WO2023121101A1 - Dispositif automatisé de diagnostic et procédé de diagnostic l'utilisant - Google Patents

Dispositif automatisé de diagnostic et procédé de diagnostic l'utilisant Download PDF

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Publication number
WO2023121101A1
WO2023121101A1 PCT/KR2022/020157 KR2022020157W WO2023121101A1 WO 2023121101 A1 WO2023121101 A1 WO 2023121101A1 KR 2022020157 W KR2022020157 W KR 2022020157W WO 2023121101 A1 WO2023121101 A1 WO 2023121101A1
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WIPO (PCT)
Prior art keywords
reaction
sample
module
sensor
diagnosis
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PCT/KR2022/020157
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English (en)
Korean (ko)
Inventor
이문근
이태재
이은영
노동기
박유민
이경균
배남호
이석재
Original Assignee
한국과학기술원
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Priority claimed from KR1020220048155A external-priority patent/KR20230097964A/ko
Application filed by 한국과학기술원 filed Critical 한국과학기술원
Publication of WO2023121101A1 publication Critical patent/WO2023121101A1/fr

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65Raman scattering
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic 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
    • G01N35/04Details of the conveyor system
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices 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 an automated device for diagnosis that reacts and senses a sample for diagnosis and a diagnosis method using the same.
  • the sample reaction is roughly performed by disrupting the sample (lysis), mixing the target material (protein, nucleic acid, etc.) with magnetic particles and a labeling material, and washing to discharge the residue. Crushing, mixing, and reaction processes should be performed sequentially in an appropriate sequence.
  • the target material can be detected by sensing the reaction-treated sample through a sensor.
  • the sample injection, sensing, washing, and channel cleaning processes must be sequentially performed in an appropriate order.
  • Patent Document 1 KR 10-2019-0179960 A
  • the present invention has been proposed to solve these problems, and reacts and senses a sample for diagnosis, controls the flow of fluid flowing on a flow path by repeatedly applying positive and negative pressure in the chamber, and automates the diagnosis process. It is an object of the present invention to provide an automated device for diagnosis that can increase diagnostic accuracy and sample processing speed, and a diagnosis method using the same.
  • An automated device for diagnosis according to the present invention for achieving the above object includes a sample module provided with at least one sample; a reaction module receiving a sample from the sample module, mixing the supplied sample with a reaction solution to form a mixed solution, and performing a reaction of the mixed solution; a sensor module having a sensor, receiving a reaction-treated sample from the reaction module, and allowing the supplied sample to be incubated on the sensor; an analysis module for detecting a target material fixed on a sensor of the sensor module; and a control unit controlling the sample module, the reaction module, the sensor module, and the analysis module.
  • control unit controls an operation of the robot arm to pick up a sample from the sample module and supply the sample to the reaction module or the reaction module.
  • a sample reacted by the module may be picked up and supplied to the sensor module.
  • the controller provides the sensor module to the analysis module by controlling an operation of the robot arm, and the sensor module detects a target material. It can be loaded or unloaded on the analysis module.
  • the control unit allows a plurality of samples to be loaded or unloaded from the sample module, and when the samples are loaded, sample information may be collected by reading barcodes of the samples.
  • the reaction module includes a storage unit provided with a plurality of accommodating chambers in which the reaction solution is accommodated; a connection unit provided below the storage unit, having a plurality of connection channels connected to the plurality of accommodating chambers, and distributing any one of the reaction solutions accommodated in the plurality of accommodation chambers through the plurality of connection channels; and a reaction channel provided below the connection part, into which a sample is injected, connected to the plurality of connection channels, and a plurality of reaction chambers connected to the reaction channel, wherein the sample and the plurality of connection channels are circulated in the reaction channel. and a reaction unit in which the reaction solution formed forms a mixed solution, and a reaction of the mixed solution is performed by repeatedly applying positive or negative pressure to the plurality of reaction chambers.
  • the control unit may allow the mixed solution to flow back and forth between the plurality of reaction chambers and the reaction channel by repeatedly applying a positive pressure or a negative pressure in the plurality of reaction chambers.
  • a magnetic material is provided below the reaction channel, and the control unit may provide magnetic force to the reaction channel by raising the magnetic material when the reaction of the mixed solution is performed.
  • the reaction module further includes a recovery unit provided below the reaction unit and connected to the reaction channel and provided with a waste liquid chamber, wherein the control unit changes the pressure in the plurality of reaction chambers to react in the plurality of reaction chambers.
  • the waste solution in the plurality of reaction chambers or the reaction channel may be discharged to the waste chamber by controlling or changing the pressure in the waste chamber.
  • the sensor module includes an upper plate having an inlet through which a sample, a buffer solution, or water is injected, and a sensor for sensing a target material is provided in the inlet; a middle plate provided at a lower end of the upper plate, having a distribution channel connected to the inlet, and circulating the sample, the buffer solution, or the water injected through the inlet through the distribution channel; and a lower plate portion provided at a lower end of the middle plate portion and provided with a discharge chamber connected to the distribution channel.
  • the control unit may allow the sample, the buffer solution, or the water injected through the inlet to flow by applying a positive pressure or a negative pressure in the discharge chamber connected to the distribution channel.
  • the control unit allows the target material present in the sample or the buffer solution to be placed on the sensor, and the target material fixed on the surface of the sensor can be detected through the analysis module.
  • a diagnosis method using an automated device for diagnosis includes the step of providing at least one sample; A reaction step of supplying a prepared sample, mixing the supplied sample with a reaction solution to form a mixed solution, and performing a reaction of the mixed solution; A stationary step of supplying a reaction-treated sample and incubating the supplied sample on a sensor; and an analysis step of detecting a target material immobilized on the sensor.
  • sample information may be collected by reading the barcode of the sample.
  • the reaction step may include distributing any one of the reaction solutions accommodated in the plurality of accommodating chambers through a plurality of connecting channels; injecting a sample into a reaction channel connected to the plurality of connection channels, and forming a mixed solution with the sample and the reaction solution distributed from the plurality of connection channels; and performing a reaction of the mixed solution by repeatedly applying positive pressure or negative pressure to a plurality of reaction chambers connected to the reaction channel.
  • the mixed solution flows back and forth between the plurality of reaction chambers and the reaction channel, and magnetic force may be provided to the reaction channel through a magnetic material provided below the reaction channel.
  • the stationary step may include injecting a sample or a buffer solution or water through an inlet; Placing the sample or the target material in the buffer solution on the sensor provided in the inlet; washing the sensor by distributing the sample, the buffer solution, or the water through a distribution channel connected to the inlet; and discharging the sample, the buffer solution, or the water into a discharge chamber connected to the distribution channel.
  • the sample, the buffer solution, or the water may flow back and forth between the sensor and the distribution channel by applying a positive pressure or a negative pressure to the discharge chamber.
  • a fixed target material may be detected by exchanging signals with the sensor in an optical, electrical, or electrochemical manner.
  • a sample is reacted and sensed for diagnosis, and the flow of fluid flowing on a flow path is controlled by repeatedly applying positive pressure and negative pressure in the chamber, and the diagnosis process By automating the diagnosis accuracy and sample processing speed can be increased.
  • FIG. 1 is a diagram schematically showing an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 2 is a diagram showing the overall form of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG 3 is a perspective view showing a storage unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 4 is a plan view showing a storage unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 5 is a bottom view showing a storage unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 6 is a perspective view showing a connection part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 7 is a plan view showing a connection part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 8 is a bottom view showing a connection part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 9 is a bottom view showing a state in which an upper valve is removed from a connection part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 10 is a view showing a coupled state of a storage unit, a connection unit, and a fixing pin of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 11 is a perspective view showing a reaction part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 12 is a plan view showing a reaction part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 13 is a bottom view showing a reaction part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 14 is a bottom view showing a state in which a lower valve is removed from a reaction part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 15 is a cross-sectional view showing a reaction chamber and a reaction channel in a reaction unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 16 is a view showing a state in which a connection part and a reaction part of a reaction module are coupled in an automated device for diagnosis according to an embodiment of the present invention.
  • 17 is a view showing an upper valve or a lower valve in a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 18 is a perspective view illustrating a recovery unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 19 is a plan view illustrating a recovery unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 20 is a bottom view illustrating a recovery unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 21 is a perspective view showing a cover part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 22 is a bottom perspective view showing a cover of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 23 is a perspective view showing a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 24 is a cross-sectional view showing a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 25 is an enlarged view showing a coupling groove formed on an inner circumferential surface of a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 26 is an enlarged view showing coupling protrusions formed on an outer circumferential surface of a storage unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 27 is a view showing the inside of a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 28 is a view showing the outside of a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 29 is a diagram showing the overall shape of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 30 is a perspective view showing an upper plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 31 is a plan view showing an upper plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 32 is a bottom view showing an upper plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG 33 is a perspective view showing a middle plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 34 is a plan view illustrating a middle plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 35 is a bottom view showing a middle plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 36 is a cross-sectional view of a state in which an upper plate part and a middle plate part of a sensor module are coupled in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 37 is a perspective view showing a lower plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 38 is a plan view illustrating a lower plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 39 is a bottom view showing a lower plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 40 is a flowchart of a diagnosis method using an automated device for diagnosis according to an embodiment of the present invention.
  • 41 is a flow chart showing reaction steps in detail in a diagnosis method using an automated device for diagnosis according to an embodiment of the present invention.
  • a “module” or “unit” for a component used in this specification performs at least one function or operation.
  • a “module” or “unit” may perform a function or operation by hardware, software, or a combination of hardware and software.
  • a plurality of “modules” or “units” other than “modules” or “units” to be executed in specific hardware or to be executed in at least one processor may be integrated into at least one module. Singular expressions include plural expressions unless the context clearly dictates otherwise.
  • 1 is a diagram schematically showing an automated device for diagnosis according to an embodiment of the present invention.
  • 2 is a diagram showing the overall form of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 3 is a perspective view showing a storage unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 4 is a plan view showing a storage unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 5 is a bottom view showing a storage unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 6 is a perspective view showing a connection part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • FIG. 7 is a plan view showing a connection part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 8 is a bottom view showing a connection part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 9 is a bottom view showing a state in which an upper valve is removed from a connection part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 10 is a view showing a coupled state of a storage unit, a connection unit, and a fixing pin of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 11 is a perspective view showing a reaction part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 12 is a plan view showing a reaction part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 13 is a bottom view showing a reaction part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 14 is a bottom view showing a state in which a lower valve is removed from a reaction part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 15 is a cross-sectional view showing a reaction chamber and a reaction channel in a reaction unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 16 is a view showing a state in which a connection part and a reaction part of a reaction module are coupled in an automated device for diagnosis according to an embodiment of the present invention.
  • 17 is a view showing an upper valve or a lower valve in a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 18 is a perspective view illustrating a recovery unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 19 is a plan view illustrating a recovery unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 20 is a bottom view illustrating a recovery unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 21 is a perspective view showing a cover part of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 22 is a bottom perspective view showing a cover of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 23 is a perspective view showing a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 24 is a cross-sectional view showing a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 25 is an enlarged view showing a coupling groove formed on an inner circumferential surface of a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 26 is an enlarged view showing coupling protrusions formed on an outer circumferential surface of a storage unit of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 27 is a view showing the inside of a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 28 is a view showing the outside of a case of a reaction module in an automated device for diagnosis according to an embodiment of the present invention.
  • 29 is a diagram showing the overall shape of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 30 is a perspective view showing an upper plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 31 is a plan view showing an upper plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 32 is a bottom view showing an upper plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 33 is a perspective view showing a middle plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 34 is a plan view illustrating a middle plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 35 is a bottom view showing a middle plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 36 is a cross-sectional view of a state in which an upper plate part and a middle plate part of a sensor module are coupled in an automated device for diagnosis according to an embodiment of the present invention.
  • 37 is a perspective view showing a lower plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 38 is a plan view illustrating a lower plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 39 is a bottom view showing a lower plate of a sensor module in an automated device for diagnosis according to an embodiment of the present invention.
  • 40 is a flowchart of a diagnosis method using an automated device for diagnosis according to an embodiment of the present invention.
  • 41 is a flow chart showing reaction steps in detail in a diagnosis method using an automated device for diagnosis according to an embodiment of the present invention.
  • 42 is a flowchart showing in detail the stationary step in the diagnosis method using an automated device for diagnosis according to an embodiment of the present invention.
  • An automated device 1 for diagnosis includes a sample module 10 provided with at least one sample; a reaction module 20 receiving a sample from the sample module 10, mixing the supplied sample with a reaction solution to form a mixed solution, and performing a reaction of the mixed solution; A sensor module 30 having a sensor, receiving a reaction-processed sample from the reaction module 20, and incubating the supplied sample on the sensor; Analysis module 40 for detecting the target material fixed on the sensor of the sensor module 30; and a controller 50 controlling the sample module 10, the reaction module 20, the sensor module 30, and the analysis module 40.
  • control unit 50 is connected to each of the modules by wire or wireless, through which control signals are transmitted and received.
  • control unit 50 is shown inside the automation device 1 for convenience in FIG. 1, it may exist outside and control each module wirelessly.
  • each module may be composed of one automated device 1 for diagnosis as shown in FIG. 1, and thus, the automated device 1 for diagnosis may be designed to have a more compact configuration. And, through the optimized arrangement, the efficiency of diagnosis can be increased.
  • the automated device 1 for diagnosis further includes at least one robot arm (not shown) that picks up a sample and supplies the picked-up sample, and in the control unit 50 By controlling the operation of the robot arm, a sample can be picked up from the sample module 10 and supplied to the reaction module 20 or a sample reacted in the reaction module 20 can be picked up and supplied to the sensor module 30 .
  • the control unit 50 allows a plurality of samples to be loaded or unloaded in the sample module 10, and when the samples are loaded, the sample information can be collected by reading the barcodes of the samples.
  • a sample rack equipped with 13 samples is loaded in the sample module 10, and a GUI for displaying a sample loading position is implemented on the screen. Then, the control unit 50 picks up the tube where the sample is located through the robot arm and transfers it to the rotation module, and the control unit 50 collects and stores sample information by rotating the rotation module and reading the barcode of the sample. will do Upon completion of barcode reading, the control unit 50 picks up the tube of the rotation module through the robot arm and transfers it to the sample rack again.
  • the reaction module 20 includes a storage unit 100 provided with a plurality of accommodating chambers 110 in which reaction solutions are accommodated; It is provided on the lower side of the storage unit 100 and is provided with a plurality of connection channels 210 connected to the plurality of accommodation chambers 110, and accommodated in the plurality of accommodation chambers 110 through the plurality of connection channels 210. Distributing any one of the reaction solution, connecting portion 200; and a reaction channel 310 connected to a plurality of connection channels 210 and a plurality of reaction chambers 320 connected to the reaction channels 310, provided on the lower side of the connection unit 200, into which samples are injected, and connected to the reaction channels 210. In 310, the reaction solution flowing from the sample and the plurality of connection channels 210 forms a mixed solution, and the reaction of the mixed solution is performed by repeatedly applying positive or negative pressure to the plurality of reaction chambers 320.
  • Part 300 may include.
  • the reaction module 20 is for reacting a sample in order to detect a target substance, and schematically crushes the sample, magnetic particles and a labeling substance It is for washing the residue after reaction with.
  • the target material is a separated protein or nucleic acid
  • molecular diagnosis or immunodiagnosis is performed by detecting the separated protein or nucleic acid using a sensor using an optical, electrical, or electrochemical method.
  • control unit 50 repeatedly applies positive pressure or negative pressure in the plurality of reaction chambers 320, thereby ,
  • the mixed solution may flow back and forth between the plurality of reaction chambers 320 and the reaction channel 310.
  • a separate negative pressure hole 305 formed penetrating the reaction unit 300 and the recovery unit 400 is provided in one of the plurality of reaction chambers 320, and the negative pressure hole 305
  • the pressure in the reaction chamber 320 may be directly applied as a positive pressure or a negative pressure by inflow or outflow of gas through the.
  • the negative pressure hole 305 is connected to the negative pressure control hole 405 provided on the side of the recovery unit 400, and the control unit 50 controls the pressure of any one of the plurality of reaction chambers 320 through the negative pressure control hole 405. is to be applied as a positive or negative pressure.
  • the sample can be mixed with the reaction solution (magnetic particle and label solution, washing buffer, illusion buffer, etc.), as follows. It is possible to fix the target material to which the magnetic particles are coupled by using the magnetic force during flow. That is, as positive or negative pressure is repeatedly applied to the plurality of reaction chambers 320, mixing, fixing, washing, etc. of the mixed solution can be performed.
  • the reaction solution magnetic particle and label solution, washing buffer, illusion buffer, etc.
  • the reaction unit 300 has a magnetic body 330 provided below the reaction channel 310, and the control unit 50 has a magnetic body when the reaction of the mixed solution is performed. It is possible to provide magnetic force to the reaction channel 310 by raising the.
  • the magnetic body 330 may be composed of a magnet shaft that ascends or descends, and the control unit 50 controls the magnetic body when the mixed solution moves back and forth between the reaction chamber 320 and the reaction channel 310 or when the movement is completed. 330 is raised, and the magnetic body 330 serves to fix the target material to which the magnetic particles are bound in the reaction channel 310 through magnetic force. When the target material is unfixed, the control unit 50 descends the magnetic material 330 to remove the magnetic force provided to the reaction channel 310, and at this time, the reacted sample is recovered through a robot arm equipped with a pipette or the like. It can be.
  • an upper valve 220 to which all of the plurality of connection channels 210 are connected is provided in the connection part 200 of the reaction module 20, The upper valve 220 may selectively connect one of the plurality of connection channels 210 to the reaction channel through shaft rotation.
  • one side of the plurality of connection channels 210 is connected to the plurality of outlet holes 120 of the plurality of accommodating chambers 100, respectively, and the other side is connected to the upper valve 220.
  • the upper valve 220 is configured such that the central portion is rotatable, and a groove is formed on the upper surface of the central portion from the center toward the outside.
  • the other side of the plurality of connection channels 210 is disposed along the circumferential direction based on the center of the upper valve 220, and thus the groove formed in the center of the upper valve 220 is rotated and the plurality of connection channels 210 ) is to selectively connect one of them.
  • reaction solution of any one connection channel 210 connected through the above process is raised from the inside of the connection part 200 through the hole in the center of the upper valve 220 of the connection part 200. Then, it descends again, rises and falls again inside the connection part 200, and flows into the reaction channel 310.
  • connection part 200 grooves are formed on the upper and lower surfaces of the connection part 200, and the grooves are closed by attaching a laminating film to the upper and lower surfaces of the connection part 200, through which Connection channels 210 are formed.
  • reaction solutions flow into the reaction channel 310 by repeating the rise and fall as described above, the reverse flow of the reaction solutions is prevented, and when a negative pressure is formed in the reaction chamber 320, the fluid in the connection channel 210 This is to prevent temporary escape (siphon phenomenon) due to negative pressure.
  • the flow of fluid can be more precisely controlled at a desired flow rate.
  • a lower valve 340 connected to the reaction channel 310 is provided in the reaction unit 300 of the reaction module 20, and the lower valve 340 may selectively open and close the discharge hole 350 formed in the reaction channel 310 through shaft rotation.
  • the upper valve 220 and the lower valve 340 are the same, and consist of a rotatable central portion and a hole formed on the upper surface of the central portion.
  • the hole has a shape extending outward from the center of the central portion, and allows the fluid introduced from the outside to flow to the center and raises it again from the center by hydraulic pressure.
  • the upper valve 220 and the lower valve 340 have mounting protrusions formed on the outer circumferential surface of the upper end, and the upper valve 220 and the lower valve 340 are mounted on the connection part 200 and the reaction part 300 at the positions A mounting groove is formed into which the mounting protrusion enters, and the upper valve 220 and the lower valve 340 have a luer lock structure in which the mounting protrusion is inserted into the mounting groove and then rotated and fixed to the connection part 200 and the reaction part 300. it will be installed
  • the reaction module 20 is provided on the lower side of the reaction unit 300 and is connected to the reaction channel 310, and the waste chamber 410 It further includes a recovery unit 400 provided; and the control unit 50 controls the reaction in the plurality of reaction chambers 320 by changing the pressure in the plurality of reaction chambers 320 or the pressure in the waste liquid chamber 410. By changing the waste solution in the plurality of reaction chambers 320 or reaction channels 310 can be discharged to the waste chamber (410).
  • the waste solution in the plurality of reaction chambers 320 or reaction channels 310 is discharged to the waste liquid chamber 410 through the discharge hole 350, and the waste liquid chamber 410 is in the chamber.
  • a pressure applying hole 415 for pressure change is provided separately, and the control unit 50 can change the pressure in the waste liquid chamber 410 by introducing or discharging gas into the pressure applying hole 415 .
  • the control unit 50 opens the lower valve 340 and applies a negative pressure to the inside of the waste chamber 410. Accordingly, the reaction chamber 320 or the remaining waste solution remaining in the reaction channel 310 is discharged to the waste chamber 410 through the discharge hole 350 by negative pressure.
  • the plurality of accommodating chambers 110 of the reaction module 20 are disposed along the circumferential direction of the storage unit 100, and the plurality of accommodating chambers Outlet holes 120 through which the received reaction solution is discharged may be formed in each of the (110).
  • a laminating film is attached to the upper surface of the storage unit 100 so that the plurality of accommodating chambers 110 are maintained in a sealed state before the reaction module 20 is used, and the plurality of accommodating chambers 110 contain magnetic Particle solution, washing buffer, etc. can be accommodated by 1 ml to several ml, and an illusion buffer (0.05 to 1 ml) with relatively small particles can be accommodated in one small receiving chamber as seen in FIG. 2 .
  • connection part 200 of the reaction module 20 is provided with a protrusion part 230 at the inlet side of each of the plurality of connection channels 210,
  • the protrusions 230 can communicate with the plurality of accommodating chambers 110 and the plurality of connection channels 210 by being inserted through the outlet holes 120 .
  • an O-ring 240 is provided at the lower end of the protrusion 230, and the O-ring 240 is the protrusion 230 When is inserted through the outflow hole 120, the connection portion 200 where the outflow hole 120 and the connection channel 210 are connected may be sealed.
  • the storage unit 100 is coupled to the coupling groove
  • the fixing pin 600 which is fixed so as not to move up and down along the 810, is removed through a robot arm, etc., and the cover part 700 coupled to the lower end of the case 800 is removed from the upper end of the case 800.
  • the protrusion 230 penetrates the film covering the outlet hole 120 and enters the outlet hole 120 and the connection channel. 210 are connected, and the effect of simplifying the manufacturing process of the storage unit 100 and the connection unit 200 through the laminating process and reducing the manufacturing cost is also derived.
  • the top of the storage unit 100 is pushed downward on the upper side of the storage unit 100, and the storage unit 100 ) And a cover portion 700 for closely contacting the connection portion 200 is provided, a plurality of punchers 710 are formed in positions corresponding to the plurality of accommodating chambers 110 in the cover portion 700, and a plurality of punchers ( 710) can communicate with the outside by penetrating the plurality of accommodating chambers 110. This is to promote the flow of the reaction solution in the channel by providing atmospheric pressure to the plurality of accommodating chambers 110 when the reaction module 20 is used in the automated device 1 for diagnosis according to an embodiment of the present invention. .
  • the reaction module 20 includes a storage unit 100, a connection unit 200, and a reaction unit 300, and a plurality of couplings are provided on the inner circumferential surface.
  • the coupling protrusion 130 is formed to have a shorter length than the coupling groove 810, which means that the coupling protrusion 130 is in a state where the fixing pin 600 below is inserted. This is because it is in close contact with the upper surface of the coupling groove 810.
  • an inclined fitting protrusion is formed at the bottom of the coupling groove 810, and the fitting protrusion is fitted into the fitting groove formed at the bottom of the coupling protrusion 130.
  • the fitting protrusion serves to guide the engaging protrusion 130 when the storage unit 100 slides downward when the fixing pin 600 is removed, and the engaging protrusion slides down gently through the inclined surface of the fitting protrusion. .
  • the fitting protrusion prevents the fluid from leaking by pushing the storage part 100 back to the top by the elastic force of the O-ring 240 provided in the connection part 200, and prevents the fluid from flowing out. ) is to maintain close contact with the connecting portion 200.
  • the reaction module 20 may inject or collect a reacted sample using a robot arm equipped with a pipette. That is, when the pipette injects or collects a sample through the robot arm equipped with the pipette, the control unit 50 passes through the storage unit 100 and the connection unit 200 and approaches the reaction channel 310 so that the reaction chamber 320 ) or injecting a sample into the reaction channel 310, or controlling the reaction chamber 320 or reaction channel 310 to collect a sample after completion of the reaction.
  • the reaction module 20 is provided between the storage unit 100 and the connection unit 200 to connect the storage unit 100 and the connection unit 200. It further includes a fixing pin 600 spaced apart, and the storage part 100 and the connection part 200 are in close contact when the fixing pin 600 is removed, so that the receiving chamber 110 and the connection channel 210 can be connected. .
  • connection part 200 and the storage part 100 are spaced apart through the fixing pin 600, and the storage part 100 is accommodated.
  • the outflow holes 120 of the chambers 110 are maintained in a sealed state to prevent inflow of foreign substances and deterioration of the reaction solution, and the reaction of the sample is performed by removing the fixing pin 600 from the controller 50 only when in use. It will be.
  • the sensor module 30 is provided with an inlet 1110 through which a sample or a buffer solution or water is injected, and the inlet 1110 senses a target material.
  • a distribution channel 1220 is provided at the bottom of the upper plate 1100 and connected to the inlet 1110, and a sample or buffer solution or water injected through the inlet 1110 is distributed through the distribution channel 1220.
  • control unit 50 causes the target material present in the sample or buffer solution to be placed on the sensor 1115, and through the analysis module 40 A target material fixed on the surface of the sensor can be detected.
  • the sensor module 30 is injected with a sample that has been pretreated in the reaction module 20, and the target material is magnetic particles and a labeling material. It exists in a combined state, and the target material is detected through the sensor 1115.
  • the target material is a separated protein or nucleic acid, which is detected by the sensor 1115, and molecular diagnosis, immunodiagnosis, etc. are performed by the analysis module 40.
  • control unit 50 causes the pressure in the discharge chamber 1315 connected to the distribution channel 1220 to be applied as a positive pressure or a negative pressure so that the inlet 1110 Through the injected sample or buffer solution or water can be made to flow.
  • the inlet 1110 is formed in a recessed shape on the upper surface of the upper plate portion 1100, so that the injected fluid gathers at the top of the sensor in the center and guides it to incubate, and the inlet ( 1110), the distribution channel 1220, and the discharge chamber 1315 are all connected, so that the fluid flow is controlled by controlling the pressure of the discharge chamber 1315, and through this, the sensor 1115 and the like are cleaned.
  • the inlet 1110 when negative pressure is applied to a sample (pretreated sample through the reaction module 20) or a buffer solution (PBS) or water (ultrapure water) injected through the inlet 1110 to the discharge chamber 1315, the inlet ( 1110 will flow toward the discharge chamber 1315 through the distribution channel 1220, and when positive pressure is applied to the discharge chamber 1315, the discharge chamber 1315 side passes through the distribution channel 1220 to the inlet ( 1110) will flow towards.
  • PBS buffer solution
  • water ultrapure water
  • the senor 1115 is located at the inlet 1110 provided in the upper plate 1100, and the inlet 1110 A cross-shaped support structure supporting the sensor 1115 is formed, and the sensor 1115 (6 x 6 x 0.7 mm) is seated on the support structure to sense a target material in the sample.
  • an injection channel 1210 connected to the injection hole 1110 is provided at the top of the middle plate 1200, and injection The channel 1210 may be configured as a groove formed along an upper surface of the middle plate portion 1200 .
  • the upper plate 1100 is provided with a connection channel 1120 at a point spaced apart from the inlet 1110, and connects Both ends of the channel 1120 are coupled to the injection channel 1210 and the distribution channel 1220, respectively, so that the injection channel 1210 and the distribution channel 1220 may be connected.
  • connection channel 1120 is a groove formed along the upper surface of the upper plate portion 1100, and both ends penetrate the lower side of the upper plate portion 1100 to penetrate the injection channel 1210 of the middle plate portion 1200. ) and the distribution channel 1220.
  • a laminating film is attached to the upper surface of the upper plate portion 1100, a groove formed along the upper surface of the upper plate portion 1100 is closed by the laminating film to form a connection channel 1120. That is, by forming grooves in the upper plate portion 1100 and the middle plate portion 1200 and then forming channels through laminating, the manufacturing process can be simplified and the manufacturing cost can be reduced.
  • the sensor module 30 of the automation device 1 for diagnosis when a sample or a buffer solution or water flows into the distribution channel 1220, it is injected through the inlet 1110.
  • the sample, buffer solution, or water may pass through the injection channel 1210, ascend, pass through the connection channel 1120, descend, and flow into the distribution channel 1220.
  • the structure configured so that the fluid repeatedly rises and falls through the connection channel 1120 and the discharge channel 1130 of the upper plate portion 1100, as negative pressure is applied to the discharge chamber 1315, the fluid flows from the inlet 1110 to the channel. This is to prevent the siphon effect in which all of my fluid is temporarily exhausted by negative pressure. After all, through this structure, the flow of fluid can be more precisely controlled at a desired flow rate.
  • O-rings are provided on the lower surface of the upper plate portion 1100 at the inlet and outlet portions of the inlet 1110, the connection channel 1120, and the discharge channel 1130, so that each portion connected to the middle plate portion 1200 Fluid leakage can be prevented.
  • the distribution channel 1220 is provided at the lower end of the middle plate 1200 and covers the lower surface of the middle plate 1200. It may be composed of a groove formed to repeat extension and bending along the.
  • the middle plate portion 1200 can simplify the manufacturing process and reduce manufacturing costs, similarly to the upper plate portion 1100 .
  • the sample, buffer solution or water distributed in the distribution channel 1220 moves through the middle plate 1200 along the groove.
  • the sensor 1115 may be cleaned by flowing back and forth between one side and the other side.
  • control unit 50 allows the sample or buffer solution or water to flow back and forth between the sensor and the distribution channel, thereby washing away impurities remaining on the sensor 1115 and substances that have non-specific reactions.
  • the distribution channel 1220 is formed as a flow path having a wide cross-sectional area along the surface of the middle plate portion 1200, when a sample is filled in the distribution channel 1220, the sensor 1115 provided in the upper plate portion 1100 It can be filled with a buffer solution or water to wash the
  • the upper plate 1100 is provided with a discharge channel 1130 at a point spaced apart from the inlet 1110, and the discharge channel 1130 may connect the distribution channel 1220 and the discharge chamber 1315 by coupling both ends to discharge holes 1310 formed in the distribution channel 1220 and the discharge chamber 1315, respectively.
  • the discharge chamber 1315 in the sensor module 30 of the automation device 1 for diagnosis according to an embodiment of the present invention.
  • a sample or buffer solution or water is introduced into the discharge chamber ( 1315).
  • a plurality of first coupling grooves 1140 spaced apart along the edge are formed in the upper plate 1100 of the sensor module 30, and the lower plate
  • a plurality of coupling protrusions 1320 are formed at positions corresponding to the plurality of first coupling grooves 1140 in the portion 1300, and the plurality of coupling protrusions 1320 are inserted into the plurality of first coupling grooves 1140, thereby The upper plate part 1100 and the lower plate part 1300 may be coupled.
  • a plurality of second coupling grooves 1230 spaced apart along the edge are formed in the middle plate 1200, A plurality of coupling protrusions 1320 are formed on the lower plate 1300 at positions corresponding to the plurality of second coupling grooves 1230, and the plurality of coupling protrusions 1320 are inserted into the plurality of second coupling grooves 1230.
  • the middle plate portion 1200 and the lower plate portion 1300 may be coupled.
  • a total of eight coupling protrusions 1320 are formed along the rim of the lower plate 1300, and the plurality of coupling protrusions 1320 are second coupling grooves 1230 and first coupling grooves. (1140) is inserted and coupled.
  • the plurality of coupling protrusions 1320 are formed in an 'L' shape at the top, and are engaged with the chin of the first coupling groove 1140, thereby forming the upper plate portion 1100, the middle plate portion 1200, and the lower plate portion 1300. ) can be maintained firmly.
  • the automation device 1 for diagnosis further includes at least one robot arm for picking up and moving the sensor module 30, and the control unit 50 controls the operation of the robot arm.
  • the control unit 50 controls the operation of the robot arm.
  • the sensor module 30 is provided to the analysis module 40, and the sensor module 30 can be loaded or unloaded on the analysis module 40 to detect a target substance.
  • control unit 50 picks up the sensor module 30 through the robot arm, places it on the analysis module 40, clamps the located sensor module 30, and performs nitrogen blowing and QR check operations.
  • the control unit 50 loads the sensor module 30 to the analysis stage loading position for analysis, and detects the fixed target material by exchanging signals with the sensor 1115 in an optical, electrical, or electrochemical manner. do.
  • the control unit 50 reports the analysis result and unloads the sensor module 30 again.
  • a diagnosis method using the automated device 1 for diagnosis includes the step of providing at least one sample (S10); A reaction step (S20) of supplying a provided sample, mixing the supplied sample with a reaction solution to form a mixed solution, and performing a reaction of the mixed solution; A stationary step (S30) of supplying the reaction-treated sample and incubating the supplied sample on the sensor 1115; and an analysis step (S40) of detecting a target material fixed on the sensor 1115.
  • sample information may be collected by reading the barcode of the sample.
  • reaction step (S20) the step of distributing any one of the reaction solution accommodated in the plurality of receiving chambers 110 through a plurality of connection channels 210 (S100); Injecting a sample into the reaction channel 310 connected to the plurality of connection channels 210, and forming a mixed solution with the sample and the reaction solution distributed from the plurality of connection channels 210 (S110); and performing a reaction of the mixed solution by repeatedly applying positive or negative pressure to the plurality of reaction chambers 320 connected to the reaction channel 310 (S120).
  • the mixed solution flows back and forth between the plurality of reaction chambers 320 and the reaction channel 310, and the magnetic body 330 provided below the reaction channel 310 Magnetic force may be provided to the reaction channel 310 through.
  • the sample eg, serum, 200ul
  • the reaction solution magnetic particle solution, washing buffer, etc., 1000ul
  • the reaction chamber 320 is supplied to the reaction chamber 320 from any one of the plurality of accommodating chambers 110 through axial rotation (60 degrees) of the upper valve 220.
  • the reaction solution and the reaction channel 310 flow back and forth (1 hour, room temperature), and the sample is Capture antibody and biomarker binding treatment, Thereafter, positive and negative pressures are repeatedly applied to one of the reaction chambers 320, and at the same time, the magnetic material 330 is raised close to the reaction channel 310 to fix the sample component combined with the magnetic material (4 minutes and 50 seconds). ) make After the operation is finished, the lower valve 340 is axially rotated (180 degrees) to open, and negative pressure is applied to the waste chamber 410 so that the remaining solution is discharged to the waste chamber 410 after the reaction is completed.
  • the sample is reacted in the order of reaction of the target material, washing 1, washing 2, washing 3, and concentrated sample preparation, and each reaction process is performed by adjusting the pressure of the reaction chamber 320 and the waste chamber 410 and the upper valve ( 220) by sequentially supplying the reaction solution of the plurality of accommodating chambers 110 to the reaction chamber 320 according to the shaft rotation.
  • the diagnosis method using the reaction module 20 in the automation device 1 for diagnosis is the pressure control of the reaction chamber 320 and the waste chamber 410 and the upper valve 220 and There is an effect that the reaction of the sample can be performed simply and quickly by controlling only two valves of the lower valve 340.
  • the stationary step (S30) is a step of injecting a sample or buffer solution or water through the inlet 1110 (S200); Placing a target material in a sample or buffer solution on the sensor 1115 provided in the inlet 1110 (S210); washing the sensor 1115 by distributing the sample or buffer solution or water through the distribution channel 1220 connected to the inlet 1110 (S220); and discharging the sample or buffer solution or water into the discharge chamber 1315 connected to the distribution channel 1220 (S230).
  • the reaction of the sample (50 ul) injected by the robot arm equipped with the pipette and the surface of the sensor 1115 at a specific temperature for about 1 hour in the controller 50 After that, the sample is discharged for about 20 seconds by forming the discharge chamber 1315 under negative pressure.
  • washing buffer PBS, 200ul
  • DI water DI water, 200ul
  • PBS washing buffer
  • DI water ultrapure water
  • the inlet 1110, the connection channel 1120, the discharge channel 1130, and the distribution channel 1220 are washed (25 minutes), and when the washing is completed, negative pressure is applied to the discharge chamber 1315 to remove the washing buffer and ultrapure water. It is discharged (10 seconds) to the discharge chamber 1315.
  • the fixed target material may be detected by exchanging signals with the sensor 1115 in an optical, electrical, or electrochemical manner.
  • the automated device 1 for diagnosis and the diagnosis method using the same include a sample module 10, a reaction module 20, a sensor module 30 and analysis in the control unit 50
  • a sample module 10 By controlling the module 40, various samples can be diagnosed in various ways, and when diagnosing samples, more accurate and rapid diagnosis can be performed, thereby improving sample processing speed for diagnosis.

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  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (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)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

La présente invention concerne un dispositif automatisé de diagnostic et un procédé de diagnostic l'utilisant, un échantillon étant amené à réagir et étant détecté à des fins de diagnostic. Le dispositif automatisé de diagnostic comprend : un module d'échantillon comprenant au moins un échantillon ; un module de réaction qui reçoit un échantillon du module d'échantillon et qui mélange l'échantillon fourni avec une solution de réaction en vue de former une solution mélangée, et dans lequel une réaction de la solution mélangée est réalisée ; un module de capteur comprenant un capteur, recevant un échantillon ayant subi un traitement de réaction à partir du module de réaction, et permettant à l'échantillon fourni d'être incubé sur le capteur ; un module d'analyse afin de détecter un matériau cible immobilisé sur le capteur du module de capteur ; et une unité de commande afin de commander le module d'échantillon, le module de réaction, le module de capteur et le module d'analyse.
PCT/KR2022/020157 2021-12-24 2022-12-12 Dispositif automatisé de diagnostic et procédé de diagnostic l'utilisant WO2023121101A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20210187746 2021-12-24
KR10-2021-0187746 2021-12-24
KR1020220048155A KR20230097964A (ko) 2021-12-24 2022-04-19 진단을 위한 자동화 장치 및 이를 이용한 진단방법
KR10-2022-0048155 2022-04-19

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WO2023121101A1 true WO2023121101A1 (fr) 2023-06-29

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20110090394A (ko) * 2010-02-03 2011-08-10 삼성전자주식회사 마이크로어레이 반응 장치 및 이를 이용하는 방법
KR20130083305A (ko) * 2012-01-12 2013-07-22 강릉원주대학교산학협력단 자성 입자를 이용한 분석물질의 전처리 장치, 이를 이용한 분석물질의 검출장치 및 검출방법
KR101868824B1 (ko) * 2017-04-17 2018-06-21 티엔에스(주) 면역반응 진단 자동화 시스템
KR20190041282A (ko) * 2017-10-12 2019-04-22 한국과학기술원 소수성 필터를 이용한 유체 제어 기술이 구비된 전자동 유전자 증폭기
JP2020073941A (ja) * 2007-10-02 2020-05-14 セラノス アイピー カンパニー エルエルシー モジュール式ポイントオブケアデバイスおよびその使用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020073941A (ja) * 2007-10-02 2020-05-14 セラノス アイピー カンパニー エルエルシー モジュール式ポイントオブケアデバイスおよびその使用
KR20110090394A (ko) * 2010-02-03 2011-08-10 삼성전자주식회사 마이크로어레이 반응 장치 및 이를 이용하는 방법
KR20130083305A (ko) * 2012-01-12 2013-07-22 강릉원주대학교산학협력단 자성 입자를 이용한 분석물질의 전처리 장치, 이를 이용한 분석물질의 검출장치 및 검출방법
KR101868824B1 (ko) * 2017-04-17 2018-06-21 티엔에스(주) 면역반응 진단 자동화 시스템
KR20190041282A (ko) * 2017-10-12 2019-04-22 한국과학기술원 소수성 필터를 이용한 유체 제어 기술이 구비된 전자동 유전자 증폭기

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