WO2018139216A1

WO2018139216A1 - Disc for testing

Info

Publication number: WO2018139216A1
Application number: PCT/JP2018/000618
Authority: WO
Inventors: 貴裕野上; 健樹山本; 謙司永冨; 靖之祖父江
Original assignee: パナソニック株式会社
Priority date: 2017-01-27
Filing date: 2018-01-12
Publication date: 2018-08-02
Also published as: JP2020056577A

Abstract

Provided is a disc for testing which is capable of suppressing the scattering of a liquid specimen when the disc for testing is rotated around the center axis of the disc for testing. This disc (1) for testing is equipped with a well-forming disc body (2), a cartridge (3), and a ventilation channel (11). The well-forming disc body (2) has a first well (21) and a second well (22). The second well (22) is connected to the first well (21), and is separated from a surface (2A) and a rear surface in the thickness direction of the well-forming disc body (2). The cartridge (3) has a storage space (31) capable of storing a liquid specimen, and is fitted into the first well (21) of the well-forming disc body (2). The ventilation channel (11) is formed between the lateral surface of the cartridge (3) and the well-forming disc body (2). The ventilation channel (11) is connected to the second well (22) and to the exterior of the well-forming disc body (2).

Description

Inspection disk

The present disclosure relates to an inspection disk, and more particularly to an inspection disk for inspecting a liquid sample.

Conventionally, as a liquid sample inspection disk, for example, an analysis chip including a first chip and two or more second chips connected to the first chip has been proposed (Patent Document 1).

In the analysis chip described in Patent Document 1, the shape of the first chip viewed from the thickness direction of the first chip is, for example, a circle. The shape of the second chip viewed from the thickness direction of the second chip is, for example, a fan shape.

The first chip includes a specimen injection part and a connection part. The sample injection part is a space into which a sample is injected. The sample injection part has a sample injection hole, and the sample is injected from the sample injection hole to the sample injection part. A specimen refers to a sample that may contain a component to be analyzed. Examples of the specimen include blood, urine, saliva and the like. A second chip is connected to the connection portion. If the second chip is connected to the first chip via the connecting portion, the sample can be sent to the second chip by centrifugal force by rotating the analysis chip.

The second chip includes an introduction path and a reagent holding unit. The second chip further includes a mixing channel, a detection unit, a quantification unit, and a discharge unit. The introduction path introduces the sample injected into the sample injection unit into the second chip when the second chip is connected to the connection unit. The specimen that has passed through the introduction path and the reagent that has flowed out of the reagent holding unit are mixed in the mixing channel. The detection unit is connected to the end of the mixing channel opposite to the end connected to the introduction path and the reagent holding unit. An air hole opened to the atmosphere is connected to the detection unit. Accordingly, the specimen and the reagent can be sent from the mixing channel to the detection unit by capillary force in addition to centrifugal force. The discharge part is connected to the air hole. As a result, an extra amount of specimen can be sent to the discharge portion by capillary force in addition to centrifugal force.

JP 2014-232023 A

In the analysis chip described in Patent Document 1, for example, when a leak occurs at the connection point between the first chip and the second chip, the air hole not only fulfills its function, but also during the rotation of the analysis chip. There is a concern that the specimen and the reagent may be scattered.

An object of the present disclosure is to provide an inspection disk capable of suppressing scattering of a liquid sample when the inspection disk is rotated around the central axis of the inspection disk.

The inspection disc according to an aspect of the present disclosure includes a well forming disc main body, a cartridge, and a ventilation channel. The well-forming disk body has a front surface and a back surface that are opposite to each other in the thickness direction. The well forming disc body has a first well and a second well. The first well is composed of a recess formed along the thickness direction from the surface side of the well forming disk main body. The second well communicates with the first well. The cartridge has a storage space in which a liquid sample can be stored. The cartridge is fitted into the first well of the well forming disc body. The ventilation channel is formed between the cartridge and the well forming disk main body. The ventilation channel communicates with the outside of the well forming disk main body and the second well.

In this test disk, the cartridge preferably has a filter for removing a specific substance from the liquid sample moving from the storage space to the second well. Here, the filter is preferably located between the storage space and the second well.

In this test disk, the cartridge preferably includes a case having an opening at the end on the second well side and holding the filter. Here, it is preferable that the filter is disposed so as to close the opening. In the cartridge, it is preferable that a space surrounded by the case and the filter constitutes a storage space.

In this inspection disk, it is preferable that the first well and the second well are arranged in this order from the center of the well forming disk main body toward the outer periphery.

In this inspection disk, the well forming disk body preferably further includes a flow path and a connection flow path. The flow path is preferably between the first well and the second well and communicates with the first well and the second well. The connecting channel is preferably adjacent to the channel in the circumferential direction of the well-forming disk body, between the vent channel and the second well, and communicated with the vent channel and the second well. It is preferable that the opening area of the flow path gradually decreases as the distance from the first well increases toward the second well.

In this inspection disk, the well forming disk main body preferably includes a rib that protrudes from the inner wall surface of the recess toward the side surface of the cartridge and faces the bottom surface of the recess. Here, it is preferable that the space between the bottom surface of the recess and the rib constitutes a part of the ventilation channel.

In this test disk, the minimum height from the bottom surface of the recess to the rib in the thickness direction of the well forming disk main body prevents the capillary force from acting on the liquid sample in the second well in the ventilation channel. It is preferable that the height is high.

In the inspection disk, the minimum height from the bottom surface of the recess to the rib in the thickness direction of the well forming disk main body is the height from the bottom surface of the second well to the top surface in the thickness direction of the well forming disk main body. It may be larger than the minimum height.

In the test disk, it is preferable that a ventilation channel is formed on both sides of the cartridge in the circumferential direction of the well forming disk main body.

In the test disk, a ventilation channel may be formed only on one side of the cartridge in the circumferential direction of the well forming disk main body.

In the test disk, the volume of the second well is preferably larger than the volume of the storage space.

In this inspection disk, it is preferable that the area of the second well is larger than the area of the first well when viewed from the thickness direction of the well forming disk main body.

In this inspection disk, the ventilation channel is a space formed between a groove provided along the thickness direction of the well forming disk main body on the inner wall surface of the first well of the well forming disk main body and the side surface of the cartridge. May be included.

In the inspection disk, the ventilation channel is a space formed between the inner wall surface of the first well of the well forming disk main body and a groove provided along the thickness direction of the well forming disk main body on the side surface of the cartridge. May be included.

An inspection disk according to the present disclosure includes a well forming disk main body having a first well and a second well, and is formed between a side surface of the cartridge and the well forming disk main body and communicates with the outside of the well forming disk main body and the second well. A ventilation channel. Therefore, it is possible to suppress scattering of the liquid sample when the inspection disk is rotated around the central axis of the inspection disk.

FIG. 1 is a plan view of an inspection disk according to an embodiment of the present disclosure. FIG. 2A is a partially cutaway plan view of the above inspection disk. FIG. 2B is a cross-sectional view taken along the line IIB-IIB of FIG. FIG. 2C is a perspective view in which the inspection disk is partially broken as seen from below. FIG. 3A is a perspective view of the inspection disk. FIG. 3B is a perspective view in which the inspection disk is partially broken as seen from above. FIG. 3C shows the above-described inspection disk, and is an enlarged view of a main part C of FIG. 3B. FIG. 4 is an exploded perspective view of the above inspection disk. FIG. 5A is a perspective view of the inspection disk as seen from above the disk body. FIG. 5B is a perspective view of the above inspection disk as seen from the lower side of the disk body. FIG. 5C is a cross-sectional view taken along the line VC-VC of FIG. FIG. 5D is an enlarged view of the main part of FIG. FIG. 6 is an enlarged plan view of a track in the above-described inspection disk. FIG. 7 is an SEM image (Scanning / Electron / Microscope / Image) of the porous structure constituting the filter in the inspection disk. FIG. 8 is a configuration diagram of a detection apparatus for inspecting a liquid sample using the above-described inspection disk. FIG. 9A is a process sectional view for explaining the manufacturing method of the inspection disk. FIG. 9B is a process sectional view for explaining the manufacturing method of the inspection disk. FIG. 9C is a process cross-sectional view for explaining the manufacturing method of the inspection disc.

Each figure described in the following embodiment is a schematic diagram, and the ratio of the size and thickness of each component in the figure does not necessarily reflect the actual dimensional ratio.

(Embodiment)
Hereinafter, an inspection disk 1 (hereinafter referred to as “disk 1”) for inspecting a liquid sample according to the present embodiment will be described with reference to FIGS. 1 to 9C.

The disk 1 includes a disk-shaped well-forming disk main body 2 and a plurality of cartridges 3. The well forming disc main body 2 has a front surface 2A and a back surface 2B that are opposite to each other in the thickness direction. The well forming disc body 2 is preferably disc-shaped. The well forming disk main body 2 has a first well 21 and a second well 22 communicating with the first well 21. As shown in FIGS. 3A to 3C and 4, the well forming disk main body 2 includes a disk main body 4 and a plate 5 that is more flexible than the disk main body 4. The disc body 4 is preferably disk-shaped. The plate 5 is preferably disc-shaped.

In the well forming disk main body 2, the disk main body 4 and the plate 5 are joined so as to overlap each other. Hereinafter, the well forming disk main body 2 may be referred to as a laminated disk main body 2. In the laminated disk main body 2, the central axis 45 (see FIG. 4) of the disk main body 4 and the central axis 56 (see FIG. 4) of the plate 5 are aligned on a straight line. The center axis 10 (see FIG. 8) of the disk 1 is preferably aligned with the center axis 45 of the disk body 4 and the center axis 56 of the plate 5.

The disk main body 4 has a chamber 400 for storing a liquid sample. The disc body 4 has a first surface 41 and a second surface 42 that are opposite to each other in the thickness direction. The plate 5 is joined to the disc body 4 so as to cover the chamber 400 on the first surface 41 side of the disc body 4. The chamber 400 includes a first chamber 401 and a second chamber 402 as shown in FIG. 5B. The first chamber 401 penetrates in the thickness direction of the disc body 4, and the opening on the plate 5 side is closed by the plate 5. As a result, in the laminated disk main body 2, the first chamber 401 is open on the side opposite to the plate 5 side in the thickness direction of the disk main body 4. The second chamber 402 is formed on the first surface 41 of the disc body 4, and the side opposite to the plate 5 side in the thickness direction of the disc body 4 is closed. In the second chamber 402, the opening on the plate 5 side is closed by the plate 5. The second chamber 402 is in communication with (connected to) the first chamber 401. Here, the disc body 4 has a channel 403 (see FIGS. 2B, 5B, and 5C) that communicates with the first chamber 401 and the second chamber 402 between the first chamber 401 and the second chamber 402, respectively. Is preferred. The channel 403 is formed on the first surface 41 of the disk main body 4, and the side opposite to the plate 5 side in the thickness direction of the disk main body 4 is closed.

In the laminated disk main body 2, the space surrounded by the inner wall surface of the first chamber 401 and the plate 5 in the disk main body 4 constitutes the first well 21 capable of storing a liquid sample. Further, in the laminated disc body 2, the space surrounded by the inner wall surface of the second chamber 402 and the plate 5 in the disc body 4 can store the liquid sample moved from the first well 21. Is configured. In the laminated disk main body 2, a space surrounded by the inner wall surface of the channel 403 and the plate 5 in the disk main body 4 is a flow path 23 (see FIG. 5) through which a liquid sample passes between the first chamber 401 and the second chamber 402. 2C and 3B).

The liquid sample contains multiple types of substances. The cartridge 3 includes a filter 35 that removes a specific substance from the liquid sample moving from the first chamber 401 to the second chamber 402. Here, “removing a specific substance” means capturing a specific substance. In short, the filter 35 includes a porous structure 36 (see FIG. 7) that captures a specific first substance from the liquid sample and passes the specific second substance. Hereinafter, the cartridge 3 is also referred to as a filter cartridge 3. The filter cartridge 3 is placed in the first chamber 401 of the disc body 4. Here, in the disk 1, the filter cartridge 3 is fitted into the first well 21 of the laminated disk main body 2.

The disk 1 is used, for example, to examine the infection rate of pathogenic microorganisms (for example, malaria protozoa) to a specimen (for example, red blood cells) in a liquid biological sample (for example, human blood). The malaria parasite, for example, invades a human body when an mosquito sucks human blood, invades red blood cells in the blood, and parasitizes in red blood cells. The “infection rate” here is {[number of samples infected with pathogenic microorganisms] / [total number of samples]} × 100 [%]. The liquid sample includes at least a liquid biological sample. In the liquid sample, for example, when the biological sample is blood, the blood is preferably diluted with a diluent in order to reduce the viscosity. As the diluted solution, a solution that does not denature blood cells (erythrocytes, leukocytes) contained in the biological sample is used. As the diluent, for example, a buffer solution, an isotonic solution, a culture solution, a surfactant and the like can be used.

In the disk 1, it is preferable that a fluorescent reagent (fluorescent dye) for staining the nucleic acid of pathogenic microorganisms is disposed in the second well 22 of the laminated disk body 2. The fluorescent reagent is preferably arranged by, for example, a freeze-drying method or a spin coating method. Thereby, the disc 1 can fluorescently label the nucleic acid of the pathogenic microorganism that is parasitic on the specimen (red blood cells) in the liquid sample moved to the second well 22. The nucleic acid stained with the fluorescent reagent emits fluorescence when excitation light is irradiated from the outside. The fluorescent reagent for staining the nucleic acid of the pathogenic microorganism may be a powder.

In the disk 1, the filter 35 is configured to pass red blood cells that are specific second substances (specimens) and to capture white blood cells that are specific first substances. In other words, the filter 35 is configured to function as a separation unit that separates red blood cells and white blood cells and extracts red blood cells. Therefore, the disk 1 can extract red blood cells from a biological sample.

Fluorescent reagents for staining nucleic acids of pathogenic microorganisms are materials that can also stain leukocytes. However, in the disk 1, white blood cells in the liquid sample placed in the first well 21 are captured by the filter 35. Therefore, in the disc 1, it becomes possible to prevent the white blood cells contained in the liquid sample put in the first well 21 from being stained with the fluorescent reagent.

In the disk 1, the filter cartridge 3 has a storage space 31 in which a liquid sample can be stored. Here, the filter 35 in the filter cartridge 3 is preferably located between the storage space 31 and the second well 22 in the radial direction of the disc body 4. In the disk 1, the filter cartridge 3 is placed in the first well 21 of the disk body 4, so that the liquid sample in the storage space 31 of the filter cartridge 3 can be regarded as the liquid sample placed in the first well 21. In the disk 1, since the filter 35 in the filter cartridge 3 is between the storage space 31 and the second well 22, red blood cells in the liquid sample placed in the storage space 31 are moved to the second well 22 through the filter 35. It becomes possible. The operation of putting the liquid sample into the storage space 31 is preferably performed in a state in which the filter cartridge 3 is fitted in the first well 21 of the laminated disk main body 2.

In the disk 1, the storage space 31, the filter 35, and the second well 22 are arranged in this order from the center side of the disk body 4 to the outer peripheral side in a state where the filter cartridge 3 is placed in the first well 21. Is preferred. In short, in the disk 1, it is preferable that the storage space 31, the filter 35, and the second well 22 are arranged in this order from the center side of the laminated disk main body 2 outward in the radial direction of the laminated disk main body 2. Thereby, the liquid sample in the storage space 31 can be moved to the second well 22 through the filter 35 by the centrifugal force acting on the liquid sample when the disk 1 is rotated around the central axis of the disk 1. It becomes. In the second well 22, surface tension or the like acts on the liquid sample in addition to centrifugal force. The rotation direction of the disk 1 is clockwise (clockwise) when viewed from the upper side of the disk 1 (the surface 2A side of the laminated disk main body 2).

The shape of the laminated disk main body 2 is preferably a disk shape as in the case of optical disks (CD, DVD, etc.). A circular hole 28 is preferably formed in the center of the laminated disk body 2. The diameter of the disk 1 is 120 mm, for example.

The laminated disk main body 2 includes the disk-shaped disk main body 4 and the disk-shaped plate 5 joined to the disk main body 4 on the first surface 41 side of the disk main body 4 as described above. Here, a circular hole 48 constituting a part of the hole 28 of the laminated disk main body 2 is formed in the center of the disk main body 4. A circular hole 58 constituting a part of the hole 28 of the laminated disk main body 2 is formed at the center of the plate 5. The plate 5 includes a disk-shaped plate body 50 (see FIG. 3C). The material of the plate body 50 is, for example, a transparent resin. The plate body 50 has a front surface 51 and a back surface 52 that are opposite to each other in the thickness direction. On the front surface 51 of the plate body 50, it is preferable that a spiral track 53 (see FIG. 6) for following the beam-like light incident through the back surface 52 of the plate body 50 is formed as in the optical disc. . The track 53 is a groove. The track 53 is formed in a spiral shape from the center to the outer periphery of the plate body 50. Address information is continuously recorded on the track 53. Thereby, in the plate body 50, the position can be specified by the address information. Therefore, for example, the position information of the second well 22 in the plane of the disk 1 is specified by the address information. As in the case of CDs and DVDs, address information is reproduced from the disk 1 by scanning the track 53 with light. The light is excitation light. The wavelength of the excitation light is preferably 400 nm to 410 nm, for example, and more preferably 405 nm. The depth of the track 53 is, for example, 50 nm.

The plate 5 further includes a dielectric film 54 (see FIG. 3C) formed on the surface 51 of the plate body 50. The dielectric film 54 is, for example, a ZnS—SiO ₂ film. The dielectric film 54 is formed so as to cover the track 53. The dielectric film 54 is configured to reflect a part of the excitation light for tracking and transmit most of the remaining part. The reflectance of the dielectric film 54 with respect to the excitation light is, for example, 5% or more and 20% or less. For example, the reflectance of the dielectric film 54 with respect to the fluorescence is preferably less than or equal to the reflectance of the dielectric film 54 with respect to the excitation light. In the disk 1, a reflection surface 55 (see FIG. 3C) that reflects the excitation light incident on the back surface 52 of the plate body 50 is configured by an interface between the dielectric film 54 and the plate body 50.

The specimen in the liquid sample sent from the first well 21 to the second well 22 through the filter 35 in the disk 1 is inspected by, for example, a detection device 70 as shown in FIG.

The detecting device 70 includes, for example, an optical system similar to an optical pickup device for an optical disc, and the operation thereof is also the same. The optical system of the detection device 70 includes a semiconductor laser 71, a polarization beam splitter 72, an objective lens 73, a dichroic prism 74, a fluorescence detector 75, an anamorphic lens 76, and a reflected excitation light detector 77. ing.

In addition to the optical system described above, the detection device 70 includes a holder 81, an actuator 82, a rotation device 83, a first signal calculation circuit 84, a servo circuit 85, a second signal calculation circuit 86, and image analysis. A device 87 and an image display device 88 are provided. The rotating device 83 is a motor. The rotating device 83 is controlled by a servo circuit 85.

In the detecting device 70, after the disk 1 is set on the rotating table by the rotating device 83, a predetermined operation is started.

The optical system, the holder 81 and the actuator 82 are installed in a housing in the same manner as an existing optical pickup device used for recording / reproducing of a CD or DVD. The housing is movable in the radial direction of the disk 1 by a predetermined guide mechanism. The servo circuit 85 also controls the movement of the housing. Since this control is the same access control as that in the existing CD player or DVD player, detailed description thereof is omitted.

The semiconductor laser 71 emits light (excitation light) having a wavelength of about 405 nm. In FIG. 8, the traveling path of light is indicated by a one-dot chain line. The excitation light emitted from the semiconductor laser 71 is reflected by the polarization beam splitter 72 and enters the objective lens 73.

The objective lens 73 has a predetermined numerical aperture (Numerical Aperture) and is configured to properly converge the excitation light on the disk 1. Specifically, the objective lens 73 is configured such that excitation light incident from the polarization beam splitter 72 side converges.

The objective lens 73 is driven by the actuator 82 in the focus direction (the thickness direction of the disk 1) and the tracking direction (the radial direction of the disk 1) while being held by the holder 81. That is, the objective lens 73 is driven so as to follow the track 53 (see FIG. 6) in a state where the excitation light is focused on the reflecting surface 55 (see FIG. 3C) of the disk 1. A part of the excitation light focused on the reflection surface 55 is reflected by the reflection surface 55 and most of the excitation light is transmitted through the reflection surface 55.

Fluorescence is generated when the excitation light focused by the objective lens 73 is irradiated onto a nucleic acid that is fluorescently labeled in red blood cells. The wavelength of fluorescence is different from the wavelength of excitation light. The fluorescence wavelength is preferably, for example, 440 nm to 490 nm, and more preferably 455 nm. For example, SYTO (registered trademark) Blue can be used as the fluorescent dye. Red blood cells that are not infected with malaria parasites are not fluorescently labeled, and therefore do not generate fluorescence even when irradiated with excitation light. Therefore, the detection apparatus 70 can distinguish between red blood cells infected with malaria parasites and red blood cells not infected by the presence or absence of fluorescence.

The dichroic prism 74 is configured to reflect light having a wavelength of about 405 nm and transmit light having a wavelength of about 440 to 600 nm.

Excitation light reflected by the reflecting surface 55 (hereinafter referred to as “reflected excitation light”) passes through the polarization beam splitter 72, is reflected by the dichroic prism 74, and enters the anamorphic lens 76.

The anamorphic lens 76 introduces astigmatism into the reflected excitation light incident from the polarization beam splitter 72 side. The reflected excitation light transmitted through the anamorphic lens 76 enters the reflected excitation light detector 77. The reflected excitation light detector 77 has a four-divided sensor for receiving reflected excitation light on the light receiving surface. The detection signal of the reflected excitation light detector 77 is input to the second signal calculation circuit 86.

The second signal calculation circuit 86 generates a focus error signal and a tracking error signal from the detection signal of the reflected excitation light detector 77, and also generates a wobble signal (Wobble Signal). The focus error signal is a signal indicating a deviation (focus error) between the focal position of the objective lens 73 and the disk 1. The tracking error signal is a signal indicating a deviation (tracking error) between the spot of the excitation light and the track 53. The wobble signal is a waveform signal corresponding to the meandering shape of the groove defined by the track 53. The focus error signal and the tracking error signal are generated according to the astigmatism method and the one-beam push-pull method. The wobble signal is generated based on the tracking error signal. Specifically, a wobble signal is generated by extracting a frequency component corresponding to the wobble signal from the tracking error signal. The servo circuit 85 controls the actuator 82 using the focus error signal and tracking error signal output from the second signal calculation circuit 86. The servo circuit 85 controls the rotating device 83 so that the disk 1 is rotated at a predetermined linear velocity using the wobble signal output from the second signal calculation circuit 86.

Also, the second signal calculation circuit 86 outputs reproduction data (address information) generated by demodulating the wobble signal to the image analysis device 87.

Fluorescence incident on the dichroic prism 74 from the objective lens 73 side passes through the dichroic prism 74 and enters the fluorescence detector 75. The fluorescence detector 75 has a sensor that converts the received fluorescence into a detection signal composed of an electrical signal and outputs the detection signal. The detection signal of the fluorescence detector 75 is input to the first signal calculation circuit 84.

The first signal calculation circuit 84 outputs fluorescence luminance information generated by amplifying the detection signal from the fluorescence detector 75 to the image analysis device 87.

The image analysis device 87 is configured to display an image of the liquid sample in the second well 22 based on the fluorescence luminance information output from the first signal calculation circuit 84 and the address information output from the second signal calculation circuit 86. Is generated and displayed on the image display device 88. The image analysis device 87 detects red blood cells in the image of the liquid sample in the second well 22 and the nucleic acid of the malaria parasite that is infected with the red blood cells, calculates the infection rate, and displays the calculation result as the image display device 88. To display. The image analysis device 87 can be realized, for example, by causing a personal computer to execute an appropriate program. Further, the image display device 88 can be constituted by a display of a personal computer, for example.

The procedure of an example of examining red blood cells using the disk 1 and the detection device 70 will be briefly described.

After preparing blood (biological sample) collected from a patient, a liquid sample is prepared by mixing the blood and a diluent.

Thereafter, a liquid sample is put into the storage space 31 of the filter cartridge 3. When putting a biological sample in the storage space 31, for example, a pipette (Pipette), a syringe (Syringe), a capillary (Capillary) or the like is used. Here, it is preferable to put the liquid sample into the storage space 31 in a state where the filter cartridge 3 is fitted in the first well 21 of the laminated disk main body 2.

Thereafter, in the detection device 70, the disk 1 is rotated at a predetermined linear velocity for a predetermined rotation time. The detection device 70 rotates the disk 1 around the central axis 25 of the laminated disk main body 2. At this time, white blood cells in the liquid sample are captured by the filter 35 of the filter cartridge 3 and do not reach the flow path 23 and the second well 22. Therefore, in the disk 1, the red blood cells contained in the liquid sample can be moved from the first well 21 to the second well 22, and the white blood cells contained in the liquid sample can be captured by the filter 35. .

Thereafter, the detection device 70 generates an image of the liquid sample in the second well 22 (here, the liquid sample moved into the second well 22 may be changed from the liquid phase state to the solid phase state). The infection rate is displayed on the image display device 88, and the infection rate is further displayed on the image display device 88. Thereby, compared with the case where a doctor etc. test | inspect using a microscope, it becomes possible to shorten test | inspection time. The liquid sample that has moved into the second well 22 may be in a liquid phase state or may be changed from a liquid phase state to a solid phase state when the detection apparatus 70 performs an inspection. On the other hand, the refractive index with respect to the excitation light of the liquid sample is the refractive index with respect to the excitation light of the material of each of the disc-shaped disc body 4, the disc-shaped plate 5, and the joint 6 that joins the disc body 4 and the plate 5. Is preferably about 1.3 to 1.6.

The disk 1 includes a filter cartridge 3, and the filter performance can be inspected with the filter cartridge 3 alone. Here, the “filter performance” is the performance of the filter 35 and is the performance of permeating red blood cells and capturing white blood cells. In the disk 1, the filter performance can be inspected with the filter cartridge 3 alone, so that the reliability of the filter performance can be improved. Thereby, for example, it is possible to improve the accuracy of the inspection of the infection rate using the disk 1 and the detection device 70.

Each component of the disk 1 will be described in detail below.

The disk 1 includes a laminated disk body 2 and a plurality (nine) of filter cartridges 3. In FIG. 1, only five filter cartridges 3 of the nine filter cartridges 3 are illustrated.

The shape of the laminated disc body 2 is a disc shape. In the laminated disk main body 2, a disk-shaped disk main body 4 and a disk-shaped plate 5 are laminated via a joint 6.

A plurality (nine) of chambers 400 corresponding to a plurality of (nine) filter cartridges 3 are formed on the disk body 4 in the laminated disk body 2. As viewed from the thickness direction of the disc body 4, the chamber 400 gradually increases in width in the direction along the circumferential direction of the disc body 4 as it moves away from the center of the disc body 4. It is getting narrower gradually. Here, the plurality of chambers 400 are arranged at substantially equal intervals in the circumferential direction of the disc body 4. Therefore, the plurality of first chambers 401, the plurality of channels 403, and the plurality of second chambers 402 are arranged at equal intervals in the circumferential direction of the disc body 4. In the laminated disk main body 2, nine sets of the first well 21, the second well 22, and the flow path 23 between the first well 21 and the second well 22 are formed.

The laminated disc body 2 is provided with a first well 21, a flow path 23, and a second well 22 in this order from the center side to the outer peripheral side of the laminated disc body 2. In the disk 1, the filter cartridge 3 can be fitted into the first well 21 from the thickness direction of the laminated disk body 2. Therefore, the filter cartridge 3 can be fitted relatively easily as compared with the case where the filter cartridge 3 is fitted from the radial direction of the laminated disk main body 2.

In the disk 1, a plurality of chambers 400 are arranged radially at equal angular intervals around the central axis 25 of the laminated disk main body 2. Therefore, in the disk 1, a plurality of first wells 21 are arranged radially at equiangular intervals around the central axis 10 of the disk 1. A plurality of second wells 22 are arranged radially at equiangular intervals around the central axis 10 of the disk 1. Thereby, the disk 1 can be used for the inspection of a plurality of liquid samples. In the method for examining red blood cells using the disk 1, a liquid sample is put in each of the storage spaces 31 of the plurality of filter cartridges 3, and the plurality of filter cartridges 3 correspond to each other in the laminated disk body 2 on a one-to-one basis. The disc 1 is rotated around the central axis 25 of the laminated disc main body 2 in a state of being fitted into the disc 21. Thus, in the inspection method, it is possible to extract red blood cells from each of the plurality of liquid samples to different second wells 22 and shorten the inspection time.

The first well 21 is a space surrounded by the inner wall surface of the first chamber 401 formed on the first surface 41 of the disc body 4, the plate 5, and the joint portion 6. In other words, the first well 21 includes a concave portion 29 (see FIGS. 1 and 2B) formed along the thickness direction of the laminated disk main body 2 on the surface 2A of the laminated disk main body 2. The first chamber 401 is provided near the hole 48 of the disc body 4 in the radial direction of the disc body 4. The shapes of the first chamber 401 and the first well 21 are substantially the same as those of the filter cartridge 3 when viewed from the thickness direction of the laminated disc body 2. As a result, in the disk 1, rattling of the filter cartridge 3 fitted in the first well 21 can be suppressed.

In the laminated disk main body 2, the first well 21 and the second well 22 are separated from each other in the radial direction of the laminated disk main body 2, and the first well 21 and the second well 22 communicate with each other through the flow path 23. Is preferred.

It is preferable that the opening area of the flow path 23 gradually decreases as the distance from the first well 21 and the approach to the second well 22 increases. Thereby, in the disk 1, it is possible to suppress the generation of bubbles in the liquid sample that has moved from the first well 21 to the second well 22.

The chamber 400 in the disk main body 4 includes two second channels 405 (see FIG. 2C) formed on both sides of the channel 403 (hereinafter also referred to as “first channel 403”) in the circumferential direction of the disk main body 4. Have. The depth of the second channel 405 is substantially the same as the depth of the second chamber 402. The second channel 405 communicates with the ventilation flow path 11 (see FIGS. 2A to 2C) in the disk 1. The ventilation channel 11 is a channel for ventilation between the inside of the second well 22 and the outside of the disk 1. In the disk 1, a connection flow path 27 that connects the ventilation flow path 11 and the second well 22 is formed between the bottom surface of the second channel 405 of the disk body 4 and the plate 5. In short, the disk 1 has a connecting flow path 27. The connection flow path 27 is adjacent to the flow path 23 in the circumferential direction of the laminated disk main body 2, is between the ventilation flow path 11 and the second well 22, and communicates with the ventilation flow path 11 and the second well 22. The ventilation channel 11 is formed between the groove 404 provided along the thickness direction of the laminated disk main body 2 on the inner wall surface of the first well 21 of the laminated disk main body 2 and the side surface of the filter cartridge 3. The ventilation channel 11 is disposed on the inner peripheral side of the disk 1 with respect to the filter 35. In the disk 1, ventilation channels 11 are formed on both sides of the filter cartridge 3 in the direction along the circumferential direction of the laminated disk main body 2. Thereby, in the disk 1, it is possible to suppress the generation of bubbles in the second well 22 when the liquid sample is moved from the storage space 31 to the second well 22. Therefore, in the disk 1, since generation | occurrence | production of the bubble which causes a noise when light is irradiated by the detection apparatus 70 can be suppressed, it becomes possible to improve the precision of the test | inspection by the detection apparatus 70. FIG. In the disk 1, the width of the ventilation channel 11 in the direction along the circumferential direction of the laminated disk body 2 is, for example, 500 μm. In the disk 1, the distance between the cartridge 3 and the laminated disk body 2 in the direction along the circumferential direction of the laminated disk body 2 is, for example, 100 μm or less. Moreover, the width | variety of the ventilation flow path 11 is 500 micrometers, for example.

The disc main body 4 in the disc 1 is integrally provided with a rib 47 (see FIG. 2C) that protrudes from the inner wall surface of the first chamber 401 toward the filter cartridge 3 in the direction along the circumferential direction of the disc main body 4. The rib 47 is separated from the bottom surface of the concave portion 29 (see FIGS. 1 and 2B) of the laminated disk main body 2, and faces the bottom surface. A space surrounded by the rib 47, the bottom surface of the recess 29, and the side surface of the filter cartridge 3 constitutes a part of the ventilation channel 11. Here, in the disc main body 4, the surface of the rib 47 facing the plate 5 and the bottom surface of the second channel 405 are continuously flush with each other. The disc 1 includes a rib 47. Accordingly, it is possible to suppress the liquid sample moving from the storage space 31 to the second well 22 from being scattered outside the disk 1 through the ventilation channel 11. Further, the disk 1 is provided with the rib 47, so that the rattling of the filter cartridge 3 can be further suppressed. The bottom surface of the second channel 405 is substantially flush with the bottom surface of the second chamber 402.

In the disk 1, the minimum height from the bottom surface of the recess 29 to the rib 47 in the thickness direction of the laminated disk main body 2 is such that capillary force acts on the liquid sample in the second well 22 in the ventilation channel 11. It is preferable that the height is not present. In the disk 1, the minimum height from the bottom surface of the recess 29 to the rib 47 in the thickness direction of the laminated disk body 2 is, for example, the same as the minimum depth of the second chamber 402 and the thickness of the joint portion 6. It is set to the same size (in other words, the distance between the plate 5 and the bottom surface of the second chamber 402). Here, the depth of the second chamber 402 is, for example, 400 μm over the entire bottom surface of the second chamber 402, and the minimum depth is also 400 μm. The minimum height is, for example, about 500 μm. The second well 22 is configured by a bottom surface 221 constituted by a part of the surface of the plate 5 on the disk body 4 side and a surface of the disk body 4 on the plate 5 side of the second chamber 402 (bottom surface of the second chamber 402). And the top surface 222. The bottom surface 221 and the top surface 222 of the second well 22 are located between the front surface 2A and the back surface 2B of the laminated disk main body 2 in the thickness direction of the laminated disk main body 2. Here, in the disk 1, the distance between the back surface 2 </ b> B of the laminated disk body 2 and the top surface 222 in the thickness direction of the laminated disk body 2 is longer than the distance between the back surface 2 </ b> B and the bottom surface 221 of the laminated disk body 2. Further, the bottom surface 221 of the second well 22 is close to the back surface 2B between the front surface 2A and the back surface 2B of the stacked disk body 2 in the thickness direction of the stacked disk body 2. In the disk 1, the depth of the recess 29 is larger than the distance between the bottom surface 221 of the second well 22 and the top surface 222 when viewed in the thickness direction of the laminated disk body 2, and from the bottom surface of the recess 29. The height to the rib 47 is larger than the minimum height.

In the laminated disk body 2, the volume of the second well 22 is preferably larger than the volume of the storage space 31 of the filter cartridge 3. Thereby, in the disk 1, when the liquid sample is moved from the storage space 31 of the filter cartridge 3 to the second well 22, the liquid sample can be stored in the second well 22 (the liquid sample is stored in the second well 22). Can be prevented from overflowing).

It is preferable that the area of the second chamber 402 is larger than the area of the first chamber 401 when viewed from the thickness direction of the disc body 4. Thereby, in the disk 1, when the liquid sample is moved from the first well 21 to the second well 22, the liquid sample can be spread in the second well 22 to a wider range than the first well 21. . Therefore, the disk 1 can suppress red blood cells from overlapping in the thickness direction of the disk 1, and the accuracy of the inspection by the detection device 70 can be improved.

In the disk 1, it is preferable that an appropriate surface treatment is performed on the bottom surface 221 of the second well 22. Here, the surface treatment is, for example, a plasma treatment in which the surface of the plate 5 facing the bottom surface of the second chamber 402 is charged with a charge having a polarity opposite to that of red blood cells. As a result, in the disk 1, it is possible to suppress the red blood cells that have moved from the storage space 31 to the second well 22 from overlapping in the thickness direction of the plate 5, and the red blood cells are monolayered over a wider area on the plate 5. It becomes possible to do. In other words, it is possible to increase the coverage of red blood cells on the plate 5 and to suppress red blood cells from overlapping in the thickness direction of the plate 5.

The thickness of the plate 5 is 0.6 mm, for example. The disk 1 is assumed to have inspection light (excitation light) incident from the back surface 52 side of the plate body 50 in the plate 5. For this reason, in the disk 1, the thickness of the plate 5 is preferably thinner than the thickness of the disk body 4. From the viewpoint of reducing the coma aberration of the beam spot of the excitation light, the thickness of the plate 5 is preferably thinner as the wavelength of the excitation light is shorter.

The material of the plate body 50 is preferably a transparent resin. The plate body 50 is formed by injection molding. As a result, holes 58 and tracks 53 (see FIG. 6) are formed in the plate body 50. The material of the plate body 50 is, for example, polycarbonate, but is not limited thereto. The material of the plate body 50 is, for example, polymethyl methacrylate, amorphous polyolefin, polyethylene, ethylene, polypropylene, polyisobutylene, polyethylene terephthalate (PET), unsaturated polyester, fluororesin, polyvinyl chloride, polyvinylidene chloride, polyacetic acid. Vinyl, polyvinyl alcohol, polyvinyl acetal, acrylic resin, polyacrylonitrile, polystyrene, acetal resin, polyamide, phenol resin, urea resin, epoxy resin, melamine resin, styrene / acrylonitrile copolymer, acrylonitrile / butadiene styrene copolymer, silicone resin Polyphenylene oxide and polysulfone may be used.

The material of the disc body 4 is, for example, acrylic resin, but is not limited thereto. The material of the disc body 4 may be the same material as the material of the plate body 50, such as polystyrene or polycarbonate. However, the material of the plate body 50 and the disk body 4 does not necessarily need to be the same material. For example, the plate body 50 may be a combination of polycarbonate and the disk body 4 may be a combination of polystyrene. The disc body 4 is formed by injection molding. As a result, a hole 48, a chamber 400, and the like are formed in the disc body 4.

The disc body 4 preferably contains a fluorescent material that emits fluorescence when excited by the excitation light from the semiconductor laser 71 in the same manner as the fluorescent dye. As a result, in the disc 1, when the red blood cell is inspected by the detection device 70, the background image of the red blood cell can be brightened in the image, the contour of the red blood cell can be easily recognized, and the inspection accuracy is improved. Is possible. The wavelength of fluorescence generated from the fluorescent material is, for example, 480 to 600 nm. As such a fluorescent material, a phosphor or the like activated by rare earth ions can be employed.

Examples of inorganic phosphors include BAM phosphors (for example, BaMgAl ₁₀ O ₁₇ : Eu ²⁺ ) and SCA phosphors (for example, (Sr, Ba, Ca) ₅ (PO ₄ ) ₃ Cl: Eu ²⁺ ), SMS phosphors (Sr ₃ MgSi ₂ O ₈ : Eu ²⁺ ), YAG phosphors (eg Y ₃ Al ₃ O ₁₂ ), CASN phosphors (eg CaAlSiN ₃ : Eu), SSE phosphors (Sr ₃ SiO ₅ : Eu) and the like. The above-described phosphor does not necessarily need to completely match the above composition, and additives may be included or the composition ratio may be different. Besides the above phosphors, phosphors for three-wavelength fluorescent lamps, phosphors for special lamps, phosphors for cold cathode lamps, phosphors for PDP (Plasma Display Panel), and phosphors for LED (Light Emitting Diode) Widely used phosphors such as fluorescent bodies and phosphors for fluorescent lamps can be used. Examples of organic phosphors include red light emitting phosphors (Eu complex compounds, Sm complex compounds, Pr complex compounds, dicyanomethylene compounds, benzopyran derivatives, rhodamine derivatives, benzothioxanthene derivatives, polyalkylthiophene derivatives), Yellow light emitting phosphor (rubrene compound, perimidone derivative), blue light emitting phosphor (perylene compound, pyrene compound, anthracene compound, distyryl derivative, polydialkylfluorene derivative, polyparaphenylene derivative), green light emitting phosphor (coumarin) Compound, Tb complex compound, quinacridone compound) and the like.

These phosphors may be used alone or in combination of two or more of those emitting light of the same color or different color. From the viewpoint of showing good fluorescence emission characteristics in a small amount, it is preferable to use an Eu complex compound of a red emission phosphor as the organic phosphor.

The thickness between the first surface 41 and the second surface 42 of the disc body 4 is, for example, 2.0 mm. Here, the depth of the second chamber 402 of the disc body 4 is preferably sufficiently larger than the size of the specimen. The depth of the second chamber 402 is, for example, 400 μm.

Incidentally, as shown in FIGS. 5A to 5D, the disc main body 4 protrudes from the gate trace 411 formed on the first surface 41 and the second surface 42 and overlaps the gate trace 411 in the thickness direction of the disc main body 4. And a protrusion 421. The gate mark 411 is, for example, the bottom surface of the concave portion 410 formed on the first surface 41 of the disc body 4. In the disk body 4, it is preferable that the area of the protrusion 421 is larger than the area of the gate mark 411 when viewed from the thickness direction of the disk body 4. The gate trace 411 can be identified by observation with a polarizing microscope, for example, even when visual confirmation is not possible.

In the disc main body 4, it is preferable that the entire tip surface of the protrusion 421 is a rough surface portion 431 having a larger surface roughness than the portion of the second surface 42 other than the protrusion 421. Here, for the surface roughness, for example, an arithmetic average roughness Ra defined in JIS B 0601-2001 (ISO 4287-1997) can be employed. The surface roughness can be measured by a three-dimensional shape measuring apparatus such as AFM (Atomic Force Microscope).

As for the thickness of the disc body 4, the thickness between the first surface 41 and the second surface 42 is, for example, 2.0 mm as described above. On the other hand, the protrusion height of the protrusion 421 from the second surface 42 is, for example, 0.5 mm. Moreover, the thickness between the 1st surface 41 and the front end surface of the protrusion 421 is 2.5 mm, for example. In this case, the arithmetic average roughness Ra of the rough surface portion 431 is preferably about 100 nm to 200 nm, for example.

In the disk 1, as described above, it is preferable that the disk body 4 includes a plurality of chambers 400, and the plurality of chambers 400 are arranged in the circumferential direction of the disk body 4. Here, in the disc 1, it is preferable that the gate trace 411 is located on the outer peripheral side of the disc body 4 with respect to each of the plurality of chambers 400 with respect to the chamber 400. In the disc body 4, the plurality of chambers 400 are preferably arranged so as to have two or more rotational symmetries around the central axis 45 of the disc body 4.

As can be seen from the above description, the disc body 4 has nine gate marks 411 formed on the first surface 41 and has nine protrusions 421 protruding from the second surface 42. Each of the nine protrusions 421 has a rectangular shape whose longitudinal direction is a direction orthogonal to the radial direction of the disk main body 4 when viewed from the thickness direction of the disk main body 4. In the disc body 4, the front end surfaces of the nine protrusions 421 are rough surface portions 431. Thereby, for example, a person (for example, a doctor or the like) who performs an examination using the disk 1 discriminates the liquid sample put into the nine chambers 400 (for example, specimen information for discriminating the subject who provided blood). Or the like can be written on the rough surface portion 431 with a pen, pencil, or the like. Further, in the disc body 4, different letters A to I are formed in the vicinity of the nine rough surface portions 431 in order to distinguish the nine rough surface portions 431. The letters A to I protrude from the second surface 42 of the disc body 4. The letters A to I are formed when the disc body 4 is formed.

The plate 5 and the disc body 4 are joined together by, for example, a joining portion 6 made of an adhesive. The adhesive is, for example, an acrylate adhesive.

The plate 5 is joined to the disc body 4 on the first surface 41 side of the disc body 4. This makes it possible to reduce the thickness of the joint portion 6 interposed between the plate 5 and the disc body 4. Further, in the disk 1, it is possible to suppress the occurrence of voids or the like at the joint 6 in the outer peripheral portion of the laminated disk main body 2. As a result, the disc 1 can improve the bondability between the plate 5 and the disc body 4 at the outer peripheral portion of the disc 1.

The filter 35 in the filter cartridge 3 includes a porous structure 36 (see FIG. 7). The porous structure 36 is configured so that, for example, a specific second substance (red blood cells) can pass through without passing a specific first substance (white blood cells). The porous structure 36 is formed of a plurality of fibrous substances 361, for example, as shown in the SEM image diagram shown in FIG. More specifically, the porous structure 36 is formed by a plurality of fibrous substances 361 entangled with each other, and a large number of voids 362 are formed. The gap 362 is between the adjacent fibrous materials 361. In the porous structure 36, a plurality of fibrous substances 361 are curved and entangled with each other. The fibrous substance 361 is made of, for example, silicon oxide. More specifically, the fibrous substance 361 is made of amorphous silicon dioxide. The thickness (fiber diameter) of the fibrous substance 361 is, for example, about 0.01 μm to 1 μm. The fibrous substance 361 may be branched. The void 362 is, for example, a size that allows red blood cells to pass through and capture white blood cells in the porous structure 36. Here, the gap 362 is preferably larger than the red blood cells, but is not necessarily larger than the red blood cells. This is because red blood cells are deformable and can pass through voids 362 that are smaller than themselves. In addition, the gap 362 is smaller than the capture target such as leukocytes. This is because leukocytes are less deformable than erythrocytes.

The filter cartridge 3 includes a case 30 that holds the filter 35. The case 30 has substantially the same shape as the first well 21 when viewed from the thickness direction of the laminated disk main body 2. The case 30 has a shape in which the width gradually increases with increasing distance from the center of the laminated disk body 2 in the radial direction of the laminated disk body 2 when viewed from the thickness direction of the laminated disk body 2. The case 30 has an opening 320 (see FIG. 2C) on one surface of the second chamber 402 side. In the filter cartridge 3, the filter 35 is disposed so as to close the opening 320 of the case 30. The filter 35 is fixed to the case 30 with, for example, an adhesive. In the filter cartridge 3, a space surrounded by the case 30 and the filter 35 constitutes a liquid sample storage space 31.

The filter cartridge 3 has a liquid sample injection hole 33. As a result, when the liquid sample is not contained in the storage space 31 of the filter cartridge 3 and the filter cartridge 3 is not fitted in the first well 21 of the laminated disk main body 2, the filter performance of the filter 35 is inspected. One type of leak test can be performed. In the leak test, for example, the pressure loss of the filter 35 is measured. The pressure loss of the filter 35 is obtained, for example, by measuring the total pressure difference between the upstream side and the downstream side when the test clean air is passed through the filter 35 with a manometer. More specifically, the pressure loss at the filter 35 when the clean air for testing at a predetermined pressure is introduced from the injection hole 33 into the case 30 is measured. Thereby, in the disk 1, the filter performance of the filter 35 can be inspected before the filter cartridge 3 is fitted into the first well 21 of the laminated disk main body 2. The injection hole 33 is preferably at a position far from the opening 320 on the upper wall of the case 30.

The shape of the storage space 31 of the filter cartridge 3 is U-shaped as shown in FIG. 1 when viewed from the thickness direction of the disk 1. In the filter cartridge 3, it is desirable that the injection hole 33 is provided so as to communicate with the first end of the U-shaped storage space 31 in the case 30 and the vent hole 38 is provided so as to communicate with the second end. . Thereby, when the liquid sample is injected into the storage space 31 of the filter cartridge 3, the air existing in the storage space 31 can be released from the portion other than the filter 35, so that the liquid sample can be smoothly supplied. Can be injected. The shape of the vent 38 is, for example, a circle. The vent hole 38 is preferably smaller from the viewpoint of preventing leakage of the liquid sample, and is preferably smaller than the injection hole 33.

When the filter cartridge 3 is manufactured, the thickness of the porous structure 36 can be measured by a laser displacement meter or the like before the filter 35 including the porous structure 36 is fixed to the case 30. When the filter cartridge 3 is manufactured, the thickness of the porous structure 36, which is one of the factors that determine the filter performance, can be inspected with a laser displacement meter or the like.

Next, an example of a method for manufacturing the disk 1 will be described.

In the manufacturing method of the disk 1, the disk body 4 formed by injection molding and the plate 5 are joined.

Here, the forming process of the disc body 4 includes a first process, a second process, a third process, and a fourth process.

In the first step, as shown in FIG. 9A, a first mold 91 and a second mold 92 are prepared, and a cavity 93 surrounded by the first mold 91 and the second mold 92 is formed. . Here, the first mold 91 has a circular first recess 911 for forming a cavity on one surface 910, and a second recess 912 for forming a cavity is formed on the bottom surface of the first recess 911. The diameter of the first recess 911 is substantially the same as the diameter of the disc body 4. The depth of the first recess 911 is substantially the same as the thickness between the first surface 41 and the second surface 42 of the disc body 4. An appropriate draft angle is provided on the inner side surface of the first recess 911. The depth of the second recess 912 is substantially the same as the protrusion height of the protrusion 421 of the disc body 4. The bottom surface of the second recess 912 is rougher than the bottom surface of the first recess 911. The bottom surface of the second recess 912 of the first mold 91 is roughened by, for example, sandblasting. Here, the bottom surface of the second recess 912 serves as a template for the rough surface portion 431 of the protrusion 421 of the disc body 4. The second mold 92 covers the opening of the first recess 911 of the first mold 91.

In the second step, a molten molding resin material (for example, an acrylic resin containing a phosphor, a polycarbonate containing a phosphor, or the like) is present in the projection region on the bottom surface of the second recess 912 in the second mold 92. By injecting into the cavity 93 through the gate 921 and curing, the resin molded body 40 that is the base of the disc body 4 is formed (see FIG. 9B). Gate 921 is preferably a pinpoint gate. Thereby, a post-process such as polishing becomes unnecessary.

In the third step, the disc body 4 having the gate marks 411 is formed by separating the second mold 92 from the first mold 91 and the resin molded body 40.

In the fourth step, a part of the disc body 4 that is in contact with the bottom surface of the first recess 911 of the first mold 91 is pushed by a plurality (nine) of ejector pins 94 to push the disc body 4 into the first mold. The mold is released from the mold 91 (see FIG. 9C). The disc body 4 is formed with a recess 44 (see FIGS. 5A and 5C) at a portion where the ejector pin 94 has been hit.

In the molding process of the disc body 4, the residual stress of the disc body 4 can be reduced and the occurrence of sink marks can be suppressed.

In the disk 1, the disk main body 4, which is a resin molded body, protrudes from the gate mark 411 formed on the first surface 41 and the second surface 42, and protrudes 421 that overlaps the gate mark 411 in the thickness direction of the disk main body 4. And having. Then, at least a part of the front end surface of the protrusion 421 is a rough surface portion 431 having a larger surface roughness than that of the second surface 42 other than the protrusion 421. Thereby, in the disk 1, the residual stress of the disk main body 4 can be reduced by having the protrusion 421. Further, by providing the rough surface portion 431, it is possible to reduce the mold release resistance of the protrusion 421. Therefore, the disc 1 can suppress warping of the disc body 4 that is a resin molded body.

In the inspection method using the disc 1 and the detection device 70 described above, the presence or absence of malaria protozoa is detected accurately during the incubation period without subjective symptoms by confirming the presence or absence of malaria protozoa in red blood cells. It becomes possible to do.

The above embodiment is only one of various embodiments of the present invention. The above-described embodiment can be variously changed according to the design or the like as long as the object of the present invention can be achieved.

For example, in the disk 1, the ventilation channel 11 may be formed only on one side of the cartridge 3 in the circumferential direction of the well forming disk main body 2.

The ventilation channel 11 is formed between the inner wall surface of the first well 21 of the well forming disk main body 2 and a groove provided in the side surface of the cartridge 3 along the thickness direction of the well forming disk main body 2. Space may be included.

Further, in the disk 1, the minimum height from the bottom surface of the recess 29 to the rib 47 in the thickness direction of the well forming disk main body 2 is such that the capillary in the vent channel 11 is a capillary with respect to the liquid sample in the second well 22. The height may be such that the force works. In this case, the disc 1 has a minimum height from the bottom surface of the recess 29 to the rib 47 in the thickness direction of the well forming disc body 2 such that the bottom surface of the second well 22 in the thickness direction of the well forming disc body 2. It is preferable that the height from 221 to the top surface 222 is larger than the minimum height.

Further, the disk 1 may be subjected to a hydrophobic treatment on the inner surface of the ventilation channel 11. For example, in the disk 1, a SAM (Self-Assembled Monolayer) for imparting hydrophobicity may be formed on the inner surface of the ventilation channel 11. The SAM for imparting hydrophobicity can be formed, for example, by applying OTS (Octadecyltrichlorosilane) or the like by a dip coating method or the like.

Further, in the disk 1, the inner wall surface of the second well 22 may be subjected to a hydrophilic treatment. As the hydrophilic treatment, for example, a surfactant represented by Triton X (registered trademark) or a polymer compound having a hydrophilic group such as a hydroxyl group, a sulfonic acid group, or a carboxyl group is applied. Further, examples of the hydrophilic treatment include oxygen plasma treatment and corona discharge treatment.

Further, in the well forming disk main body 2, the plurality of first wells 21 are arranged so as to have n-fold rotational symmetry about the central axis 45 of the disk main body 4 when an integer n of 2 or more is used. Is preferred. Similarly, in the well forming disk main body 2, the plurality of second wells 22 are arranged to have n-fold rotational symmetry about the central axis 45 of the disk main body 4 when an integer n of 2 or more is used. It is preferable.

The method of joining the plate 5 and the disc body 4 is not limited to an adhesive, and examples thereof include welding (thermal welding, ultrasonic welding, vibration welding, spin welding, laser welding), plasma bonding, surface activated bonding, and the like. It may be adopted.

Further, the liquid sample put in the storage space 31 of the filter cartridge 3 may contain a staining solution for staining the nucleic acid of the pathogenic microorganism. In this case, it is not necessary to arrange a fluorescent reagent for staining nucleic acid in the laminated disk main body 2. As a staining method using a staining solution, for example, Giemsa staining, acridine orange staining, Wright staining, Jenner staining, Leishmann staining, Romanovsky staining, and the like can be employed. An appropriate staining solution may be used as the staining solution according to the type of pathogenic microorganism and the staining method.

Although the example in which the disk 1 is used for testing red blood cells has been described, the use of the disk 1 is not limited to this, and for example, it can be used for DNA testing, protein testing, and the like.

As is clear from the above-described embodiment, the disk 1 according to the first aspect includes a well forming disk main body 2, a cartridge 3, and a ventilation channel 11. The well forming disc main body 2 has a front surface 2A and a back surface 2B that are opposite to each other in the thickness direction. The well forming disk main body 2 has a first well 21 and a second well 22. The first well 21 includes a concave portion 29 formed along the thickness direction from the surface 2A side of the well forming disc main body 2. The second well 22 communicates with the first well 21. The cartridge 3 has a storage space 31 in which a liquid sample can be stored. The cartridge 3 is fitted into the first well 21 of the well forming disk main body 2. The ventilation channel 11 is formed between the side surface of the cartridge 3 and the well forming disk main body 2. The ventilation channel 11 communicates with the outside of the well forming disk main body 2 and the second well 22.

With the above configuration, in the disk 1, the well-formed disk main body 2 having the first well 21 and the second well 22, and the outer surface of the well-formed disk main body 2 formed between the side surface of the cartridge 3 and the well-formed disk main body 2. And the air flow path 11 communicating with the second well 22, it is possible to suppress scattering of the liquid sample when the disk 1 is rotated around the central axis 10 of the disk 1.

The disc 1 according to the second aspect has the filter 35 in which the cartridge 3 removes a specific substance from the liquid sample moving from the storage space 31 to the second well 22 in the first aspect. Here, the filter 35 is located between the storage space 31 and the second well 22. Thereby, in the disk 1, since the filter 35 of the cartridge 3 is between the storage space 31 and the second well 22, a specific substance in the liquid sample placed in the storage space 31 moves to the second well 22. Can be suppressed. In the disk 1, the filter performance of the filter 35 of the cartridge 3 can be inspected before the cartridge 3 is fitted into the first well 21. As a result, the reliability of the filter performance can be improved in the disk 1, so that the reliability of the disk 1 can be improved.

In the disc 1 according to the third aspect, in the second aspect, the cartridge 3 preferably includes a case 30. The case 30 has an opening 320 at the end on the second well 22 side and holds the filter 35. Here, the filter 35 is preferably disposed so as to close the opening 320 of the case 30. In the cartridge 3, a space surrounded by the case 30 and the filter 35 constitutes a storage space 31. As a result, the disk 1 can further increase the volume of the storage space 31 of the cartridge 3.

In the disc 1 according to the fourth aspect, in any one of the first to third aspects, the first well 21 and the second well 22 are arranged in this order from the center side of the well forming disc main body 2 toward the outer peripheral side. Are lined up. Thereby, the disk 1 can move the liquid sample in the storage space 31 of the cartridge 3 to the second well 22 by the centrifugal force acting on the liquid sample when the disk 1 is rotated.

In the disk 1 according to the fifth aspect, in any one of the first to fourth aspects, the well forming disk main body 2 further includes a flow path 23 and a connection flow path 27. The flow path 23 is between the first well 21 and the second well 22 and communicates with the first well 21 and the second well 22. The connection flow path 27 is adjacent to the flow path 23 in the circumferential direction of the well forming disk main body 2, between the ventilation flow path 11 and the second well 22, and communicates with the ventilation flow path 11 and the second well 22. . The opening area of the channel 23 gradually decreases as the distance from the first well 21 approaches the second well 22. Thereby, the disk 1 can suppress the generation of bubbles in the liquid sample moved from the storage space 31 to the second well 22.

In the disk 1 according to the sixth aspect, in the fifth aspect, the well forming disk main body 2 includes a rib 47 that protrudes from the inner wall surface of the recess 29 toward the side surface of the cartridge 3 and faces the bottom surface of the recess 29. A space between the bottom surface of the recess 29 and the rib 47 constitutes a part of the ventilation channel 11. Accordingly, the disk 1 can suppress the liquid sample moving from the storage space 31 to the second well 22 from being scattered outside the disk 1 through the ventilation channel 11.

In the disc 1 according to the seventh aspect, in the sixth aspect, the minimum height from the bottom surface of the recess 29 to the rib 47 in the thickness direction of the well forming disc main body 2 is the second height in the ventilation channel 11. The height is such that no capillary force acts on the liquid sample in the well 22. Thereby, the disk 1 can suppress the liquid sample in the second well 22 from moving to the ventilation channel 11.

In the disk 1 according to the eighth aspect, in the sixth aspect, the minimum height from the bottom surface of the recess 29 to the rib 47 in the thickness direction of the well forming disk main body 2 is the thickness of the well forming disk main body 2. It is higher than the minimum height from the bottom surface 221 to the top surface 222 of the second well 22 in the vertical direction. Accordingly, the disk 1 can suppress the capillary force from acting on the liquid sample in the second well 22 in the ventilation channel 11 and moving to the ventilation channel 11.

In the disk 1 according to the ninth aspect, in any one of the first to eighth aspects, the ventilation channel 11 is formed on both sides of the cartridge 3 in the circumferential direction of the well forming disk main body 2. Thereby, the disc 1 can suppress the liquid sample from being scattered from the ventilation channel 11 regardless of the rotation direction of the disc 1.

In the disk 1 according to the tenth aspect, in any one of the first to eighth aspects, the ventilation channel 11 is formed only on one side of the cartridge 3 in the circumferential direction of the well forming disk main body 2. As a result, when the disk 1 is used by being rotated to the side where the ventilation channel 11 is formed when viewed from the cartridge 3 in the circumferential direction of the well forming disc main body 2, the liquid sample is scattered from the ventilation channel 11. Can be suppressed. In short, when the rotation direction of the disk 1 is schematically indicated by an arrow, the cartridge 3 only needs to have the ventilation channel 11 on the side where the arrowhead is located.

In the disc 1 according to the eleventh aspect, the volume of the second well 22 is larger than the volume of the storage space 31 in any one of the first to tenth aspects. Thereby, in the disk 1, when the liquid sample is moved from the storage space 31 of the cartridge 3 to the second well 22, the liquid sample can be reliably stored in the second well 22.

In the disc 1 according to the twelfth aspect, in any one of the first to eleventh aspects, the area of the second well 22 is larger than the area of the first well 21 when viewed from the thickness direction of the well forming disk main body 2. Is also big. Thereby, in the disk 1, when the liquid sample is moved from the storage space 31 of the cartridge 3 to the second well 22, the liquid sample can be spread in the second well 22 to a wider range than the first well 21. It becomes.

In the disc 1 according to the thirteenth aspect, in any one of the first to twelfth aspects, the ventilation channel 11 is formed on the inner wall surface of the first well 21 of the well forming disc main body 2 with the thickness of the well forming disc main body 2. A space formed between the groove 404 provided along the vertical direction and the side surface of the cartridge 3 is included. As a result, in the disk 1, the ventilation channel 11 can be formed by fitting the cartridge 3 into the first well 21 of the well forming disk main body 2.

In the disk 1 according to the fourteenth aspect, in any one of the first to twelfth aspects, the ventilation channel 11 is formed with a well on the inner wall surface of the first well 21 of the well forming disk main body 2 and the side surface of the cartridge 3. It includes a space formed between the grooves provided along the thickness direction of the disc body 2. As a result, in the disk 1, the ventilation channel 11 can be formed by fitting the cartridge 3 into the first well 21 of the well forming disk main body 2.

The disc of the present disclosure and the manufacturing method thereof are industrially useful because the scattering of the liquid sample can be suppressed when the test disc is rotated around the central axis of the test disc.

1 disc (inspection disc)
10, 25, 45, 56 Central axis 11 Ventilation flow path 2 Well forming disk body (laminated disk body)
2A, 51

Front surface

2B, 52 Back surface 21 First well 22 Second well 221 Bottom surface 222 Top surface 23 Channel 27 Connection channel 29,410 Recess 3 Cartridge (filter cartridge)
30 Case 31 Storage space 35 Filter 47 Rib 320 Opening 404 Groove 91 First mold 911 First recess 92 Second mold 912 Second recess

Claims

A first well having a front surface and a back surface opposite to each other in the thickness direction, and formed of a recess formed along the thickness direction from the front surface side; and a second well communicating with the first well A well-forming disc body having,
A cartridge having a storage space in which a liquid sample can be stored, and being fitted into the first well of the well-forming disk body;
An inspection disk, comprising: a vent channel formed between the cartridge and the well forming disk main body and communicating with the outside of the well forming disk main body and the second well.
The cartridge has a filter for removing a specific substance from the liquid sample moving from the storage space to the second well;
The inspection disk according to claim 1, wherein the filter is between the storage space and the second well.
The cartridge has an opening at an end facing the second well, and a case for holding the filter.
The filter is arranged to close the opening;
3. The inspection disk according to claim 2, wherein in the cartridge, a space surrounded by the case and the filter constitutes the storage space.
4. The inspection according to claim 1, wherein the first well and the second well are arranged in this order in a direction from the center of the well forming disk main body to the outer periphery. 5. disk.
The well forming disk main body includes a flow path that is between the first well and the second well and communicates with the first well and the second well, and the flow path in a circumferential direction of the well forming disk main body. And a connection channel that is between the vent channel and the second well and communicates with the vent channel and the second well,
The inspection disk according to any one of claims 1 to 4, wherein an opening area of the flow path gradually decreases as the distance from the first well increases and the second well is approached.
The well forming disk main body includes a rib that protrudes from the inner wall surface of the recess toward the side surface of the cartridge and faces the bottom surface of the recess.
The inspection disk according to claim 5, wherein a space between a bottom surface of the concave portion and the rib forms a part of the ventilation channel.
The minimum height from the bottom surface of the recess to the rib in the thickness direction of the well forming disk main body is such that a capillary force acts on the liquid sample in the second well in the ventilation channel. The inspection disk according to claim 6, wherein the inspection disk has a height that does not exist.
The minimum height from the bottom surface of the recess to the rib in the thickness direction of the well forming disk main body is from the bottom surface to the top surface of the second well in the thickness direction of the well forming disk main body. The inspection disk according to claim 6, wherein the inspection disk is larger than a minimum height.
The test disk according to claim 1, wherein the ventilation channel is formed on both sides of the cartridge in a circumferential direction of the well forming disk main body.
9. The inspection disk according to claim 1, wherein the ventilation channel is formed only on one side of the cartridge in a circumferential direction of the well forming disk main body.
11. The inspection disk according to claim 1, wherein a volume of the second well is larger than a volume of the storage space.
12. The inspection according to claim 1, wherein an area of the second well is larger than an area of the first well when viewed from the thickness direction of the well forming disk main body. disk.
The vent flow path includes a space formed between a groove provided in the inner wall surface of the first well of the well forming disk main body along the thickness direction of the well forming disk main body and the cartridge. The inspection disk according to claim 1, wherein the inspection disk is a disk.
The air flow path includes a space formed between an inner wall surface of the first well of the well forming disk main body and a groove provided in the cartridge along the thickness direction of the well forming disk main body. The inspection disk according to claim 1, wherein the inspection disk is a disk.