WO2024214721A1 - 分析システム - Google Patents

分析システム Download PDF

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Publication number
WO2024214721A1
WO2024214721A1 PCT/JP2024/014479 JP2024014479W WO2024214721A1 WO 2024214721 A1 WO2024214721 A1 WO 2024214721A1 JP 2024014479 W JP2024014479 W JP 2024014479W WO 2024214721 A1 WO2024214721 A1 WO 2024214721A1
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Prior art keywords
pretreatment
analysis
sample
cartridge
fluid
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PCT/JP2024/014479
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English (en)
French (fr)
Japanese (ja)
Inventor
和也 辻本
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Pittan
Pittan Inc
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Pittan
Pittan Inc
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Priority to JP2025513972A priority Critical patent/JPWO2024214721A1/ja
Publication of WO2024214721A1 publication Critical patent/WO2024214721A1/ja
Anticipated expiration legal-status Critical
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers

Definitions

  • the present invention relates to an analytical system for analyzing a specific component in a test sample.
  • liquid chromatography devices are often used to analyze components contained in bodily fluids (blood, urine, tears, saliva, sweat, etc.) secreted and excreted inside and outside the body.
  • bodily fluids blood, urine, tears, saliva, sweat, etc.
  • analysts are required to have advanced specialized knowledge, and the location where the analysis can be performed is limited to research facilities, etc., making it difficult to reduce the cost of analysis.
  • the devices themselves are expensive and large, which also limits the location of analysis and increases costs.
  • on-site environmental measurement devices that can analyze specific components, such as nutrients contained in liquids in soil, rivers, and plant factories.
  • the present invention has been made in consideration of the above-mentioned circumstances, and its purpose is to provide an analytical system that is small and has a simple structure and allows analysts without specialized knowledge to easily perform analyses.
  • an analysis system for analyzing a specific component in a test object comprising: A pretreatment device that performs a pretreatment on a specimen collected from an analysis subject to enable detection of the specific component, and an analysis device that performs an analysis of the specific component on the specimen that has been pretreated,
  • the pretreatment device comprises: a pre-treatment section for extracting the specific component from the specimen and performing pre-treatment to generate a fluid sample for analysis; a first mounting portion to which an analytical cartridge that is replaceable and that contains the fluid sample containing the specific component is mounted; a sample supply unit that supplies the fluid sample generated in the pretreatment unit to the analysis cartridge mounted in the first mounting unit, a second mounting portion for mounting the analysis cartridge containing the fluid sample supplied by the sample supplying portion; and an analysis unit that detects and analyzes the specific component contained in the fluid sample.
  • the analysis system in the present disclosure includes a pretreatment device that performs pretreatment on the specimen collected from the analysis target, and an analysis device that performs analysis of specific components on the pretreated specimen. That is, the pretreatment, which was previously performed at least partially manually, is performed in the pretreatment device. The analysis of the specific components is also performed automatically in the analysis device.
  • the pretreatment device has a pretreatment device that extracts specific components from the specimen, performs pretreatment, and generates a fluid sample, a first mounting unit to which a replaceable analysis cartridge that stores the fluid sample is attached, and a sample supply unit that supplies the fluid sample generated in the pretreatment device to the analysis cartridge attached to the first mounting unit. That is, in the present disclosure, an analysis cartridge can be attached to the pretreatment device, and the pretreated fluid sample is supplied to the analysis cartridge and stored therein. This eliminates the need for the analyst to directly handle the fluid sample using laboratory equipment, etc.
  • the analytical device has a second mounting section for mounting an analytical cartridge containing a fluid sample supplied by the sample supply section, and an analytical section for detecting and analyzing specific components contained in the fluid sample. That is, the analyst receives the fluid sample in the pretreatment device, and transfers the analytical cartridge containing the fluid sample from the pretreatment device to the analytical device. The specific components are then analyzed in the analytical section of the analytical device. Therefore, even during analysis, the analyst does not need to directly handle the fluid sample using laboratory equipment or the like.
  • test object in this disclosure is a specimen such as blood, urine, tears, saliva, sweat, etc. when the subject of analysis is a living body such as a human or animal
  • the specific component may be a biological component such as amino acids, proteins, bases, lipids, extracellular vesicles, etc.
  • the pretreatment device and analysis device in this disclosure may be housed in separate housings and have separate structures, or may be housed in the same housing and have an integrated structure.
  • the pre-treatment unit includes: a pretreatment cartridge mounting portion for mounting a replaceable pretreatment cartridge;
  • the pretreatment cartridge includes: a test object setting device for setting a test object-containing element containing the test object collected from the analysis subject;
  • a sample generator may be provided for extracting the analyte from the analyte-containing element into a pretreatment fluid to generate the fluid sample.
  • the analyst does not need to directly handle the test object using laboratory equipment or the like when pretreatment is performed on the test object. More specifically, the analyst only needs to set the test object-containing element, which contains the test object collected from the subject of analysis, into the pretreatment cartridge.
  • An example of this test object-containing element is a patch containing sweat as the test object.
  • the sample preparation device in the pretreatment cartridge comprises: a pre-treatment fluid controller for moving the pre-treatment fluid into contact with the specimen-containing element; In the pretreatment section, outside the pretreatment cartridge, A drive mechanism may be provided for driving the pre-treatment fluid controller.
  • the pretreatment cartridge includes a pretreatment fluid controller that controls the pretreatment fluid so that the pretreatment fluid comes into contact with the test substance-containing element.
  • a drive mechanism that drives the pretreatment fluid controller is provided outside the pretreatment cartridge in the pretreatment section.
  • the pretreatment cartridge in the pretreatment section includes: A temperature control mechanism for adjusting the temperature of the pretreatment fluid and/or the fluid sample, Further, the second detecting means 14 may be provided.
  • a temperature control mechanism is provided outside the pretreatment cartridge in the pretreatment device, making it possible to adjust the temperature of the pretreatment fluid and fluid sample inside the pretreatment cartridge. This simplifies the configuration inside the pretreatment cartridge, and makes it possible to maintain the temperature of the pretreatment fluid and fluid sample at an appropriate temperature when the pretreatment cartridge is attached to the pretreatment device.
  • the pretreatment cartridge in the pretreatment section includes: A mixing and stirring mechanism for mixing or stirring the pretreatment fluid and/or the fluid sample, Further, the second detecting means 14 may be provided.
  • a mixing and stirring mechanism is provided outside the pretreatment cartridge in the pretreatment device, making it possible to mix or stir the pretreatment fluid and fluid sample inside the pretreatment cartridge.
  • the pretreatment fluid controller may include a valve body that switches the flow path of the pretreatment fluid, and a pump body that pumps the pretreatment fluid into the flow path.
  • a valve body that switches the flow path of the pretreatment fluid
  • a pump body that pumps the pretreatment fluid into the flow path.
  • a detection optical system may be further provided which directs test light to the fluid sample moving within the analytical chip, receives output light, and outputs a signal corresponding to the output light.
  • the analysis cartridge By installing the analysis cartridge in an analysis device, it becomes possible to optically analyze specific components in a fluid sample. As a result, it becomes possible to analyze specific components in a non-contact manner more easily or quickly.
  • the analysis cartridge in the analysis device includes: a waste tank for storing the fluid sample and the mobile phase after analysis that have moved within the analytical chip; Further, the second detection section 110 may be provided.
  • the sample controller further comprises: a first pump body and a first valve body for moving a mobile phase, which is a fluid for causing the fluid sample to flow into the analysis chip; a second pump body and a second valve body for moving the fluid sample for application to the mobile phase;
  • the sample drive mechanism includes: a first drive mechanism for driving the first pump body and the first valve body; a second drive mechanism for driving the second pump body and the second valve body; It may also include.
  • the first pump body, first valve body, second pump body, and first valve body provided in the analysis cartridge can more easily and accurately control the fluid sample and mobile phase.
  • the first pump body and the second pump body may be of different configurations or may be of the same configuration.
  • the first valve body and the second valve body may also be of different configurations or may be of the same configuration.
  • the analysis chip comprises: an analytical flow path through which the mobile phase and the fluid sample move when the mobile phase is energized; a sample flow path through which the fluid sample travels before being applied to the mobile phase; Including,
  • the analysis flow path may be configured so that a plurality of columnar structures are distributed therein, and the mobile phase and the fluid sample applied to the mobile phase move through gaps between the plurality of columnar structures.
  • the present disclosure also provides a pretreatment device that performs pretreatment for analysis on a specific component in a test object, comprising: a pre-processing unit that extracts the specific component from a specimen collected from an analysis subject and performs pre-processing to generate a fluid sample for analysis; the pretreatment section has a pretreatment cartridge mounting section for mounting a replaceable pretreatment cartridge;
  • the pretreatment cartridge includes: a test object installation device for installing a test object-containing element containing the test object;
  • the pretreatment device may further comprise a sample generator for extracting the specimen from the specimen-containing element into a pretreatment fluid to generate the fluid sample.
  • the sample preparation device in the pretreatment cartridge comprises: a pre-treatment fluid controller for moving the pre-treatment fluid into contact with the specimen-containing element; In the pretreatment section, outside the pretreatment cartridge, a drive mechanism for driving the pretreatment fluid controller;
  • the pre-treatment device may be characterized in that it is provided with:
  • the pretreatment cartridge in the pretreatment section includes: A temperature control mechanism for adjusting the temperature of the pretreatment fluid and/or the fluid sample,
  • the pre-treatment device may further include the above-mentioned pre-treatment device.
  • the pretreatment cartridge in the pretreatment section includes: A mixing and stirring mechanism for mixing or stirring the pretreatment fluid and/or the fluid sample,
  • the pre-treatment device may further include the above-mentioned pre-treatment device.
  • the pretreatment device may be characterized in that the pretreatment fluid controller includes a valve body that switches the flow path of the pretreatment fluid, and a pump body that pressurizes the pretreatment fluid into the flow path.
  • the present disclosure also provides an analysis device for analyzing a specific component in a test object, comprising: an analysis cartridge mounting portion for mounting an analysis cartridge for storing a fluid sample for analysis in a replaceable manner;
  • the analytical cartridge includes: An analysis chip for performing the analysis;
  • a sample controller is provided to control a mobile phase, which is a fluid for causing the fluid sample to flow into the analysis chip, and the fluid sample;
  • the analytical device may further comprise a sample drive mechanism for driving the sample controller.
  • a detection optical system that irradiates an inspection light onto the fluid sample moving within the analysis chip, receives an output light, and outputs a signal corresponding to the output light;
  • the above-mentioned analysis device may further include:
  • the analytical cartridge further comprises: a waste tank for storing the fluid sample and the mobile phase after analysis that have moved within the analytical chip;
  • the above-mentioned analysis device may further include:
  • the sample controller further comprises: a first pump body and a first valve body for moving a mobile phase, which is a fluid for causing the fluid sample to flow into the analysis chip; a second pump body and a second valve body for moving the fluid sample for application to the mobile phase;
  • the sample drive mechanism includes: a first drive mechanism for driving the first pump body and the first valve body; a second drive mechanism for driving the second pump body and the second valve body;
  • the above-mentioned analysis device may include:
  • the analysis chip comprises: an analytical flow path through which the mobile phase and the fluid sample move when the mobile phase is energized; a sample flow path through which the fluid sample travels before being applied to the mobile phase; Including,
  • the above-mentioned analytical device may be characterized in that the analysis flow path has a plurality of columnar structures distributed therein, and the mobile phase and the fluid sample applied to the mobile phase are configured to move through gaps between the plurality of columnar structures.
  • the present disclosure also provides a pretreatment cartridge that is attached to a pretreatment device that extracts a specific component from a test object and performs pretreatment to generate a fluid sample for analysis, the pretreatment cartridge comprising: a test object setting device for setting a test object-containing element containing the test object collected from the analysis subject;
  • the pretreatment cartridge may further comprise a sample generator for extracting the specimen from the specimen-containing element into a pretreatment fluid to generate the fluid sample.
  • the present disclosure also provides a pretreatment cartridge that is attached to a pretreatment device that extracts a specific component from a test object and performs pretreatment to generate a fluid sample for analysis
  • the pretreatment cartridge comprising: a test object setting device for setting a test object-containing element containing the test object collected from the analysis subject; a pretreatment liquid tank in which a pretreatment fluid for extracting the specimen is stored; a sample tank for storing the pretreated fluid sample; a modifying liquid tank in which a modifying liquid used in the pretreatment is stored; A pump body that sucks and pumps various chemical liquids; A valve body for controlling which tank the chemical solution is drawn from and which tank it is pumped to;
  • the pretreatment cartridge may be provided with at least one of the above.
  • the sample preparation device further comprises: a pre-treatment fluid controller for moving the pre-treatment fluid into contact with the specimen-containing element;
  • the pretreatment cartridge may be characterized in that the pretreatment fluid controller is driven by a drive mechanism provided outside the pretreatment cartridge in the pretreatment device.
  • the pretreatment cartridge may be characterized in that the temperature of the pretreatment fluid and/or the fluid sample is regulated by a temperature control mechanism provided outside the pretreatment cartridge in the pretreatment device.
  • the pretreatment cartridge may be characterized in that the pretreatment fluid and/or the fluid sample are mixed or stirred by a mixing and stirring mechanism provided outside the pretreatment cartridge in the pretreatment device.
  • the pretreatment fluid controller may be the above pretreatment cartridge, characterized in that it includes a valve body that switches the flow path of the pretreatment fluid, and a pump body that pressurizes the pretreatment fluid into the flow path.
  • the present disclosure also provides an analysis cartridge that is mounted on an analysis device for analyzing a specific component in a test object and contains a fluid sample for analysis, the analysis cartridge comprising: An analysis chip for performing the analysis; A sample controller is provided to control a mobile phase, which is a fluid for causing the fluid sample to flow into the analysis chip, and the fluid sample;
  • the analysis cartridge may be characterized in that the sample controller is driven by a sample drive mechanism provided outside the analysis cartridge in the analysis device.
  • an inspection light is incident on the fluid sample moving in the analysis chip from a detection optical system provided outside the analysis cartridge in the analysis device
  • the above-mentioned analysis cartridge may be characterized in that the output light is received by the detection optical system and a signal corresponding to the output light is output.
  • the present disclosure may be directed to the above-mentioned analysis cartridge, further comprising a waste tank for storing the fluid sample and the mobile phase after analysis that have moved through the analysis chip.
  • the sample controller further comprises: a first pump body and a first valve body for moving a mobile phase, which is a fluid for causing the fluid sample to flow into the analysis chip; a second pump body and a second valve body for moving the fluid sample for application to the mobile phase;
  • the sample drive mechanism includes: a first drive mechanism for driving the first pump body and the first valve body; a second drive mechanism for driving the second pump body and the second valve body;
  • the above analytical cartridge may be characterized by including:
  • the analysis chip further comprises: an analytical flow path through which the mobile phase and the fluid sample move when the mobile phase is energized; a sample flow path through which the fluid sample travels before being applied to the mobile phase; Including,
  • the above-mentioned analysis cartridge may be characterized in that the analysis flow path has a plurality of columnar structures distributed therein, and the mobile phase and the fluid sample applied to the mobile phase are configured to move through gaps between the plurality of columnar structures.
  • the specific component may include at least one of an amino acid, a protein, a base, a lipid, and an extracellular vesicle.
  • the present disclosure also provides a pretreatment cartridge for extracting specific components from a test object and performing pretreatment to generate a fluid sample for analysis of the test object, comprising: a test specimen holder for holding a test specimen collected from the subject to be analyzed;
  • the pretreatment cartridge may further comprise a sample preparation device for pretreatment of the test object in the test object holder to prepare the fluid sample.
  • a pretreatment liquid tank for storing a pretreatment fluid for extracting the specimen.
  • a sample tank for storing the pretreated fluid sample;
  • a modifying liquid tank in which a modifying liquid used in the pretreatment is stored;
  • the sample generator includes: A pump body that sucks and pumps various chemical liquids;
  • a valve body for controlling which tank the chemical solution is drawn from and which tank it is pumped to; The above configuration may also be adopted.
  • the liquid supply device further includes a flow path for moving the specimen to the sample reservoir after the pretreatment liquid is supplied, a cleaning liquid tank for storing a cleaning liquid for cleaning at least one of the specimen holder, the sample tank, the flow path, and the sample preparation device using the sample preparation device; a waste liquid tank for storing at least one waste liquid of the test object, the pretreatment liquid, the fluid sample, and the cleaning liquid; It may further comprise:
  • the sample tank may be installed so that the fluid sample in the sample tank can be analyzed from the outside.
  • the sample tank may have an analysis window that allows the fluid sample to be optically analyzed from the outside.
  • the present disclosure may further include an analyzer that analyzes the fluid sample stored in the sample tank.
  • the present disclosure also provides a third mounting portion to which any one of the pretreatment cartridges described above is mounted; and an analyzer that analyzes the fluid sample in the pretreatment cartridge mounted in the third mounting portion.
  • the present invention allows analysts without specialist knowledge to easily perform analysis, and makes it possible to realize an analysis system that is small and has a simple structure.
  • FIG. 1 is a diagram showing an outline of a conventional method for analyzing a biological component.
  • 1 is a conceptual diagram of a measurement principle in a liquid chromatograph device according to the present disclosure.
  • 2 is an example of a biological component obtained by a liquid chromatograph device according to the present disclosure.
  • FIG. 1 is a diagram showing an outline of a method for analyzing a biological component according to an embodiment of the present disclosure.
  • FIG. 1 is a block diagram of an analysis system according to an embodiment of the present invention.
  • FIG. 2 is a diagram showing a specific structure of a pretreatment device according to an embodiment of the present invention.
  • FIG. 2 is a diagram showing a specific structure of an analysis device according to an embodiment of the present invention.
  • FIG. 1 is a diagram showing an outline of a conventional method for analyzing a biological component.
  • 1 is a conceptual diagram of a measurement principle in a liquid chromatograph device according to the present disclosure.
  • 2 is an example of a biological component obtained by a
  • FIG. 1 is a diagram showing a schematic configuration of a pillar array column according to an embodiment of the present invention.
  • FIG. 1 is a diagram showing a schematic configuration of a detection optical system according to an embodiment of the present invention.
  • FIG. 13 is a diagram showing a specific structure of an analysis device according to a modified example of the present invention.
  • FIG. 1 shows an outline of a conventional method for analyzing biological components (amino acids, proteins, bases, lipids, extracellular vesicles, etc.) as an example of a specific component.
  • the collection method may be, for example, as shown in FIG. 1, to collect blood from the analysis target 2 with a syringe.
  • biological components are manually extracted from the blood as the test object, and pre-processing that enables analysis is performed to generate a liquid sample as a fluid sample.
  • separation and analysis of the liquid sample are performed in an analysis device 5. Thereafter, the results of the separation and analysis are provided to a medical institution or directly to the user as paper media or electronic data, as appropriate.
  • FIG. 2 shows a conceptual diagram of the measurement principle in a liquid chromatograph 110 as a conventional analytical device 5.
  • a column (stationary phase) 120 has a structure in which a carrier such as diatomaceous earth is filled in a container.
  • a liquid sample 122 which is produced in the pretreatment process described above by, for example, fluorescently modifying biological components in blood as the test object, is passed through a sample path 120a in the column 120.
  • a mobile phase 121 which is a liquid for separating biological components in sweat, is passed through the column 120.
  • This mobile phase 121 flows at a constant speed through the column 120 (stationary phase) from a sample introduction section 120b toward a detection section 120d by a liquid delivery pump (not shown).
  • the liquid sample 122 is injected into the sample introduction section 120b of the column 120 and is placed in the flow of the mobile phase 121 in the column 120.
  • the biocomponents in the liquid sample move through the separation section 120c in the column 120 by the flow of the mobile phase 121, but since the moving speed differs depending on the type of biocomponent, the biocomponents are separated by type in the separation section 120c.
  • Each separated biocomponent is detected by detecting the fluorescence generated by each biocomponent using excitation light irradiated from the light source 123 with the light receiving element 124.
  • the type of each biocomponent is identified by the time at which it is detected in the detection section 120d, and the amount of each biocomponent is detected from the fluorescence intensity.
  • analysis such as mass spectrometry may be performed in the external detector 125.
  • Figure 3 shows an example of a biocomponent profile obtained by the liquid chromatograph device 110.
  • the horizontal axis in Figure 3 represents the time that each type of biocomponent is retained in the column 120, and corresponds to the migration speed of each type of biocomponent.
  • the vertical axis in Figure 3 represents the signal intensity (fluorescence intensity, etc.) detected by the detection unit 120d, and corresponds to the amount of each type of biocomponent.
  • FIG. 4 provides an overview of the method for analyzing biological components in this embodiment. Note that in this embodiment, the case where the subject of analysis 2 is a human is described. However, the subject of analysis 2 is not limited to a human, and may be an animal other than a human. Furthermore, soil, rivers, plant factories, etc. may also be used as the subject of analysis.
  • the collection method may be to collect sweat from the skin of the analysis subject 2 using a hygroscopic patch 3.
  • hygroscopicity means either or both of the properties of water absorption and oil absorption.
  • the pretreatment device 10 of the analysis system biological components in the sweat as the test object are extracted, and pretreatment that enables analysis is performed to generate a liquid sample.
  • the analysis device 20 may be a device that performs liquid chromatography as a measurement principle (liquid chromatograph).
  • the results of the separation analysis and associated information may then be provided to the user in a form as shown on the display screen 7.
  • the patch 3 is used as a collector for collecting the test object
  • sweat as the test object may be collected by another method.
  • a method of directly collecting the test object using a collection liquid is conceivable.
  • the collection liquid refers to water, an organic solvent, or a mixed liquid prepared with other components. This point is also true in the following description of this specification.
  • the test object is not limited to sweat, but may be blood, urine, tears, or saliva, and the optimal collection method may be selected according to each test object.
  • the results of the separation analysis are provided to the user by displaying them on a device such as a smartphone, but the method of using the information is not limited to this.
  • a device such as a smartphone
  • the method of using the information is not limited to this.
  • an example of analyzing amino acids in sweat as biological components will be described below, but this disclosure also includes collecting and analyzing proteins, bases, lipids, extracellular vesicles, etc. other than amino acids as biological components.
  • FIG. 5 shows a block diagram of the analysis system 1 in this embodiment.
  • the analysis system 1 includes a pretreatment device 10 and an analysis device 20.
  • the pretreatment device 10 is a device that pretreats sweat, which is a test object collected from the analysis subject 2, to generate a liquid sample that can be detected by the analysis device 20.
  • an example of the pretreatment in this embodiment is fluorescent modification of amino acids in sweat.
  • the pretreatment device 10 is detachably equipped with a pretreatment cartridge 50 that contains most of the instruments and chemicals required for this pretreatment.
  • an analytical cartridge 60 containing most of the instruments and chemical solutions for analyzing the pretreated liquid sample is also removably attached to the pretreatment device 10. That is, in the pretreatment device 10, a patch 3 containing sweat collected from the subject 2 is placed in the pretreatment cartridge 50, and then the pretreatment cartridge 50 is attached to the pretreatment device 10, thereby making it possible to pretreatment of amino acids in sweat. Then, in the pretreatment device 10, the pretreated liquid sample in the pretreatment cartridge 50 is supplied to the analytical cartridge 60.
  • the analysis cartridge 60 containing the liquid sample is removed from the pretreatment device 10, and is then attached to the analysis device 20.
  • This makes it possible to analyze the liquid sample in the analysis device 20.
  • the analyst does not need to perform specific pretreatment work.
  • FIG. 6 shows the specific structure of the pretreatment device 10.
  • the pretreatment device 10 is provided with a pretreatment cartridge mounting section 50a, which is a mechanism for mounting the pretreatment cartridge 50, and the pretreatment cartridge 50 is removably mounted therein.
  • an analytical cartridge mounting section 60a is provided as a first mounting section, which is a mechanism for mounting the analytical cartridge 60, and the analytical cartridge 60 is removably mounted therein.
  • the pretreatment cartridge mounting section 50a and the analytical cartridge mounting section 60a each have a so-called loading mechanism, and the loading mechanism may be operated when the analyst pushes the pretreatment cartridge 50 and the analytical cartridge 60 into the pretreatment device 10, which pulls them in and automatically mounts them.
  • the mechanism may be such that the analyst manually mounts them at a specified mounting location.
  • a patch 52 is set inside the pretreatment cartridge 50 as a test object-containing element that contains sweat collected from the subject 2.
  • a holder 52a is provided as a test object setting device that holds the patch 52, and the analyst may set the patch 52 in the holder 52a of the pretreatment cartridge 50 outside the pretreatment device 10 and then attach it to the pretreatment device 10.
  • the pretreatment cartridge 50 is also provided with a pretreatment liquid tank 53 that stores a pretreatment liquid as a pretreatment fluid, and a sample tank 54 that stores the liquid sample after pretreatment.
  • a modification liquid tank 56 is provided in which a modification liquid for fluorescent modification in pretreatment is stored.
  • the number of modification liquid tanks 56 may be multiple depending on the type of modification liquid.
  • the pretreatment cartridge 50 is also provided with a syringe pump body 51 as a pump body that draws and pumps various chemical liquids, and a valve body 55 as a valve body for controlling which tank the chemical liquid is drawn from and pumped to.
  • the syringe pump body 51 and valve body 55 correspond to the pretreatment fluid controller in this embodiment.
  • valve drive unit 15 for driving the valve body 55
  • syringe pump drive unit 13 for driving the syringe pump body 51.
  • the valve drive unit 15 and the syringe pump drive unit 13 correspond to the drive mechanism in this embodiment.
  • a temperature adjustment unit 14 as a temperature control mechanism for maintaining the temperature of the pretreatment liquid in the pretreatment liquid tank 53 or the liquid temperature of the liquid sample in the sample tank 54 at an appropriate temperature.
  • a mixing and stirring unit 16 is provided as a mixing and stirring mechanism for mixing and stirring the pretreatment liquid in the pretreatment liquid tank 53 or the liquid sample in the sample tank 54.
  • This mixing and stirring unit 16 homogenizes the pretreatment liquid or the liquid sample and promotes the reaction by applying, for example, ultrasonic vibration to the pretreatment liquid in the pretreatment liquid tank 53 or the liquid sample in the sample tank 54.
  • This mixing and stirring unit 16 does not necessarily have to apply ultrasonic vibration to the pretreatment liquid in the pretreatment liquid tank 53 or the liquid sample in the sample tank 54.
  • it may be a mechanism that applies at least one of light, heat, an electric field, a magnetic field, gravity, and inertial force to the pretreatment liquid in the pretreatment liquid tank 53 or the liquid sample in the sample tank 54 to mix and stir them.
  • the pretreatment liquid in the pretreatment liquid tank 53 or the liquid sample in the sample tank 54 may be mixed and stirred by generating convection.
  • an electric field or magnetic field is applied, the charge in the pretreatment liquid in the pretreatment liquid tank 53 or the liquid sample in the sample tank 54 may be moved, or a rotor made of a magnetic material may be provided in the pretreatment liquid tank 53 or the sample tank 54, and the pretreatment liquid may be mixed and stirred by the movement of the rotor.
  • gravity or inertia is applied, the pretreatment liquid tank 53 or the sample tank 54 may be physically vibrated or its position may be changed.
  • a mechanism for mixing and stirring the pretreatment liquid or the liquid sample may be provided in the pretreatment cartridge 50.
  • a structure such as a pillar array mixer for mixing and stirring the fluid may be provided in the pretreatment liquid tank 53 or the sample tank 54, or in the flow path of the pretreatment liquid or the liquid sample.
  • the device includes a control board 12 that sends drive signals to the valve drive unit 15 and the temperature adjustment unit 14, and a control unit 11 that sends command signals to the control board 12.
  • This control unit 11 may be a computer that is connected to an external cloud server via a network and constitutes a cloud system. Alternatively, it may be an edge computer that constitutes an edge computing system that performs all or part of the drive mechanism, temperature control, and data processing within the device.
  • the control unit 11 may be provided inside the device housing, or outside the device housing.
  • the syringe pump body 51 and the valve body 55 are controlled by the syringe pump drive unit 13 and the valve drive unit 15 to supply the pretreatment liquid from the pretreatment liquid tank 53 to the set patch 52, and move the pretreatment liquid from which sweat has been extracted to the sample tank 54.
  • the modification liquid in the modification liquid tank 56 is added to the sample tank 54 containing sweat.
  • a pretreated liquid sample is generated in the sample tank 54.
  • the sample generator in this embodiment is composed of the syringe pump body 51, the valve body 55, the syringe pump drive unit 13, and the valve drive unit 15.
  • the pretreatment unit in this embodiment is composed of components other than the analysis cartridge mounting unit 60a, the analysis cartridge 60, and the sample supply mechanism 59 (described later) in the pretreatment device 10.
  • the analysis cartridge 60 is installed in the pretreatment device 10, and a portion of the liquid sample stored in the sample tank 54 of the pretreatment cartridge 50 is supplied to the sample tank 61 in the analysis cartridge 60.
  • This process may be achieved by the operation of the syringe pump body 51 and the valve body 55 in the pretreatment cartridge 50, or by the operation of a dedicated mechanism provided in the analysis cartridge 60. Alternatively, it may be achieved by another mechanism in the pretreatment device 10.
  • the amount of liquid sample stored in the sample tank 54 in the pretreatment cartridge 50 is on the order of several milliliters, and the amount of liquid sample stored in the sample tank 61 in the analysis cartridge 60 is on the order of several microliters. Therefore, the mechanism for supplying the liquid sample from the sample tank 54 to the sample tank 61 may be, for example, a mechanism for the liquid sample to fall by its own weight, or a mechanism for moving the liquid sample by utilizing capillary action. In this way, in the pretreatment device 10, the liquid sample after pretreatment is automatically moved and stored from the sample tank 54 in the pretreatment cartridge 50 to the sample tank 61 in the analysis cartridge 60.
  • the mechanism for supplying a portion of the liquid sample stored in the sample tank 54 to the sample tank 61 is the sample supply mechanism 59, which corresponds to the sample supply unit in this embodiment.
  • the analyst detaches the analysis cartridge 60, which contains the sample tank 61 in which the liquid sample is stored, from the pretreatment device 10 and attaches it to the analysis device 20.
  • FIG. 7 shows the specific structure of the analysis device 20.
  • the analysis device 20 is provided with a second analysis cartridge mounting section 60b as a second mounting section to which the analysis cartridge 60 can be mounted, and the analysis cartridge 60 is removably mounted.
  • the second analysis cartridge mounting section 60b may have a so-called loading mechanism, and the loading mechanism may be operated by the analyst pushing the analysis cartridge 60 into the analysis device 20, and the analysis cartridge 60 may be pulled inside and automatically mounted. Alternatively, the mechanism may be such that the analyst manually mounts the analysis cartridge 60 at a predetermined mounting location.
  • the analysis cartridge 60 is provided with a sample tank 61 in which a liquid sample after pretreatment is stored.
  • a second syringe pump body 62 as a second pump body for moving the liquid sample in the sample tank 61 and a second valve body 66 as a second valve body are provided.
  • a mobile phase tank 63 is provided in which the mobile phase is stored.
  • a first syringe pump body 64 and a third syringe pump body 65 are provided as first pump bodies for moving the mobile phase in the mobile phase tank 63
  • a first valve body 67 is provided as a first valve body.
  • the sample controller includes components corresponding to the first pump body, the first valve body, the second pump body, and the second valve body.
  • an analysis chip 68 and a waste liquid tank 69 are provided as a waste tank in which waste liquid after passing through the analysis chip 68 is stored.
  • the first syringe pump body 64 is used for a hydrophilic mobile phase
  • the third syringe pump body 65 is used for a lipophilic mobile phase.
  • a second valve drive unit 26 for driving the second valve body 66, and a second syringe pump drive unit 23 for driving the second syringe pump body 62.
  • the second valve drive unit 26 and the second syringe pump drive unit 23 correspond to the second drive mechanism in this embodiment.
  • a first valve drive unit 27 for driving the first valve body 67, and a first syringe pump drive unit 24 and a third syringe pump drive unit 25 for driving the first syringe pump body 64 and the third syringe pump body 65.
  • the first valve drive unit 27, the first syringe pump drive unit 24, and the third syringe pump drive unit 25 correspond to the first drive mechanism in this embodiment.
  • the sample drive mechanism includes components corresponding to the first drive mechanism and the second drive mechanism. It further includes a control board 22 that sends drive signals to the second syringe pump drive unit 23, the second valve drive unit 26, the first syringe pump drive unit 24, the third syringe pump drive unit 25, and the first valve drive unit 27, and a control unit 21 that sends command signals to the control board 22. It also includes a detection optical system 28 for detecting amino acids by irradiating detection light onto the liquid sample moving inside the analysis chip 68 and receiving the output light.
  • the mobile phase in the mobile phase tank 63 is delivered to the analysis chip 68 at a flow rate equal to that of the analysis chip 68 by controlling the first syringe pump drive unit 24 or the third syringe pump drive unit 25 and the first valve drive unit 27.
  • the first syringe pump body 64 or the third syringe pump body 65 is set so that one analysis is completed with one forward drive of the piston. Therefore, there is no need for complex operations such as repeatedly sucking up and discharging the mobile phase into the first syringe pump body 64 or the third syringe pump body 65, and analysis can be performed with easier control.
  • the second syringe pump body 62 is set so that one analysis is completed with one reciprocating drive of the piston (one sucking up and discharging operation of the second syringe pump body 62). Therefore, there is no need for complex operations such as repeatedly sucking up and discharging the liquid sample into the second syringe pump body 62, and analysis can be performed with easier control.
  • the analysis device 20 amino acids are analyzed by irradiating the liquid sample moving inside the analysis chip 68 with test light from the detection optical system 28 and detecting the emitted fluorescence, and the analysis result data may be stored in memory in the control unit 21.
  • the analysis device 20 is provided with a waste liquid tank 69 inside the analysis cartridge 60 for storing waste liquid after analysis. Therefore, there is no need to dispose of the chemical liquid outside the analysis device 20, and it is possible to increase the flexibility of the installation location of the analysis device 20.
  • Figure 8 shows a schematic configuration of the pillar array column 70 used in the analytical chip 68 in this embodiment.
  • Figure 8(a) is a plan view of the pillar array column 70
  • Figure 8(b) is an enlarged view of the internal structure of the separation channel 72 serving as the analytical channel of the pillar array column 70
  • Figure 8(c) shows an enlarged view of the curved structure of the separation channel 72 of the pillar array column 70.
  • the pillar array column 70 uses a silicon substrate, and the separation channel 72 is created by photolithography and dry etching.
  • the mobile phase flows in from the first inlet 71.
  • the liquid sample flows in from the second inlet 76.
  • the sample injection channel 77 which serves as a sample channel, and the separation channel 72
  • the liquid sample flows into the separation channel 72 by being placed on the flow of the mobile phase.
  • fine pillar structures (columnar structures) 72a as shown in FIG. 8(b) are formed.
  • the liquid sample is separated by the movement of the mobile phase and liquid sample through the gaps in the pillar structures 72a.
  • the pillar structures may be square or diamond-shaped pillars with sides of several ⁇ m.
  • the gap width in the pillar structure may be set to a width smaller than the length of one side of the pillar.
  • the separation channel 72 is formed into a folded curved channel to increase the channel length.
  • this curved structure 73 as shown in FIG. 8(c), the outer and inner circumferences of the channel are made equal in length to suppress the generation of turbulence in the separation channel 72 and to suppress the diffusion of the separated liquid sample.
  • the density of the pillars is made higher on the inner circumference side than on the outer circumference side.
  • a pillar array column 70 in which pillars of such uniform shape are distributed is used as the analytical chip 68, which reduces the liquid transfer resistance and makes it possible to miniaturize the device. It also makes it possible to improve separation efficiency and shorten the analysis time.
  • the liquid transfer resistance is high and high pressure is generated inside the column case, so the case needs to be made of metal, and the liquid sample and mobile phase need to be put into a glass tube outside the case before optical measurement can be performed.
  • the liquid transfer resistance is small as described above, and therefore the housing of the pillar array column 70 can be made of glass.
  • the pillar array column 70 can be directly irradiated with the test light from the detection optical system 28 and the output light can be received.
  • the output light from the liquid sample which is derived from the light reflected by the metal surface of the test light, and the light reflected by the metal surface of the output light itself can also be received by the detection optical system 28, making it possible to obtain higher sensitivity.
  • the pillar array column 70 it is possible to analyze liquid samples with a mobile phase and liquid sample flow rate of about several ⁇ l/min. In this way, by using the pillar array column 70, analysis can be performed at a lower flow rate compared to analysis using conventional columns, and the amount of mobile phase and liquid sample can be reduced, making it possible to miniaturize the pretreatment device 10 and the analysis device 20.
  • Figure 9 shows an example of the schematic configuration of the detection optical system 28 in this embodiment.
  • an LD 28a with a fluorescence excitation wavelength of the fluorescently modified amino acid is used as a light source.
  • the detection light emitted from the LD 28a passes through the beam splitter 28b and is redirected by the mirror 28c, and then is focused by the objective lens 28d and irradiated onto the separation channel 72 in the analysis chip 68.
  • the analysis cartridge 60 may be entirely made of a transparent material such as glass, or may be entirely made of a metal or the like with a transparent window provided near the entrance of the inspection light.
  • the analytical chip 68 may be made of glass on the detection optical system 28 side and of a metal such as SUS on the opposite side.
  • the fluorescence from the liquid sample passes through objective lens 28d, is reflected by mirror 28c, is reflected by beam splitter 28b, and then only the fluorescent components are selected by filter 28e, which passes light of the fluorescent wavelength, and is detected by photodetector 28f.
  • the analysis device 20 of this embodiment can employ a detection optical system having a configuration similar to that of the recording and playback optical system used in optical recording devices such as DVDs. This makes it possible to miniaturize the analysis device 20.
  • the liquid sample was irradiated with detection light from a light source and the fluorescence from the amino acids in the liquid sample was detected with a photodetector to detect separated amino acids.
  • the biological component is, for example, an autoluminescent protein
  • the light from the autoluminescent protein can be detected with a photodetector.
  • amino acids were analyzed by liquid chromatography, but other methods may be used depending on the specific component (biological component). Examples of other methods include electrophoresis, gas chromatography, and immunoassays. Alternatively, a method of measuring electrical conductivity using an electrical conductivity meter, a method of measuring the amount of ions or dissolved substances using an electrochemical sensor, or a method of measuring the amount of substance adsorbed to the sensor surface using a QCM (Quartz Crystal Microbalance) sensor may be used.
  • QCM Quadrat Crystal Microbalance
  • the fluid sample in this disclosure is a gas sample.
  • a pretreatment cartridge 50 and an analysis cartridge 60 are attached to the pretreatment device 10. Then, in the closed space inside the pretreatment device 10, pretreatment is performed to generate a liquid sample.
  • an analysis cartridge 60 containing a liquid sample is attached to the analysis device 20, and the liquid sample is analyzed inside the analysis device 20.
  • waste liquid is also stored in the analysis cartridge 60. Therefore, there is no need to connect the pretreatment device 10 and the analysis device 20 to the outside with piping, and there is no flow of chemical liquids in or out. Therefore, it is possible to easily analyze biological components regardless of location. It also eliminates the inconvenience of liquid samples remaining in the dead volume at the connection points of the piping, which reduces the accuracy of analysis.
  • the pretreatment device 10 of this embodiment is not necessarily limited to a configuration in which pretreatment is performed and liquid samples are produced within the pretreatment cartridge 50.
  • the pretreatment device 10 is configured to be able to mount an analysis cartridge 60, and pretreatment and liquid sample production may be performed outside the analysis cartridge 60 within the pretreatment device 10.
  • the part within the pretreatment device 10 where pretreatment and liquid sample production are performed corresponds to the pretreatment section.
  • test object is collected from a living body as an analysis target, and the biological components (amino acids) in the test object are analyzed.
  • biological components amino acids
  • specific components in the present disclosure are not limited to biological components. Any substance (including organic substances, inorganic substances, lipophilic substances, and hydrophilic substances) contained in a fluid (liquid or gas) can be treated as a specific component.
  • the analysis target may be a living body such as a human or animal, or soil, river, plant factory, etc.
  • a pretreatment cartridge 50 and an analysis cartridge 60 were attached to the pretreatment device 10. Then, pretreatment was performed in the closed space inside the pretreatment device 10 to generate a liquid sample. The liquid sample generated in the pretreatment cartridge 50 was transferred to the analysis cartridge 60, and the analysis cartridge 60 containing the liquid sample was attached to the analysis device 20, and the liquid sample was analyzed in the analysis device 20.
  • a liquid sample is automatically generated in the pretreatment cartridge, and the generated liquid sample is analyzed in the analysis device.
  • FIG. 10 shows a schematic diagram of the analysis device 100 in this modified example.
  • a pretreatment cartridge 90 is removably attached to the analysis device 100 in this modified example. Then, the test object is pretreated in the pretreatment cartridge 90, and the components of the test object can be analyzed by an analyzer 101 in the analysis device 100.
  • an analyzer 101 in the analysis device 100.
  • the analyzer 100 is provided with a pretreatment cartridge mounting section 90a, which is a mechanism for mounting the pretreatment cartridge 90.
  • a holder 92a is provided as a test object holder for holding a patch 92, and the analyst sets the patch 92 containing the test object in the holder 92a of the pretreatment cartridge 90.
  • the test object in addition to extracting the test object from the patch 92, the test object may be introduced into the pretreatment cartridge 90 by storing a liquid containing the test object in the test object holder or by having the test object holder hold a liquid container.
  • the test object holder may be a test object setting device for setting a test object-containing element, or may have another configuration.
  • the pretreatment cartridge 90 is also provided with a pretreatment liquid tank 93 in which a pretreatment liquid is stored, and a sample tank 94 in which a liquid sample after pretreatment is stored.
  • the pretreatment cartridge 90 is provided with a syringe pump body 91 that draws out and pumps out various chemical liquids, and a valve body 95 that controls which tank the chemical liquid is drawn out from and pumped to which location.
  • the pretreatment cartridge 90 is also provided with a valve drive unit 85 for driving the valve body 95, and a syringe pump drive unit 83 for driving the syringe pump body 91.
  • the sample generator is composed of the syringe pump body 91, the valve body 95, the syringe pump drive unit 83, and the valve drive unit 85.
  • the pretreatment cartridge 90 is also provided with a temperature control unit 84 as a temperature control mechanism for maintaining the temperature of the pretreatment liquid in the pretreatment liquid tank 93, the liquid sample in the sample tank 94, the modification liquid in the modification liquid tank 99, and the chemical liquid in the flow path at an appropriate temperature.
  • a mixing and stirring unit 86 is provided as a mixing and stirring mechanism for mixing and stirring the pretreatment liquid in the pretreatment liquid tank 93, the liquid sample in the sample tank 94, the modification liquid in the modification liquid tank 99, and the chemical liquid in the flow path. The mixing and stirring unit 86 physically stirs the chemical liquid in each tank and flow path to homogenize the pretreatment liquid or the liquid sample and promote the reaction.
  • the mixing and stirring unit 86 may apply ultrasonic vibration to the chemical liquid in each tank and flow path, or may be a mechanism for mixing and stirring by applying at least one of light, heat, an electric field, a magnetic field, gravity, and inertial force.
  • the function of the modification liquid is not limited to fluorescent modification of the test object.
  • control board 82 that sends drive signals to the syringe pump drive unit 83, the valve drive unit 85, the temperature adjustment unit 84, and the mixing and stirring unit 86, and a control unit 81 that sends command signals to the control board 82.
  • This control unit 81 is connected to an external cloud server via a network, and may be a computer that constitutes a cloud system.
  • the syringe pump body 91 and valve body 95 are controlled by the syringe pump drive unit 83 and valve drive unit 85 to supply pretreatment liquid from the pretreatment liquid tank 93 to the patch 92 containing the test substance, and the pretreatment liquid containing the test substance is further moved, and the pretreated liquid sample is stored in the sample tank 94.
  • the pretreatment cartridge 90 is provided with an analysis window 97.
  • This analysis window 97 and the sample tank 94 are made of a light-transmitting material. This makes it possible to optically analyze the sample from outside the pretreatment cartridge 90.
  • the sample is analyzed by an optical method, such as taking an image of the sample stored in the sample tank 94 through the above-mentioned analysis window 97 with the analyzer 101, or projecting light from the analyzer 101 onto the sample tank 94 and acquiring the reflected or scattered light with the analyzer 101.
  • the analyzer 101 in this case include a camera for acquiring images, and an optical head equipped with a laser light source and a photodetector.
  • the pretreatment cartridge 90 is also provided with a cleaning liquid tank 96 that stores cleaning liquid, and after the analysis is completed, it is possible to clean at least one of the holder 92a, the sample tank 94, the syringe pump body 91, the valve body 95, and the flow paths connecting them.
  • the pretreatment cartridge 90 may also be provided with a waste liquid tank 98 that stores waste liquid such as pretreatment liquid and samples after analysis, and waste liquid after cleaning.
  • the process of pretreating the test object and storing the liquid sample containing the test object in the sample tank 94 is carried out automatically within the pretreatment cartridge 90.
  • the liquid sample is then analyzed by an analyzer 101 provided outside the pretreatment cartridge 90 of the analysis device 100.
  • the analyzer 101, control board 82, and control unit 81 are described as being provided inside the analysis device 100 and outside the pretreatment cartridge 90, but at least one of the analyzer 101, control board 82, and control unit 81 may be provided inside the pretreatment cartridge 90.
  • the sample tank 94 is arranged so that the analyzer 101 can optically analyze the liquid sample from the outside through the analysis window 97.
  • the structure that allows the liquid sample in the sample tank 94 to be analyzed from the outside is not limited to this.
  • the outer wall of the pretreatment cartridge 90 near the sample tank 94 may be made of a non-metallic material, so that the analysis can be performed by an external analyzer using an electromagnetic method.
  • an opening may be provided near the sample tank 94 in the pretreatment cartridge 90, and a probe or sensor that detects the physical properties or electrical properties of the liquid sample may be inserted into the pretreatment cartridge 90 through this opening to analyze the liquid sample.
  • electrodes may be provided inside the sample tank 94 so as to sandwich the liquid sample, and the resistance between the electrodes may be measured from the outside of the sample tank 94.
  • a sensor that can measure the physical properties or electrical properties of the sample may be incorporated into the sample tank 94 itself, and an output terminal of the sensor may be provided on the outer surface of the sample tank 94.
  • the various tanks in the pretreatment cartridge 90 such as the pretreatment liquid tank 93, sample tank 94, cleaning liquid tank 96, and waste liquid tank 98, are provided so as to be replaceable, and by replacing them, it is possible to introduce or replace new chemical solutions or remove waste liquid from the device.
  • the pretreatment cartridge 90 is attached to the analysis device 100, and the liquid sample produced in the pretreatment cartridge 90 is analyzed by the analyzer 101 in the analysis device 100, but the analysis device may be provided separately from the pretreatment cartridge 90, and the liquid sample produced in the pretreatment cartridge 90 may be transferred to an independent analysis device for analysis of the liquid sample.
  • Reference Signs List 1 Analysis system 10: Pretreatment device 20, 100: Analysis device 50, 90: Pretreatment cartridge 60: Analysis cartridge 68: Analysis chip 70: Pillar array column

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Citations (7)

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JP2004245831A (ja) * 2003-01-21 2004-09-02 Denka Seiken Co Ltd メンブレンアッセイ法
JP2010271259A (ja) * 2009-05-25 2010-12-02 Sysmex Corp 生体成分分析方法、生体成分分析装置、生体成分分析用カートリッジおよび生体成分分析用キット
WO2011004653A1 (ja) * 2009-07-09 2011-01-13 凸版印刷株式会社 核酸抽出用キット、核酸抽出方法及び核酸抽出装置
JP2013101144A (ja) * 2008-09-30 2013-05-23 Sekisui Chem Co Ltd 検出用カートリッジ
JP2021151258A (ja) * 2020-02-25 2021-09-30 Ｂｌｕｅ Ｉｎｄｕｓｔｒｉｅｓ株式会社 遺伝子解析用前処理キット、核酸分析用チップ、解析システム、生体物質分析用チップ
WO2022065119A1 (ja) * 2020-09-28 2022-03-31 積水化学工業株式会社 検査チップ
WO2023032883A1 (ja) * 2021-08-30 2023-03-09 株式会社ダイセル マイクロ流体デバイス、及びその製造方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004245831A (ja) * 2003-01-21 2004-09-02 Denka Seiken Co Ltd メンブレンアッセイ法
JP2013101144A (ja) * 2008-09-30 2013-05-23 Sekisui Chem Co Ltd 検出用カートリッジ
JP2010271259A (ja) * 2009-05-25 2010-12-02 Sysmex Corp 生体成分分析方法、生体成分分析装置、生体成分分析用カートリッジおよび生体成分分析用キット
WO2011004653A1 (ja) * 2009-07-09 2011-01-13 凸版印刷株式会社 核酸抽出用キット、核酸抽出方法及び核酸抽出装置
JP2021151258A (ja) * 2020-02-25 2021-09-30 Ｂｌｕｅ Ｉｎｄｕｓｔｒｉｅｓ株式会社 遺伝子解析用前処理キット、核酸分析用チップ、解析システム、生体物質分析用チップ
WO2022065119A1 (ja) * 2020-09-28 2022-03-31 積水化学工業株式会社 検査チップ
WO2023032883A1 (ja) * 2021-08-30 2023-03-09 株式会社ダイセル マイクロ流体デバイス、及びその製造方法

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