharged into the centrifuge tube 14. After that, the used disposable chips 116 are dumped into the dumping pot 7.
3, the cap 12 is attached to the sample tube 10 by the cap attaching / detaching mechanism 138, and the sample tube 10 is returned to the sample tube holding unit 74 of the circular turntable 48.

Next, the processing turntable 50 is rotated to move the centrifuge tube 14 held by the centrifuge tube holding section 78 and containing the sample solution to the solvent dispensing position. Then, the dispensing arm 140 of the solvent dispensing unit 56 is rotated in the θ direction (rotated in a horizontal plane) and then lowered, and the distal ends of the liquid sending tubes 144 and 146 fixed to the nozzle unit 142 are processed. It is inserted into the centrifuge tube 14 held by the centrifuge tube holding portion 78 of the turntable 50 (see a two-dot chain line in FIG. 16), and ethyl acetate (organic solvent), methanol and p are introduced into the centrifuge tube 14.
Dispense H buffer. Next, the sample dispensing unit 52
After the arm 84, the dispensing head 86, and the chuck unit 90 are respectively moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, the chuck unit 90 is operated to be held on the cap holding unit 80 of the processing turntable 50. The centrifugal tube cap 16 thus obtained is connected to a pair of chuck claws 118 and 11.
8 and take out the cap 16 from the cap holder 80. The arm 8 of the sample dispensing unit 52
4. After moving the dispensing head 86 and the chuck unit 90 in the Y-axis direction, the X-axis direction, and the Z-axis direction, the chuck unit 90 is operated to be held by the centrifuge tube holding unit 78 of the processing turntable 50. Centrifuge tube 14
The cap 16 is attached to the.

When the cap 16 is attached to the centrifuge tube 14, a pair of chuck claws 118 of the chuck unit 90
While holding the cap 16 at 118, the arm 84, the dispensing head 86, and the chuck unit 90 of the sample dispensing unit 52 are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction.
After each movement in the axial direction, the chuck unit 90
Is operated to move the centrifuge tube 14 held in the centrifuge tube holder 78 of the processing turntable 50 to the shaking stage 58, and set the centrifuge tube 14 on the shaker 194. Then, the shaker 194 is driven to shake the centrifuge tube 14,
The target component substance in the sample liquid is transferred into the organic solvent in the centrifuge tube 14. When the shaking is completed, the arm 84, the dispensing head 86, and the chuck unit 90 of the sample dispensing unit 52 are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, respectively, and the chuck unit 90 is operated to operate the centrifuge tube 14. Is moved from the shaking stage 58 to the centrifuge 60, and the centrifuge tube 14 is set in the centrifuge 60. Then, the liquid is centrifuged by driving the centrifugal separator 60.

After the centrifugation, the arm 196 of the separation liquid dispensing unit 62, the dispensing head 198, and the chuck unit (not shown) for transferring the centrifuge tube are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction. The centrifuge tube 14 is moved and the chuck unit is operated to move the centrifuge tube 14
0, and the centrifuge tube 14 is moved to the separation liquid suction stage 64.
And fixed to a centrifuge tube fixing unit (not shown). Subsequently, the cap 16 is removed from the centrifuge tube 14 by a cap removal unit (not shown). This operation example is for the case where the sample separation liquid is separated into the upper layer side in the centrifuge tube 14 by centrifugation, and when the sample separation liquid is separated to the lower layer side in the centrifuge tube 30 by centrifugation. As shown in FIG. 10, it is not necessary to remove the cap 31 from the centrifuge tube 30.

When the cap 16 is removed from the centrifuge tube 14, the arm 196 of the separation liquid dispensing unit 62 is moved in the Y-axis direction, the dispensing head 198 is moved in the X-axis direction, and the dispensing nozzle 25 is moved.
The disposable chips 2 are moved in the Z-axis direction, and the disposable tips 276 held by the disposable tip holding portions 278 of the disposable tip rack 72 are attached to the tip of the dispensing nozzle 252. Next, the arm 19 of the separation liquid dispensing unit 62
6. The dispensing head 198 and the dispensing nozzle 252 are respectively moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, and the tip (lower end) of the disposable tip 276 of the dispensing nozzle 252 is moved to the separation liquid suction stage. The sample separation liquid is immersed in the centrifuge tube 14 fixed to the 64 centrifuge tube fixing units, and the sample separation liquid is sucked into the disposable chip 276 (see FIG. 18). Subsequently, the arm 196 of the separation liquid dispensing unit 62, the dispensing head 198, and the dispensing nozzle 25
2 is moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, respectively, and the tip of the disposable tip 276 of the dispensing nozzle 252 is dispensed to the dispensing position A of the test tube holder 82 of the processing turntable 50 (FIG. ), And the sample separation liquid sucked into the disposable chip 276 is discharged into the test tube 24. Thereafter, the used disposable chip 276 is discarded into the dump pot 73. Further, the liquid remaining in the centrifuge tube 14 is sucked by a suction nozzle (not shown) mounted on the separation liquid dispensing unit 62, and is sucked into a waste liquid bottle (not shown) in the liquid supply / drainage section 38. Discard. Subsequently, the separation liquid dispensing unit 62 is operated,
After the cap 16 is attached to the centrifuge tube 14 using the centrifuge tube transfer chuck unit, the used centrifuge tube 14 is discarded into the dumping pot 73.

Next, the test turntable 50 is rotated to move and hold the test tube 24 to the evaporating and drying stage 66. The test tube 24 is heated from the surroundings by a heater block (not shown), and the gas is removed. A supply unit (not shown) blows nitrogen gas into the test tube 24 through its upper opening and discharges waste gas to evaporate the sample separation liquid in the test tube 24 and dry the sample separation liquid. Let it.

Next, the arm 196, the dispensing head 198, and the centrifugal tube transfer chuck unit of the separation liquid dispensing unit 62 are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, and the chuck unit is operated. Then, the test tube 24 is removed from the removal position B (see FIG. 13) of the test tube holding portion 82 of the processing turntable 50, and the test tube 24 is moved to the solvent dispensing stage 68 and fixed to a shaker (not shown). I do. Then, the injection unit 70 is operated to dispense an organic solvent, for example, methanol, into the test tube 24. Subsequently, the test tube 24 is shaken by driving a shaker, and the dried residue is dissolved in methanol. When the shaking is completed, the injection unit 70 is operated to suck a sample solution in which the component substances are dissolved in the organic solvent from the test tube 24 into the injection nozzle 316, and a predetermined amount of the sucked sample solution is subjected to HPLC. And then measure the concentration of the component substances. Then, the separation liquid dispensing unit 62 is operated, and the used test tube 24 is discarded into the dumping pot 73 using the centrifuge tube transfer chuck unit. Further, the injection unit 70 is operated to clean the injection nozzle 316 and the inside of the pipe with methanol. FIG. 23 and FIG. 24 show flowcharts of this series of operations.

In the above-described embodiment, the sample separation liquid dispensed into the container (test tube 24) is formed by the apparatus configuration including the evaporating and drying stage 66 and the solvent dispensing stage 68 provided with a shaker. After evaporating to dryness, an organic solvent is dispensed into a container, and the container is shaken to dissolve in the organic solvent, thereby preparing a sample solution to be injected into an analytical instrument such as HPLC. By using an apparatus configuration including a concentration stage without providing the solvent dispensing stage 68, a part of the organic solvent of the sample separated solution dispensed into the container is evaporated to prepare a concentrated sample separated solution. You may. When the sample separation liquid obtained by the solvent extraction has a necessary concentration, it is not necessary to particularly provide the evaporation to dryness stage and the concentration stage. Further, with the apparatus configuration including the evaporation / drying stage 66 without the solvent dispensing stage 68, all of the organic solvent of the sample separation liquid dispensed into the container is evaporated, and the dried residue is finally obtained. From the dry residue obtained by the automatic extraction device,
A sample liquid to be injected into an analytical instrument such as an HPLC or a gas chromatograph analyzer may be prepared. Further, an automatic concentration measuring device is configured without the separation liquid dispensing unit 62 in addition to the evaporating and drying stage 66, the concentration stage and the solvent dispensing stage 68, and the separation liquid dispensing unit 6
The sample separation liquid separated into layers in the centrifuge tube may be directly sucked from the centrifuge tube and injected into an analytical instrument such as HPLC by an injection unit having a function such as 2.

[0091]

According to the present invention, when a specific component substance contained in a liquid sample such as serum, plasma, whole blood, homogenate, reaction mixture or the like is extracted with a solvent and its concentration is measured, When an automatic extraction device is used, the extraction container into which the liquid sample and the organic solvent are respectively injected is shaken to extract the component substances from the liquid sample into the organic solvent, regardless of the type of the liquid sample and the organic solvent. In addition, since no emulsion is formed in the extraction container, it is possible to avoid a situation in which an emulsion is formed in the extraction container, extraction of the component substances becomes impossible, and measurement cannot be performed. Then, the desired number of rotations and shaking time can be set freely. In addition, since the extraction efficiency of the component substances is improved, more accurate measurement can be performed.

In the automatic extracting apparatus according to the second aspect of the present invention,
By the shaking means, it is possible to reliably shake the extraction container so as to draw a figure eight.

When the automatic concentration measuring apparatus according to the ninth aspect of the present invention is used, the container into which the liquid sample and the organic solvent are respectively injected is shaken to extract the component substances from the liquid sample into the organic solvent. Regardless of the type of liquid sample and organic solvent, no emulsion is formed in the container, so avoiding the formation of an emulsion in the container, making it impossible to extract component substances and making measurements impossible. Can be. Then, the desired number of rotations and shaking time can be set freely. In addition, since the extraction efficiency of the component substances is improved, more accurate measurement can be performed.

In the automatic concentration measuring apparatus according to the tenth aspect of the present invention, the container can be reliably shaken so as to draw a figure 8 by the shaking means.

Further, by using the automatic apparatus for extracting component substances in a liquid sample according to each of the first to seventh aspects of the present invention, a series of processes for extracting a specific component substance contained in a liquid sample with a solvent can be performed. Since operations can be performed automatically,
It is possible to reduce the labor and time of the operator required for the series of operations, and to effectively use the space. Further, when the automatic concentration measuring device for component substances in a liquid sample according to each of the inventions according to claims 8 to 11 is used, a specific component substance contained in a liquid sample is extracted with a solvent and then the solvent is extracted. The whole process of the series of operations up to the measurement of the concentration of the component substances can be performed automatically, so that the labor and time required for the operators required for the series of operations can be reduced, Can be effectively used.

According to the extraction method of the twelfth aspect, no emulsion is formed in the container irrespective of the type of the liquid sample and the type of the organic solvent. This makes it possible to prevent the measurement from being performed. Then, when shaking the container, the desired number of rotations and shaking time can be freely set. In addition, since the extraction efficiency of the component substances is improved, more accurate measurement can be performed.

In the extraction method according to the thirteenth aspect, the components such as drugs contained in the homogenate such as serum, plasma, whole blood, urine or living tissue can be reliably used as a solvent regardless of the type of organic solvent. Can be extracted.

[0098] In the extraction method according to the fourteenth aspect, when the liquid sample and the organic solvent are mixed in the container, the component substances are dissolved in the lower layer liquid, and the solvent extraction can be reliably performed. .

[Brief description of the drawings]

FIG. 1 is a longitudinal sectional view showing one embodiment of the present invention and showing an entire configuration of a shaker which is one of components of an automatic extraction device for a component substance in a liquid sample.

FIG. 2 is a view showing a part of the shaker shown in FIG. 1 as viewed from the side.

FIG. 3 is a perspective view of a horizontal rocking plate constituting a part of the shaker shown in FIG.

FIG. 4 is a perspective view of a balancer constituting a part of the shaker shown in FIG.

FIG. 5 is a perspective view of another balancer constituting a part of the shaker shown in FIG.

FIG. 6 shows a centrifuge tube holder with the shaker shown in FIG.
It is a figure for explaining requirements for shaking so that figure 8 may be drawn.

FIG. 7 is a plan view showing a state in which the centrifuge tube holder makes a figure eight movement in the shaker shown in FIG.

FIG. 8 is a diagram illustrating an example of a series of operation steps for measuring the concentration of a drug contained in a blood sample.

FIG. 9 is a flowchart of the operation process shown in FIG.

FIG. 10 is a diagram for explaining another example of a series of operation steps for measuring the concentration of a drug contained in a blood sample.

FIG. 11 is a diagram for explaining still another example of a series of operation steps for measuring the concentration of a drug contained in a blood sample.

FIG. 12 is a perspective view showing an example of an entire configuration of an automatic concentration measuring device for a component substance in a liquid sample.

13 is a plan layout view of the automatic concentration measuring device shown in FIG.

FIG. 14 is a front view of a dispensing head of a sample dispensing unit which is one of the components of the automatic concentration measuring device shown in FIGS. 12 and 13.

15 is a left side view of the dispensing head shown in FIG.

FIG. 16 is a diagram showing a configuration of a solvent dispensing unit which is one of the components of the automatic concentration measuring device shown in FIGS. 12 and 13.

FIG. 17 is a side view of a dispensing head of a separation liquid dispensing unit, which is one of the components of the automatic concentration measuring device shown in FIGS. 12 and 13.

FIG. 18 is a longitudinal sectional view for explaining a method of performing a dispensing operation of a sample separation liquid in a centrifuge tube using a separation liquid dispensing unit.

FIG. 19 is a longitudinal sectional view showing a centrifuge tube and a cap used when a sample separation liquid separated into a lower layer side in a centrifuge tube is sucked into a disposable tip of a dispensing nozzle.

20 is a perspective view showing a state where the centrifuge tube and the cap shown in FIG. 19 are separated into respective components.

FIG. 21 is a longitudinal section for explaining a method of using the centrifuge tube shown in FIGS. 19 and 20, and inhaling only the sample separated liquid separated into the lower layer side of the liquid separated into the upper liquid and the lower liquid. FIG.

FIG. 22 is a partially cutaway side view showing a configuration of a main part of an injection unit, which is one of the components of the automatic concentration measurement device shown in FIGS. 12 and 13.

FIG. 23 is a flowchart showing an example of a series of operations for automatically measuring the concentration of a specific component substance contained in frozen serum by the automatic concentration measuring device shown in FIGS. 12 and 13.

FIG. 24 is also a flowchart.

[Explanation of symbols]

REFERENCE SIGNS LIST 10 Sample tube with lid 14, 30 Centrifuge tube 16, 31 Centrifuge tube cap 24 Test tube 32 Centrifuge tube with lid 36 Automatic solvent extraction unit 38 Supply / drainage unit 40 Syringe pump unit 42 Storage container 44 High-performance liquid chromatography (HPLC) 48 Circular turntable 50 Processing turntable 52 Sample dispensing unit 54 Sample suction stage 56 Solvent dispensing unit 58 Shaking stage 60 Centrifuge 62 Separation liquid dispensing unit 64 Separation liquid suction stage 66 Evaporation to dryness stage 68 Solvent Dispensing stage 70 Injection unit 72 Rack for disposable tip 74 Sample tube holder for circular turntable 76 Disposable chip holder for circular turntable 78 Centrifuge tube holder for processing turntable 80 Capacitor for processing turntable Holder 82 Test tube holder for processing turntable 86 Sample dispensing head 88 Sample dispensing nozzle 90 Cap chuck unit 116, 276 Disposable tip 140 Dispensing arm for solvent dispensing unit 194 Shaker 198 Separation liquid dispensing head 200 centrifuge tube holder 202 groove at bottom of centrifuge tube holder 204 horizontal rocking plate 206 long hole of horizontal rocking plate 208 circular hole of horizontal rocking plate 210 rotary drive motor 212 rotary shaft of rotary drive motor 214 horizontal mounting plate 216, 220 Connecting column 218 Horizontal bearing plate 222 Shaker base plate 224 Boss 226, 238 Bearing 227 Coupling 228 Horizontal rotating disk 229 Lower shaft of horizontal rotating disk 230 Connecting shaft 232 Horizontal connecting arm 234 Eccentric shaft 236 Engaging member 240 Detent member 24 , 250 Balancer 252 Separation liquid dispensing nozzle 258 Dispensing nozzle elevating drive motor (stepping motor) 280 Sample separation liquid 282 Inner cylinder 284 Screw part of centrifuge tube 286 Screw part of cap 288 Cap through hole 290 Connection ring 292 Inner cylinder 294 O-ring 296 Centrifugation chamber 298 Stopper 300 Upper liquid (water layer) 302 Lower liquid (chloroform) 304 Boundary surface between upper liquid and lower liquid 316 Injection nozzle

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Hajime Miyoshi 22-6 Hiyoshidai Ichibancho, Takatsuki-shi, Osaka (72) Inventor Shintaro Nishimura 1-5-21 Nishinishi, Tsuchiura-shi, Ibaraki F-term (reference) 2G058 AA09 BA06 BA08 CA02 CB04 CD04 CE08 EA02 EA04 EA14 ED02 ED03 ED07 ED35 FA01 GA14 GB10 GE02 GE03 4D056 AB12 AC06 AC09 AC11 AC27 BA08 BA09 CA11 CA15 CA31 CA34 CA36 CA40 DA05

Claims (14)

[Claims] 1. A sample holding unit that holds a plurality of sample containers containing a liquid sample, an extraction container holding unit that holds a plurality of extraction containers, and a sample holding unit that is taken out of the sample holding unit. A predetermined amount of a liquid sample is sucked from the sample container held in the container, and the sucked liquid sample is taken out of the extraction container holding portion or into the extraction container held in the extraction container holding portion. Dispensing means for dispensing a sample; Dispensing means for dispensing a predetermined amount of organic solvent for extraction into the container for extraction; Dispensing means for dispensing a solvent; and A shaking means for transferring the target component substance therein into the organic solvent for extraction, a storage container holding section for holding a plurality of storage containers, and a target component substance separated in the extraction container. Separates a predetermined amount of a sample separation liquid dissolved in an organic solvent, and removes the sucked sample separation liquid from the storage container holding portion or discharges the sucked sample separation liquid into a storage container held by the storage container holding portion. An automatic extraction device for component substances in a liquid sample, comprising: a liquid dispensing unit; wherein the shaking unit is configured to shake the extraction container so as to draw a figure 8 in a horizontal plane. An automatic extraction device for component substances in a liquid sample. 2. A container holder for holding the extraction container in an upright posture; a rotation drive motor having a rotation axis arranged in a vertical direction; and a shaking means connected to the rotation shaft of the rotation drive motor. An eccentric shaft arranged eccentrically from the rotation shaft, disposed horizontally, one end of the eccentric shaft is rotatably engaged with the eccentric shaft, the other end is connected to the container holder, and the other end, A long hole is formed along a straight line connecting the center position of the eccentric shaft and the center position of the container holder, and swings in a horizontal plane with the revolving motion of the eccentric shaft with respect to the rotation shaft of the rotary drive motor, and shakes the container holder. A horizontal oscillating member to be fixed, and a detent member fixed to an apparatus fixing portion and slidably engaged with the elongated hole of the horizontal oscillating member. When you separate The detent member is disposed such that the distance between the center position of the container holder and the center position of the detent member is smaller than twice the eccentric distance between the rotation shaft of the rotary drive motor and the eccentric shaft. Item 6. An automatic extraction device for a component substance in a liquid sample according to Item 1. 3. The component substance in a liquid sample according to claim 1, further comprising an evaporation / drying means for evaporating the sample separation liquid contained in the storage container to dry the sample separation liquid. Automatic extraction equipment. 4. A dissolving solvent dispensing means for discharging a predetermined amount of an organic solvent for dissolution into the storage container, and a dissolving means for dissolving a dried residue in the organic solvent for dissolution in the storage container. 4. The automatic extraction device for a component substance in a liquid sample according to claim 3, further comprising: 5. The liquid sample according to claim 1, further comprising a concentrating means for evaporating a part of the organic solvent of the sample separation liquid contained in the storage container and concentrating the sample separation liquid. Automatic extraction device for component substances. 6. A dispensing nozzle for aspirating a predetermined amount of the sample separation liquid contained in the extraction container from a lower end port and discharging the sample separation liquid from a lower end port, A nozzle holding means for holding a dispensing nozzle; and a lower position where the lower end of the dispensing nozzle is immersed in the sample separation liquid in the extraction container, and a lower end of the dispensing nozzle is provided for the extraction container. Nozzle raising and lowering means for raising and lowering between an upper position separated upward from the nozzle, nozzle moving means for moving the nozzle holding means between a position immediately above the extraction container and a dispensing position, and the dispensing nozzle A syringe for allowing a predetermined amount of the sample separation liquid in the extraction container to be sucked in from the lower end thereof, and discharging the sample separation liquid in the dispensing nozzle from the lower end of the dispensing nozzle at the dispensing position; A syringe driving means for driving the syringe driving means; a syringe controlling means for controlling the syringe driving means;
The apparatus for automatically extracting a component substance in a liquid sample according to any one of claims 1 to 5, comprising: 7. A centrifuge for centrifuging a liquid in which a target component substance has been transferred from a liquid sample into an organic solvent for extraction by said shaking means. The automatic extraction device for a component substance in a liquid sample according to any one of the above. 8. An automatic extraction device for a component substance in a liquid sample according to claim 1, 2 or 4 or 7, wherein the concentration of the component substance in the liquid sample is measured. Concentration measuring means, liquid injecting means for inhaling a component solution in which an intended component substance is dissolved in an organic solvent from the container, and injecting the inhaled component solution by a predetermined amount into the concentration measuring means; An automatic concentration measuring device for a component substance in a liquid sample, comprising: 9. A sample holding unit for holding a plurality of sample containers containing a liquid sample, a container holding unit for holding a plurality of containers, taken out of the sample holding unit or held by the sample holding unit. Sample dispensing means for sucking a predetermined amount of a liquid sample from the inside of a sample container and taking out the sucked liquid sample from the container holding unit or discharging the sucked liquid sample into a container held by the container holding unit; An extraction solvent dispensing means for discharging a predetermined amount of the organic solvent for extraction into the container, and shaking the container to transfer a target component substance in the liquid sample contained in the container into the organic solvent for extraction. A shaking means, a concentration measuring means for measuring the concentration of the component substances in the liquid sample, and a sample separation liquid in which the target component substances are dissolved in an organic solvent and separated in the container, and then inhaled. A separating liquid injecting means for injecting a predetermined amount of the sample separated liquid into the concentration measuring means, wherein the shaking means is disposed on a horizontal surface of the container. An automatic concentration device for a component substance in a liquid sample, wherein the apparatus has a mechanism for shaking so as to draw a figure 8 therein. 10. A shaking means comprising: a container holder for holding the container in an upright position; a rotary drive motor having a rotating shaft arranged in a vertical direction; and a rotating shaft of the rotating drive motor, the rotating shaft being connected to the rotating shaft. An eccentric shaft disposed eccentrically from the eccentric shaft, one end of the eccentric shaft is rotatably engaged with the eccentric shaft, the other end is connected to the container holder, and the other end of the eccentric shaft. A long hole is formed along a straight line connecting the center position of the container holder and the center position of the container holder, and the horizontal hole swings in a horizontal plane with the revolving motion of the eccentric shaft with respect to the rotation axis of the rotary drive motor to shake the container holder. A swinging member, and a detent member fixed to the device fixing portion and slidably engaged with the elongated hole of the horizontal oscillating member, wherein the container holder is most separated from the detent member. In time The detent member is arranged such that the distance between the center position of the container holder and the center position of the detent member is smaller than twice the eccentric distance between the rotation shaft of the rotary drive motor and the eccentric shaft. 10. The apparatus for automatically measuring the concentration of a component substance in a liquid sample according to claim 9. 11. The centrifuge according to claim 9, wherein a centrifugal separator is provided for centrifuging a liquid in which a target component substance is transferred from the liquid sample into the organic solvent for extraction by the shaking means. Automatic concentration measuring device for component substances in liquid samples. 12. A method for extracting a component substance contained in a liquid sample with an organic solvent, wherein a container containing at least the liquid sample and the organic solvent is shaken so as to draw a figure 8 in a horizontal plane. A method for extracting a component substance from a liquid sample. 13. The liquid sample may be serum, plasma, whole blood,
The method for extracting a component substance from a liquid sample according to claim 12, which is a homogenate such as urine or a biological tissue. 14. The method for extracting a component substance from a liquid sample according to claim 12, wherein the organic solvent is a liquid having a higher specific gravity than water.