WO2023021791A1 - 前処理装置及びその制御方法 - Google Patents

前処理装置及びその制御方法 Download PDF

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Publication number
WO2023021791A1
WO2023021791A1 PCT/JP2022/019282 JP2022019282W WO2023021791A1 WO 2023021791 A1 WO2023021791 A1 WO 2023021791A1 JP 2022019282 W JP2022019282 W JP 2022019282W WO 2023021791 A1 WO2023021791 A1 WO 2023021791A1
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WIPO (PCT)
Prior art keywords
tip
liquid
sample
detachment
attachment
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Application number
PCT/JP2022/019282
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English (en)
French (fr)
Japanese (ja)
Inventor
哲朗 古田
Original Assignee
株式会社島津製作所
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.)
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Publication date
Application filed by 株式会社島津製作所 filed Critical 株式会社島津製作所
Priority to JP2023542220A priority Critical patent/JP7632654B2/ja
Publication of WO2023021791A1 publication Critical patent/WO2023021791A1/ja

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    • 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
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations

Definitions

  • the present invention relates to a pretreatment device and its control method.
  • liquid is dispensed by moving a nozzle with a dispensing tip attached to its tip.
  • part of the liquid sucked into the tip may drop as droplets from the tip of the tip while the nozzle is moving and scatter inside the device.
  • droplets may drop from the tip of the tip during the movement and scatter inside the device.
  • the liquid sucked into the tip is a highly viscous liquid such as saliva
  • the nozzle when the nozzle is moved after the liquid is sucked or discharged, the liquid will flow from the tip of the tip to the thread. may pull.
  • the string of the liquid may break and the liquid may scatter.
  • the liquid may splash into the apparatus from the tip of the tip, which may cause contamination.
  • the present invention has been made in view of the above circumstances, and provides a pretreatment device and a method of controlling the same that can prevent liquid from scattering from the tip of the tip into the device after liquid is aspirated or discharged during dispensing. for the purpose.
  • a first aspect of the present invention is provided with a tip attachment/detachment unit capable of attaching and detaching a tip, and after a liquid used for pretreatment is sucked into the tip, the liquid is ejected to an ejection destination before performing a dispensing operation.
  • a processing device comprising a dispensing processing section and a tip insertion processing section.
  • the dispensing processing unit ejects the liquid sucked into the tip to the ejection destination.
  • the tip insertion processing unit inserts the tip of the tip into the liquid at the ejection destination by displacing the tip attaching/detaching unit downward after the liquid is ejected to the ejection destination by the dispensing processing unit.
  • a second aspect of the present invention is provided with a tip attachment/detachment unit capable of attaching and detaching a tip, and after a liquid used for pretreatment is sucked into the tip, the liquid is ejected to an ejection destination before performing a dispensing operation.
  • a control method for a processing device comprising a dispensing step and a tip inserting step. In the dispensing step, the liquid sucked into the chip is discharged to the discharge destination. In the tip inserting step, after the liquid is ejected to the ejection destination in the dispensing step, the tip attaching/detaching portion is displaced downward to insert the tip of the tip into the liquid of the ejection destination.
  • the present invention it is possible to prevent the liquid from scattering into the device from the tip end after the liquid is aspirated or discharged during dispensing.
  • FIG. 5 is a schematic plan view for explaining a displacement route of the chip attaching/detaching part;
  • FIG. 5 is a schematic plan view for explaining a displacement route of the chip attaching/detaching part;
  • FIG. 5 is a schematic plan view for explaining a displacement route of the chip attaching/detaching part;
  • FIG. 5 is a schematic plan view for explaining a displacement route of the chip attaching/detaching part;
  • FIG. 5 is a schematic plan view for explaining a displacement route of the chip attaching/detaching part;
  • FIG. 5 is a schematic plan view for explaining a displacement route of the chip attaching/detaching part;
  • FIG. 5 is a schematic plan view for explaining a displacement route of the chip attaching/detaching part;
  • FIG. 5 is a schematic plan view for explaining a displacement route of the chip attaching/detaching part;
  • FIG. 10 is a schematic diagram for explaining an example of standby processing during suction;
  • FIG. 5 is a schematic diagram for explaining an example of chip insertion processing during ejection.
  • FIG. 11 is a schematic diagram for explaining another example of tip insertion processing during ejection.
  • It is a block diagram showing an example of the electrical configuration of the pretreatment device of the present embodiment. It is a figure which shows an example of the memory map of RAM of this embodiment. 2 is a block diagram specifically showing the electrical configuration of the pretreatment device of the present embodiment;
  • FIG. It is a flow figure showing an example of the whole processing of CPU of this embodiment.
  • FIG. 1 is a block diagram showing an example of the configuration of a pretreatment system 10 of this embodiment. As shown in FIG. 1, pretreatment system 10 includes pretreatment device 12 and user terminal 14 .
  • the pretreatment device 12 is a device for previously treating the liquid by aspirating and discharging the liquid and performing a dispensing operation. In this embodiment, a series of dispensing processes is executed by performing the dispensing operation at least once. A liquid sample or a liquid reagent can be exemplified as the liquid used for the pretreatment.
  • the pretreatment device 12 in this embodiment is capable of sucking and discharging liquid via a chip 40 (see FIG. 3).
  • the user terminal 14 is a device including at least a CPU, a communication unit for communicating with the outside, a non-volatile memory, and the like, and is a desktop PC, notebook (laptop) PC, tablet PC, or the like.
  • the preprocessing device 12 and the user terminal 14 are connected via a network 16.
  • the network 16 here includes a LAN (Local Area Network), the Internet, and the like.
  • the preprocessing device 12 and the user terminal 14 may be directly connected.
  • FIG. 2 is an exploded perspective view showing a part of an example of the configuration of the pretreatment apparatus 12 of the present embodiment.
  • the pretreatment device 12 has a main body 20 and a table 21 .
  • the main body 20 is configured by a hollow housing.
  • the table 21 also includes a container holding portion 22 and a first chip holding portion 24 .
  • the table 21 is configured such that the container holding portion 22 and the first chip holding portion 24 are integrated.
  • the pretreatment device 12 includes a second chip holding section 26 .
  • the second chip holder 26 is shown separated from the table 21, but the second chip holder 26 is accommodated in the space 28 of the table 21 when used.
  • openings 32 are provided in the walls that partition the space 30 .
  • the second chip holding part 26 can be removed from and attached to the table 21 through the opening 32 . Further, as described above, since the table 21 is built in the main body 20 , it can be said that the second chip holding portion 26 can be removed from the main body 20 and attached to the main body 20 .
  • FIG. 3 is a schematic plan view showing an example of the configuration of the table 21 of this embodiment.
  • FIG. 4 is a schematic cross-sectional view showing the internal configuration of the pretreatment device 12 of this embodiment.
  • the container holder 22 holds a plurality of containers containing liquids used for pretreatment.
  • the container holding section 22 includes a sample container holding section 22a and a mixing container holding section 22b.
  • the sample container holding part 22a holds a plurality of sample containers 34 that contain liquid samples.
  • a liquid sample is, for example, a specimen sample collected from a living body, and can be exemplified by saliva, blood, or the like.
  • the mixing container holding section 22b holds a plurality of mixing containers 36 for mixing the liquid samples dispensed from the plurality of sample containers 34 .
  • the first chip holder 24 holds a plurality of chips 40 . During the dispensing operation, the tip 40 held by the first tip holding portion 24 is attached to the tip attaching/detaching portion 48b.
  • the mixing container 36 is an example of a discharge destination of liquid sucked into the chip 40 .
  • the table 21 is provided with a cover member 42 .
  • the cover member 42 is a thin plate-like member that covers the space 28 inside the table 21 . That is, when the second chip holding portion 26 is attached to the table 21 , the cover member 42 covers the second chip holding portion 26 .
  • the cover member 42 has a through hole 42a. Further, the cover member 42 is formed with a plurality of hooking portions 42b for hooking the chip 40 about to pass through the through hole 42a.
  • the width of the hook portion 42b in the Y direction is larger than the outer diameter of the lower end portion of the tip attachment/detachment portion 48b and smaller than the outer diameter of the upper end portion of the tip 40. As shown in FIG.
  • the tip (used tip) 40 after being used for the dispensing operation is removed from the tip attachment/detachment portion 48b by displacing the tip attachment/detachment portion 48b so that the upper end surface thereof is hooked on the hook portion 42b, thereby holding the second tip. It can be held in the portion 26 (chip accommodation processing).
  • the tip 40 is newly attached from the first tip holding portion 24 to the tip attachment/detachment portion 48b each time a dispensing operation is performed, and is held by the second tip holding portion 26 after use. A plurality of used chips 40 can be held in the second chip holding portion 26 .
  • the sample container holding section 22a can hold a total of 20 sample containers 34, 4 columns in the X direction and 5 rows in the Y direction.
  • Each sample container 34 contains a sample collected from a different living body.
  • the first chip holder 24 can hold the same number of chips 40 as the sample containers 34 (four columns in the X direction and five rows in the Y direction, totaling 20).
  • the mixing container holding portion 22b can hold four mixing containers 36 arranged in the X direction.
  • the number of sample containers 34, the number of mixing containers 36, and the number of chips 40 are not limited to the above numbers.
  • Each mixing container 36 is associated with five sample containers 34 and five chips 40 arranged in the same row in the X direction. Each mixing container 36 is dispensed with the liquid sample in each sample container 34 lined up in the same row using each chip 40 lined up in the same row. Thereby, the liquid samples in the plurality of sample containers 34 lined up in the same row can be mixed in each mixing container 36 .
  • the liquid sample in each sample container 34 in the mixing container 36 on the first column in the X direction is held in the first row of the first column in the first chip holding unit 24 .
  • the tip 40 that is attached is attached to the tip attachment/detachment portion 48b.
  • the liquid sample in the sample container 34 held in the first row of the first column in the sample container holding portion 22a is sucked into the chip 40, it is held in the first row in the mixing container holding portion 22b.
  • the liquid sample in the chip 40 is discharged into the mixing container 36 which is in the state. After ejection of the liquid sample, the used tip 40 is removed and held in the second tip holder 26 .
  • the chip 40 held in the first column and the second row in the first chip holding portion 24 is attached to the chip attaching/detaching portion 48b.
  • the liquid sample in the sample container 34 held in the first row and second row of the sample container holding portion 22a is sucked into the chip 40, it is held in the first row of the mixing container holding portion 22b.
  • the liquid sample in the chip 40 is discharged into the mixing container 36 which is in the state.
  • the liquid sample discharged from inside the chip 40 can be mixed with the liquid sample already stored in the mixing container 36 .
  • the used tip 40 is removed and held in the second tip holder 26 .
  • the chips 40 held in the first column and each row of the first chip holding portion 24 are attached to the chip attachment/detachment portion 48b and are held in the first column and each row of the sample container holding portion 22a.
  • the liquid sample in the sample container 34 is sequentially sucked into the chip 40, it is discharged into the mixing container 36 held in the first row in the mixing container holding part 22b.
  • the liquid sample in the sample container 34 held in each row of the first column of the sample container holding part 22a is mixed into the mixing container 36 of the first row of the mixing container holding part 22b. Aggregated and mixed.
  • the liquid samples dispensed from the plurality of sample containers 34 are mixed in the mixing container 36 in each row. be able to.
  • This kind of dispensing method is used in an inspection called the pool inspection method.
  • the liquid sample mixed in the mixing container 36 is subjected to the PCR test, and if the result is negative, all the liquid samples in the mixed sample containers 34 are negative. You can check one thing at a time. Therefore, the efficiency of inspection can be improved, and the cost of inspection can be reduced.
  • the plurality of mixing containers 36 held by the mixing container holding portion 22b are integrally held using a mixing container rack (not shown).
  • a plurality of mixing containers 36 can be brought into the PCR inspection apparatus at once.
  • the plurality of sample containers 34 held by the sample container holding section 22a the plurality of sample containers 34 can be taken in and out integrally for each row using a sample container rack (not shown). All the sample containers 34 can also be put in and taken out at once.
  • the pretreatment device 12 has an electrically controllable dispensing mechanism 48 .
  • the dispensing mechanism 48 is a mechanism for aspirating and discharging liquid, and includes a syringe 48a, a tip attaching/detaching part 48b, and a plunger 48c.
  • the syringe 48a is a cylindrical member into which a plunger 48c is slidably inserted.
  • the tip attachment/detachment part 48b is a cylindrical member with a diameter smaller than that of the syringe 48a, and the tip 40 can be attached and detached.
  • As the tip attaching/detaching part 48b for example, an elongated cylindrical nozzle communicating with the inside of the syringe 48a is used.
  • the tip 40 is formed in an elongated cylindrical shape that gradually tapers toward the lower end, and the tip 40 is attached to the tip attachment/detachment portion 48b by press-fitting the lower end of the tip attachment/detachment portion 48b into the upper end thereof.
  • the dispensing mechanism 48 includes an actuator such as a motor, a connecting member connected to the plunger 48c, and a transmission mechanism for transmitting the driving force of the actuator to the connecting member as Z-direction movement.
  • an actuator such as a motor
  • a connecting member connected to the plunger 48c
  • a transmission mechanism for transmitting the driving force of the actuator to the connecting member as Z-direction movement.
  • the dispensing mechanism 48 an amount of liquid corresponding to the stroke amount of the plunger 48c can be sucked and discharged.
  • a dispensing operation can be performed by using the dispensing mechanism 48 to suck and discharge the liquid in the container (sample container 34 ) held by the container holding section 22 .
  • the dispensing mechanism 48 described above is merely an example, and the configuration of the dispensing mechanism 48 is not particularly limited as long as it has the tip attachment/detachment portion 48b and is capable of sucking and discharging liquid.
  • the pretreatment device 12 includes an electrically controllable support mechanism 50 .
  • the support mechanism 50 is a mechanism that supports the dispensing mechanism 48 so as to be displaceable.
  • a transmission mechanism or the like for transmitting to the support member 50a is provided.
  • the dispensing mechanism 48 can be displaced in the Z direction while being supported.
  • the support mechanism 50 can displace the tip attachment/detachment portion 48b in the Z direction while supporting it.
  • the support mechanism 50 described above is merely an example, and the configuration of the support mechanism 50 is not particularly limited as long as it can displace in the Z direction while supporting the chip attachment/detachment portion 48b and the like.
  • the support mechanism 50 may be configured so that the dispensing mechanism 48 can also be displaced in the horizontal direction (XY directions).
  • the pretreatment device 12 includes an electrically controllable holding mechanism 52 .
  • the holding mechanism 52 is a mechanism that holds the table 21 in a displaceable manner, and includes an actuator such as a motor, a holding member that holds the table 21, and the like.
  • the holding mechanism 52 also includes a transmission mechanism that transmits the driving force of the actuator to the holding member as movement in the X and Y directions.
  • the table 21 can be horizontally displaced while being held. That is, the holding mechanism 52 can hold the container holding portion 22 and displace the container holding portion 22 in the horizontal direction to perform positioning with respect to the dispensing mechanism 48 .
  • the tip 40 held by the first tip holder 24 can be positioned below the tip attachment/detachment portion 48b, or the sample container 34 held by the sample container holder 22a or the mixing container holder 22b can be held. It is possible to align the mixing container 36 attached to the bottom of the tip 40 attached to the tip attaching/detaching portion 48b.
  • the holding mechanism 52 described above is merely an example, and the configuration of the table 21 is not particularly limited as long as it can be horizontally displaced while holding the table 21 . Moreover, the holding mechanism 52 may be configured to allow the table 21 to be displaced in the Z direction as well.
  • FIGS. 5A to 5D are schematic plan views for explaining displacement routes of the tip attachment/detachment portion 48b.
  • 5A and 5C show an example of the displacement route of the tip attachment/detachment portion 48b during the dispensing operation
  • FIGS. 5B and 5D show an example of the displacement route of the tip attachment/detachment portion 48b during the tip accommodating process.
  • the tip 40, the sample container 34, and the mixing container 36 held on the table 21 are displaced relative to the tip attaching/detaching portion 48b by displacing the holding mechanism 52, the shortest processing time can be achieved. Displacement at the root is preferred. However, after the liquid sample is sucked into the tip 40 or after the liquid sample in the tip 40 is discharged into the mixing container 36, when the tip attachment/detachment part 48b is relatively displaced by the shortest route, that During the displacement, the liquid sample may drop as droplets from the tip of the tip 40 and mix into the sample container 34 or the mixing container 36 .
  • control is performed so that the relative displacement route of the tip attachment/detachment portion 48b with respect to the table 21 includes both the shortest route and the detour route. That is, for an operation in which the possibility of the liquid sample entering the sample container 34 or the mixing container 36 is low, the chip attachment/detachment part 48b is moved relative to the sample container 34 or the mixing container 36 by the shortest route. For operations in which there is a high possibility of sample contamination, the tip attachment/detachment part 48b is relatively moved by a detour route.
  • the table 21 is displaced in the XY directions with respect to the tip attachment/detachment portion 48b. However, for the sake of simplification of explanation, it is assumed that the tip attachment/detachment portion 48b is displaced with respect to the table 21 below.
  • the shortest route is indicated by a solid line arrow
  • the detour route is indicated by a broken line arrow.
  • the containers 34 and 36 pass below the tip detaching portion 48b, whereas in the detour route the containers 34 and 36 do not pass below the tip detaching portion 48b.
  • the tip attachment/detachment part 48b may pass above the containers 34 and 36 to which the liquid sample is to be aspirated or discharged, and the tip attachment/detachment part 48b may pass above the other containers 34 and 36. 48b does not pass.
  • the containers 34 and 36 may not pass below the tip attachment/detachment portion 48b at least part of the route depending on the arrangement of the containers 34 and 36 .
  • the tip attaching/detaching part 48b is mounted.
  • the tip attachment/detachment part 48b is displaced by the shortest route to the sample container 34 held in the first row of .
  • the tip attaching/detaching portion 48b is displaced along a bypass route to the mixing container 36 held in the first row in the mixing container holding portion 22b.
  • the area A1 between the rows holding the containers 34, 36 and the chips 40 is set as a detour route. That is, in the detour route when the tip detachable part 48b is displaced from the sample container holding part 22a to the mixing vessel holding part 22b, the tip 40 attached to the tip detachable part 48b is displaced above the adjacent region A1.
  • the detour route when the tip detachable portion 48b is displaced from the sample container holding portion 22a to the mixing container holding portion 22b is not limited to the area A1 as described above, and may be set to another area.
  • the tip detachable part 48b may be displaced by the shortest route instead of the detour route as shown in FIG. 5A.
  • the liquid sample in the tip 40 is discharged into the mixing container 36 held in the first row in the mixing container holding part 22b, the liquid sample is sent to the second tip holding part 26 by a detour route as shown in FIG. 5B.
  • the chip attaching/detaching portion 48b is displaced. After the chip 40 is removed from the chip attaching/detaching portion 48b and held by the second chip holding portion 26, the chip 40 held in the first column and second row of the first chip holding portion 24 is reached by the shortest route. , the chip attaching/detaching portion 48b is displaced.
  • an area A2 on the side opposite to the sample container holding portion 22a is set as a detour route with respect to the mixing container 36 held by the mixing container holding portion 22b. That is, in the detour route when the tip detachable part 48b is displaced from the mixing container holding part 22b to the second tip holding part 26, the tip 40 attached to the tip detachable part 48b is displaced above the area A2.
  • the detour route for displacing the tip attaching/detaching portion 48b from the mixing container holding portion 22b to the second tip holding portion 26 is not limited to the area A2 as described above, and may be set to another area.
  • a region between the sample container holding portion 22a and the mixing container holding portion 22b may be set as a detour route.
  • the tip attaching/detaching part 48b is displaced by the shortest route to the sample container 34 held in the second row. After the liquid sample in the sample container 34 is sucked into the tip 40, the tip attaching/detaching portion 48b is displaced along a bypass route to the mixing container 36 held in the first row in the mixing container holding portion 22b.
  • the liquid sample in the tip 40 is discharged into the mixing container 36 held in the first row in the mixing container holding part 22b, the liquid sample is sent to the second tip holding part 26 by a detour route as shown in FIG. 5D.
  • the chip attaching/detaching portion 48b is displaced.
  • the chip 40 is removed from the chip attaching/detaching portion 48b and held by the second chip holding portion 26, the shortest route to the chip 40 held in the first column and third row of the first chip holding portion 24 is reached. , the chip attaching/detaching portion 48b is displaced.
  • control is performed so that the tip detachable part 48b is displaced on the displacement route including the shortest route and the detour route, so that the sample container is placed in the mixing container 36 on the first row in the mixing container holding part 22b.
  • the liquid samples in the sample containers 34 held in each row of the first column in the holding portion 22a are aggregated and mixed.
  • the other columns are similarly controlled such that the tip attachment/detachment portion 48b is displaced on displacement routes including the shortest route and the detour route.
  • the tip attachment/detachment part 48b is displaced so that at least one of the sample container 34 and the mixing vessel 36 does not pass under the tip 40 attached to the tip attachment/detachment part 48b.
  • the tip attaching/detaching portion 48b is displaced so that at least one of the sample container 34 and the mixing container 36 does not pass under the tip 40 attached to the tip attaching/detaching portion 48b.
  • FIG. 6 is a schematic diagram for explaining an example of standby processing during suction.
  • the tip attaching/detaching portion 48b is displaced upward after the suction to separate the tip of the tip 40 from the liquid surface.
  • the liquid sample may string between the tip of the tip 40 and the liquid surface in the sample container 34 .
  • standby processing during suction as illustrated in FIG. 6 is executed.
  • the tip of the tip 40 is inserted into the liquid sample 1 in the sample container 34, as shown in FIG. 6(a).
  • part of the liquid sample 1 in the sample container 34 is sucked into the chip 40 as shown in FIG. 6(b).
  • the tip detachable portion 48b is displaced upward, so that the tip of the tip 40 is separated from the liquid surface of the liquid sample 1 as shown in FIG. 6(c).
  • the liquid sample 1 may pull a string 3 between the tip of the tip 40 and the liquid surface in the sample container 34, as shown in FIG. 6(c).
  • the state shown in FIG. 6(c) is maintained until a predetermined period of time elapses.
  • the predetermined time is a time sufficient for the thread 3 to break when the liquid sample 1 pulls the thread 3, for example, 3 seconds or more, 5 seconds or more, or 7 seconds or more.
  • the predetermined time may be a constant time, or may be arbitrarily set by the user.
  • the distance between the tip of the tip 40 and the liquid surface of the liquid sample 1 in the state of FIG. 6(c) is a sufficient distance for the thread 3 to break when the liquid sample 1 pulls the thread 3. , for example 1 cm or more, or 3 cm or more, or 5 cm or more.
  • the above distance is such that the tip of the tip 40 is not exposed to the outside of the sample container 34 .
  • the thread 3 between the tip of the tip 40 and the liquid surface in the sample container 34 will be removed after the predetermined time has passed, as shown in FIG. 6(d). is cut.
  • the tip attachment/detachment part 48b toward the mixing container 36 after waiting until a predetermined time has passed, it is possible to prevent the tip 40 from leaving the sample container 34 while the string 3 is being pulled.
  • FIG. 7A is a schematic diagram for explaining an example of chip insertion processing during ejection.
  • the liquid sample sucked into the chip 40 from the sample container 34 is discharged into the mixing container 36 , part of the discharged liquid sample may remain as droplets at the tip of the chip 40 .
  • a tip insertion process during ejection is performed as illustrated in FIG. 7A.
  • FIG. 7A(a) the case where the liquid sample 1 has already been discharged into the mixing container 36 from another sample container 34 will be described.
  • the tip of the tip 40 is inserted into the liquid sample 1 in the mixing container 36 as shown in FIG. 7A(b).
  • the liquid sample 1 in the chip 40 is discharged into the mixing container 36 as shown in FIG. 7A(c).
  • the tip of the tip 40 is separated from the liquid surface of the liquid sample 1 by displacing the tip attachment/detachment part 48b upward.
  • part of the ejected liquid sample may remain as droplets 5 at the tip of the tip 40 .
  • the tip attachment/detachment part 48b which has been displaced upward after the liquid sample 1 is discharged, is again displaced downward as shown in FIG.
  • the tip of the tip 40 is inserted into the . After that, when the tip of the tip 40 is separated from the liquid surface of the liquid sample 1 as shown in FIG. be.
  • FIG. 7B is a schematic diagram for explaining another example of tip insertion processing during ejection.
  • FIG. 7A a case has been described in which the discharge operation is performed with the tip of the tip 40 inserted into the liquid sample 1 in the mixing container 36 (see FIGS. 7A(b) and (c)).
  • the ejection operation is performed in a state where the tip of the tip 40 is not inserted into the liquid sample 1 in the mixing container 36 .
  • part of the ejected liquid sample may remain as droplets 5 at the tip of the tip 40, as shown in FIG. 7B(c). Therefore, in this example, after the liquid sample 1 is discharged into the mixing container 36, the tip detachable portion 48b is displaced downward so that the liquid sample 1 in the mixing container 36 is displaced as shown in FIG. 7B(d). to insert the tip of the tip 40 into. Thereafter, when the tip detachable portion 48b is displaced upward, the tip of the tip 40 is separated from the liquid surface of the liquid sample 1 as shown in FIG. be.
  • the distance between the tip of the tip 40 and the liquid surface of the liquid sample 1 in the states of FIGS. 7A(d) and 7B(c) is not particularly limited. It is preferable that the distance is such that the droplet 5 is separated from the liquid surface in the mixing container 36 when the liquid droplet 5 is present.
  • the insertion amount of the tip of the tip 40 inserted into the liquid sample in the mixing vessel 36 is not particularly limited, but the insertion amount is If it is too large, the liquid sample 1 tends to remain on the outer surface of the tip 40, so the minimum insertion amount is preferable, for example, 10 mm or less, 7 mm or less, or 5 mm or less.
  • an operation of ejecting air from the tip 40 may be performed in order to completely eject the liquid sample in the tip 40 .
  • the droplets 5 tend to remain at the tip of the tip 40, the droplets 5 can be reliably removed by performing the tip inserting process at the time of ejection as described above.
  • FIG. 8 is a block diagram showing an example of the electrical configuration of the pretreatment apparatus 12 of the present embodiment.
  • the pretreatment device 12 includes a control section 100, an operation control circuit 110, and a communication section 112 in addition to the dispensing mechanism 48, the support mechanism 50, the holding mechanism 52, and the like.
  • control unit 100 the operation control circuit 110, and the communication unit 112 are electrically connected to each other via wiring 108 such as a bus.
  • dispensing mechanism 48 the support mechanism 50 and the holding mechanism 52 are electrically connected to the operation control circuit 110 .
  • the control unit 100 is responsible for overall control of the pretreatment device 12 .
  • the control unit 100 includes a CPU (Central Processing Unit) 102 .
  • the control unit 100 also includes a RAM (Random Access Memory) 104 and a storage unit 106 that can be directly accessed by the CPU 102 .
  • CPU Central Processing Unit
  • RAM Random Access Memory
  • the CPU 102 controls each component of the pretreatment device 12 .
  • a RAM 104 is used as a work area and a buffer area for the CPU 102 .
  • Storage unit 106 is a non-volatile memory, and for example, HDD (Hard Disc Drive) or SSD (Solid State Drive) is used as storage unit 106 .
  • the storage unit 106 stores a control program for controlling each component of the preprocessing device 12 and data required for executing the control program (execution data). Note that the storage unit 106 may be configured to include the RAM 104 .
  • the operation control circuit 110 generates voltages for driving the dispensing mechanism 48, the support mechanism 50, the holding mechanism 52, etc., and appropriately applies the voltages to them.
  • the communication unit 112 is means for communicating with the outside.
  • the communication unit 112 is communicably connected to the user terminal 14 via the network 16 .
  • FIG. 9 is a diagram showing an example of a memory map 200 of the RAM 104 of this embodiment. As shown in FIG. 9, RAM 104 includes program area 201 and data area 202 .
  • the program area 201 stores a control program read in advance from the storage unit 106 .
  • the control program includes an operating program 201a, a communication program 201e, and the like.
  • the operation program 201a also includes a dispensing program 201b, a tip insertion program 201c, a tip accommodation program 201d, and the like.
  • the operation program 201 a is a program that controls the operation of the pretreatment device 12 .
  • the dispensing program 201b is a program corresponding to dispensing operations as illustrated in FIGS. 5A and 5C.
  • the dispensing program 201b is a program that performs a dispensing operation of aspirating and discharging the liquid sample in the sample container 34 .
  • One or more dispensing operations are performed in a series of dispensing processes.
  • the chip insertion program 201c is a program corresponding to chip insertion processing. That is, the tip insertion program 201c is a program for inserting the tip of the tip 40 into the liquid sample 1 in the mixing container 36 by displacing the tip attachment/detachment part 48b downward during the dispensing operation.
  • the chip accommodation program 201d is a program corresponding to the chip accommodation process illustrated in FIGS. 5B and 5D. That is, the chip accommodation program 201d is a program for removing the chip 40 attached to the chip attachment/detachment portion 48b and accommodating it in the second chip holding portion 26.
  • FIG. 5B and 5D The chip accommodation program 201d is a program for removing the chip 40 attached to the chip attachment/detachment portion 48b and accommodating it in the second chip holding portion 26.
  • the communication program 201e is a program for controlling the communication unit 112 and communicating with the user terminal 14.
  • the program area 201 also stores control programs other than the operation program 201a and the like.
  • the data area 202 stores execution data read from the storage unit 106 in advance.
  • the data area 202 stores control data 202a, displacement route data 202b, standby time data 202c, and the like.
  • the control data 202a is various data necessary to control the operation of the preprocessing device 12.
  • the displacement route data 202b is data of the displacement route of the tip attachment/detachment part 48b as illustrated in FIGS. 5A to 5D.
  • the displacement route data 202b includes shortest route data indicated by solid line arrows in FIGS. 5A to 5D and detour route data indicated by broken line arrows.
  • the displaced route data 202b is not limited to data on the shortest route and detour route, and may include data on other routes.
  • the standby time data 202c is obtained when the liquid sample in the sample container 34 is aspirated into the tip 40 and the tip attachment/detachment portion 48b is displaced upward in the aspiration standby process performed during the dispensing operation. It is the data of the waiting time (predetermined time) until the part 48b is directed to the mixing container 36.
  • the data area 202 may store other execution data. Further, the data area 202 may be provided with timers (counters) and registers necessary for executing the control program.
  • FIG. 10 is a block diagram specifically showing the electrical configuration of the pretreatment apparatus 12 of the present embodiment.
  • the CPU 102 executes the operation program 201 a so that the control unit 100 functions as an operation processing unit 300 that controls the operation of the preprocessing device 12 .
  • the operation processing unit 300 performs processing using control data 202a stored in the RAM 104 .
  • the CPU 102 executes the dispensing program 201b, so that the control unit 100 functions as the dispensing processing unit 302.
  • the dispensing processing unit 302 performs a dispensing operation of sucking and discharging liquid through the tip 40, as shown in FIGS. 5A and 5C.
  • This dispensing operation includes an operation of displacing the table 21 in the XY directions and an operation of displacing the tip attaching/detaching part 48b in the Z direction.
  • the dispensing processing unit 302 displaces the table 21 in the XY directions based on the displacement route data 202b. Further, in the standby process during aspiration performed during the dispensing operation, the dispensing processing unit 302 displaces the tip attachment/detachment part 48b upward after aspiration, and waits until a predetermined time has elapsed based on the standby time data 202c. After that, the tip attaching/detaching part 48b is directed to the mixing container 36. As shown in FIG.
  • the CPU 102 executes the chip insertion program 201c, so that the control section 100 functions as a chip insertion processing section 304.
  • the tip insertion processing unit 304 displaces the tip attachment/detachment part 48b downward, thereby inserting the tip of the tip 40 into the liquid sample 1 in the mixing container 36 as shown in FIG. 7A or 7B. insert the part.
  • the CPU 102 executes the chip accommodation program 201d, so that the control unit 100 functions as the chip accommodation processing unit 306.
  • the chip accommodation processing section 306 removes the chip 40 attached to the chip attaching/detaching section 48b and accommodates it in the second chip holding section 26 to carry out the chip accommodation process.
  • This chip accommodation processing includes an operation of displacing the table 21 in the XY directions and an operation of displacing the chip attaching/detaching portion 48b in the Z direction.
  • the chip accommodation processing unit 306 displaces the table 21 in the XY directions based on the displacement route data 202b.
  • control unit 100 functions as the communication processing unit 308 by the CPU 102 executing the communication program 201e.
  • the communication processing unit 308 communicates with the user terminal 14 using the communication unit 112 .
  • FIG. 11 is a flow diagram showing an example of the overall processing of the CPU 102 of this embodiment.
  • the overall process is started, for example, when the pretreatment device 12 receives a command from the user terminal 14 instructing execution of the dispensing process.
  • the tip 40 held by the first tip holding portion 24 is attached to the tip attaching/detaching portion 48b (step S1). Then, as indicated by the solid arrow in FIG. 5A, the tip attachment/detachment portion 48b is displaced to the sample container 34 by the shortest route (step S2).
  • step S3 the liquid sample in the sample container 34 is sucked into the tip 40 (step S3), and the tip attachment/detachment portion 48b is displaced upward, so that the tip of the tip 40 is exposed to the liquid as shown in FIG. 6(c). It is separated from the liquid surface of the sample 1 (step S4).
  • step S5 after waiting until a predetermined time elapses (YES in step S5), the tip attachment/detachment part 48b is displaced to the mixing container 36 by a detour route as indicated by the dashed arrow in FIG. 5A (step S6). .
  • the liquid sample sucked into the chip 40 is discharged into the mixing container 36 (step S7).
  • the tip detachable portion 48b is displaced upward so that the tip of the tip 40 is separated from the liquid surface of the liquid sample 1.
  • the tip inserting process is performed so that the tip inserting process is performed.
  • FIG. 7B(d) the tip attaching/detaching portion 48b is displaced downward again, and the tip of the tip 40 is inserted into the liquid sample in the mixing vessel 36 (step S8).
  • the tip attachment/detachment part 48b is displaced to the second tip holding part 26 along a detour route, thereby carrying out the tip accommodation process (step S9).
  • the dispensing process for all the liquid samples has not been completed (NO in step S10), so the tip attaching/detaching part 48b is the shortest route to the first tip holding part 24 as indicated by the solid arrow in FIG. 5B. , and the next tip 40 is attached to the tip attachment/detachment portion 48b (step S1).
  • step S10 the processes of steps S1 to S10 are repeated. Then, when the dispensing process for all liquid samples is completed (YES in step S10), the process by the control unit 100 ends.
  • the liquid sample sucked from the sample container 34 is discharged into the mixing container 36, but the configuration is not limited to this. That is, the liquid to be sucked into the chip 40 is not limited to liquid samples, and may be other liquids such as reagents. Further, the discharge destination of the liquid sucked into the chip 40 is not limited to the mixing container 36, but may be another container such as a reagent container containing a reagent or a reaction container for reacting a reagent with a liquid sample. There may be.
  • Relative displacement of the tip attachment/detachment portion 48b with respect to the containers 34 and 36 is not limited to the configuration in which the container holding portion 22 is displaced in the XY directions. It may be configured such that it is also displaced.
  • the tip attachment/detachment part 48b is reciprocated in the Z direction to apply vibration. Processing can also be performed.
  • a pretreatment device includes: A pretreatment device comprising a tip attachment/detachment unit capable of attaching and detaching a tip, and performing a dispensing operation by aspirating a liquid used for pretreatment into the tip and then ejecting the liquid to an ejection destination, a dispensing processing unit that discharges the liquid sucked into the tip to the discharge destination; a tip inserting processor for inserting the tip of the tip into the liquid at the ejection destination by displacing the tip attachment/detachment unit downward after the liquid is ejected to the ejection destination by the dispensing processor; may be provided.
  • the tip attachment/detachment portion is displaced downward. Droplets can be removed from the tip of the tip by inserting the tip of the tip into the liquid to be discharged. Therefore, it is possible to prevent the liquid from scattering into the apparatus from the tip end after the liquid is discharged during dispensing.
  • the dispensing processing unit displaces the chip attaching/detaching unit upward after ejecting the liquid to the ejection destination,
  • the tip insertion processing unit may insert the tip end of the tip into the liquid to be discharged by downwardly displacing the tip attachment/detachment unit that has been displaced upward by the dispensing processing unit.
  • the tip attachment/detachment part is displaced downward again to insert the tip of the tip into the liquid to be discharged, whereby the droplet can be removed from the tip of the tip.
  • a sample container holder that holds a plurality of sample containers each containing a liquid sample
  • a mixing container holding unit that holds a plurality of mixing containers for mixing the liquid samples dispensed by the dispensing processing unit from within the plurality of sample containers
  • the tip insertion processing section displaces the tip attachment/detachment section downward to insert the tip into the liquid sample in the mixing vessel. The tip may be inserted.
  • the tip attachment/detachment part is positioned downward. Droplets can be removed from the tip tip by displacement to insert the tip tip into the liquid sample in the mixing vessel.
  • the dispensing processing unit is configured to move the tip attached to the tip attachment/detachment part to the mixing container before the tip attachment/detachment part moves toward the mixing container.
  • the tip attachment/detachment part may be relatively displaced so that at least one of the sample container and the mixing container does not pass under the .
  • the sample container and the mixing container are positioned below the tip. does not pass through, even if the liquid sample drops from the tip of the tip as droplets, the droplets do not enter the sample container or the mixing container. Therefore, it is possible to prevent the liquid from splashing into the apparatus from the tip end after the liquid is aspirated during dispensing.
  • a first chip holder that holds a plurality of chips
  • a second tip holding part that holds a plurality of used tips that are the tips after being attached to the tip attachment/detachment part and used for a dispensing operation
  • a chip accommodation processing unit that removes the chip attached to the chip attachment/detachment unit and stores the chip in the second chip holding unit
  • the tip accommodation processing section is configured to hold the tip attached to the tip attachment/detachment section until the tip attachment/detachment section moves toward the second tip holding section.
  • the tip attachment/detachment part may be relatively displaced so that at least one of the sample container and the mixing container does not pass below.
  • the sample container is moved below the tip until the tip attaching/detaching portion moves toward the second tip holding portion. Since at least one of the tip and the mixing container does not pass through, even if the liquid sample drops as droplets from the tip of the tip, the droplets do not enter the sample container or the mixing container. Therefore, it is possible to prevent the liquid from scattering into the apparatus from the tip end after the liquid is discharged during dispensing.
  • the pretreatment device of item 6 when the liquid sample in the sample container is sucked into the tip and the tip attachment/detachment part is displaced upward, there is a gap between the tip of the tip and the liquid surface in the sample container. Even when the liquid sample is stringy, the chip can be prevented from leaving the sample container while the string is being pulled by moving the tip attachment/detachment part toward the mixing container after waiting until a predetermined time has passed. Therefore, it is possible to prevent the liquid from scattering into the apparatus from the tip end after the liquid is discharged during dispensing.
  • a method for controlling a pretreatment device includes: A control method for a pretreatment device comprising a tip attachment/detachment unit capable of attaching and detaching a tip, and performing a dispensing operation by aspirating a liquid used for pretreatment into the tip and then ejecting the liquid to an ejection destination, the method comprising the steps of: a dispensing step of discharging the liquid sucked into the tip to the discharge destination; a tip inserting step of displacing the tip attachment/detachment part downward to insert the tip of the tip into the liquid at the ejection destination after the liquid is ejected to the ejection destination in the dispensing step; You can
  • the tip attachment/detachment part can be moved downward. Droplets can be removed from the tip of the tip by displacing and inserting the tip of the tip into the liquid to be discharged. Therefore, it is possible to prevent the liquid from scattering into the apparatus from the tip end after the liquid is discharged during dispensing.

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PCT/JP2022/019282 2021-08-18 2022-04-28 前処理装置及びその制御方法 WO2023021791A1 (ja)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993007494A1 (en) * 1991-10-04 1993-04-15 Aloka Kabushiki Kaisha Method of pipetting of blood sample
JPH09184846A (ja) * 1995-12-28 1997-07-15 Shimadzu Corp 液体試料分注装置
JP2008241508A (ja) * 2007-03-28 2008-10-09 Fujifilm Corp 液体攪拌方法
JP2013134069A (ja) * 2011-12-26 2013-07-08 Hitachi High-Technologies Corp 自動分析装置
JP2014224749A (ja) * 2013-05-16 2014-12-04 バイオテック株式会社 自動検体処理装置
JP2016015922A (ja) * 2014-07-09 2016-02-01 株式会社日立ハイテクノロジーズ 核酸分析装置
WO2021246325A1 (ja) * 2020-06-02 2021-12-09 東洋紡株式会社 遺伝子解析装置

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993007494A1 (en) * 1991-10-04 1993-04-15 Aloka Kabushiki Kaisha Method of pipetting of blood sample
JPH09184846A (ja) * 1995-12-28 1997-07-15 Shimadzu Corp 液体試料分注装置
JP2008241508A (ja) * 2007-03-28 2008-10-09 Fujifilm Corp 液体攪拌方法
JP2013134069A (ja) * 2011-12-26 2013-07-08 Hitachi High-Technologies Corp 自動分析装置
JP2014224749A (ja) * 2013-05-16 2014-12-04 バイオテック株式会社 自動検体処理装置
JP2016015922A (ja) * 2014-07-09 2016-02-01 株式会社日立ハイテクノロジーズ 核酸分析装置
WO2021246325A1 (ja) * 2020-06-02 2021-12-09 東洋紡株式会社 遺伝子解析装置

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