WO2019123746A1 - Temperature regulating system - Google Patents

Temperature regulating system Download PDF

Info

Publication number
WO2019123746A1
WO2019123746A1 PCT/JP2018/034785 JP2018034785W WO2019123746A1 WO 2019123746 A1 WO2019123746 A1 WO 2019123746A1 JP 2018034785 W JP2018034785 W JP 2018034785W WO 2019123746 A1 WO2019123746 A1 WO 2019123746A1
Authority
WO
WIPO (PCT)
Prior art keywords
liquid
temperature
pipette tip
temperature control
control system
Prior art date
Application number
PCT/JP2018/034785
Other languages
French (fr)
Japanese (ja)
Inventor
貴紀 村山
Original Assignee
コニカミノルタ株式会社
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 コニカミノルタ株式会社 filed Critical コニカミノルタ株式会社
Priority to JP2019560802A priority Critical patent/JP7212632B2/en
Publication of WO2019123746A1 publication Critical patent/WO2019123746A1/en

Links

Images

Classifications

    • 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
    • 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
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices

Definitions

  • the present invention relates to a temperature control system applied to a device that performs an appropriate analysis process using a pipette tip and a reaction container.
  • the temperature in the sensor chip is a reagent to be introduced in order to sequentially introduce a reagent such as a reaction solution or a washing solution into the sensor chip.
  • a reagent such as a reaction solution or a washing solution into the sensor chip.
  • the temperature in the sensor chip is greatly influenced by the temperature of the reagent to be used, it is necessary to control the temperature of the reagent.
  • the reagent temperature various cases are assumed such as after being adapted to the ambient temperature, that is, the temperature of the measurement environment (hereinafter referred to as ambient temperature) or immediately after taking it out of the storage (refrigerator), and used for each measurement
  • the liquid temperature may be different. This affects system performance such as measurement repeatability.
  • an analyzer described in Patent Document 1 determines a heater setting value for bringing the reaction unit to a desired temperature based on the ambient temperature and the temperature gradient between the position at which the ambient temperature is measured and the reaction unit, and sets the obtained temperature as a target value. Also, the temperature control unit is feedback controlled using the temperature detected by the second temperature sensor as an output value.
  • an analyzer described in Patent Document 2 comprises a plurality of storage tanks capable of separately storing a reagent, a diluent, a washing solution, or a buffer for reacting with a sample (specimen) such as an antibody, a sample, and an appropriate liquid (reaction liquid).
  • a sample such as an antibody, a sample, and an appropriate liquid (reaction liquid).
  • the cartridge having the reaction vessel for reacting is held on the stage formed by the heat block, and the temperature and heating time of the heat block are controlled to raise the reagents in the cartridge to the target temperature (reaction temperature) It is a thing.
  • the reaction vessel is also temperature-controlled by the heat block.
  • an automatic dispensing method described in Patent Document 3 is known.
  • the pipette tip is inserted into a box-like heating device in which a heater and a fan are disposed and a pipette tip insertion hole is formed on the upper surface, and the pipette tip is heated. It is a method of heating a liquid.
  • the initial temperature is also different for each measurement, so the saturation time is not constant There's a problem.
  • An object of the present invention is to provide a temperature control system capable of performing stable temperature control of liquids such as reagents without being affected by ambient temperature.
  • the present invention includes the following matters.
  • the temperature control system wherein the pump tip performs suction and discharge repeatedly in a state in which the pipette tip is lowered by the drive unit and the temperature control unit performs air flow.
  • the temperature control system according to [1] comprising: a stage temperature control heater configured to heat the stage.
  • the temperature control unit A housing capable of containing at least a portion of the pipette tip; A heat source disposed inside the housing; The temperature control system according to [1] or [2], further comprising: an opening formed in the housing for permitting vertical movement of the pipette tip.
  • the test cartridge includes a reaction container for reacting a reagent and a sample, The suction and discharge are performed in a preheating step of heating the liquid in the storage tank prior to the reaction in the reaction container, The temperature control system according to [2] or [3], wherein the liquid sucked into the pipette tip lastly in the suction and discharge of the preheating stage is discharged to the storage tank containing the liquid.
  • the aspiration and discharge are performed in a measurement step of measuring a reaction between a reagent and a sample in the reaction container,
  • the temperature control system according to [4] wherein the liquid sucked into the pipette tip last in the suction and discharge of the measurement step is discharged to the reaction container.
  • the temperature control system according to [5] wherein the suction and discharge of the liquid is performed in the reaction container.
  • a liquid temperature acquisition unit for acquiring the temperature of the liquid The temperature control system according to [5] or [6], further comprising: a determination unit that determines at least one of necessity of suction and discharge and condition change using the temperature acquired by the liquid temperature acquisition unit.
  • thermocontrol system capable of performing stable temperature control of liquids such as reagents without being affected by ambient temperature.
  • FIG. 3 is a view corresponding to FIG. 2 in a state where the pipette nozzle in the embodiment is lowered by a predetermined distance from a reference position.
  • the temperature control system X is applied to, for example, the analyzer 1 shown in FIG.
  • the analyzer 1 is a device for analyzing a sample by using a pipette tip 51 which is used to suction the reagents and the sample in the storage tank 21 and discharge the reagent and the sample into the reaction container 3 for reaction.
  • the test cartridge 2 in the present embodiment is a container having a storage tank 21 in which necessary reagents such as a labeled antibody and a washing solution are prepackaged individually, and a reaction container 3 in which the reagents and the sample are reacted.
  • the reaction vessel 3 may be a separate part independent of the test cartridge 2.
  • the test cartridge 2 is mounted on a stage 4 (see FIG. 2) of the analyzer 1 in a state where a sample containing a substance to be detected is dispensed in a predetermined storage tank 21 in advance.
  • the sample include blood, serum, plasma, urine, nasal fluid, saliva, semen and the like.
  • examples of the substance to be detected include nucleic acids (such as DNA and RNA), proteins (such as polypeptides and oligopeptides), amino acids, carbohydrates, lipids, and modified molecules thereof.
  • the inspection cartridge 2 schematically shown in FIG. 1 is mounted on the stage 4.
  • the stage 4 is fixed on, for example, a slide base 41 as shown in FIGS. 1 and 2.
  • the stage drive unit not shown
  • the stage 4 moves horizontally while holding the inspection cartridge 2.
  • the reaction container 3 has a container 31 capable of containing a liquid, and the liquid is injected or removed from the container 31 through the tip 511 of the pipette tip 51 inserted from the upper opening of the container 31. is there.
  • a sample containing a substance to be analyzed and reagents (reaction reagents) containing a substance that causes an antigen-antibody reaction with the substance to be analyzed are dispensed into the storage portion 31 of the reaction container 3. Then, after dispensing processing, information on the presence or absence and degree of aggregation, color development, fluorescence, etc. generated as a result of the reaction generated in the reaction container 3 is acquired by an appropriate means, and the acquired data are used to It is possible to carry out the analysis.
  • the analyzer 1 includes at least a liquid sending unit 5 that sucks and discharges liquid in the storage unit 31 of the reaction container 3 and a control unit 6 that controls the operation of the liquid sending unit 5.
  • the liquid delivery unit 5 has a pipette nozzle 52 to which a pipette tip 51 is attached at its tip, a pump 53 connected to the pipette nozzle 52, and a nozzle drive unit 54 (drive unit) that moves the pipette nozzle 52 up and down.
  • each part with which the analyzer 1 is equipped except the stage 4, the liquid feeding part 5, and the control part 6 is abbreviate
  • the pump 53 includes a syringe 531 and a plunger 532 that can reciprocate in the syringe 531, and reciprocates the plunger 532 by a pump drive unit (not shown) including a drive motor (for example, a stepping motor).
  • a pump drive unit including a drive motor (for example, a stepping motor).
  • An external liquid is sucked into the pipette tip 51 or a liquid in the pipette tip 51 is discharged to the outside by reciprocating such a plunger 532 in a state of being connected to the pipette nozzle 52 through the pipe 55, for example.
  • the treatment can be performed quantitatively.
  • the nozzle drive unit 54 freely moves the pipette nozzle 52 in the axial direction (vertical direction in the present embodiment) by, for example, a solenoid actuator or a stepping motor.
  • each unit constituting the liquid delivery unit 5 is configured to be united and handled as a sampler unit 5U.
  • the temperature control system X heats the pipette tip temperature control unit 7 (temperature control unit) that heats the pipette tip 51 and the reaction container 3.
  • a reaction container temperature control unit 8 is provided.
  • the reaction container temperature control unit 8 is configured using a stage temperature control heater 81 that heats the stage 4. By heating the stage 4 by the stage temperature control heater 81, the reaction vessel 3 disposed on the stage 4 can be heated. In the present embodiment, the temperature of the stage 4 heated by the stage temperature control heater 81 can be detected by an appropriate sensor.
  • the pipette tip temperature control unit 7 intensively heats at least the tip portion of the pipette tip 51 of the pipette nozzles 52 positioned at a predetermined heating position by the warm air released from the heat source 72.
  • the pipette tip temperature control unit 7 includes a housing 71 capable of housing at least the tip portion of the pipette tip 51, and a heat source 72 disposed inside the housing 71.
  • a fan 73 for sending warm air discharged from the heat source 72 in a predetermined direction is provided, and the internal space of the housing 71 is heated by the warm air discharged from the heat source 72.
  • the housing 71 has a box-like shape, and an upper wall 711 and a lower wall 712 of the outer wall that partitions the internal space from the outside form an opening that allows the pipette tip 51 to move up and down.
  • insertion holes (upper insertion holes 713 and lower insertion holes 714) through which the pipette tip 51 can be inserted are applied as the opening.
  • the casing 71 is configured using a bottomed casing main body 715 having a large opening at the upper side, and a top plate 716 disposed at a position closing the upper opening of the casing main body 715. .
  • the upper insertion hole 713 of the casing 71 is a round hole formed in the top plate 716
  • the lower insertion hole 714 of the casing 71 is a round hole formed in the bottom of the casing main body 715.
  • the upper insertion hole 713 and the lower insertion hole 714 are in a positional relationship opposed in the vertical direction (the moving direction of the pipette nozzle 52).
  • the pipette tip temperature control unit 7 applies warm air discharged from the heat source 72 to the pipette tip 51 inserted into the internal space of the housing 71 through the upper insertion hole 713 and the lower insertion hole 714.
  • the pipette tip 51 can be heated.
  • a sensor 717 for example, a thermistor
  • the radiation fin 718 equipped with a thermal fuse functions as a safety device.
  • the fan 73 can also be disposed in the internal space of the housing 71.
  • the fan 73 is outside the housing 71 and on the outer wall (side wall in the illustrated example) of the housing 71. It is fixed at a position facing the formed fan opening 719 so that the warm air discharged from the heat source 72 can be sent in a predetermined direction by the fan 73.
  • the size of the casing 71 is narrowed, and the temperature of the internal space of the casing 71 is raised to a predetermined target temperature set in advance by the warm air. ⁇ Processing to keep warm can be performed efficiently.
  • the pipette tip temperature control unit 7 is unitized in a state where the bracket 74 is fixed to the housing 71. Then, by attaching the bracket 74 to the sampler unit 5U, the pipette tip temperature control unit 7 can be fixed to the sampler unit 5U (see FIG. 2).
  • the pipette tip temperature control unit 7 is disposed in the vicinity of the reaction container 3. Specifically, as shown in FIG. 4, the separation distance (the distance indicated by “L” in FIG. 4) from the lower end (bottom of the housing 71) of the pipette tip temperature control unit 7 to the top surface of the reaction container page is For example, it is set to about 5 mm.
  • the flow of the warm air generated from the heat source 72 of the pipette tip temperature control unit 7 is schematically indicated by a relatively thick arrow.
  • the control unit 6 is constituted by, for example, a known computer or microcomputer including an arithmetic unit, a control unit, a storage unit, an input unit, an output unit and the like, and the liquid sending unit 5, the pipette tip temperature adjustment unit 7, the reaction container temperature adjustment
  • the operation of each part of the analyzer 1 including the part 8 is controlled according to a predetermined program.
  • the control unit 6 acquires a pipette tip temperature acquisition unit 61 that acquires the temperature in the housing 71 constituting the pipette tip temperature adjustment unit 7 from the sensor 717, and a reaction container temperature acquisition that acquires the temperature of the reaction container 3 And a unit 62.
  • the temperature of the reaction vessel 3 is indirectly acquired by acquiring the temperature of the stage 4.
  • the temperature control system X of the analyzer 1 starts the measurement using the test cartridge 2 by the analyzer 1 and during the detection process of the substance to be detected, the reaction container temperature controller 8 by the controller 6 And temperature control of the pipette tip temperature control unit 7 is executed.
  • the control unit 6 performs temperature acquisition processing by the pipette tip temperature acquisition unit 61 and the reaction container temperature acquisition unit 62 at an appropriate timing, and based on the acquired temperature, the pipette tip temperature adjustment temperature by the pipette tip temperature adjustment unit 7
  • the reaction container temperature control unit 8 adjusts the reaction container temperature control temperature (stage temperature control temperature) to a preset pipette tip temperature control target temperature and reaction container temperature control target temperature (stage temperature control target temperature). Control.
  • the pipette tip temperature control target temperature and the reaction container temperature control target temperature may be the same or different.
  • the reaction container temperature control target temperature stage temperature control target temperature
  • the pipette tip temperature control target temperature is aspirated and discharged by the pipette tip
  • the effect that the temperature does not fall can be expected, and the adverse effect on the reagent and the thermal deformation of the pipette tip itself can be set to a temperature that can be avoided.
  • control unit 6 includes a liquid temperature acquisition unit 63 that acquires the temperature of the liquid contained in the storage tank 21.
  • the control unit 6 uses the temperature of the reaction container 3 acquired by the reaction container temperature acquisition unit 62 and the temperature of the liquid acquired by the liquid temperature acquisition unit 63 to change the necessity of suction and discharge described later, the suction and discharge conditions, etc.
  • a thermopile, a contact type thermistor, etc. can be considered as an example of a sensor which acquires the temperature of reaction container 3, and the temperature of a liquid.
  • the temperature control system X of this embodiment accommodates at least the tip portion of the pipette tip 51 inside the housing 71 with the pipette nozzle 52 positioned at a predetermined heating position. It is configured to be. Specifically, in the state where the pipette nozzle 52 is positioned at the heating position, the tip 511 of the pipette tip 51 is positioned in the lower insertion hole 714 of the housing 71, and from the tip of the pipette tip 51 to a predetermined dimension Is set so as to be disposed inside the housing 71. In the present embodiment, the origin position of the pipette nozzle 52 is set to the “heating position”. Therefore, the tip portion of the pipette tip 51 can be heated inside the housing 71 by making the pipette nozzle 52 stand by at the origin position.
  • a predetermined gap is formed between the tip 511 of the pipette tip 51 and the lower insertion hole 714, and the pipette tip 51 and the upper insertion hole A predetermined gap is also formed between 713, and the pipette tip 51 is set so as not to contact the housing 71. From the gap between the pipette tip 51 and the insertion hole (upper insertion hole 713, lower insertion hole 714), the warm air in the housing 71 blows out to the outside of the housing 71, and the ambient temperature of the housing 71 is The internal temperature of the housing 71 can be maintained at the same level (see FIG. 4).
  • the process at the time of using the temperature control system X of the analyzer 1 which concerns on this embodiment is demonstrated.
  • the inspection cartridge 2 stored at a temperature of about 2 to 8 ° C. is taken out of the refrigerator (not shown) by the user.
  • the temperature of the inspection cartridge 2 is returned to the room temperature of about 10 to 30.degree.
  • the inspection cartridge 2 is mounted on the stage 4 heated by the stage temperature control heater 81 which is the reaction container temperature control unit 8.
  • the stage temperature control heater 81 which is the reaction container temperature control unit 8.
  • each storage tank 21 of the test cartridge 2 and the storage section 31 of the reaction container 3 are also heated on the stage 4, and the liquid to be sucked stored in each storage tank 21 is also heated. That is, prior to the reaction between the reagent and the sample in the storage unit 31 of the reaction container 3, preheating is performed to heat the liquid in the storage tank 21.
  • the preheating time is preferably about 1 to 10 minutes.
  • the process proceeds to the measurement step of measuring the reaction between the reagent and the sample in the storage unit 31 of the reaction container 3.
  • the control unit 6 drives the stage drive unit (not shown) to move the stage 4 to a position where the storage tank 21 containing the liquid to be sucked is directly below the pipette nozzle 52.
  • control unit 6 causes the pipette tip temperature control unit 7 to release warm air from the heat source 72, and heats the pipette nozzle 52 located at the heating position. Hot air of a temperature of 30 to 60 ° C. is released from the heat source 72.
  • the control unit 6 drives the nozzle drive unit 54 to lower the pipette nozzle 52 from the heating position, and sucks the liquid of the test cartridge 2 into the pipette tip 51. Specifically, in a state where the pipette nozzle 52 is lowered by a predetermined distance from the heating position and stopped, the control unit 6 drives the pump 53 to suction from the tip of the pipette nozzle 52, that is, the tip 511 of the pipette tip 51 Aspirate the target fluid.
  • the control unit 6 discharges the liquid sucked into the pipette nozzle 52 from the tip 511 into the storage tank 21 by the pump 53 in this state.
  • the controller 6 sucks the liquid in the storage tank 21 again into the pipette tip 51 by the pump 53 and discharges the liquid into the storage tank 21.
  • suction and discharge repeating suction and discharge of liquid by the pipette tip 51 is referred to as "suction and discharge".
  • the tip portion of the pipette tip 51 is pulled out of the casing 71 of the pipette tip temperature control unit 7 and exposed to the external ambient temperature, but the ambient temperature of the casing 71 is an insertion portion with the pipette tip 51
  • the hot air in the casing 71 is sprayed to the outside of the casing 71 from the gap between the holes (upper insertion holes 713 and lower insertion holes 714), and the temperature is maintained at about the same as the internal temperature of the casing 71.
  • the distal end portion of the pipette tip 51 is also heated by the warm air in a state of being detached from the housing 71 of the pipette tip temperature control unit 7.
  • the liquid in which storage tank 21 is sucked and discharged may be determined according to the amount of liquid in each storage tank 21 or the like. Further, suction and discharge may be performed on the liquid in all the storage tanks 21, and suction and discharge may be performed on only the liquid in the selected storage tank 21.
  • the tip of the pipette tip 51 is disposed in the housing 71, and the pipette tip temperature control unit 7
  • the liquid is heated directly. From the heat source 72, warm air at a temperature suitable for the reaction of 30 ° C. or more and 40 ° C. or less is emitted for 30 seconds or more and 300 seconds or less.
  • the gas may be continuously released from the heat source 72 at a temperature of 40 ° C. or more and 60 ° C. or less for 10 seconds or more and 120 seconds or less to rapidly heat the liquid at a high temperature.
  • the liquid since the liquid is previously pulled up to a predetermined temperature by suction and discharge, when heating in the housing 71, the heating of the liquid is accelerated, and the liquid is heated to the target temperature in a short time can do.
  • control unit 6 drives the stage drive unit to discharge the liquid held in the pipette tip 51, specifically, the storage tank 21 of the inspection cartridge 2 or the storage unit 31 of the reaction container 3
  • the stage 4 is moved to a position immediately below the pipette nozzle 52.
  • the control unit 6 drives the pump 53 to drive the tip of the pipette nozzle 52, that is, the tip of the pipette tip 51 From 511, the liquid in the pipette tip 51 is discharged toward the discharge destination.
  • the discharge destination is the storage portion 31 of the reaction container 3
  • the liquid sucked into the pipette tip 51 at the end of the suction and discharge discharges the storage portion 31 of the reaction container 3.
  • the operation from the above-mentioned suction and discharge to the discharge of the liquid toward the discharge destination is, for example, the type of liquid to be targeted in the order of the measurement liquid, diluted sample, washing liquid, labeled antibody, washing liquid, and measurement liquid. It will be repeated instead.
  • suction and discharge in the state where the pipette tip 51 is heated with warm air are performed on the dilution solution.
  • the cleaning liquid since the cleaning liquid is particularly used in a large amount and it is difficult to heat it, it is useful to perform the above-mentioned suction and discharge in advance to heat it to a predetermined temperature.
  • the liquid discharged into the storage portion 31 of the reaction container 3 may be further absorbed and discharged. After the measurement of the reaction between the reagent and the sample in the storage unit 31 of the reaction container 3 is performed, the measurement step ends.
  • the temperature control system X before the liquid is discharged to the storage unit 31 by performing suction and discharge in a state in which the pipette tip 51 is heated with warm air to the target liquid.
  • the pipet tip 51 can be sucked and discharged in a state of being heated by warm air in advance and can be raised beforehand to a predetermined temperature, stable liquid temperature control can be performed without being affected by the ambient temperature. Can.
  • the warm air from the heat source 72 may be discharged from any direction as long as the warm air can be blown to the tip end 511 of the pipette tip 51 at the position where the pipette tip 51 descends.
  • the heat source 72 may be provided at the top of the housing 71 and the warm air may be discharged from the heat source 72 in the axial direction of the pipette tip 51.
  • a plurality of heat sources 72 may be disposed so as to surround the pipette tip 51, and warm air may be blown around the entire circumference of the pipette tip 51.
  • the heat source 72 was provided in the inside of the housing
  • the pipette tip 51 sucks the liquid in the storage tank 21 and discharges it to the storage section 31.
  • suction and discharge may be performed in the preheating in which the stage 4 is heated in advance. In this case, the liquid sucked into the pipette tip 51 at the end of suction and discharge in the preheating stage is discharged to the storage tank 21 containing the liquid.
  • the temperature of the reaction container 3 may be acquired by the reaction container temperature acquisition unit 62 or the temperature of the liquid may be acquired by the liquid temperature acquisition unit 63 in the preheating stage or the measurement stage.
  • the temperature of the liquid and the temperature of the reaction container 3 may be measured during suction and discharge in the measurement stage. It is desirable to acquire and control pumping.
  • the control unit 6 changes the necessity of suction and discharge and change the suction and discharge conditions based on at least one of the temperature of the reaction container 3 acquired by the reaction container temperature acquisition unit 62 and the temperature of the liquid acquired by the liquid temperature acquisition unit 63. Determine For example, when it is determined that there is no need for suction and discharge, such as when the temperature of the liquid reaches a target temperature, the control unit 6 stops the suction and discharge, and when it is determined that there is a need for suction and discharge. Continue to suck and discharge.
  • the suction and discharge conditions include, for example, the duration of suction and discharge, the amount of liquid sucked and discharged by the pipette tip 51, and the like.
  • the suction and discharge duration time is 0.5 minutes or more and 5 minutes or less if repetition of the suction and discharge is 11 to 50 times.
  • the liquid volume of the liquid absorbed and discharged by the pipette tip 51 is 50 ⁇ l or more and 300 ⁇ l or less, preferably 50 ⁇ l or more and 200 ⁇ l or less.
  • the control unit 6 appropriately changes these suction and discharge conditions based on the determination result. Thereby, temperature control of the liquid can be performed more accurately.

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

This temperature regulating system (X) is provided with a drive unit (54) which raises and lowers a pipette tip (51), a temperature regulating unit (7) which blows air onto the pipette tip (51), and a pump for sucking a liquid into the pipette tip (51) and discharging the liquid inside the pipette tip (51), wherein the temperature regulating system (X) is capable of performing stable temperature control of the liquid, such as a reagent, without being affected by ambient temperature, by performing suction and discharge in which the pump (53) repeats the sucking and the discharging in a state in which the pipette tip (51) has been lowered by the drive unit (54) and air has been blown by the temperature regulating unit (7).

Description

温調システムTemperature control system
　本発明は、ピペットチップ及び反応容器を用いて適宜の分析処理を行う装置に適用される温調システムに関する。 The present invention relates to a temperature control system applied to a device that performs an appropriate analysis process using a pipette tip and a reaction container.
　従来、生化学反応や免疫反応は温度の影響を大きく受けることが知られている。たとえば、センサーチップを用いた全自動式の生化学反応装置や免疫反応装置においては、装置内でセンサーチップに反応液や洗浄液などの試薬を順次導入するため、センサーチップ内の温度は導入する試薬温度の影響を大きく受ける。 Conventionally, it is known that biochemical reactions and immune reactions are greatly affected by temperature. For example, in a fully automatic biochemical reaction apparatus or immune reaction apparatus using a sensor chip, the temperature in the sensor chip is a reagent to be introduced in order to sequentially introduce a reagent such as a reaction solution or a washing solution into the sensor chip. Greatly affected by temperature.
　ここで、センサーチップ内（反応場）の温度は、使用する試薬温度の影響を大きく受けることがわかっていることから、試薬温度を制御することが必要となる。
　試薬温度としては、周囲の温度、すなわち測定環境の温度（以下、周囲温度という。）に馴染ませた後、または保管庫（冷蔵庫）から取り出し直後など様々なケースが想定され、測定毎に使用する液温が異なる可能性がある。それにより測定の繰り返し再現性等のシステム性能に影響を与えてしまう。 Here, since it is known that the temperature in the sensor chip (reaction site) is greatly influenced by the temperature of the reagent to be used, it is necessary to control the temperature of the reagent.
As the reagent temperature, various cases are assumed such as after being adapted to the ambient temperature, that is, the temperature of the measurement environment (hereinafter referred to as ambient temperature) or immediately after taking it out of the storage (refrigerator), and used for each measurement The liquid temperature may be different. This affects system performance such as measurement repeatability.
　このような問題に対処する手法としては、例えば、特許文献１に記載された分析装置が知られている。この分析装置は、周囲温度および、周囲温度を測定する位置と反応部との間の温度勾配に基づいて、反応部を所望温度にするヒータ設定値を求め、この求めた温度を目標値とし、かつ第２温度センサが検出した温度を出力値として温調部をフィードバック制御するものである。 As a method for coping with such a problem, for example, an analyzer described in Patent Document 1 is known. The analyzer determines a heater setting value for bringing the reaction unit to a desired temperature based on the ambient temperature and the temperature gradient between the position at which the ambient temperature is measured and the reaction unit, and sets the obtained temperature as a target value. Also, the temperature control unit is feedback controlled using the temperature detected by the second temperature sensor as an output value.
　また、特許文献２に記載された分析装置が知られている。この分析装置は、抗体などの試料（検体）と反応させるための試薬や希釈液、洗浄液、あるいは緩衝液をそれぞれ個別に収容可能な複数の収容槽や、検体と適宜の液体（反応液）とを反応させる反応槽を有するカートリッジを、ヒートブロックで形成されたステージ上に保持し、ヒートブロックの温度および加熱時間を制御して、カートリッジ内の試薬類を目的温度（反応温度）に昇温するものである。なお、この分析装置によれば、ヒートブロックによって反応槽も温調される。 In addition, an analyzer described in Patent Document 2 is known. The analyzer comprises a plurality of storage tanks capable of separately storing a reagent, a diluent, a washing solution, or a buffer for reacting with a sample (specimen) such as an antibody, a sample, and an appropriate liquid (reaction liquid). The cartridge having the reaction vessel for reacting is held on the stage formed by the heat block, and the temperature and heating time of the heat block are controlled to raise the reagents in the cartridge to the target temperature (reaction temperature) It is a thing. In addition, according to this analyzer, the reaction vessel is also temperature-controlled by the heat block.
　他にも、特許文献３に記載された自動分注方法が知られている。この自動分注方法は、内部にヒータとファンが配置され、上面にピペットチップ挿入孔が形成された箱状の加温装置に、ピペットチップを挿入した状態で加温し、ピペットチップ内にて液体を加温する方法である。 Besides, an automatic dispensing method described in Patent Document 3 is known. In this automatic dispensing method, the pipette tip is inserted into a box-like heating device in which a heater and a fan are disposed and a pipette tip insertion hole is formed on the upper surface, and the pipette tip is heated. It is a method of heating a liquid.
特開２０１２－２１５４６５号公報JP 2012-215465 A 特許第４４３７２１５号公報Patent No. 4437215 gazette 特開２００９－０５８２８８号公報JP, 2009-058288, A
　しかしながら、特許文献１に記載された分析装置によれば、周囲の温度が低い場合には、目標値を高く設定することにより、センサーチップの反応部の温度を一定に制御しようとしているため、センサーチップの温調部に近い部分と遠い部分（もしくは放熱しやすい部分）において、温度勾配や温度ムラが生じてしまう。かつ、接触型の温調部の場合、熱容量が大きく、温度の変化に対して敏感に追従することが難しいという問題もある。 However, according to the analyzer described in Patent Document 1, when the ambient temperature is low, the temperature of the reaction part of the sensor chip is controlled to be constant by setting the target value high. Temperature gradients and temperature non-uniformities occur in a portion close to the temperature control portion of the chip and a portion far from (or a portion where heat is likely to be dissipated). In addition, in the case of the contact-type temperature control unit, there is a problem that the heat capacity is large and it is difficult to sensitively follow changes in temperature.
　また、特許文献２に記載された分析装置によれば、カートリッジの収容槽内液体（試薬類）を目標温度付近まで昇温することができるが、使用液種により液量も異なるため、飽和するまでに時間がかかる。その一方で時間を区切ってしまうと液温にバラつきが生じる。 Moreover, according to the analyzer described in Patent Document 2, although the liquid (reagents) in the storage tank of the cartridge can be heated to the vicinity of the target temperature, the liquid amount is different depending on the type of liquid used, so saturation occurs It takes time. On the other hand, if the time is separated, the temperature of the liquid will vary.
　また、カートリッジ内の液体は周囲温度に馴染ませた後あるいは保管庫（冷蔵庫）から取り出し直後に使用されるなど様々なケースを考慮すると測定毎に初期温度も異なるため、飽和時間が一定ではないという問題がある。 Also, considering the various cases where the liquid in the cartridge is used after being made compatible with the ambient temperature or taken out immediately after taking it out of the storage (fridge), the initial temperature is also different for each measurement, so the saturation time is not constant There's a problem.
　また、特許文献３に記載された自動分注方法によれば、箱状加温装置内で加温された気体およびピペットチップを介して、ピペットチップ内の液体を加温処理することができるものの、検体や試薬によっては非常に低温で保存されている場合もあり、反応温度までに温度を上昇させるためには時間がかかるという問題があった。また、箱状加温装置と液槽(カートリッジ内試薬)が分離されているため、液槽内の液体を含めた大容量の液体を加温することは困難であった。 Further, according to the automatic dispensing method described in Patent Document 3, it is possible to heat the liquid in the pipette tip through the gas and the pipette tip which are heated in the box-like heating device. However, some samples and reagents may be stored at very low temperatures, and there is a problem that it takes time to raise the temperature to the reaction temperature. Moreover, since the box-like heating device and the liquid tank (reagent in the cartridge) are separated, it was difficult to heat a large volume of liquid including the liquid in the liquid tank.
　さらに、これら先行技術による方法、すなわち、周囲温度による制御温度変更やヒートブロックによるカートリッジ内試薬加温、箱状加温装置による気体およびピペットチップを介して、ピペットチップ内試薬加温のそれぞれもしくは組合せにより周囲温度を考慮したカートリッジを保持するステージとピペットチップの両方を加温する方法では、短時間、多種多様な試薬温度条件に対応できないという問題があった。
　本発明の目的は、周囲温度の影響を受けることなく安定した試薬等の液体の温度制御を行うことができる温調システムを提供することである。 Furthermore, each of these prior art methods, namely, control temperature change according to ambient temperature, reagent heating in a cartridge by heat block, gas by a box-like heating device, and reagent tip heating in a pipette tip via a pipette tip Thus, in the method of heating both the stage for holding the cartridge considering the ambient temperature and the pipette tip, there has been a problem that it can not cope with various reagent temperature conditions for a short time.
An object of the present invention is to provide a temperature control system capable of performing stable temperature control of liquids such as reagents without being affected by ambient temperature.
　上記課題を解決するため、本願発明は下記の事項を包含する。
［１］　ピペットチップを昇降させる駆動部と、
　前記ピペットチップに送風を行う温調部と、
　液体を前記ピペットチップに吸入し、かつ前記ピペットチップ内の前記液体を排出するためのポンプとを備え、
　前記駆動部により前記ピペットチップが降下し、前記温調部が送風を行った状態で前記ポンプが前記吸入と前記排出とを繰り返す吸排を行う、温調システム。
［２］　前記液体を収容する収容槽が形成された検査カートリッジを架設するステージと、
　前記ステージを加温するステージ温調ヒータとを備える、［１］記載の温調システム。
［３］　前記温調部は、
　前記ピペットチップの少なくとも一部を収容可能な筐体と、
　前記筐体の内部に配置された熱源と、
　前記筐体に形成された、前記ピペットチップの昇降移動を許容する開口部とを備える、［１］または［２］記載の温調システム。
［４］　前記検査カートリッジには、試薬と検体を反応させるための反応容器が含まれ、
　前記反応容器内における前記反応に先立ち前記収容槽内の前記液体を加温するプレヒート段階で前記吸排を行い、
　前記プレヒート段階の前記吸排において最後に前記ピペットチップに吸入された前記液体が、前記液体を収容する前記収容槽に吐出される、［２］または［３］記載の温調システム。
［５］　前記反応容器内における試薬と検体の反応を測定する測定段階で前記吸排を行い、
　前記測定段階の前記吸排において最後に前記ピペットチップに吸入された前記液体が前記反応容器に吐出される、［４］記載の温調システム。
［６］　前記反応容器において前記液体の前記吸排を行う、［５］記載の温調システム。
［７］　前記液体の温度を取得する液体温度取得部と、
　前記液体温度取得部により取得された温度を用いて吸排の必要性、条件変更の少なくとも一方を判定する判定部とを備える、［５］または［６］記載の温調システム。
［８］　前記液体温度取得部は、前記測定段階における前記吸排の際に前記液体の温度を取得する、［７］記載の温調システム。
［９］　前記ピペットチップは、５０μｌ以上２００μｌ以下の前記液体を吸排する、［１］～［８］の何れかに記載の温調システム。
［１０］　前記温調部は、３０℃以上４０℃以下の温風を３０秒以上３００秒以下前記ピペットチップに送風する、［１］～［９］の何れかに記載の温調システム。
［１１］　前記温調部は、４０℃以上６０℃以下の温風を１０秒以上１２０秒以下前記ピペットチップに送風する、［１］～［９］の何れかに記載の温調システム。
［１２］　前記液体は、測定液、検体、洗浄液、希釈液、標識抗体の中の少なくとも一つである、［１］～［１１］の何れかに記載の温調システム。 In order to solve the above-mentioned subject, the present invention includes the following matters.
[1] A drive for raising and lowering the pipette tip,
A temperature control unit for blowing air to the pipette tip;
A pump for sucking liquid into the pipette tip and for discharging the liquid in the pipette tip;
The temperature control system, wherein the pump tip performs suction and discharge repeatedly in a state in which the pipette tip is lowered by the drive unit and the temperature control unit performs air flow.
[2] A stage for constructing an inspection cartridge in which a storage tank for storing the liquid is formed;
The temperature control system according to [1], comprising: a stage temperature control heater configured to heat the stage.
[3] The temperature control unit
A housing capable of containing at least a portion of the pipette tip;
A heat source disposed inside the housing;
The temperature control system according to [1] or [2], further comprising: an opening formed in the housing for permitting vertical movement of the pipette tip.
[4] The test cartridge includes a reaction container for reacting a reagent and a sample,
The suction and discharge are performed in a preheating step of heating the liquid in the storage tank prior to the reaction in the reaction container,
The temperature control system according to [2] or [3], wherein the liquid sucked into the pipette tip lastly in the suction and discharge of the preheating stage is discharged to the storage tank containing the liquid.
[5] The aspiration and discharge are performed in a measurement step of measuring a reaction between a reagent and a sample in the reaction container,
The temperature control system according to [4], wherein the liquid sucked into the pipette tip last in the suction and discharge of the measurement step is discharged to the reaction container.
[6] The temperature control system according to [5], wherein the suction and discharge of the liquid is performed in the reaction container.
[7] A liquid temperature acquisition unit for acquiring the temperature of the liquid,
The temperature control system according to [5] or [6], further comprising: a determination unit that determines at least one of necessity of suction and discharge and condition change using the temperature acquired by the liquid temperature acquisition unit.
[8] The temperature control system according to [7], wherein the liquid temperature acquisition unit acquires the temperature of the liquid at the time of the suction and discharge in the measurement step.
[9] The temperature control system according to any one of [1] to [8], wherein the pipette tip sucks and discharges the liquid of 50 μl to 200 μl.
[10] The temperature control system according to any one of [1] to [9], wherein the temperature control unit blows warm air of 30 ° C. or more and 40 ° C. or less to the pipette tip for 30 seconds or more and 300 seconds or less.
[11] The temperature control system according to any one of [1] to [9], wherein the temperature control unit blows warm air of 40 ° C. or more and 60 ° C. or less to the pipette tip for 10 seconds or more and 120 seconds or less.
[12] The temperature control system according to any one of [1] to [11], wherein the liquid is at least one of a measurement solution, a sample, a washing solution, a dilution solution, and a labeled antibody.
　本発明によれば、周囲温度の影響を受けることなく安定した試薬等の液体の温度制御を行うことができる温調システムを提供することができる。 According to the present invention, it is possible to provide a temperature control system capable of performing stable temperature control of liquids such as reagents without being affected by ambient temperature.
本発明に係る温調システムを適用した分析装置の要部の構成を模式的に示す図である。It is a figure which shows typically the structure of the principal part of the analyzer to which the temperature control system which concerns on this invention is applied. 同実施形態に係る温調システムとその周辺パーツの相対位置関係を示す図である。It is a figure which shows the relative positional relationship of the temperature control system which concerns on the embodiment, and its periphery parts. 同実施形態におけるピペットチップ温調部の全体斜視図である。It is a whole perspective view of the pipette tip temperature control part in the embodiment. 同実施形態のピペットチップ温調部における温風の流れを模式的に示す図である。It is a figure which shows typically the flow of the warm air in the pipette tip temperature control part of the embodiment. 同実施形態におけるピペットノズルを基準位置から所定距離降下させた状態の図２対応図である。FIG. 3 is a view corresponding to FIG. 2 in a state where the pipette nozzle in the embodiment is lowered by a predetermined distance from a reference position.
　以下、本発明の一実施形態を、図面を参照して説明する。
　本実施形態に係る温調システムＸは、例えば図１に示す分析装置１に適用されるものである。分析装置１は、収容槽２１内の試薬類や検体を吸引し、反応容器３内に吐出して反応させるために使用されるピペットチップ５１を用いて検体を分析する装置である。 Hereinafter, an embodiment of the present invention will be described with reference to the drawings.
The temperature control system X according to the present embodiment is applied to, for example, the analyzer 1 shown in FIG. The analyzer 1 is a device for analyzing a sample by using a pipette tip 51 which is used to suction the reagents and the sample in the storage tank 21 and discharge the reagent and the sample into the reaction container 3 for reaction.
　本実施形態における検査カートリッジ２は、標識抗体や洗浄液など必要な試薬類が個別にプリパッケージされた収容槽２１と、試薬類と検体とを反応させる反応容器３とを有する容器である。ここで、反応容器３は、検査カートリッジ２とは独立した別個の部品であってもよい。この検査カートリッジ２は、被検出物質を含む検体を所定の収容槽２１に予め分注した状態で分析装置１のステージ４（図２参照）に架設される。検体としては、例えば、血液や血清、血漿、尿、鼻孔液、唾液、精液等が挙げられる。また、被検出物質としては、核酸（ＤＮＡやＲＮＡなど）、タンパク質（ポリペプチドやオリゴペプチドなど）、アミノ酸、糖質、脂質及びこれらの修飾分子等を挙げることができる。 The test cartridge 2 in the present embodiment is a container having a storage tank 21 in which necessary reagents such as a labeled antibody and a washing solution are prepackaged individually, and a reaction container 3 in which the reagents and the sample are reacted. Here, the reaction vessel 3 may be a separate part independent of the test cartridge 2. The test cartridge 2 is mounted on a stage 4 (see FIG. 2) of the analyzer 1 in a state where a sample containing a substance to be detected is dispensed in a predetermined storage tank 21 in advance. Examples of the sample include blood, serum, plasma, urine, nasal fluid, saliva, semen and the like. Further, examples of the substance to be detected include nucleic acids (such as DNA and RNA), proteins (such as polypeptides and oligopeptides), amino acids, carbohydrates, lipids, and modified molecules thereof.
　図１に模式的に示す検査カートリッジ２はステージ４に架設される。ステージ４は、図１及び図２に示すように、例えばスライドベース４１上に固定されている。ステージ駆動部（図示省略）によってスライドベース４１をリニアガイド部４２に沿って水平移動させると、ステージ４は検査カートリッジ２を保持した状態で水平移動する。 The inspection cartridge 2 schematically shown in FIG. 1 is mounted on the stage 4. The stage 4 is fixed on, for example, a slide base 41 as shown in FIGS. 1 and 2. When the slide base 41 is moved horizontally along the linear guide 42 by the stage drive unit (not shown), the stage 4 moves horizontally while holding the inspection cartridge 2.
　反応容器３は、液体を収容可能な収容部３１を有し、収容部３１の上方開口部から挿入したピペットチップ５１の先端５１１を通じて収容部３１に液体が注入されたり、除去されたりするものである。 The reaction container 3 has a container 31 capable of containing a liquid, and the liquid is injected or removed from the container 31 through the tip 511 of the pipette tip 51 inserted from the upper opening of the container 31. is there.
　反応容器３の収容部３１には、分析対象の物質を含む検体、および分析対象の物質と抗原抗体反応を起こす物質を含む試薬類（反応試薬）が分注される。そして、分注処理後、反応容器３内で生じた反応の結果として生じる凝集や発色、蛍光などの有無や程度に関する情報を、適宜の手段で取得し、取得したデータを用いて検体の成分の分析を行うことが可能である。 A sample containing a substance to be analyzed and reagents (reaction reagents) containing a substance that causes an antigen-antibody reaction with the substance to be analyzed are dispensed into the storage portion 31 of the reaction container 3. Then, after dispensing processing, information on the presence or absence and degree of aggregation, color development, fluorescence, etc. generated as a result of the reaction generated in the reaction container 3 is acquired by an appropriate means, and the acquired data are used to It is possible to carry out the analysis.
　分析装置１は、図１に示すように、反応容器３の収容部３１に液の吸入や排出を行う送液部５と、送液部５の作動を制御する制御部６とを少なくとも備えている。送液部５は、先端にピペットチップ５１が装着されるピペットノズル５２と、ピペットノズル５２に接続されたポンプ５３と、ピペットノズル５２を昇降移動させるノズル駆動部５４（駆動部）とを有する。なお、図１ではステージ４、送液部５及び制御部６以外に分析装置１が備える各部は省略している。 As shown in FIG. 1, the analyzer 1 includes at least a liquid sending unit 5 that sucks and discharges liquid in the storage unit 31 of the reaction container 3 and a control unit 6 that controls the operation of the liquid sending unit 5. There is. The liquid delivery unit 5 has a pipette nozzle 52 to which a pipette tip 51 is attached at its tip, a pump 53 connected to the pipette nozzle 52, and a nozzle drive unit 54 (drive unit) that moves the pipette nozzle 52 up and down. In addition, each part with which the analyzer 1 is equipped except the stage 4, the liquid feeding part 5, and the control part 6 is abbreviate | omitted in FIG.
　ポンプ５３は、シリンジ５３１と、シリンジ５３１内を往復動作可能なプランジャ５３２とを備え、駆動モータ（例えばステッピングモータ）を含む図示しないポンプ駆動部によってプランジャ５３２を往復運動させるものである。このようなプランジャ５３２を例えば配管５５を介してピペットノズル５２に接続した状態で往復運動させることによって、外部の液体をピペットチップ５１内に吸入させたり、ピペットチップ５１内の液体を外部に排出する処理を定量的に行うことができる。また、ピペットチップ５１の先端５１１を、反応容器３の収容部３１の底面に近接させた状態で、シリンジ５３１に対するプランジャ５３２の往復動作を繰り返すことで、収容部３１内の液体を攪拌し、液体の濃度の均一化や反応の促進等を図ることができる。ポンプ５３の駆動をステッピングモータで行うことにより、ピペットチップ５１の送液量や送液速度を管理することが可能であり、反応容器３の収容部３１内の残液量を管理することも可能になる。 The pump 53 includes a syringe 531 and a plunger 532 that can reciprocate in the syringe 531, and reciprocates the plunger 532 by a pump drive unit (not shown) including a drive motor (for example, a stepping motor). An external liquid is sucked into the pipette tip 51 or a liquid in the pipette tip 51 is discharged to the outside by reciprocating such a plunger 532 in a state of being connected to the pipette nozzle 52 through the pipe 55, for example. The treatment can be performed quantitatively. In addition, by repeating the reciprocating operation of the plunger 532 with respect to the syringe 531 in a state in which the tip end 511 of the pipette tip 51 is brought close to the bottom surface of the storage portion 31 of the reaction container 3, the liquid in the storage portion 31 is agitated, The reaction can be promoted, etc. By driving the pump 53 with a stepping motor, it is possible to manage the amount of liquid transfer and the liquid transfer speed of the pipette tip 51, and it is also possible to manage the amount of residual liquid in the storage section 31 of the reaction container 3 become.
　ノズル駆動部５４は、例えば、ソレノイドアクチュエータやステッピングモータによってピペットノズル５２を軸方向（本実施形態では鉛直方向）に自在に移動させるものである。 The nozzle drive unit 54 freely moves the pipette nozzle 52 in the axial direction (vertical direction in the present embodiment) by, for example, a solenoid actuator or a stepping motor.
　このようなピペットノズル５２、ポンプ５３及びノズル駆動部５４を備えた送液部５によって、反応容器３の収容部３１内に検体を排出して注入したり、収容部３１内から液体を吸引して除去することができる。本実施形態では、図２に示すように、送液部５を構成する各部をユニット化し、サンプラユニット５Ｕとして取り扱えるように構成している。なお、図２ではポンプ５３等を省略している。 The sample is discharged and injected into the storage unit 31 of the reaction container 3 by the liquid feeding unit 5 including the pipette nozzle 52, the pump 53, and the nozzle drive unit 54, or the liquid is sucked from inside the storage unit 31. Can be removed. In the present embodiment, as shown in FIG. 2, each unit constituting the liquid delivery unit 5 is configured to be united and handled as a sampler unit 5U. In addition, pump 53 grade | etc., Is abbreviate | omitted in FIG.
　そして、本実施形態に係る温調システムＸは、図１及び図２に示すように、ピペットチップ５１を加温するピペットチップ温調部７（温調部）と、反応容器３を加温する反応容器温調部８とを備えている。 Then, as shown in FIG. 1 and FIG. 2, the temperature control system X according to the present embodiment heats the pipette tip temperature control unit 7 (temperature control unit) that heats the pipette tip 51 and the reaction container 3. A reaction container temperature control unit 8 is provided.
　反応容器温調部８は、ステージ４を加温するステージ温調用ヒータ８１を用いて構成している。ステージ温調用ヒータ８１によってステージ４を加温することにより、ステージ４上に配置されている反応容器３を加温することができる。本実施形態では、ステージ温調用ヒータ８１によって加温されるステージ４の温度を適宜のセンサで検知可能に構成している。 The reaction container temperature control unit 8 is configured using a stage temperature control heater 81 that heats the stage 4. By heating the stage 4 by the stage temperature control heater 81, the reaction vessel 3 disposed on the stage 4 can be heated. In the present embodiment, the temperature of the stage 4 heated by the stage temperature control heater 81 can be detected by an appropriate sensor.
　ピペットチップ温調部７は、所定の加温位置に位置付けられたピペットノズル５２のうち少なくともピペットチップ５１の先端部分を熱源７２から放出される温風によって集中的に加温するものである。本実施形態にかかるピペットチップ温調部７は、図１～図３に示すように、少なくともピペットチップ５１の先端部分を収容可能な筐体７１と、筐体７１の内部に配置した熱源７２と、熱源７２から放出される温風を所定方向に送るファン７３とを備え、筐体７１の内部空間を熱源７２から放出される温風によって加温するものである。筐体７１は、箱状をなし、内部空間を外部から仕切る外壁のうち上壁７１１及び下壁７１２に、ピペットチップ５１の昇降移動を許容する開口部を形成している。本実施形態のピペットチップ温調部７では、開口部として、ピペットチップ５１が挿通可能な挿通孔（上側挿通孔７１３、下側挿通孔７１４）を適用している。本実施形態では、筐体７１を、上方が大きく開口した有底の筐体本体７１５と、筐体本体７１５の上方開口部を閉鎖する位置に配置した天板７１６とを用いて構成している。筐体７１の上側挿通孔７１３は、天板７１６に形成した丸孔であり、筐体７１の下側挿通孔７１４は、筐体本体７１５の底部に形成した丸孔である。これら上側挿通孔７１３及び下側挿通孔７１４は鉛直方向（ピペットノズル５２の昇降移動方向）に対向する位置関係にある。 The pipette tip temperature control unit 7 intensively heats at least the tip portion of the pipette tip 51 of the pipette nozzles 52 positioned at a predetermined heating position by the warm air released from the heat source 72. As shown in FIGS. 1 to 3, the pipette tip temperature control unit 7 according to the present embodiment includes a housing 71 capable of housing at least the tip portion of the pipette tip 51, and a heat source 72 disposed inside the housing 71. A fan 73 for sending warm air discharged from the heat source 72 in a predetermined direction is provided, and the internal space of the housing 71 is heated by the warm air discharged from the heat source 72. The housing 71 has a box-like shape, and an upper wall 711 and a lower wall 712 of the outer wall that partitions the internal space from the outside form an opening that allows the pipette tip 51 to move up and down. In the pipette tip temperature control unit 7 according to the present embodiment, insertion holes (upper insertion holes 713 and lower insertion holes 714) through which the pipette tip 51 can be inserted are applied as the opening. In the present embodiment, the casing 71 is configured using a bottomed casing main body 715 having a large opening at the upper side, and a top plate 716 disposed at a position closing the upper opening of the casing main body 715. . The upper insertion hole 713 of the casing 71 is a round hole formed in the top plate 716, and the lower insertion hole 714 of the casing 71 is a round hole formed in the bottom of the casing main body 715. The upper insertion hole 713 and the lower insertion hole 714 are in a positional relationship opposed in the vertical direction (the moving direction of the pipette nozzle 52).
　そして、ピペットチップ温調部７は、上側挿通孔７１３及び下側挿通孔７１４を通じて筐体７１の内部空間に挿入されたピペットチップ５１に対して、熱源７２から放出される温風を当てることで、ピペットチップ５１を加温することができる。なお、筐体７１の内部には、筐体７１内の温度を検知可能なセンサ７１７（例えばサーミスタ）や放熱フィン７１８を配置している（図３参照）。温度ヒューズを搭載した放熱フィン７１８は、安全装置として機能する。また、ファン７３は、筐体７１の内部空間に配置することもできるが、本実施形態では、ファン７３を筐体７１の外部であって、且つ筐体７１の外壁（図示例では側壁）に形成したファン用開口部７１９に臨む位置に固定し、熱源７２から放出される温風をファン７３によって所定方向に送ることができるように設定している。筐体７１の内部に配置する部品を最小限に留めることで、筐体７１のサイズの狭小化を図り、温風によって筐体７１の内部空間を予め設定されている所定の目標温度に昇温・保温する処理を効率良く行うことができる。 The pipette tip temperature control unit 7 applies warm air discharged from the heat source 72 to the pipette tip 51 inserted into the internal space of the housing 71 through the upper insertion hole 713 and the lower insertion hole 714. , The pipette tip 51 can be heated. In the inside of the housing 71, a sensor 717 (for example, a thermistor) capable of detecting the temperature inside the housing 71 and a radiation fin 718 are disposed (see FIG. 3). The radiation fin 718 equipped with a thermal fuse functions as a safety device. The fan 73 can also be disposed in the internal space of the housing 71. However, in the present embodiment, the fan 73 is outside the housing 71 and on the outer wall (side wall in the illustrated example) of the housing 71. It is fixed at a position facing the formed fan opening 719 so that the warm air discharged from the heat source 72 can be sent in a predetermined direction by the fan 73. By minimizing the number of parts disposed inside the casing 71, the size of the casing 71 is narrowed, and the temperature of the internal space of the casing 71 is raised to a predetermined target temperature set in advance by the warm air.・ Processing to keep warm can be performed efficiently.
　ピペットチップ温調部７は、筐体７１にブラケット７４を固定した状態でユニット化されている。そして、ブラケット７４をサンプラユニット５Ｕに取り付けることで、ピペットチップ温調部７をサンプラユニット５Ｕに固定することができる（図２参照）。 The pipette tip temperature control unit 7 is unitized in a state where the bracket 74 is fixed to the housing 71. Then, by attaching the bracket 74 to the sampler unit 5U, the pipette tip temperature control unit 7 can be fixed to the sampler unit 5U (see FIG. 2).
　本実施形態では、反応容器３の近傍にピペットチップ温調部７を配置している。具体的には、図４に示すように、ピペットチップ温調部７の下端（筐体７１の底）から反応容器ページの上面までの離間距離（同図において「Ｌ」で示す距離）を、例えば５ｍｍ程度に設定している。 In the present embodiment, the pipette tip temperature control unit 7 is disposed in the vicinity of the reaction container 3. Specifically, as shown in FIG. 4, the separation distance (the distance indicated by “L” in FIG. 4) from the lower end (bottom of the housing 71) of the pipette tip temperature control unit 7 to the top surface of the reaction container page is For example, it is set to about 5 mm.
　このようなレイアウトを採用したことによって、図４に示すように、反応容器３が、筐体７１の挿通孔（特に下側挿通孔７１４）を通じて筐体７１の内部から外部に放出される温風に晒されることになる。同図では、ピペットチップ温調部７の熱源７２から発生する温風の流れを相対的に太い矢印で模式的に示している。 By adopting such a layout, as shown in FIG. 4, the hot air discharged from the inside of the casing 71 to the outside through the insertion hole (in particular, the lower insertion hole 714) of the casing 71. Will be exposed to In the figure, the flow of the warm air generated from the heat source 72 of the pipette tip temperature control unit 7 is schematically indicated by a relatively thick arrow.
　制御部６は、例えば、演算装置、制御装置、記憶装置、入力装置及び出力装置等を含む公知のコンピュータやマイコンなどによって構成され、送液部５、ピペットチップ温調部７、反応容器温調部８を含む分析装置１の各部の作動を所定のプログラムに従って制御するものである。制御部６は、ピペットチップ温調部７を構成する筐体７１内の温度をセンサ７１７から取得するピペットチップ温度取得部６１と、反応容器３の温度を図示しないセンサから取得する反応容器温度取得部６２とを備えている。本実施形態では、ステージ４の温度を取得することで反応容器３の温度を間接的に取得するように構成している。 The control unit 6 is constituted by, for example, a known computer or microcomputer including an arithmetic unit, a control unit, a storage unit, an input unit, an output unit and the like, and the liquid sending unit 5, the pipette tip temperature adjustment unit 7, the reaction container temperature adjustment The operation of each part of the analyzer 1 including the part 8 is controlled according to a predetermined program. The control unit 6 acquires a pipette tip temperature acquisition unit 61 that acquires the temperature in the housing 71 constituting the pipette tip temperature adjustment unit 7 from the sensor 717, and a reaction container temperature acquisition that acquires the temperature of the reaction container 3 And a unit 62. In the present embodiment, the temperature of the reaction vessel 3 is indirectly acquired by acquiring the temperature of the stage 4.
　本実施形態に係る分析装置１の温調システムＸは、分析装置１による検査カートリッジ２を用いた測定が開始され、被検出物質の検出処理の実行中、制御部６による反応容器温調部８及びピペットチップ温調部７の温調制御を実行する。制御部６は、適宜のタイミングでピペットチップ温度取得部６１、反応容器温度取得部６２による温度取得処理を行い、取得した温度に基づいて、ピペットチップ温調部７によるピペットチップ温調温度と、反応容器温調部８による反応容器温調温度（ステージ温調温度）を、予め設定されているピペットチップ温調目標温度、反応容器温調目標温度（ステージ温調目標温度）に近付けるように温調制御する。ピペットチップ温調目標温度と反応容器温調目標温度（ステージ温調目標温度）は、同じであってもよいが、異ならせてもよい。例えば、反応容器温調目標温度（ステージ温調目標温度）を、試薬の反応温度に応じて設定したり、ピペットチップ温調目標温度を、所定温度の液体をピペットチップが吸入、排出を行う時、温度が下がらない効果を期待でき、且つ、試薬への悪影響やピペットチップ自身の熱変形を回避可能な温度に設定することができる。 The temperature control system X of the analyzer 1 according to the present embodiment starts the measurement using the test cartridge 2 by the analyzer 1 and during the detection process of the substance to be detected, the reaction container temperature controller 8 by the controller 6 And temperature control of the pipette tip temperature control unit 7 is executed. The control unit 6 performs temperature acquisition processing by the pipette tip temperature acquisition unit 61 and the reaction container temperature acquisition unit 62 at an appropriate timing, and based on the acquired temperature, the pipette tip temperature adjustment temperature by the pipette tip temperature adjustment unit 7 The reaction container temperature control unit 8 adjusts the reaction container temperature control temperature (stage temperature control temperature) to a preset pipette tip temperature control target temperature and reaction container temperature control target temperature (stage temperature control target temperature). Control. The pipette tip temperature control target temperature and the reaction container temperature control target temperature (stage temperature control target temperature) may be the same or different. For example, when the reaction container temperature control target temperature (stage temperature control target temperature) is set according to the reaction temperature of the reagent, or the pipette tip temperature control target temperature is aspirated and discharged by the pipette tip The effect that the temperature does not fall can be expected, and the adverse effect on the reagent and the thermal deformation of the pipette tip itself can be set to a temperature that can be avoided.
　さらに、制御部６は、収容槽２１内に収容された液体の温度を取得する液体温度取得部６３を備えている。制御部６は、反応容器温度取得部６２によって取得された反応容器３の温度、および液体温度取得部６３によって取得された液体の温度を用いて、後述する吸排の必要性や吸排条件の変更などを判定する判定部としての機能を併せて有している。ここで、反応容器３の温度や液体の温度を取得するセンサの例としては、サーモパイルや接触型サーミスタなどが考えられる。 Furthermore, the control unit 6 includes a liquid temperature acquisition unit 63 that acquires the temperature of the liquid contained in the storage tank 21. The control unit 6 uses the temperature of the reaction container 3 acquired by the reaction container temperature acquisition unit 62 and the temperature of the liquid acquired by the liquid temperature acquisition unit 63 to change the necessity of suction and discharge described later, the suction and discharge conditions, etc. Has a function as a determination unit to determine Here, a thermopile, a contact type thermistor, etc. can be considered as an example of a sensor which acquires the temperature of reaction container 3, and the temperature of a liquid.
　本実施形態の温調システムＸは、図２及び図４に示すように、ピペットノズル５２を所定の加温位置に位置付けた状態で、少なくともピペットチップ５１の先端部分が筐体７１の内部に収容されるように構成されている。具体的には、ピペットノズル５２を加温位置に位置付けた状態では、ピペットチップ５１の先端５１１が筐体７１の下側挿通孔７１４内に位置付けられ、ピペットチップ５１のうち先端から所定寸法分までの領域（先端部分）が筐体７１の内部に配置されるように設定している。本実施形態では、ピペットノズル５２の原点位置を「加温位置」に設定している。したがって、ピペットノズル５２を原点位置で待機させることによって、筐体７１の内部でピペットチップ５１の先端部分を加温することができる。 As shown in FIG. 2 and FIG. 4, the temperature control system X of this embodiment accommodates at least the tip portion of the pipette tip 51 inside the housing 71 with the pipette nozzle 52 positioned at a predetermined heating position. It is configured to be. Specifically, in the state where the pipette nozzle 52 is positioned at the heating position, the tip 511 of the pipette tip 51 is positioned in the lower insertion hole 714 of the housing 71, and from the tip of the pipette tip 51 to a predetermined dimension Is set so as to be disposed inside the housing 71. In the present embodiment, the origin position of the pipette nozzle 52 is set to the “heating position”. Therefore, the tip portion of the pipette tip 51 can be heated inside the housing 71 by making the pipette nozzle 52 stand by at the origin position.
　また、本実施形態では、ピペットノズル５２を加温位置に位置付けた状態で、ピペットチップ５１の先端５１１と下側挿通孔７１４の間には所定の隙間が形成され、ピペットチップ５１と上側挿通孔７１３の間にも所定の隙間が形成され、ピペットチップ５１が筐体７１に接触しないように設定している。このようなピペットチップ５１と挿通孔（上側挿通孔７１３、下側挿通孔７１４）との隙間から、筐体７１内の温風が筐体７１の外部に噴き出し、筐体７１の周辺温度を、筐体７１の内部温度と同程度に保つことができる（図４参照）。 In the present embodiment, with the pipette nozzle 52 positioned at the heating position, a predetermined gap is formed between the tip 511 of the pipette tip 51 and the lower insertion hole 714, and the pipette tip 51 and the upper insertion hole A predetermined gap is also formed between 713, and the pipette tip 51 is set so as not to contact the housing 71. From the gap between the pipette tip 51 and the insertion hole (upper insertion hole 713, lower insertion hole 714), the warm air in the housing 71 blows out to the outside of the housing 71, and the ambient temperature of the housing 71 is The internal temperature of the housing 71 can be maintained at the same level (see FIG. 4).
　ここで、本実施形態に係る分析装置１の温調システムＸを使用する際の処理について説明する。まず、ユーザにより、図示しない冷蔵庫から、２～８℃程度の温度で保存されている検査カートリッジ２が取り出される。冷蔵庫から取り出されると、検査カートリッジ２の温度は、１０～３０℃程度の室内温度に戻される。 Here, the process at the time of using the temperature control system X of the analyzer 1 which concerns on this embodiment is demonstrated. First, the inspection cartridge 2 stored at a temperature of about 2 to 8 ° C. is taken out of the refrigerator (not shown) by the user. When removed from the refrigerator, the temperature of the inspection cartridge 2 is returned to the room temperature of about 10 to 30.degree.
　次に、検査カートリッジ２は、反応容器温調部８であるステージ温調用ヒータ８１で加温されたステージ４に架設される。これにより、ステージ４上において検査カートリッジ２の各収容槽２１及び反応容器３の収容部３１も加温され、さらに、各収容槽２１内に収容されている吸入対象の液体も加温される。すなわち、反応容器３の収容部３１内での試薬類と検体の反応に先立ち収容槽２１内の液体を加温するプレヒートが行われる。プレヒートの時間は、１～１０分程度が好ましい。 Next, the inspection cartridge 2 is mounted on the stage 4 heated by the stage temperature control heater 81 which is the reaction container temperature control unit 8. As a result, each storage tank 21 of the test cartridge 2 and the storage section 31 of the reaction container 3 are also heated on the stage 4, and the liquid to be sucked stored in each storage tank 21 is also heated. That is, prior to the reaction between the reagent and the sample in the storage unit 31 of the reaction container 3, preheating is performed to heat the liquid in the storage tank 21. The preheating time is preferably about 1 to 10 minutes.
　プレヒート後、図示しない測定開始ボタンが操作されると、反応容器３の収容部３１内での試薬類と検体の反応を測定する測定段階に移行する。まず、制御部６は、ステージ駆動部（図示省略）を駆動させ、吸入対象の液体が収容されている収容槽２１がピペットノズル５２の直下となる位置にステージ４を移動させる。 After the preheating, when the measurement start button (not shown) is operated, the process proceeds to the measurement step of measuring the reaction between the reagent and the sample in the storage unit 31 of the reaction container 3. First, the control unit 6 drives the stage drive unit (not shown) to move the stage 4 to a position where the storage tank 21 containing the liquid to be sucked is directly below the pipette nozzle 52.
　次に、制御部６は、ピペットチップ温調部７により、熱源７２から温風を放出させ、加温位置に位置するピペットノズル５２を加温する。熱源７２からは、３０～６０℃の温度の温風が放出される。 Next, the control unit 6 causes the pipette tip temperature control unit 7 to release warm air from the heat source 72, and heats the pipette nozzle 52 located at the heating position. Hot air of a temperature of 30 to 60 ° C. is released from the heat source 72.
　次に、制御部６は、図５に示すように、ノズル駆動部５４を駆動させてピペットノズル５２を加温位置から降下させ、ピペットチップ５１内に検査カートリッジ２の液体を吸入する。具体的には、制御部６は、ピペットノズル５２を加温位置から所定距離降下させて停止させた状態で、ポンプ５３を駆動させてピペットノズル５２の先端、つまりピペットチップ５１の先端５１１から吸入対象の液体を吸引する。 Next, as shown in FIG. 5, the control unit 6 drives the nozzle drive unit 54 to lower the pipette nozzle 52 from the heating position, and sucks the liquid of the test cartridge 2 into the pipette tip 51. Specifically, in a state where the pipette nozzle 52 is lowered by a predetermined distance from the heating position and stopped, the control unit 6 drives the pump 53 to suction from the tip of the pipette nozzle 52, that is, the tip 511 of the pipette tip 51 Aspirate the target fluid.
　そして、制御部６は、この状態でポンプ５３により、ピペットノズル５２内に吸入された液体を先端５１１から収容槽２１内に排出する。制御部６は、この状態でポンプ５３により再び収容槽２１内の液体をピペットチップ５１内に吸入し、さらに収容槽２１内に排出する。このように、ピペットチップ５１により、液体の吸入と排出を繰り返すことを「吸排」という。 Then, the control unit 6 discharges the liquid sucked into the pipette nozzle 52 from the tip 511 into the storage tank 21 by the pump 53 in this state. In this state, the controller 6 sucks the liquid in the storage tank 21 again into the pipette tip 51 by the pump 53 and discharges the liquid into the storage tank 21. As described above, repeating suction and discharge of liquid by the pipette tip 51 is referred to as "suction and discharge".
　なお、この間、ピペットチップ５１の先端部分は、ピペットチップ温調部７の筐体７１から抜け出して外部周辺温度に晒されるが、筐体７１の周辺温度は、ピペットチップ５１と開口部である挿通孔（上側挿通孔７１３、下側挿通孔７１４）の隙間から筐体７１の外部に噴き出す筐体７１内の温風によって、筐体７１の内部温度と同程度に維持される。このため、ピペットチップ５１の先端部分は、ピペットチップ温調部７の筐体７１から抜け出した状態においても温風によって加温されている。 During this time, the tip portion of the pipette tip 51 is pulled out of the casing 71 of the pipette tip temperature control unit 7 and exposed to the external ambient temperature, but the ambient temperature of the casing 71 is an insertion portion with the pipette tip 51 The hot air in the casing 71 is sprayed to the outside of the casing 71 from the gap between the holes (upper insertion holes 713 and lower insertion holes 714), and the temperature is maintained at about the same as the internal temperature of the casing 71. For this reason, the distal end portion of the pipette tip 51 is also heated by the warm air in a state of being detached from the housing 71 of the pipette tip temperature control unit 7.
　このように、ピペットチップ５１を温風で加温した状態で吸排を行うことにより、収容槽２１内に収容されている液体自体を所定の温度に加温することが可能となる。
　ここで、各収容槽２１内には、測定液、検体、希釈液、洗浄液、標識抗体などの異なる種類の液体が収容されている。これらの液体は、検査カートリッジ２がステージ４に架設された時点の初期温度や液量もそれぞれ異なる。このため、それぞれの液体を収容部３１に吐出する前に、事前にピペットチップ５１を温風で加温した状態で吸排を行い、予め所定の温度まで引き上げておくことにより、後に筐体７１内部で目標温度まで加温し易いようにすることができる。 Thus, it is possible to heat the liquid itself stored in the storage tank 21 to a predetermined temperature by performing suction and discharge in a state where the pipette tip 51 is heated by warm air.
Here, in each storage tank 21, different types of liquids such as a measurement liquid, a specimen, a dilution liquid, a washing liquid, and a labeled antibody are contained. These liquids also differ in initial temperature and liquid amount when the inspection cartridge 2 is mounted on the stage 4 respectively. For this reason, before discharging the respective liquids into the storage section 31, suction and discharge are performed in a state where the pipette tip 51 is heated with warm air in advance, and the temperature is raised to a predetermined temperature in advance. Can be easily heated to the target temperature.
　なお、どの収容槽２１内の液体について吸排行うかについては、各収容槽２１内の液体量等に応じて判断してもよい。また、全ての収容槽２１内の液体について吸排を行ってもよいし、いずれか選択された収容槽２１内の液体のみについて吸排を行ってもよい。 The liquid in which storage tank 21 is sucked and discharged may be determined according to the amount of liquid in each storage tank 21 or the like. Further, suction and discharge may be performed on the liquid in all the storage tanks 21, and suction and discharge may be performed on only the liquid in the selected storage tank 21.
　次に、ノズル駆動部５４を駆動させてピペットノズル５２が加温位置に戻されると、ピペットチップ５１の先端部分が筐体７１内に配置され、ピペットチップ温調部７によってピペットチップ５１内の液体が直接加温される。熱源７２からは、３０℃以上４０℃以下の反応に適した温度の温風が３０秒以上３００秒以下の間放出される。 Next, when the nozzle driving unit 54 is driven to return the pipette nozzle 52 to the heating position, the tip of the pipette tip 51 is disposed in the housing 71, and the pipette tip temperature control unit 7 The liquid is heated directly. From the heat source 72, warm air at a temperature suitable for the reaction of 30 ° C. or more and 40 ° C. or less is emitted for 30 seconds or more and 300 seconds or less.
　なお、熱源７２から４０℃以上６０℃以下の気体を１０秒以上１２０秒以下の間放出し続け、液体を高温で一気に加温するようにしてもよい。
　ここで、液体は、予め吸排によって所定の温度まで引き上げられていることから、筐体７１内で加温する際には、液体の加温が加速され、短時間で液体を目標温度まで加温することができる。 Note that the gas may be continuously released from the heat source 72 at a temperature of 40 ° C. or more and 60 ° C. or less for 10 seconds or more and 120 seconds or less to rapidly heat the liquid at a high temperature.
Here, since the liquid is previously pulled up to a predetermined temperature by suction and discharge, when heating in the housing 71, the heating of the liquid is accelerated, and the liquid is heated to the target temperature in a short time can do.
　この状態で、制御部６は、ステージ駆動部を駆動させて、ピペットチップ５１内に保持している液体の吐出先、具体的には検査カートリッジ２の収容槽２１または反応容器３の収容部３１がピペットノズル５２の直下となる位置にステージ４を移動させる。 In this state, the control unit 6 drives the stage drive unit to discharge the liquid held in the pipette tip 51, specifically, the storage tank 21 of the inspection cartridge 2 or the storage unit 31 of the reaction container 3 The stage 4 is moved to a position immediately below the pipette nozzle 52.
　そして、図５に示すように、ピペットノズル５２を加温位置から所定距離降下させて停止させた状態で、制御部６によってポンプ５３を駆動させてピペットノズル５２の先端、つまりピペットチップ５１の先端５１１からピペットチップ５１内の液体を吐出先に向けて吐出する。ここで、吐出先が反応容器３の収容部３１である場合、吸排の最後にピペットチップ５１内に吸入された液体が反応容器３の収容部３１に吐出される。 Then, as shown in FIG. 5, in a state where the pipette nozzle 52 is lowered by a predetermined distance from the heating position and stopped, the control unit 6 drives the pump 53 to drive the tip of the pipette nozzle 52, that is, the tip of the pipette tip 51 From 511, the liquid in the pipette tip 51 is discharged toward the discharge destination. Here, when the discharge destination is the storage portion 31 of the reaction container 3, the liquid sucked into the pipette tip 51 at the end of the suction and discharge discharges the storage portion 31 of the reaction container 3.
　なお、上述の吸排を行ってから液体を吐出先に向けて吐出するまでの作業は、たとえば、測定液、希釈した検体、洗浄液、標識抗体、洗浄液、測定液の順に対象となる液体の種類を代えて繰り返される。また、希釈液を分注して検体を希釈する場合においても、希釈液に対して、ピペットチップ５１を温風で加温した状態での吸排が行われる。また、液体の中でも特に洗浄液は使用量が多く加温し難いため、事前に上述の吸排を行って所定の温度に加温しておくことは有益である。また、反応容器３の収容部３１に吐出された液体についてさらに吸排を行うようにしてもよい。
　反応容器３の収容部３１内における試薬類と検体の反応の測定が行われた後測定段階が終了する。 The operation from the above-mentioned suction and discharge to the discharge of the liquid toward the discharge destination is, for example, the type of liquid to be targeted in the order of the measurement liquid, diluted sample, washing liquid, labeled antibody, washing liquid, and measurement liquid. It will be repeated instead. In addition, even in the case of diluting the sample by dispensing the dilution solution, suction and discharge in the state where the pipette tip 51 is heated with warm air are performed on the dilution solution. Further, among the liquids, since the cleaning liquid is particularly used in a large amount and it is difficult to heat it, it is useful to perform the above-mentioned suction and discharge in advance to heat it to a predetermined temperature. In addition, the liquid discharged into the storage portion 31 of the reaction container 3 may be further absorbed and discharged.
After the measurement of the reaction between the reagent and the sample in the storage unit 31 of the reaction container 3 is performed, the measurement step ends.
　このように、本実施形態に係る温調システムＸによれば、対象となる液体にピペットチップ５１を温風で加温した状態での吸排を行うことにより、液体を収容部３１に吐出する前に、事前にピペットチップ５１を温風で加温した状態で吸排を行い、予め所定の温度まで引き上げておくことができるため、周囲温度の影響を受けることなく安定した液体の温度制御を行うことができる。 As described above, according to the temperature control system X according to the present embodiment, before the liquid is discharged to the storage unit 31 by performing suction and discharge in a state in which the pipette tip 51 is heated with warm air to the target liquid. In addition, since the pipet tip 51 can be sucked and discharged in a state of being heated by warm air in advance and can be raised beforehand to a predetermined temperature, stable liquid temperature control can be performed without being affected by the ambient temperature. Can.
　なお、上述の実施形態において、ピペットチップ５１が降下した位置で温風をピペットチップ５１の先端５１１に吹き当てることができれば、熱源７２からの温風はいずれの方向から放出されてもよい。たとえば、筐体７１の上部に熱源７２を設け、熱源７２からピペットチップ５１の軸方向に温風を放出してもよい。また、ピペットチップ５１を囲むように複数の熱源７２を配置し、ピペットチップ５１の全周囲方向に温風を吹き当ててもよい。 In the above-described embodiment, the warm air from the heat source 72 may be discharged from any direction as long as the warm air can be blown to the tip end 511 of the pipette tip 51 at the position where the pipette tip 51 descends. For example, the heat source 72 may be provided at the top of the housing 71 and the warm air may be discharged from the heat source 72 in the axial direction of the pipette tip 51. In addition, a plurality of heat sources 72 may be disposed so as to surround the pipette tip 51, and warm air may be blown around the entire circumference of the pipette tip 51.
　また、上述の実施形態では、ピペットチップ５１を効率よく加温するため、筐体７１の内部に熱源７２を設けたが、ピペットチップ５１を覆う筐体７１は設けなくてもよい。
　また、上述の実施形態において、検査カートリッジ２をステージ温調用ヒータ８１で加温されたステージ４に架設した後、ピペットチップ５１で収容槽２１の液体を吸入して収容部３１へ吐出する一連の動作を開始する前（ピペットチップ５１が反応容器３へ吐出するための液体を吸入する前）において、予めステージ４の加温を行うプレヒートの際に吸排を行ってもよい。この場合、プレヒート段階の吸排において最後にピペットチップ５１に吸入された液体は、該液体を収容する収容槽２１に吐出される。 Moreover, in the above-mentioned embodiment, in order to heat the pipette tip 51 efficiently, the heat source 72 was provided in the inside of the housing | casing 71, but the housing | casing 71 which covers the pipette tip 51 does not need to provide.
In the above embodiment, after the test cartridge 2 is mounted on the stage 4 heated by the stage temperature control heater 81, the pipette tip 51 sucks the liquid in the storage tank 21 and discharges it to the storage section 31. Before starting the operation (before the pipette tip 51 sucks in the liquid for discharging to the reaction container 3), suction and discharge may be performed in the preheating in which the stage 4 is heated in advance. In this case, the liquid sucked into the pipette tip 51 at the end of suction and discharge in the preheating stage is discharged to the storage tank 21 containing the liquid.
　抗原抗体反応がなされた場合、反応終了後から抗体の解離が発生する上、解離の速度は抗体種によって異なる。このため、反応後の工程において長時間液体を加温すると抗体の解離が進行し、性能低下を引き起こすことがある。よって、解離の速度が速い抗体を使用する場合は、反応容器３に液体を供給する前に予め各収容槽２１で液体の吸排を行うことにより、液体を加温しておく必要がある。 In the case of an antigen-antibody reaction, dissociation of the antibody occurs after completion of the reaction, and the rate of dissociation differs depending on the antibody species. For this reason, if the liquid is heated for a long time in the step after reaction, the dissociation of the antibody may progress, which may cause a decrease in performance. Therefore, when using an antibody having a high dissociation rate, it is necessary to heat the liquid by supplying and discharging the liquid in each storage tank 21 before supplying the liquid to the reaction container 3.
　一方、事前に液体の加温を行った場合、環境温度が低ければ外気によって液体が冷却され、液体の温度低下が発生する。従って、適温で抗原抗体反応が開始できるように、吸排タイミングは、抗体種や検査カートリッジ２の保管状態、環境温度等を考慮して決定する必要がある。 On the other hand, when the liquid is heated in advance, if the environmental temperature is low, the liquid is cooled by the outside air, and a temperature drop of the liquid occurs. Therefore, in order to start the antigen-antibody reaction at an appropriate temperature, it is necessary to determine the timing of absorption and removal in consideration of the antibody species, the storage condition of the test cartridge 2, the environmental temperature and the like.
　また、上述の実施形態において、プレヒート段階や測定段階に、反応容器温度取得部６２によって反応容器３の温度を取得したり、液体温度取得部６３によって液体の温度を取得するようにしてもよい。 In the above embodiment, the temperature of the reaction container 3 may be acquired by the reaction container temperature acquisition unit 62 or the temperature of the liquid may be acquired by the liquid temperature acquisition unit 63 in the preheating stage or the measurement stage.
　なお、検査カートリッジ２がステージ４に架設されてから収容部３１に液体が吐出されるまでには時間が掛かる場合もあるため、測定段階における吸排の際に液体の温度や反応容器３の温度を取得し、吸排を制御するのが望ましい。 In addition, since it may take time until the liquid is discharged into the storage unit 31 after the inspection cartridge 2 is installed on the stage 4, the temperature of the liquid and the temperature of the reaction container 3 may be measured during suction and discharge in the measurement stage. It is desirable to acquire and control pumping.
　この場合、制御部６は、反応容器温度取得部６２によって取得した反応容器３の温度、液体温度取得部６３によって取得した液体の温度の少なくとも一方に基づいて吸排の必要性や吸排条件の変更などを判定する。制御部６は、たとえば、液体の温度が目標の温度となった場合など、吸排の必要性がないと判定した場合には、吸排を中止し、吸排の必要性があると判定した場合には、吸排を継続する。また、吸排条件とは、たとえば、吸排の継続時間、ピペットチップ５１によって吸排する液体の液量などである。 In this case, the control unit 6 changes the necessity of suction and discharge and change the suction and discharge conditions based on at least one of the temperature of the reaction container 3 acquired by the reaction container temperature acquisition unit 62 and the temperature of the liquid acquired by the liquid temperature acquisition unit 63. Determine For example, when it is determined that there is no need for suction and discharge, such as when the temperature of the liquid reaches a target temperature, the control unit 6 stops the suction and discharge, and when it is determined that there is a need for suction and discharge. Continue to suck and discharge. The suction and discharge conditions include, for example, the duration of suction and discharge, the amount of liquid sucked and discharged by the pipette tip 51, and the like.
　具体的には、吸排継続時間は、吸排の繰り返しが１１～５０回であれば０．５分以上５分以下である。また、ピペットチップ５１によって吸排する液体の液量は、５０μｌ以上３００μｌ以下、好ましくは５０μｌ以上２００μｌ以下である。制御部６は、判定結果に基づいて適宜これらの吸排条件を変更する。これにより、さらに的確に液体の温度制御を行うことができる。 Specifically, the suction and discharge duration time is 0.5 minutes or more and 5 minutes or less if repetition of the suction and discharge is 11 to 50 times. In addition, the liquid volume of the liquid absorbed and discharged by the pipette tip 51 is 50 μl or more and 300 μl or less, preferably 50 μl or more and 200 μl or less. The control unit 6 appropriately changes these suction and discharge conditions based on the determination result. Thereby, temperature control of the liquid can be performed more accurately.
１     分析装置
２     検査カートリッジ
３     反応容器
４     ステージ
５     送液部
５Ｕ   サンプラユニット
６     制御部
７     ピペットチップ温調部
８     反応容器温調部
２１   収容槽
３１   収容部
４１   スライドベース
４２   リニアガイド部
５１   ピペットチップ
５２   ピペットノズル
５３   ポンプ
５４   ノズル駆動部
５５   配管
６１   ピペットチップ温度取得部
６２   反応容器温度取得部
６３   液体温度取得部
７１   筐体
７２   熱源
７３   ファン
７４   ブラケット
８１   ステージ温調用ヒータ
５１１ 先端
５３１ シリンジ
５３２ プランジャ
７１１ 上壁
７１２ 下壁
７１３ 上側挿通孔
７１４ 下側挿通孔
７１５ 筐体本体
７１６ 天板
７１７ センサ
７１８ 放熱フィン
７１９ ファン用開口部 Reference Signs List 1 analyzer 2 inspection cartridge 3 reaction container 4 stage 5 liquid transfer unit 5 U sampler unit 6 control unit 7 pipette tip temperature adjustment unit 8 reaction container temperature adjustment unit 21 accommodation tank 31 accommodation unit 41 slide base 42 linear guide unit 51 pipette tip 52 Pipette nozzle 53 Pump 54 Nozzle drive unit 55 Piping 61 Pipette tip temperature acquisition unit 62 Reaction container temperature acquisition unit 63 Liquid temperature acquisition unit 71 Housing 72 Heat source 73 Fan 74 Bracket 81 Stage temperature control heater 511 Tip 531 Syringe 532 Plunger 711 Top wall 712 lower wall 713 upper insertion hole 714 lower insertion hole 715 case main body 716 top plate 717 sensor 718 heat dissipation fin 719 opening for fan

Claims (12)

  1. 　ピペットチップを昇降させる駆動部と、
    　前記ピペットチップに送風を行う温調部と、
    　液体を前記ピペットチップに吸入し、かつ前記ピペットチップ内の前記液体を排出するためのポンプとを備え、
    　前記駆動部により前記ピペットチップが降下し、前記温調部が送風を行った状態で前記ポンプが前記吸入と前記排出とを繰り返す吸排を行う、温調システム。     A drive for raising and lowering the pipette tip,
    A temperature control unit for blowing air to the pipette tip;
    A pump for sucking liquid into the pipette tip and for discharging the liquid in the pipette tip;
    The temperature control system, wherein the pump tip performs suction and discharge repeatedly in a state in which the pipette tip is lowered by the drive unit and the temperature control unit performs air flow.
  2. 　前記液体を収容する収容槽が形成された検査カートリッジを架設するステージと、
    　前記ステージを加温するステージ温調ヒータとを備える、請求項１記載の温調システム。     A stage for setting up an inspection cartridge in which a storage tank for storing the liquid is formed;
    The temperature control system according to claim 1, further comprising: a stage temperature control heater configured to heat the stage.
  3. 　前記温調部は、
    　前記ピペットチップの少なくとも一部を収容可能な筐体と、
    　前記筐体の内部に配置された熱源と、
    　前記筐体に形成された、前記ピペットチップの昇降移動を許容する開口部とを備える、請求項１または２記載の温調システム。     The temperature control unit is
    A housing capable of containing at least a portion of the pipette tip;
    A heat source disposed inside the housing;
    The temperature control system according to claim 1 or 2, further comprising: an opening formed in the housing for permitting vertical movement of the pipette tip.
  4. 　前記検査カートリッジには、試薬と検体を反応させるための反応容器が含まれ、
    　前記反応容器内における前記反応に先立ち前記収容槽内の前記液体を加温するプレヒート段階で前記吸排を行い、
    　前記プレヒート段階の前記吸排において最後に前記ピペットチップに吸入された前記液体が、前記液体を収容する前記収容槽に吐出される、請求項２または３記載の温調システム。     The test cartridge includes a reaction container for reacting a reagent and a sample,
    The suction and discharge are performed in a preheating step of heating the liquid in the storage tank prior to the reaction in the reaction container,
    The temperature control system according to claim 2 or 3, wherein the liquid sucked into the pipette tip lastly in the suction and discharge of the preheating stage is discharged to the storage tank containing the liquid.
  5. 　前記反応容器内における試薬と検体の反応を測定する測定段階で前記吸排を行い、
    　前記測定段階の前記吸排において最後に前記ピペットチップに吸入された前記液体が前記反応容器に吐出される、請求項４記載の温調システム。     Performing the suction and discharge in a measurement step of measuring a reaction between a reagent and a sample in the reaction container;
    The temperature control system according to claim 4, wherein the liquid sucked into the pipette tip lastly in the suction and discharge of the measurement step is discharged to the reaction container.
  6. 　前記反応容器において前記液体の前記吸排を行う、請求項５記載の温調システム。 The temperature control system according to claim 5, wherein the suction and discharge of the liquid is performed in the reaction container.
  7. 　前記液体の温度を取得する液体温度取得部と、
    　前記液体温度取得部により取得された温度を用いて吸排の必要性、条件変更の少なくとも一方を判定する判定部とを備える、請求項５または６記載の温調システム。     A liquid temperature acquisition unit that acquires the temperature of the liquid;
    The temperature control system according to claim 5, further comprising: a determination unit that determines at least one of necessity of suction and discharge and condition change using the temperature acquired by the liquid temperature acquisition unit.
  8. 　前記液体温度取得部は、前記測定段階における前記吸排の際に前記液体の温度を取得する、請求項７記載の温調システム。 The temperature control system according to claim 7, wherein the liquid temperature acquisition unit acquires the temperature of the liquid during the suction and discharge in the measurement step.
  9. 　前記ピペットチップは、５０μｌ以上２００μｌ以下の前記液体を吸排する、請求項１～８の何れか一項に記載の温調システム。 The temperature control system according to any one of claims 1 to 8, wherein the pipette tip sucks and discharges the liquid of 50 μl to 200 μl.
  10. 　前記温調部は、３０℃以上４０℃以下の温風を３０秒以上３００秒以下前記ピペットチップに送風する、請求項１～９の何れか一項に記載の温調システム。 The temperature control system according to any one of claims 1 to 9, wherein the temperature control unit blows hot air of 30 ° C to 40 ° C to the pipette tip for 30 seconds to 300 seconds.
  11. 　前記温調部は、４０℃以上６０℃以下の温風を１０秒以上１２０秒以下前記ピペットチップに送風する、請求項１～９の何れか一項に記載の温調システム。 The temperature control system according to any one of claims 1 to 9, wherein the temperature control unit blows hot air of 40 属 C to 60 属 C to the pipette tip for 10 seconds to 120 seconds.
  12. 　前記液体は、測定液、検体、洗浄液、希釈液、標識抗体の中の少なくとも一つである、請求項１～１１の何れか一項に記載の温調システム。 The temperature control system according to any one of claims 1 to 11, wherein the liquid is at least one of a measurement liquid, a sample, a washing solution, a dilution liquid, and a labeled antibody.
PCT/JP2018/034785 2017-12-21 2018-09-20 Temperature regulating system WO2019123746A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2019560802A JP7212632B2 (en) 2017-12-21 2018-09-20 temperature control system

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2017-244991 2017-12-21
JP2017244991 2017-12-21

Publications (1)

Publication Number Publication Date
WO2019123746A1 true WO2019123746A1 (en) 2019-06-27

Family

ID=66994021

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2018/034785 WO2019123746A1 (en) 2017-12-21 2018-09-20 Temperature regulating system

Country Status (2)

Country Link
JP (1) JP7212632B2 (en)
WO (1) WO2019123746A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3779459A4 (en) * 2018-04-05 2021-05-05 Konica Minolta, Inc. Temperature adjustment system and temperature adjustment method

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5858471A (en) * 1981-10-02 1983-04-07 Toshiba Corp Stirrer device for automatic biochemical analysis
JPH06289032A (en) * 1993-04-01 1994-10-18 Toshiba Corp Dispensing method for automatic analyzer and dispensing system
JPH07209306A (en) * 1994-01-11 1995-08-11 Toshiba Corp Reagent dispensing device for automatic chemical analyser
JPH1094535A (en) * 1996-09-25 1998-04-14 Teruaki Ito Specimen splitting dispenser
JP2007175006A (en) * 2005-12-28 2007-07-12 Shimadzu Corp Genetic analyzer
JP2009058288A (en) * 2007-08-30 2009-03-19 Olympus Corp Liquid sample dispensation method, heating device, and automatic dispensation method and automatic dispensing device of liquid sample
WO2016132945A1 (en) * 2015-02-20 2016-08-25 コニカミノルタ株式会社 Reaction method and reaction device
WO2017082069A1 (en) * 2015-11-13 2017-05-18 コニカミノルタ株式会社 Reaction method
WO2017082142A1 (en) * 2015-11-13 2017-05-18 コニカミノルタ株式会社 Inspection system
WO2018163990A1 (en) * 2017-03-06 2018-09-13 コニカミノルタ株式会社 Temperature control system

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5858471A (en) * 1981-10-02 1983-04-07 Toshiba Corp Stirrer device for automatic biochemical analysis
JPH06289032A (en) * 1993-04-01 1994-10-18 Toshiba Corp Dispensing method for automatic analyzer and dispensing system
JPH07209306A (en) * 1994-01-11 1995-08-11 Toshiba Corp Reagent dispensing device for automatic chemical analyser
JPH1094535A (en) * 1996-09-25 1998-04-14 Teruaki Ito Specimen splitting dispenser
JP2007175006A (en) * 2005-12-28 2007-07-12 Shimadzu Corp Genetic analyzer
JP2009058288A (en) * 2007-08-30 2009-03-19 Olympus Corp Liquid sample dispensation method, heating device, and automatic dispensation method and automatic dispensing device of liquid sample
WO2016132945A1 (en) * 2015-02-20 2016-08-25 コニカミノルタ株式会社 Reaction method and reaction device
WO2017082069A1 (en) * 2015-11-13 2017-05-18 コニカミノルタ株式会社 Reaction method
WO2017082142A1 (en) * 2015-11-13 2017-05-18 コニカミノルタ株式会社 Inspection system
WO2018163990A1 (en) * 2017-03-06 2018-09-13 コニカミノルタ株式会社 Temperature control system

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3779459A4 (en) * 2018-04-05 2021-05-05 Konica Minolta, Inc. Temperature adjustment system and temperature adjustment method

Also Published As

Publication number Publication date
JP7212632B2 (en) 2023-01-25
JPWO2019123746A1 (en) 2020-12-24

Similar Documents

Publication Publication Date Title
US11703519B2 (en) Temperature control system
JP6581905B2 (en) Automatic analyzer
US8337754B2 (en) Automated developer for immuno-stained biological samples
KR101646549B1 (en) System for test device with integrated reaction and detection means
JP6549329B2 (en) Automatic analyzer
US11879904B2 (en) Method of washing an aspiration probe of an in-vitro diagnostic system, in-vitro diagnostic method, and in-vitro diagnostic system
JP6319937B2 (en) Method for heating a constant volume of liquid in a heated pipette needle
CN113711052B (en) Automatic analysis device
CN110582354A (en) Method and apparatus for rapid heating of biological samples
WO2019123746A1 (en) Temperature regulating system
JP2014092427A (en) Automatic analyzer
JP7278262B2 (en) Temperature control system and temperature control method
JP2023074493A (en) Automated analytical system for processing biological samples
JP6151096B2 (en) Automatic analyzer
JP3304936B2 (en) Dispensing device
JPWO2020090283A1 (en) Method and detection device for detecting abnormal detection
JP2009265057A (en) Inspection apparatus
JP2023122764A (en) Liquid sample dispensing method and automatic analyzer
WO2017163567A1 (en) Solution discharge device and solution-discharge controlling method
WO2007105391A1 (en) Inspecting apparatus using microchip and inspecting system using microchip

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18892929

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2019560802

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18892929

Country of ref document: EP

Kind code of ref document: A1