WO2001024904A1 - Appareil d'extraction automatique, instrument de mesure de concentration automatique et procede d'extraction d'un composant contenu dans un echantillon liquide - Google Patents

Appareil d'extraction automatique, instrument de mesure de concentration automatique et procede d'extraction d'un composant contenu dans un echantillon liquide Download PDF

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Publication number
WO2001024904A1
WO2001024904A1 PCT/JP2000/006680 JP0006680W WO0124904A1 WO 2001024904 A1 WO2001024904 A1 WO 2001024904A1 JP 0006680 W JP0006680 W JP 0006680W WO 0124904 A1 WO0124904 A1 WO 0124904A1
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WO
WIPO (PCT)
Prior art keywords
sample
container
liquid
extraction
organic solvent
Prior art date
Application number
PCT/JP2000/006680
Other languages
English (en)
Japanese (ja)
Inventor
Akiyoshi Banba
Katsuhiko Saito
Hajime Miyoshi
Shintaro Nishimura
Original Assignee
Dainippon Seiki Co., Ltd.
Fujisawa Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dainippon Seiki Co., Ltd., Fujisawa Pharmaceutical Co., Ltd. filed Critical Dainippon Seiki Co., Ltd.
Publication of WO2001024904A1 publication Critical patent/WO2001024904A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/20—Mixing the contents of independent containers, e.g. test tubes
    • B01F31/22—Mixing the contents of independent containers, e.g. test tubes with supporting means moving in a horizontal plane, e.g. describing an orbital path for moving the containers about an axis which intersects the receptacle axis at an angle
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4055—Concentrating samples by solubility techniques
    • G01N2001/4061—Solvent extraction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00524—Mixing by agitating sample carrier

Definitions

  • the present invention automatically performs a solvent extraction operation for a specific component substance contained in a liquid sample such as a serum, plasma, whole blood, urine, a homogenate (refining) of a biological tissue, or a reaction mixture.
  • a liquid sample such as a serum, plasma, whole blood, urine, a homogenate (refining) of a biological tissue, or a reaction mixture.
  • An automatic extraction device capable of automatically extracting all the components contained in a liquid sample and measuring the concentration of the components, and an automatic concentration measurement device capable of automatically performing all operations up to the measurement of the concentration.
  • the present invention also relates to an extraction method for extracting a specific component substance contained in a liquid sample with a solvent.
  • an organic solvent is used to measure the concentration of a drug contained in a biological sample, for example, blood.
  • the drug component is dissolved in the organic solvent from the blood and separated (solvent extraction), and the drug component is dissolved in the organic solvent.
  • the sample separation solution is injected into analytical equipment such as high-performance liquid chromatography.
  • analytical equipment such as high-performance liquid chromatography.
  • the operation of shaking the centrifuge tube is usually performed using a shaker, but with a conventional shaker, the centrifuge tube is held in an upright posture by a container holder, and the container holder is moved in a horizontal plane by a rotary drive mechanism. The centrifuge tube was shaken by rotating it in a circular motion.
  • the liquid sample such as blood and the centrifuge tube into which the organic solvent has been dispensed are each shaken with a shaker to obtain the liquid sample.
  • the components contained therein are transferred to the organic solvent, and the components are dissolved in the organic solvent and separated from the liquid sample.
  • the organic solvent insoluble in water and the liquid sample such as blood are usually separated into two layers in a centrifuge tube.
  • the liquid sample is, for example, a homogenate (such as a biological tissue).
  • the solution in the centrifuge tube may mix evenly in appearance to form an emulsion. is there. Once the emulsion is formed in the centrifuge tube, it is no longer possible to dissolve the component substances in an organic solvent and separate them from the liquid sample.
  • the rotation speed of the centrifuge tube during the shaking operation 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.
  • the present invention has been made in view of the circumstances described above, and a solvent extraction of a specific component substance such as a drug contained in a liquid sample such as serum, plasma, whole blood, homogenate, and reaction mixture. Then, when measuring the concentration, shake the container such as the centrifuge tube into which the liquid sample and the organic solvent are respectively injected, and extract the component material from the liquid sample into the organic solvent. Regardless of the type of organic solvent and the type of organic solvent, an automatic extraction device for component substances in a liquid sample and a component substance in a liquid sample that do not form an emulsion in the container and improve the extraction efficiency of the component substances
  • the first and second objects are to provide an automatic concentration measuring device.
  • the first invention includes a sample holding unit for holding a plurality of sample containers containing a liquid sample, and an extraction container holding unit for holding a plurality of extraction containers A predetermined amount of a liquid sample is taken out of the sample container taken out of the sample holding unit or held in the sample holding unit, and the sucked liquid sample is taken out of the extraction container holding unit or Sample dispensing means for discharging into an extraction container held in an extraction container holding unit, and extracting a predetermined amount into the extraction container A dispensing means for dispensing an extraction solvent for discharging an organic solvent for extraction, and shaking the container for extraction to transfer a target component substance in a liquid sample contained in the container for extraction into the organic solvent for extraction.
  • An apparatus for automatically extracting component substances in a liquid sample comprising: a separation liquid dispensing unit that removes a sample separation liquid from the storage container holding unit or discharges the sample separation liquid into a storage container held by the storage container holding unit.
  • the shaking means is characterized by a mechanism for shaking the extraction container so as to draw a figure 8 in a horizontal plane.
  • 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 extraction container. Discharged.
  • a predetermined amount of the organic solvent for extraction is discharged into the extraction container by the solvent dispensing means for extraction, and the target component substance in the liquid sample contained in the extraction container is discharged by the shaking means. It is transferred into the organic solvent for extraction.
  • the extraction container is shaken so as to draw a figure 8 in a horizontal plane.
  • the invention of the first invention is described.
  • 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.
  • the desired number of rotations and shaking time can be freely set.
  • the extraction efficiency of the component substances is improved, more accurate measurement can be performed.
  • 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 rotation shaft of the rotation drive motor
  • An eccentric shaft which is connected and eccentrically arranged from the rotation shaft, is disposed in a horizontal direction, one end of the eccentric shaft is rotatably engaged with the eccentric shaft, and the other end is connected to the container holder.
  • an elongated hole is formed on the other end side along a straight line connecting the center position of the eccentric shaft and the center position of the container holder, and the revolving motion of the eccentric shaft with respect to the rotating shaft of the rotary drive motor is formed.
  • the shaking means includes: a horizontal rocking member that rocks in a horizontal plane to shake the container holder; and a detent member fixed to a device fixing unit and slidably engaged with the elongated hole of the horizontal rocking member.
  • a detent member fixed to a device fixing unit and slidably engaged with the elongated hole of the horizontal rocking member.
  • the eccentric shaft arranged eccentrically from the rotation axis performs a circular motion about the rotation axis in a horizontal plane.
  • the eccentric shaft makes a circular motion
  • the horizontal swinging member whose one end is rotatably engaged with the eccentric shaft swings in a horizontal plane.
  • the other end of the horizontal swinging 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. While reciprocating, it reciprocates in the direction connecting the rotation shaft of the rotation drive motor and the detent member.
  • the container holder connected to the other end of the horizontal pivoting member also reciprocates while swinging in the horizontal plane, but when the container holder is most separated from the detent member, that is, the rotation 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 shaft, the eccentric shaft and the detent member are located on a straight line is twice the eccentric distance between the rotary shaft of the rotary drive motor and the eccentric shaft.
  • the automatic extraction device may further include a vaporization and drying means for evaporating the sample separation liquid contained in the storage container to dry the sample separation liquid,
  • a dissolving solvent dispensing means for discharging a predetermined amount of the dissolving organic solvent into the storage container,
  • a dissolving means for dissolving the dried residue in an organic solvent for dissolution can be provided in the container.
  • the organic solvent of the sample separation liquid contained in the container is evaporated by the evaporation to dryness means, and the sample separation liquid is dried to dryness. A hardened residue is obtained. Then, a predetermined amount of the organic solvent for dissolution is discharged into the container by the dispensing means for dissolving solvent, and the residue dried in the organic solvent is dissolved by the dissolving means, and the target component substance is dissolved. A sample solution dissolved in an organic solvent is obtained.
  • the automatic extraction device may further include 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.
  • the concentrating means evaporates a part of the organic solvent of the sample separation liquid contained in the storage container and concentrates the sample separation liquid to obtain a concentrated sample separation liquid.
  • a predetermined amount of the sample separation liquid that has entered the extraction container is suctioned from the lower end port, and the sample separation liquid is discharged from the lower end port.
  • Nozzle elevating means for elevating and lowering the end port between the extraction container and an upper position separated upward, and nozzle movement for moving the nozzle holding means between a position immediately above the extraction container and a dispensing position Means, and a predetermined amount of the sample separation liquid in the extraction container is sucked into the dispensing nozzle from the lower end port thereof.
  • a syringe for discharging the sample separation liquid in the dispensing nozzle from the lower end port at the dispensing position, a syringe driving means for driving the syringe, and a syringe control means for controlling the syringe driving means
  • the dispensing nozzle held by the nozzle holding means is moved to a position immediately above the extraction container by the nozzle moving means, and then lowered by the nozzle elevating means, and then moved downward.
  • the end opening is immersed in the sample separation liquid in the extraction container.
  • the syringe is driven by the syringe driving means
  • a predetermined amount of the sample separation liquid that has entered the extraction container is sucked into the dispensing nozzle.
  • the dispensing nozzle is raised by the nozzle elevating means, and then moved to the dispensing position by the nozzle moving means.
  • the sample separation liquid is discharged into the container from the lower end of the dispensing nozzle.
  • a centrifuge for centrifuging a liquid in which a target component substance is transferred from a liquid sample into an organic solvent for extraction by a shaking means is provided.
  • the liquid is centrifuged by a centrifugal separator, so that a sample separation liquid in which the target component substance is dissolved in an organic solvent can be formed in an extraction container in a short time and reliably.
  • a sample separation liquid in which the target component substance is dissolved in an organic solvent can be formed in an extraction container in a short time and reliably.
  • the organic solvent layer is on the upper side, and an organic solvent having a higher specific gravity than water is used.
  • an organic solvent having a higher specific gravity than water is used.
  • the use of the above-described apparatus for automatically extracting component substances in a liquid sample can automatically perform a series of operations for extracting a specific component substance contained in the liquid sample with a solvent.
  • a second invention is directed to an automatic extraction device having the above-described configuration, a concentration measuring means for measuring the concentration of a component substance in a liquid sample, and A liquid injecting means for inhaling a component solution obtained by dissolving a target component substance 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 component substances in a liquid sample is configured.
  • the liquid dissolving means is a component solution obtained by dissolving a target component substance obtained by an automatic extraction device in an organic solvent.
  • the sample separation liquid, sample lysis liquid or 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 substances in the liquid sample is measured by the concentration measuring means. Is measured.
  • a third invention provides a sample holding section for holding a plurality of sample containers containing a liquid sample, and a container for holding a plurality of containers.
  • a holding unit, a predetermined amount of a liquid sample taken out of the sample container taken out of the sample holding unit or held in the sample holding unit, and the sucked liquid sample is taken out of the container holding unit or The sun discharged into the container held by the container holder Pull dispensing means, extraction solvent dispensing means for discharging a predetermined amount of the organic solvent for extraction into the container, and shaking the container to remove the target component substance in the liquid sample contained in the container.
  • Shaking means for transferring into the organic solvent for extraction, concentration measuring means for measuring the concentration of the component substances in the liquid sample, sample separation in which the target component substances are dissolved in the organic solvent and separated in the container
  • An automatic concentration measuring device for a component substance in a liquid sample comprising: a liquid inhaling solution; and a separating liquid injecting means for injecting a predetermined amount of the inhaled sample separating liquid into the concentration measuring means.
  • a mechanism for shaking the container so as to draw a figure 8 in a horizontal plane is provided.
  • 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.
  • a predetermined amount of the extraction organic solvent is discharged into the container by the extraction solvent dispensing means, and the target component substance in the liquid sample contained in the container is extracted by the shaking means into the organic solvent for extraction. Moved inside. At this time, the container is shaken so as to draw a figure 8 in a horizontal plane.
  • 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.
  • the desired rotation speed and shaking time can be freely set.
  • the extraction efficiency of the component substances is improved, more accurate measurement can be performed.
  • a container holder for holding the container in an upright posture, a rotary drive motor having a rotating shaft arranged in a vertical direction, and being connected to the rotary shaft of the rotary drive motor
  • An eccentric shaft arranged eccentrically from the rotation shaft, horizontally disposed, one end of the eccentric shaft is rotatably engaged with the eccentric shaft, and the other end is connected to the container holder.
  • an elongated 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 rotating shaft of the rotary drive motor.
  • the shaking means is constituted by a horizontal rocking member for moving and shaking the container holder, and a detent member fixed to the device fixing portion and slidably engaged with the elongated hole of the horizontal rocking member;
  • Container holder The distance between the center position of the container holder and the center position of the detent member when most distant from the detent member is set to be smaller than twice the eccentric distance between the rotation axis of the rotary drive motor and the eccentric axis.
  • a detent member can be arranged. In the automatic concentration measuring device having such a configuration, the container held in the container holder is shaken so as to draw a figure 8 by the same operation as in the automatic extracting device described above.
  • a centrifuge for centrifuging a liquid in which a target component substance is transferred from a liquid sample into an organic solvent for extraction by a shaking means is provided. be able to.
  • the sample separated liquid in which the target component substance is dissolved in an organic solvent is separated in a short time and reliably in a container by centrifuging the liquid using a centrifuge. I do.
  • a fourth invention is a method of extracting a component substance contained in a liquid sample with an organic solvent, wherein at least the liquid sample and the liquid sample are extracted. It is characterized in that a container containing an organic solvent is shaken so as to draw a figure 8 in a horizontal plane.
  • the container containing the liquid sample and the organic solvent is shaken in a horizontal plane so as to draw a figure of eight, a circle is formed in the horizontal plane as in the related art. Air is less likely to enter the liquid phase in the container than if the container were shaken as depicted, resulting in the formation of an emulsion in the container regardless of the type of liquid sample and organic solvent. Is Since it does not exist, it is possible to set a desired rotation speed and shaking time. In addition, 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.
  • the extraction method of the fourth invention no emulsion is formed in the container irrespective of the type of the liquid sample and the organic solvent, so that the emulsion is formed in the container and extraction of the component substances becomes impossible. And the measurement can no longer be performed. Then, when shaking the container, the desired number of rotations and shaking time can be freely set. Moreover, since the extraction efficiency of the component substances is improved, more accurate measurement can be performed.
  • a homogenate such as serum, plasma, whole blood, urine, or biological tissue can be used as the liquid sample.
  • the organic solvent one having a specific gravity larger than that of water, for example, black-mouthed form can be used.
  • an organic solvent for example, cloper form
  • a lower layer solution when a liquid sample and an organic solvent are mixed in a container, an organic solvent, for example, cloper form, becomes a lower layer solution, and the component substances extracted from the liquid sample by the solvent are added to the lower layer solution. After dissolution, solvent extraction can be performed reliably.
  • FIG. 1 shows one embodiment of the present invention, and is a longitudinal sectional view showing the overall configuration of a shaker, which is one of the components of an automatic extraction device for a component substance in a liquid sample.
  • FIG. 2 is a diagram 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.
  • FIG. 6 is a diagram for explaining the requirements for shaking the centrifuge tube holder so as to draw a figure 8 using the shaker shown in FIG.
  • FIG. 7 is a plan view showing a state in which the centrifuge tube holder is moving in a figure 8 in the shaker shown in FIG.
  • FIG. 8 is a diagram for explaining 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 the entire configuration of an automatic concentration measuring device for a component substance in a liquid sample.
  • FIG. 13 is a plan 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.
  • FIG. 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 solution dispensing unit, which is one of the components of the automatic concentration measuring device shown in FIGS.
  • FIG. 4 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 pipe.
  • FIG. 19 is a vertical cross-sectional view showing a centrifuge tube and a cap used when a sample separated liquid separated into a lower layer side in a centrifuge tube is sucked into a dispensing tip of a dispensing nozzle.
  • FIG. 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 explains how to use the centrifuge tubes shown in Figs. 19 and 20 to inhale only the sample separated liquid separated into the lower layer of the liquid separated into the upper liquid and the lower liquid.
  • FIG. Figure 22 explains how to use the centrifuge tubes shown in Figs. 19 and 20 to inhale only the sample separated liquid separated into the lower layer of the liquid separated into the upper liquid and the lower liquid.
  • FIG. 4 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 measuring device shown in FIGS. 12 and 13.
  • Fig. 23 is a flow chart showing an example of a series of operations for automatically measuring the concentration of specific component substances contained in frozen serum using the automatic concentration measurement device shown in Figs. 12 and 13. It is a chart.
  • Figure 24 is also a flowchart.
  • a frozen serum (sample) obtained by centrifuging blood collected by administering a drug to an animal is placed in a sample tube 10 with a lid, and the sample is collected. After thawing the frozen serum contained in the tube 10, the cap 12 of the sample tube 10 is removed, and the disposable disposable tip attached to the tip of the dispensing nozzle of the liquid dispensing device (hereinafter referred to as the disposable tip)
  • a sample solution for example, 0.1 ml of a sample solution (serum) is sucked into the sample tube 10 (referred to as “disposal tip”) (not shown) from the sample tube 10 ((b) in FIG. 8), and The sample solution is discharged into a centrifuge tube 14 and an organic solvent, for example, ethyl acetate, is added to 4 ml, pH buffer (0.5 ml) and methanol (0.1 ml). ) Is 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.
  • the centrifuge tube 14 makes sure that the target component (drug) in the sample solution 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 and the solution is centrifuged (Fig. 8).
  • FIG. 11 shows an example of a blood analysis operation using the direct protein removal method.
  • the frozen serum (specimen) contained in the sample tube 10 with the lid is thawed, then the cap 12 of the sample tube 10 is removed, and the liquid is dispensed.
  • a sample liquid, for example, 0.1 m1 is sucked into the disposable tip (not shown) attached to the tip of the dispensing nozzle of the device from the sample tube 10 (Fig. 11 (b)), and the suction is performed.
  • the sample solution thus obtained is discharged into a centrifuge tube 32 with a lid, and a predetermined amount of an organic solvent, for example, 0.2 ml of methanol or 0.5 ml of acetonitrile is poured into the centrifuge tube 32. Dispense (Fig. 11 (c)).
  • the centrifuge tube 32 is shaken by a shaker ((e) in FIG. 11).
  • 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).
  • the liquid in the centrifuge tube 32 is separated into a liquid layer and a sedimentation part. To separate. 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 separated from the liquid layer in the centrifuge tube 32 by the nozzle 28. (G in Fig. 11), and inject only 20 to 501 of the inhaled sample separation solution into analytical equipment such as high-performance liquid chromatography to measure the concentration of the component substances. I do.
  • FIG. 12 is a perspective view showing the entire configuration of the automatic concentration measuring device
  • FIG. 13 is a plan layout diagram thereof.
  • This automatic concentration measurement device automatically performs a series of operations to extract a specific component substance (for example, a drug) contained in a sample solution such as blood with a solvent.
  • a liquid supply / drainage unit provided with a syringe pump unit 40 for sending organic solvent, etc. to 40, a plurality of liquid storage containers 42 for storing organic solvent, etc., a waste liquid tank (not shown), etc.
  • the automatic solvent extraction unit 36 is provided on the upper surface of the apparatus, and the liquid supply / drainage unit 38 and the HPLC 44 are housed in the cabinet below the automatic solvent extraction unit 36, respectively. .
  • An operation panel 46 is provided on the front of the device.
  • the automatic solvent extraction unit 36 is covered with a transparent cover that can be opened and closed.
  • an apparatus for automatically extracting a solvent from a component substance in a liquid sample without using an integrated analytical instrument such as an HPLC as in the illustrated example is provided. It is also possible to adopt a configuration in which the liquid finally obtained by the automatic extraction device is injected into an attached analytical device or into a separate analytical device.
  • An apparatus having such a configuration in which the analytical instrument is omitted from the automatic concentration measuring apparatus is an automatic extracting apparatus according to claims 1 to 7.
  • 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, and solvent dispensing.
  • Unit 56 Shaking stage 58, Centrifuge 60, Separation unit dispensing unit 62 (Structure is not shown in Fig. 12), Separator suction stage 64, Evaporation drying stage 66 It consists of a solvent dispensing stage 68, an injection unit 70, a disposable tip rack 72, and a waste pot 73.
  • the circular turntable 48 has a large number of sample tube holders 74 that hold sample tubes with lids (for example, 1.5 ml microtubes) containing samples such as frozen serum, and disposable tips. It has a large number of disposable chip holding parts 76 that are held, and is rotated by a rotation drive mechanism (not shown) to control the stop position. Also, the processing turntable 50 has a number of centrifuge tube holders 78 for holding centrifuge tubes (for example, 7 cc centrifuge tubes) 14 and a number of cap holders for holding centrifuge tube caps 16. 80, and a plurality of test tube holders 82 holding glass test tubes 24 on the outer periphery. The stop position is controlled by being rotated by a rotation drive mechanism (not shown). ing.
  • sample tube holders 74 that hold sample tubes with lids (for example, 1.5 ml microtubes) containing samples such as frozen serum, and disposable tips. It has a large number of disposable chip holding parts 76 that are held, and is 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 that is supported by the arm 84 and moves back and forth in the left-right direction (X-axis direction). 8 and 6 (Each reciprocating drive mechanism is shown
  • the dispensing head 86 is provided with a sample dispensing nozzle 88 and a capping chuck unit 90 which reciprocate in the vertical direction (Z-axis direction).
  • the dispensing nozzle 88 is connected via a tube 89 to a syringe (not shown) driven by a motor.
  • a syringe not shown
  • the dispensing nozzle 88 has a vertical slide that engages with the dispensing head 86 and is supported and reciprocates in the vertical direction. It is held by member 92.
  • the dispensing nozzle 88 is driven by a forward / reverse rotatable drive motor 94 fixed to the dispensing head 86, with a pinion 96 fixed to the motor rotation shaft and a vertical slide member 92.
  • Driving force is transmitted via a rack 98 fixed to the rack, and the rack 98 reciprocates up and down.
  • Reference numeral 100 in FIG. 14 is an ascending limit sensor for detecting the ascending limit position of the dispensing nozzle 88, and 102 is a detecting origin position in the vertical direction of the dispensing nozzle 88.
  • Reference numeral 110 in FIG. 15 denotes a slide bearing
  • reference numeral 112 denotes an upper and lower slide guide
  • reference numeral 114 denotes a disposable tip attached to the lower end of a dispensing nozzle 88. This is a chip presence / absence sensor for confirming that the operation is performed.
  • the cap chuck unit 90 includes a pair of chuck jaws 111, 118, an opening / closing mechanism section 120 for opening and closing the pair of chuck jaws 111, 118, and an opening / closing mechanism.
  • the chuck unit 90 is held by an upper and lower slide member 124 that is engaged with and supported by the dispensing head 86 and reciprocates vertically. And Chuckunit 90 goes to dispensing
  • a drive motor (not shown) that can be rotated forward and backward is fixed to the head 86, and the pinion 126 fixed to the motor rotation shaft and the rack fixed to the upper and lower slide members 124 are mounted.
  • Driving force is transmitted via 8 to reciprocate up and down.
  • the reference numeral 130 in FIG. 14 is an ascending limit sensor for detecting the ascending limit position of the chuck unit 90, and the reference numeral 132 is for detecting the origin position in the vertical direction of the chuck unit 90.
  • the sample suction stage 54 is provided with a cap attachment / detachment mechanism 138.
  • the sample tube 10 with the lid containing the sample solution is taken out of the sample tube holder 74 of the circular turntable 48 by the chuck unit 90 of the sample dispensing unit 52, and the sample tube 10 is
  • the sample tube 10 placed on the sample suction stage 54 and fixed on the stage 54 is removed by the cap 1 2 force cap attachment / detachment mechanism 1 38 of the sample tube 10.
  • the cap 12 is attached to the sample tube 10 after the sample is sucked by the cap attachment / detachment mechanism 1 38, and the sample is sucked by the sample tube 10 and the chuck unit 90 of the sample dispensing unit 52. It is returned from the stage 54 to the sample tube holder 74 of the circular turntable 48.
  • the solvent dispensing unit 56 has a dispensing arm 140 that rotates in a horizontal plane about one end, and as shown in FIG. 16, the tip of the dispensing arm 140 is A nozzle portion 142 is provided in the portion.
  • the nozzle section 14 2 has a plurality of, for example, three liquid feed tubes 1 4 4 and 1 4 6 (one liquid feed tube). Is not shown). 3 transfer tubes 1 44,
  • 14 6 is a syringe pump unit 40 for the liquid supply / drainage unit 40
  • pH buffer supply syringes 15 4 are connected to the flow paths via switching valves, respectively, and each of the syringes 150, 15 2 and 15 4 Channels are connected to respective storage containers (not shown) in which required liquids are stored.
  • the dispensing arm 140 has one end lower surface fixed to the arm support shaft 156.
  • the arm support shaft 156 is connected to the ball spline shaft 158, and is supported so as to be rotatable around a vertical axis and movable vertically along the vertical axis.
  • the arm support shaft 156 is reciprocated in the vertical direction by the lifting drive mechanism, and is rotated by the rotation drive mechanism.
  • the dispensing arm 140 fixed to 156 is adapted to move up and down and rotate.
  • the lifting / lowering drive mechanism includes a drive motor 16 2 fixed to the upper mounting plate 16 0, a timing pulley 16 4 fixed to the rotating shaft of the drive motor 16 2, an upper mounting plate 16 0 A screw shaft 168 whose upper end and lower end are rotatably supported on the lower mounting plate 1666, respectively, and a timing pulley 1700 fixed near the upper end of the screw shaft 1680, both ties A timing belt 172 stretched between the ming pulleys 16 4 and 17 0, a change nut 17 4 screwed to the screw shaft 16 8 and an arm connected to this change nut 1 74
  • An elevating member 176 engaged with the support shaft 156 to allow its rotation and move integrally in the vertical direction, as well as to the upper mounting plate 160 and the lower mounting plate 166 Upper and lower ends are fixed, bearing 1 7 A guide rod 180 is engaged with the elevating member 176 so as to be freely slidable through 8.
  • an ascending limit sensor and a descending limit sensor for detecting an ascending limit position and a descending limit position of the dispensing arm 140, respectively, and in a vertical direction of the dispensing arm 140.
  • An upper and lower origin sensor for detecting the origin position and a sensor detection plate are provided.
  • the rotation drive mechanism includes a drive motor 18 2 fixed to the lower mounting plate 16 6, a timing pulley 18 2 fixed to the rotating shaft of the drive motor 18 2, and a lower mounting plate 1
  • a support block 18 4 fixed to 6 6 is rotatably supported by this support block 18 4, and allows the ball spline shaft 15 8 to move in the vertical direction and a key to rotate integrally with it.
  • Rotating member 186 having a boss hole with a groove formed, a timing pulley that rotates integrally with this rotary member 186, a hook between both timing pulleys 182, 188 It is composed of the passed timing belt 190 and a positioning sensor 192 for detecting the rotation angle position of the dispensing arm 140.
  • the dispensing arm 140 is rotated by the rotary drive mechanism, and the dispensing arm 140 is rotated as shown by the solid line in FIG.
  • the tip nozzle section 14 2 is moved to the position immediately above the centrifuge tube 14 held by the centrifuge tube holding section 78 (see FIG. 13) of the processing turntable 50.
  • the dispensing arm 140 is lowered, and as shown by the two-dot chain line in FIG. 16, the nozzle portion 142 at the tip of the dispensing arm 140 is inserted into the centrifuge tube 14.
  • each syringe 150, 152, 154 see Fig.
  • centrifuge tube 14 Methanol, ethyl acetate (Organic solvent) and pH buffer should be discharged into centrifuge tube 14.
  • the shaking stage 58 is provided with a shaker 194.
  • the centrifuge 60 is installed inside the annular processing turntable 50 in order to make the apparatus compact by effectively using space. If the centrifuge tube 14 in which the sample solution and the organic solvent are dispensed is shaken and the centrifuge tube 14 is left standing, the liquid in the centrifuge tube 14 can be quickly separated into layers.
  • the centrifuge 60 may not be particularly provided.
  • the centrifuge 60 has been used conventionally, and illustration and description of its detailed structure are omitted, and a configuration example and operation of the shaker 1994 will be described based on FIGS. 1 to 7. .
  • FIG. 1 is a longitudinal sectional view showing an example of the entire configuration of the shaker 194, and FIG. 2 is a view showing a part of the shaker 194 as viewed from the side.
  • the shaker 194 includes a centrifuge tube holder 200 for holding the centrifuge tube 30 in an upright posture, and a groove 202 is formed at the bottom of the centrifuge tube holder 200.
  • a horizontal oscillating plate 204 disposed horizontally is physically connected to the bottom of the centrifuge tube holder 200.
  • the horizontal rocking plate 204 has a long hole 206 formed in the longitudinal direction thereof, and the centrifugal tube holder 200 and the horizontal rocking plate 2 No.
  • 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 has its rotary shaft 211 disposed vertically and vertically, and a horizontal mounting plate. It is fixed to 2 1 4. Horizontal mounting plate 2 1 4 The horizontal support plate 2 18 is connected to the base plate 222 via the connection support 210, and is fixed to the base plate 222 via the connection support 220. The upper end of the rotary shaft 2 12 of the rotary drive motor 2 10 is coaxial with the lower shaft 2 9 9 fixed vertically to the center of the lower surface of the horizontal rotating disk 2 2 8 via the coupling 2 2 7. It is linked above.
  • a boss 224 is fixed to the center of the horizontal support plate 218, and the lower shaft 229 of the horizontal rotating disk 228 is inserted into the boss 224, and the lower shaft 229 is The boss 2 24 is rotatably supported via a bearing 226.
  • a connecting shaft 230 is vertically fixed at a position eccentric from the center of the horizontal rotating disk 228, and the horizontal connecting arm is connected to the connecting shaft 230.
  • the eccentric shaft 2 3 4 is connected via 2 3 2.
  • the eccentric shaft 234 is vertically disposed through the circular hole 208 of the horizontal rocking plate 204, and is integrally fixed to the upper surface on one end side of the horizontal rocking plate 204.
  • the engaging member 2336 is rotatably engaged via the bearing 238.
  • the eccentric shaft 234 is eccentrically arranged from the rotary shaft 212 of the rotary drive motor 210.
  • the eccentric shaft 2 3 4 and the centrifugal tube holder 2 0 0 are connected to each other by an engaging member 2 3 6 and a horizontal rocking plate 2 0 4.
  • a detent member 240 suspended from the horizontal support plate 218 is slidably engaged with the elongated hole 206 formed on the side of the side 200. Then, when the rotary drive motor 210 is started, the eccentric shaft 234 revolves in a circular orbit with respect to the rotary shaft 212, so that the horizontal moving plate 204 becomes horizontal.
  • the rocking motion at that time is regulated by the detent member 240 to a constant state.
  • the fixed position of the detent member 240 is the center position and the centrifuge tube holder 2
  • the horizontal distance from the center position of 0 0 is the largest, that is, the rotation shaft 2 12 of the rotary drive motor 210, the eccentric shaft 2 3 4, and the long hole 2 0 6 of the horizontal swing plate 2 4
  • the position is determined so that the maximum value of the horizontal distance is smaller than twice the eccentric distance between the rotating shaft 2 12 and the eccentric shaft 2 3 4.
  • the centrifuge tube holder 200 is shaken so as to draw a figure 8 in a horizontal plane. This point will be described with reference to FIG.
  • the point O is the center position of the rotation axis 211, and the circle c including the points A to F is the trajectory of the eccentric axis 234.
  • the point X is the center position of the detent pin 240, and the locus of the center position of the centrifuge tube holder 200 corresponding to the points A ′ to F ′ and the points A to F.
  • the center position of the detent member 240 is on the locus A 'to F' of the center position of the centrifuge tube holder 200, in other words, the center position of the centrifuge tube holder 200 is the center position of the detent member 240.
  • the centrifuge tube holder 200 When moving to pass through the centrifugal tube, the centrifuge tube holder 200 is shaken so as to draw a figure 8 with the circular motion of the eccentric shaft 234.
  • the maximum horizontal distance 1 between the center position of the centrifuge tube holder 200 and the center position of the detent member 240, twice the eccentric distance r between the rotating shaft 211 and the eccentric shaft 234 When it is smaller than r, the centrifuge tube holder 200 will make a figure-eight movement.
  • FIG. 7 is a plan view showing a state in which the centrifuge tube holder 200 is making a figure-eight movement. (A) to (e) of FIG. 7 and the state where the eccentric shafts 234 are located at points A to E in FIG. 6, respectively.
  • the centrifuge tube holder 200 and thus the centrifuge tube 30 held in the centrifuge tube holder 200 is shaken in the shape of a figure 8, so that the centrifuge tube is simply drawn in a circle.
  • a solution in which a sample solution such as a molten serum and an organic solvent are mixed is less likely to be emulsified (emulsified), and the stirring efficiency is improved and the extraction efficiency is increased. .
  • the comparative experiments performed in this regard are described below.
  • the connecting shaft 230 has a long hole 244 as shown in a perspective view in FIG.
  • a balancer 242 is rotatably mounted via a bearing 246 and is supported in a cantilever manner. Further, a detent member 248 suspended from the horizontal support plate 218 is engaged with the elongated hole 244 formed in the balancer 242 in sliding contact with itself. Then, the rotating shaft 2 12 of the rotary drive motor 2 10 rotates and the horizontal rotating disk 2 28 fixed to the upper end rotates, thereby eccentrically fixing on the horizontal rotating disk 2 28.
  • a balancer 250 having a shape as shown in FIG. 5 is externally fitted to the rotary shaft 2 12 of the rotary drive motor 210.
  • the eccentric shaft 234 arranged eccentrically from the rotary shaft 212 causes the rotary shaft 2 Perform a circular motion about 1 and 2.
  • the separated liquid dispensing unit 62 has an arm 196 that reciprocates in the front-rear direction (Y-axis direction) and an arm 196 that reciprocates in the left-right direction (X-axis direction) supported by the arm 196. And a dispensing head 198 (the reciprocating drive mechanism is not shown), and the dispensing head 198 has a vertical direction (Z-axis direction) as shown in FIG.
  • a separation liquid dispensing nozzle 2 52 that reciprocates in The dispensing nozzle 255 is connected to a motor-driven syringe (not shown) via a tube 254 (see FIG. 18).
  • the nozzle elevating mechanism for vertically reciprocating the dispensing nozzle 25 2 includes a drive motor (stepping motor) 2 58 8 fixed to the mounting plate 256 fixed to the dispensing head 1 98.
  • the timing plate 260 fixed to the rotating shaft of the drive motor 258, the upper mounting plate 262 fixed to the dispensing head 198, and the upper mounting plate 264 fixed to the lower mounting plate 264.
  • a screw shaft 266 whose lower end is supported rotatably, a timing tool 266 fixed to the lower end of the screw shaft 266, and both timing tools 266, 268
  • a timing nut 272 which is threaded around the screw shaft 26, is screwed onto the screw shaft 26, and the change nut 27 2 moves up and down with the forward and reverse rotation of the screw shaft 2 66, and Is connected to this change nut 27 2 and is engaged with the dispensing nozzle 25 2 to change the change nut 27 2 and dispensing.
  • a nozzle 2 5 2 and the elevating member 2 7 4 to move integrally with the vertical direction.
  • an upward limit sensor and a downward limit sensor for detecting an ascending limit position and a descending limit position of the dispensing nozzle 25 2, respectively, and a vertical direction of the dispensing nozzle 25 2.
  • An upper / lower origin sensor for detecting the origin position in the sensor and a sensor detection plate are provided, and a disposable tip 2 76 is attached to the lower end of the dispensing nozzle 25 2.
  • a chip presence / absence sensor for confirmation is provided. The disposable tip 276 attached to the lower end of the dispensing nozzle 25 2 is held by a large number of disposable tip holding portions 278 of the disposable tip rack 72.
  • the dispensing head 1 98 has a capping chuck unit 9 provided on the dispensing head 86 of the sample dispensing unit 52.
  • a chuck unit for transferring centrifuge tubes having the same configuration as that of 0 (see Fig. 14) is provided.
  • a cap removing unit and a centrifugal tube fixing unit are fixed to the mounting substrate of the separated liquid suction stage 64.
  • the suction speed at this time depends on the diameter of the lower end of the disposable tip 276 divided by the viscosity of the sample separation liquid 280.For example, when the lower end of the disposable tip 276 has a diameter of 1 mm, the sample separation liquid 28 When the organic solvent of 0 is ethyl acetate, getyl ether or a substance having properties similar to those, it is 0.2 to 0.3 cc / sec.
  • the sample separation liquid 280 in the disposable chip 276 floats toward the liquid surface, and flows into the gas portion above the sample separation liquid 280 in the disposable chip 276.
  • the suction speed at this time is, for example, in the range of 0.04 to 0.2 cc Z sec under the same conditions as above, but about 0.1 cc Z sec is appropriate.
  • the minute flow rate is sucked into the disposable tip 2 76 until the dispensing nozzle 25 2 moves to the position above the centrifuge tube 14 and then to the position above the test tube 24 at the dispensing position, or Then, the dispensing nozzle 25 2 descends and continues until the lower end of the disposable tip 27 6 is inserted into the test tube 24. During this time, an upward suction force is always applied to the vicinity of the lower end of the disposable tip 276. Therefore, even if the sample separation liquid 288 is of a type that easily causes dripping, the disposable tip 276 is The sample separation liquid 280 does not drop down from the lower end of the sample.
  • FIG. 19 is a longitudinal sectional view of the centrifuge tube
  • FIG. 20 is a perspective view showing the centrifuge tube in a state where it is separated into components.
  • the centrifuge tube 30 has a bottomed cylindrical shape with an open upper surface, and is provided with an inner cylinder 282 inserted therein.
  • a cap 3 is provided at the upper end of the centrifuge tube 30. One is crowned.
  • a screw portion 284 is formed on the outer peripheral surface of the upper end portion of the centrifuge tube 30, and a screw that is screwed into the screw portion 284 of the centrifuge tube 30 is formed on the inner peripheral surface of the cap 31. Part 286 is formed.
  • the cap 31 has a through hole 2888 formed in the center of the upper surface.
  • the 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 centrifuge tube 30 and has a cylindrical shape in which the lower part is gradually reduced in diameter.
  • a flange portion 292 is formed at the upper end of the inner cylinder 282, and when the inner cylinder 2822 is inserted into the centrifuge tube 30, the flange portion 292 becomes a liquid-tight member. For example, it is engaged with the upper edge of the centrifuge tube 30 with an O-ring 294 interposed therebetween so as to come into close contact therewith. It should be noted that the O-ring 294 need not be particularly interposed as long as the flange portion 292 can be appropriately closely contacted with the upper end edge of the centrifuge tube 30.
  • a centrifuge chamber 296 is formed between the inner peripheral surface of the centrifuge tube 30 and the outer peripheral surface of the inner cylinder 282. . Also, when the inner cylinder 28 2 is inserted into the centrifuge tube 30, there is a sufficient amount of air between the upper outer peripheral surface of the inner cylinder 28 2 and the upper inner peripheral surface of the centrifuge tube 30. There are very small gaps. The length of the inner tube 2 82 is such that when the inner tube 2 82 is inserted all the way It is assumed that it is located near the inner bottom surface.
  • a closing plug 298 is inserted upward at the lower end thereof, and the lower end of the inner cylinder 282 is liquid-tightly closed.
  • the obturator plug 298 is easily dropped off 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.
  • the mixture to be separated by centrifugal force is injected into the centrifuge tube 30 with the cap 31 removed from the centrifuge tube 30 and the inner cylinder 282 taken out.
  • 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 are sequentially placed in a centrifuge tube 30.
  • the cap 31 is put on the upper end of the centrifuge tube 30 and screwed to the end.
  • the flange 292 at the upper end of the inner cylinder 282 is pressed against the upper end of the centrifugal 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.
  • Can be The flange 292 of the inner cylinder 282 and the upper end edge of the centrifuge tube 30 are in close contact with each other and formed between the inner peripheral surface of the centrifuge tube 30 and the outer peripheral surface of the inner cylinder 282.
  • the centrifugation chamber 296 is hermetically and liquid-tightly sealed. The centrifuge tube 30 in this state is placed on a shaker to transfer the drug in the serum into the black hole form, and then placed on the centrifuge.
  • the liquid contained in the centrifugal separation chamber 296 is separated from the upper liquid (aqueous layer) 300 and the lower liquid (cloth form) by the difference in specific gravity. It is separated into 302.
  • the lower end of the inner cylinder 282 Since the lower end of the inner cylinder 282 is located near the inner bottom surface of the centrifuge tube 30, the lower end of the inner cylinder 282 is located at the boundary surface 3 between the upper liquid 300 and the lower liquid 302. It is located below 04. Therefore, the vicinity of the lower end of the inner cylinder 282 is in a state of being inserted into the lower liquid 302.
  • the centrifugation operation When the centrifugation operation is completed, remove the centrifuge tube from the centrifuge, and extract only the lower layer liquid from the centrifuge tube 30 using the separation liquid dispensing unit 62. To do this, first, the cap 31 placed on the upper end of the centrifuge tube 30 is loosened by twisting.
  • the close contact between the flange portion 292 of the inner tube 282 and the upper edge of the centrifuge tube 30 is released, and the inner peripheral surface of the upper portion of the centrifuge tube 30 and the outer periphery of the upper portion of the inner cylinder 282
  • the centrifuge chamber 296 communicates with the outside air through the gap between the outer surface and the gap between the flange portion 292 of the inner cylinder 282 and the upper edge of the centrifuge tube 30.
  • the dispensing nozzle 25 is lowered, and as shown in FIG. 19, the disposable nozzle 2 forming the lower end of the dispensing nozzle 25 2 is formed.
  • the lower side of the is shaped like a cone, so it can fall to the left or right. Therefore, as shown in (c) of FIG. 21, even if the lower end of the disposable tip 276 is inserted close to the inner bottom surface of the centrifuge tube 30, the obstruction plug is closed by the lower end of the disposable tip 276.
  • the lower end surface of the disposable tip 276 comes into close contact with the obturator plug 298, the lower end surface of the disposable tip 278 is pushed away, or only a part of the lower end surface of the disposable tip 276 comes into contact with the obturator plug 298. Thus, the entire lower end opening is not closed by the obstruction plug 298.
  • the syringe (not shown) connected to the dispensing nozzle 25 2 is driven by the disposable tip.
  • the lower liquid 302 is sucked into the disposable chip 276 through the lower end of the chip 276.
  • the lower layer liquid 302 is surely sucked into the disposable tip 276.
  • the lower end of the disposable tip 276 is positioned below the boundary surface 304 between the upper liquid 300 and the lower liquid 302, a part of the upper liquid 300 is removed.
  • the inner cylinder 282 and the cap 31 are separated from each other.
  • the inner cylinder and the cap may be integrated or formed integrally.
  • the lower surface side of the closure plug 298 is formed in a conical shape, but the shape of the lower surface side of the closure plug is such that the closure plug falls off from the lower end of the inner cylinder and the container body has Any shape other than a cone may be used as long as it falls down to the left or right from the falling position when it reaches the inner bottom surface.
  • a bar-shaped protrusion may be formed in the center of the lower surface of the obstruction plug.
  • the solvent dispensing stage 68 is provided with a shaker similar to the shaker 1994 installed on the shake stage 58.
  • the injection unit 70 has an injection arm 300 that rotates in a horizontal plane with one end as a center.
  • the nozzle holding shaft 310 is attached via a slide bearing 308, and the nozzle holding shaft 310 is developed at the tip of the injection arm 303 by a compression coil spring 314. Is supported.
  • a chuck 314 is provided at the lower end of the nozzle holding shaft 310, and the chuck 314 holds an injection nozzle 316.
  • One end of the injection arm 360 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 around a vertical axis and to be vertically movable along the vertical axis.
  • the arm support shaft 318 is moved up and down by a lifting drive mechanism, and is rotated by a rotary drive mechanism, whereby the injection arm 310 fixed to the arm support shaft 318 is moved.
  • a lifting drive mechanism is moved up and down by a rotary drive mechanism, whereby the injection arm 310 fixed to the arm support shaft 318 is moved.
  • the structure of the lifting drive mechanism and the rotary drive mechanism is the same as the lift drive mechanism and the rotation drive mechanism of the solvent dispensing unit 56 shown in FIG.
  • an organic solvent such as methanol
  • a solvent dispensing unit and a reaction unit for aspirating the sample separation liquid from the test tube 24 may be separately provided (see the operation steps shown in FIGS. 8 and 9). ),
  • the operation of dispensing the organic solvent into the test tube 24 is also performed by the injection unit 70.
  • a plurality of sample tubes 10 with lids containing frozen serum are set in the sample tube holding portion 74 of the circular turntable 48 of the automatic solvent extraction portion 36.
  • the sample tube 10 is moved from the circular turntable 48 to the sample tube suction stage 54 by the chuck unit 90 of the sample dispensing unit 52, and the sample is sucked. Fix sample tube 10 on stage 54.
  • the cap 12 of the sample tube 10 is removed by the cap attaching / detaching mechanism 13.
  • 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
  • the dispensing nozzle 88 is moved in the Z-axis direction.
  • the disposable tip 1 16 held by the disposable tip holding portion 76 of the bull 4 8 is attached to the tip of the dispensing nozzle 88.
  • the arm 84 of the sample dispensing unit 52, the dispensing head 86, and the dispensing nozzle 88 are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, respectively.
  • the tip (lower end) of the disposable tip 1 16 is immersed in the sample solution (melted serum) in the sample tube 10 fixed on the sample suction stage 54 (see the two-dot chain line in Fig. 14). ), Suction the sample solution into the disposable tip 1 16.
  • the used disposable tip 1 16 is discarded to the dumping port 73, the cap 12 is attached to the sample tube 10 by the cap attaching / detaching mechanism 13 8, and then the sample tube 10 is turned into a circular turntable. 4 Return to sample tube holder 7 4.
  • the processing turntable 50 is rotated to move the centrifuge tube 14 held in the centrifuge tube holding unit 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 ⁇ direction (rotated in a horizontal plane), then lowered, and the liquid sending tube fixed to the nozzle portion 142 is rotated. Insert the tips of the tubes 144 and 1146 into the centrifuge tube 14 held by the centrifuge tube holding section 78 of the processing turntable 50 (see the two-dot chain line in Fig. 16). Dispense ethyl acetate (organic solvent), methanol and pH buffer into the sedimentation tube 14.
  • the arm 84 of the sample dispensing unit 52, the dispensing head 86, and the chuck unit 90 are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, respectively.
  • Activate 90 to dispose of the centrifuge tube cap 16 held by the cap holder 80 of the turntable 50 with a pair of chuck claws 1 18, 1 18 Remove the cap 16 from 0.
  • 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 then the chuck unit 90 is moved. Is operated, and the cap 16 is attached to the centrifuge tube 14 held by the centrifuge tube holder 78 of the processing turntable 50.
  • the chuck unit 90 While holding the cap 16 with the pair of chuck jaws 1 18 and 1 18, set the arm 84 of the sample dispensing unit 52, the dispensing head 86 and the chuck unit 90 to Y. After moving in the axial direction, the X-axis direction, and the Z-axis direction, the chuck unit 90 is operated to shake the centrifuge tube 14 held in the centrifuge tube holder 78 of the processing turntable 50. Move to stage 58 and set centrifuge tube 14 on shaker 1994. Then, the shaker 1994 is driven to shake the centrifuge tube 14, and the target component substance in the sample solution is transferred into the organic solvent in the centrifuge tube 14.
  • the arm 84 of the sample dispensing unit 52, the dispensing head 86, and the chuck unit 90 are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, and the chuck unit is displaced. Then, move the centrifuge tube 14 from the shaking stage 58 to the centrifuge 60, and set the centrifuge tube 14 in the centrifuge 60. Then, the centrifuge 60 is driven to centrifuge the liquid. After the centrifugation is completed, 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 and the X-axis direction.
  • the chuck unit to remove the centrifuge tube 14 from the centrifuge 60, and move the centrifuge tube 14 to the separation liquid suction stage 64 to fix the centrifuge tube. (Not shown).
  • the cap 16 is removed from the centrifuge tube 14 using the cap removal unit (not shown).
  • This operation example is for the case where the sample separation liquid is separated into the upper layer in the centrifuge tube 14 by centrifugation, and the sample separation liquid is separated into the lower layer in the centrifuge tube 30 by centrifugation. In such a case, there is no need to remove the cap 31 from the centrifuge tube 30 as shown in FIG.
  • the separation liquid dispensing unit is for the case where the sample separation liquid is separated into the upper layer in the centrifuge tube 14 by centrifugation, and the sample separation liquid is separated into the lower layer in the centrifuge tube 30 by centrifugation. In such a case, there is no need to remove the cap 31 from the centrifuge tube 30 as shown in FIG.
  • the arm 1996, the dispensing head 198, and the dispensing nozzle 252 of the separation liquid dispensing unit 62 are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, respectively.
  • the sample separation liquid sucked into the day spot 276 into the test tube 24. After that, the used disposable tip 276 is discarded to the dumping pot 73.
  • the liquid remaining in the centrifuge tube 14 is suctioned by a suction nozzle (not shown) mounted on the separation liquid dispensing unit 62, and the waste liquid bottle (supply / drain unit 38) (Not shown). Subsequently, the separation liquid dispensing unit 62 is operated, and the cap 16 is attached to the centrifuge tube 14 using the chuck unit for transferring the centrifuge tube, and then the used centrifuge tube 14 is discarded. Discard to 7-3.
  • test tube 24 is moved to and held on the stage 66, and the test tube 24 is heated from the surroundings by a heater block (not shown), and the upper part of the tube is opened into the test tube 24 by a gas supply unit (not shown).
  • the sample separation liquid in the test tube 24 is vaporized by injecting nitrogen gas through the exhaust pipe and discharging the waste gas, and the sample separation liquid is dried.
  • the arm 196 of the separation liquid dispensing unit 62, the dispensing head 198, and the chuck unit for transferring the centrifuge tube are moved in the Y-axis direction, the X-axis direction, and the Z-axis direction, respectively.
  • the injection unit 70 is operated, and an organic solvent, for example, methanol is dispensed into the test tube 24.
  • the test tube 24 is shaken by driving a shaker, and the dried residue is dissolved in methanol.
  • the injection unit 70 was operated, and the sample solution in which the component substances were dissolved in the organic solvent was sucked into the injection nozzle 3 16 from the test tube 24 and the suction was performed. Inject a predetermined amount of the sample solution into the HPLC column and measure the concentration of the component substances.
  • the separation liquid dispensing unit 62 is operated, and the used test tube 24 is discarded to the dumping pot 73 using the chuck unit for transferring the centrifuge tube.
  • the injection unit 70 is operated, and the injection nozzle 316 and the inside of the pipe are washed with methanol.
  • Figures 23 and 24 show flowcharts of this series of operations.
  • the container (testing) was performed by using an apparatus configuration including the evaporating and drying stage 66 and the solvent dispensing stage 68 provided with a shaker. After evaporating the sample separation liquid dispensed in the tube 24) to dryness, the organic solvent is dispensed into the container, and the container is shaken to dissolve in the organic solvent.
  • the sample solution to be injected into the sample is prepared, a part of the organic solvent of the sample separated solution dispensed into the container is provided by the device configuration that does not have the solvent dispensing stage 68 and has a concentration stage. May be evaporated to prepare a concentrated sample separation liquid.
  • the evaporating and drying stage and the concentration stage may not be particularly provided.
  • the organic solvent of the sample separation liquid dispensed into the container was evaporated and dried by the equipment configuration equipped with the evaporation / drying stage 66 without the solvent dispensing stage 68.
  • An automatic extraction device that finally obtains the residue may be used to prepare a sample liquid to be injected into analytical equipment such as an HPLC or gas chromatograph analyzer from the dried residue obtained by the automatic extraction device. .
  • an automatic concentration measurement 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 62
  • a sample separation solution that has been separated into layers in a centrifuge tube can be directly sucked from the centrifuge tube and injected into an analytical instrument such as HPLC using a junction unit with such functions.
  • the automatic extraction device is used for automatically measuring the concentration of a specific component substance contained in a liquid sample such as a homogenate such as serum, plasma, whole blood, urine, and biological tissue, and a reaction mixture. It can be used to automatically perform a solvent extraction operation for a specific component substance in a liquid sample.

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  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
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  • Extraction Or Liquid Replacement (AREA)

Abstract

Cette invention se rapporte à un appareil d'extraction automatique servant à extraire un composant spécifique contenu dans un échantillon liquide, afin de déterminer la concentration de ce composant. A cet effet, ledit appareil comprend un moyen vibrant destiné à faire vibrer un récipient d'extraction contenant l'échantillon liquide et un solvant organique, en vue d'extraire le composant à l'aide du solvant organique, cet appareil se caractérisant en ce que le moyen vibrant est capable de fonctionner de façon à faire vibrer le récipient en suivant des mouvements formant un 8 dans un plan horizontal. Cet appareil est exempt de toute formation d'émulsion dans le récipient pour n'importe quel type d'échantillon liquide et de solvant organique et il permet d'atteindre une plus grande efficacité d'extraction du composant.
PCT/JP2000/006680 1999-10-07 2000-09-27 Appareil d'extraction automatique, instrument de mesure de concentration automatique et procede d'extraction d'un composant contenu dans un echantillon liquide WO2001024904A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP28689399A JP2001108688A (ja) 1999-10-07 1999-10-07 液体試料中の成分物質の自動抽出装置および液体試料中の成分物質の自動濃度測定装置ならびに液体試料中の成分物質の抽出方法
JP11/286893 1999-10-07

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CN109612815A (zh) * 2019-02-19 2019-04-12 徐桂清 一种检验科室用血液采集混匀装置
EP3505906A1 (fr) * 2017-12-29 2019-07-03 Nuctech Company Limited Dispositif et procédé de prétraitement pour la détection de sécurité alimentaire
CN112717467A (zh) * 2020-12-16 2021-04-30 鼎泰（湖北）生化科技设备制造有限公司 一种便于控制的间歇式萃取池
CN113198206A (zh) * 2020-02-03 2021-08-03 瑞基海洋生物科技股份有限公司 生化反应器及其搅拌装置与萃取方法

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JP5395847B2 (ja) * 2011-06-17 2014-01-22 日清食品ホールディングス株式会社 残留農薬自動前処理システム及びそれを用いた残留農薬抽出方法
CN103512849B (zh) * 2013-09-29 2015-10-14 华东理工大学 用于分散液液微萃取光谱在线检测的装置及检测方法
JP6327751B2 (ja) * 2015-10-06 2018-05-23 株式会社セルピック 自動血液分離装置
US20240280602A1 (en) 2021-07-08 2024-08-22 Hitachi High-Tech Corporation Automatic analysis device control method and automatic analysis device

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EP3505906A1 (fr) * 2017-12-29 2019-07-03 Nuctech Company Limited Dispositif et procédé de prétraitement pour la détection de sécurité alimentaire
CN109991049A (zh) * 2017-12-29 2019-07-09 同方威视技术股份有限公司 用于食品安全检测的前处理装置以及前处理方法
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CN109991049B (zh) * 2017-12-29 2024-03-01 同方威视技术股份有限公司 用于食品安全检测的前处理装置以及前处理方法
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CN109612815A (zh) * 2019-02-19 2019-04-12 徐桂清 一种检验科室用血液采集混匀装置
CN113198206A (zh) * 2020-02-03 2021-08-03 瑞基海洋生物科技股份有限公司 生化反应器及其搅拌装置与萃取方法
CN113198206B (zh) * 2020-02-03 2022-07-26 瑞基海洋生物科技股份有限公司 生化反应器及其搅拌装置与萃取方法
CN112717467A (zh) * 2020-12-16 2021-04-30 鼎泰（湖北）生化科技设备制造有限公司 一种便于控制的间歇式萃取池

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